Safety of robotic cholecystectomy as index training procedure: the UK experience.

AIMS: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. METHODS: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. RESULTS: A total of 600 patients were included. The median age was 53 (IQR 65-41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0-1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). CONCLUSION: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy.

Apraxia Patterns for the Differentiation between Alzheimer's Disease and Frontotemporal Dementia Variants.

Background and Objectives: Despite the increasing use of biomarkers, differentiation between Alzheimer's disease (AD), behavioral variant Frontotemporal Dementia (bvFTD), and Primary Progressive Aphasia (PPA) remains a challenge. Apraxia is a supportive feature for diagnosing AD but is underrepresented in other dementia types. Herein, we investigated the presence and characteristic profiles of limb, verbal, and non-verbal apraxia in three major dementia types. Materials and Methods: Test for Upper Limb Apraxia (TULIA) and Apraxia Battery for Adults-2 (ABA-2) were administered in patients with AD (n = 22), bvFTD (n = 41), and PPA (n = 22), with 20 individuals serving as healthy controls (HC). Composite and subdomain scores were compared between each patient group and the HC. Praxis profiles indicative of each dementia type and a possible predictive value were sought. Results: Apraxia provided high diagnostic accuracy for detecting dementia compared with HC (sensitivity: 63.6-100%, specificity: 79.2-100%). Patients with AD performed worse when imitating intransitive gestures as well as pantomiming transitive gestures (mean differences: 2.10 and 3.12, respectively), compared with bvFTD. PPA patients, compared with bvFTD, had comparable results in limb, verbal, and non-verbal praxis assessments, despite the greater deterioration in the outcome. Compared with patients with AD, PPA had increased pathological outcomes in verbal (86.4% vs. 40.9%) and non-verbal apraxia (31.8% vs. 0%), while bvFTD had increased pathological outcomes in verbal apraxia (85.4% vs. 44.5%). Finally, apraxia is correlated with cognitive decline. Conclusions: Apraxia profile evaluation could contribute to the differentiation between AD and Frontotemporal Dementia (FTD). Both TULIA and ABA-2 are reliable tools that can be performed as bed-side tests in clinical practice.

Structural and Biochemical Characterization of the Human Angiogenin-Proliferating Cell Nuclear Antigen Interaction.

The molecular details of the interaction between human angiogenin (hAng) and proliferating cell nuclear antigen (PCNA) have been investigated by isothermal titration calorimetry (ITC), mutagenesis, and NMR spectroscopy. The two proteins were shown to interact directly through immunoprecipitation studies of hAng with PCNA in vitro, and their interaction was quantified by ITC, obtaining information on stoichiometry, enthalpy, entropy, and binding kinetics of the association. The hAng-PCNA association is strong, with a Kd value of 126 nM. The interaction surface was mapped by NMR spectroscopy, indicating participating residues. A structural model for the PCNA-hAng complex was constructed by docking and molecular dynamics simulations based on NMR data. The model was validated by mutating the hAng residues Arg5 and Arg101, which seem critical for the complex formation, to glutamate. ITC experiments showed that the angiogenin variants R5E and R5ER101E displayed 6.5 and 7.8 times higher Kd values, respectively, than that of the native protein, indicating the correctness of the model. The hAng S28AT36AS37A and hAng S28AT36AS37AS87A variants were also tested as positive controls, further supporting the validity of the model. The crystal structures of the hAng variants S28AT36AS37A and S28AT36AS37AS87A showed that the mutations did not cause any significant conformational change. This study presents evidence for the structural mode of the hAng-PCNA interaction, revealing valuable information about the angiogenin and PCNA biological roles in the cytoplasm.

West Nile virus-associated HLA-DRB1 alleles in the Greek population: A structural perspective.

The HLA system plays a significant role via the regulation of the immune system and contributes to the progression and protection of many diseases. In our previous study, several HLA-DRB1 alleles were found to have a susceptible or protective role toward infection and neuroinvasion of West Nile Virus (WNV) in the Greek population. As expected, the majority of polymorphic positions are located in the peptide-binding region of the molecule. In the present work, the structure of these alleles was studied in silico, to examine the effect of polymorphism on the conformation of DRB1 proteins, with the aspect of WNV association. More specifically, molecular dynamics simulations were used for structural prediction of 23 available alleles. These modeled alleles were evaluated using root-mean-square deviation (RMSD) and root-mean-square fluctuation analysis. Low RMSD values indicate that different alleles have similar structures. Furthermore, low fluctuation was observed in the peptide-binding region between alleles with the higher and the lowest RMSD values. These findings indicate that probably variable residues do not affect the behavior of DRB1 alleles in WNV disease, by causing structural differences between them.

Yet Another Compact Time Series Data Representation Using CBOR Templates (YACTS).

The Internet of Things (IoT) technology is growing rapidly, while the IoT devices are being deployed massively. However, interoperability with information systems remains a major challenge for this accelerated device deployment. Furthermore, most of the time, IoT information is presented as Time Series (TS), and while the majority of the studies in the literature focus on the prediction, compression, or processing of TS, no standardized representation format has emerged. Moreover, apart from interoperability, IoT networks contain multiple constrained devices which are designed with limitations, e.g., processing power, memory, or battery life. Therefore, in order to reduce the interoperability challenges and increase the lifetime of IoT devices, this article introduces a new format for TS based on CBOR. The format exploits the compactness of CBOR by leveraging delta values to represent measurements, employing tags to represent variables, and utilizing templates to convert the TS data representation into the appropriate format for the cloud-based application. Moreover, we introduce a new refined and structured metadata to represent additional information for the measurements, then we provide a Concise Data Definition Language (CDDL) code to validate the CBOR structures against our proposal, and finally, we present a detailed performance evaluation to validate the adaptability and the extensibility of our approach. Our performance evaluation results show that the actual data sent by IoT devices can be reduced by between 88% and 94% compared to JavaScript Object Notation (JSON), between 82% and 91% compared to Concise Binary Object Representation (CBOR) and ASN.1, and between 60% and 88% compared to Protocol buffers. At the same time, it can reduce Time-on-Air by between 84% and 94% when a Low Power Wide Area Networks (LPWAN) technology such as LoRaWAN is employed, leading to a 12-fold increase in battery life compared to CBOR format or between a 9-fold and 16-fold increase when compared to Protocol buffers and ASN.1, respectively. In addition, the proposed metadata represent an additional 0.5% of the overall data transmitted in cases where networks such as LPWAN or Wi-Fi are employed. Finally, the proposed template and data format provide a compact representation of TS that can significantly reduce the amount of data transmitted containing the same information, extend the battery life of IoT devices, and improve their lifetime. Moreover, the results show that the proposed approach is effective for different data types and it can be integrated seamlessly into existing IoT systems.

Chemical and Sensory Characterization of Xinomavro Red Wine Using Grapes from Protected Designations of Northern Greece.

Despite Xinomavro (Vitis vinifera L.) being a well-known noble red grape variety of northern Greece, little is known about its ''bouquet'' typicity. Volatile compounds of Xinomavro wines produced using a common vinification protocol were analyzed by gas chromatography-mass spectrometry and sensory descriptive analysis was carried out with a trained panel. Wines were characterized by the presence of fatty acids, ethyl and acetate esters, and alcohols, with contributions from terpenes and a volatile phenol. The most active aroma compounds were determined to be 3-methylbutyl acetate, ß-damascenone, ethyl esters of octanoic and hexanoic acids, and eugenol. Those compounds positively correlated with fruity and spicy odor descriptors, with the wines being mostly characterized by five typical aroma terms: strawberry, berry fruit, spices, tomato, and green bell pepper. Partial least squares regression (PLSR) analysis was used to visualize relationship between the orthonasal sensory attributes and the volatile aroma compounds with calculated OAVs > 1. Key aroma-active volatiles in the wines were identified using GC-MS/olfactometry, providing a list of 40 compounds, among which 13 presented a modified detection frequency > 70%. This study is the first of its kind and provided strong indications regarding the aroma compounds defining the sensory characteristics of Xinomavro wines.

A Comprehensive Survey on Nanophotonic Neural Networks: Architectures, Training Methods, Optimization, and Activations Functions.

In the last years, materializations of neuromorphic circuits based on nanophotonic arrangements have been proposed, which contain complete optical circuits, laser, photodetectors, photonic crystals, optical fibers, flat waveguides and other passive optical elements of nanostructured materials, which eliminate the time of simultaneous processing of big groups of data, taking advantage of the quantum perspective, and thus highly increasing the potentials of contemporary intelligent computational systems. This article is an effort to record and study the research that has been conducted concerning the methods of development and materialization of neuromorphic circuits of neural networks of nanophotonic arrangements. In particular, an investigative study of the methods of developing nanophotonic neuromorphic processors, their originality in neuronic architectural structure, their training methods and their optimization was realized along with the study of special issues such as optical activation functions and cost functions. The main contribution of this research work is that it is the first time in the literature that the most well-known architectures, training methods, optimization and activations functions of the nanophotonic networks are presented in a single paper. This study also includes an extensive detailed meta-review analysis of the advantages and disadvantages of nanophotonic networks.

The effect of type 2 diabetes mellitus on perioperative neurocognitive disorders in patients undergoing elective noncardiac surgery under general anesthesia. A prospective cohort study.

Background and Aims: Preliminary evidence suggests a possible relationship between type 2 diabetes mellitus (T2DM) and perioperative neurocognitive disorders (NCD). We sought to investigate whether patients with T2DM, undergoing elective noncardiac surgery under general anesthesia, are at increased risk of perioperative NCD. Material and Methods: A prospective cohort study was designed. One-hundred and forty-four patients with T2DM and 144 healthy controls were recruited. Controls were matched for sex, age, type of operation, and educational background. Postoperative delirium (POD), delayed neurocognitive recovery and postoperative NCD were evaluated. Results: Two hundred twenty-eight patients were analyzed. Compared to controls, patients with T2DM were diagnosed with higher rates of NCD preoperatively (n = 96 vs. n = 26, P < 0.05) and higher POD up to 4 days postoperatively (n = 204 vs. n = 68, P < 0.05). Increased rates of delayed neurocognitive recovery and postoperative NCD were recorded in patients with T2DM up to 9 months postoperatively (n = 473 vs. n = 192, P < 0.05). Insulin-dependent patients had higher rates of POD on the second (n = 38 vs. n = 24, P < 0.05) and third day (n = 27 vs. n = 16, P < 0.05) when compared to noninsulin-dependent patients. Logistic multivariable analysis revealed that patients with T2DM are at increased risk for postoperative cognitive disorders. Conclusion: Patients with type 2 diabetes mellitus appear to be at a higher risk of perioperative NCDs up to 9 months after elective noncardiac surgery under general anesthesia.

Defragmenting the 6LoWPAN Fragmentation Landscape: A Performance Evaluation.

The emergence of the Internet of Things (IoT) has made wireless connectivity ubiquitous and necessary. Extending the IoT to the Industrial Internet of Things (IIoT) places significant demands in terms of reliability on wireless connectivity. The Institute of Electrical and Electronics Engineers (IEEE) Std 802.15.4-2015 standard was designed in response to these demands, and the IPv6 over Low power Wireless Personal Area Networks (6LoWPAN) adaptation layer was introduced to address (among other issues) its payload size limitations by performing packet compression and fragmentation. However, the standardised method does not cope well with low link-quality situations and, thus, we present the state-of-the-art Forward Error Correction (FEC) methods and introduce our own contribution, Network Coding FEC (NCFEC), to improve performance in these situations. We present and analyse the existing methods as well as our own theoretically, and we then implement them and perform an experimental evaluation using the 6TiSCH simulator. The simulation results demonstrate that when high reliability is required and only low quality links are available, NCFEC performs best, with a trade-off between additional network and computational overhead. In situations where the link quality can be guaranteed to be higher, simpler solutions also start to be feasible, but with reduced adaptation flexibility.

Proteome-based classification of Nonmuscle Invasive Bladder Cancer.

DNA/RNA-based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high-resolution proteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype-specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low-risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross-omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.

Boswellic acids and their derivatives as potent regulators of glucocorticoid receptor actions.

Glucocorticoid (GCs) hormones exert their actions via their cognate steroid receptors the Glucocorticoid Receptors (GR), by genomic or non-genomic mechanisms of actions. GCs regulate many cellular functions among them growth, metabolism, immune response and apoptosis. Due to their cell type specific induction of apoptosis GCs are used for the treatment of certain type of cancer. In addition, due to their anti-inflammatory actions, GCs are among the most highly prescribed drug to treat chronic inflammatory disorders, albeit to the many adverse side effects arising by their long term and high doses use. Thus, there is a high need for selective glucocorticoid receptor agonist - modulators (SEGRA- SGRMs) as effective as classic GCs, but with a reduced side effect profile. Boswellic acids (BAs) are triterpenes that show structural similarities with GCs and exhibit anti-inflammatory and anti-cancer activities. In this study we examined whether BA alpha and beta and certain BAs derivatives exert their actions, at least in part, through the regulation of GR activities. Applying docking analysis we found that BAs can bind stably into the deacylcortivazol (DAC) accommodation pocket of GR. Moreover we showed that certain boswellic acids derivatives induce glucocorticoid receptor nuclear translocation, no activation of GRE dependent luciferase gene expression, and suppression of the TNF-α induced NF-κB transcriptional activation in GR positive HeLa and HEK293 cells, but not in low GR level COS-7 cells. Furthermore, certain boswellic acids compounds exert antagonistic effect on the DEX-induced GR transcriptional activation and induce cell type specific mitochondrial dependent apoptosis. Our results indicate that certain BAs are potent selective glucocorticoid receptor regulators and could have great potential for therapeutic use.

Patients with severe aortic stenosis and coexisting pulmonary hypertension treated by transapical transcatheter aortic valve replacement-Is there a need for increased attention?

OBJECTIVES: Aim of this study is to elucidate the impact of pulmonary hypertension on patients treated with a transapical aortic valve replacement. BACKGROUND: In patients with aortic stenosis (AS) the coexistence of pulmonary hypertension (PH) is associated with increased peri-operative risk for surgical aortic valve replacement. For transcatheter aortic valve replacement (TAVR), it is unknown whether transapical TAVR (TA-TAVR) is associated with increased peri-interventional risk in PH patients. METHODS: We performed a single center analysis in 189 patients with severe AS with (AS + PH) or without PH (AS - PH) undergoing TA-TAVR. PH was defined by mean pulmonary artery pressure ≥25 mmHg assessed by right heart catheterization (exclusion of 64 patients due to missing results). As the primary endpoint a combination of 30-day mortality or cardiopulmonary resuscitation (CPR) was analyzed. RESULTS: Seventy three patients (58.4%) had PH. Increased peri-interventional risk in AS + PH patients was reflected by an increased rate of the primary endpoint in comparison to AS - PH patients (24.7 vs. 3.8%; p = .002). A higher proportion of acute kidney injury (34.2 vs. 15.7%; p = .025) was found in AS + PH patients while AS - PH patients showed a higher rate of bleeding in comparison AS + PH patients (18.5 vs. 6.8% p = .050). CONCLUSION: Patients with AS + PH treated by TA-TAVR are at increased peri-interventional risk for severe complications in comparison to AS - PH patients. Therefore, the identification of preventive therapeutic strategies is needed. CLASSIFICATIONS: TAVR, transapical, pulmonary hypertension, aortic stenosis.

Cardioplegic storage solution: Is it the guardian of saphenous vein graft endothelium?

INTRODUCTION: Despite their suboptimal long-term patency, saphenous vein grafts are the most widely used conduits to achieve complete revascularization during coronary artery bypass grafting (CABG). Although vein storage critically impairs endothelial integrity, contradictory data concerning optimal storage solutions exist. The aim of this study is to explore any in vitro impact of cardioplegic solutions and temperature on vein grafts endothelial integrity during their storage. MATERIALS AND METHODS: A single-center, prospective trial including 40 consecutive patients was conducted. Eligibility criteria included patients submitted to CABG receiving at least one vein graft. An excess segment of the graft was harvested and divided into four different parts. Each one of them was stored under different conditions; either in a conventional heparin-enriched blood solution or in a cardioplegic solution, at room temperature (20°C-22°C) and in the refrigerator (5°C). Endothelial integrity was evaluated via immunohistochemistry using an antibody against CD31. RESULTS: Endothelial integrity (measured in a scale from 1-worst to 5-best) was significantly better after cardioplegic solution storage (2.83 ± 0.15 and 3.10 ± 0.13 in cold and room temperature, respectively) compared with storage in conventional solutions (2.23 ± 0.16 and 2.0 ± 0.15 in cold and room temperature, respectively). A significant effect of cardioplegic storage solution, as well as of cold temperature and cardioplegic solution interaction on endothelial preservation was reported, whereas storage temperature did not prove a significant factor by its own. CONCLUSIONS: Cardioplegic storage solutions result in significantly better endothelial preservation compared with conventional heparin-enriched blood solutions. The association with superior clinical outcomes remains to be proved.

Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a "toxin-like" amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375-390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). We present the 3D structural location of this "toxin-like" sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 Spike Glycoprotein. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381-386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189-192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the "toxin-binding site" of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients.

Effect of honey on glucose and insulin concentrations in obese girls.

BACKGROUND: Childhood obesity represents a major health problem of our century. The benefits of natural products, such as honey, in the management of obesity have gained renewed interest. In this study, we investigated the effect of honey on glucose and insulin concentrations in obese prepubertal girls. MATERIALS AND METHODS: Thirty healthy obese girls aged 10.55 (±SEM:0.34) years with a mean body mass index (BMI) above the 97th centile for age (28.58 ± 1.40 kg/m2 , BMI z-score 2.96) underwent a standard oral glucose tolerance test (OGTT) followed by an oral honey tolerance test (OHTT) 2 weeks later. Both solutions contained 75 g of glucose. Subsequently, subjects were randomized to receive either 15 g of honey or 15 g of marmalade daily, while both groups complied with dietetic instructions. Six months later all subjects were re-evaluated with an OGTT and an OHTT. RESULTS: At the end of the study, all subjects demonstrated a significant reduction in BMI (27.57 ± 1.40, z-score: 2.54 vs 28.58 ± 1.40 kg/m2 , z-score: 2.96, P < 0.001), however, there were no significant differences in BMI and all parameters tested between the group that received honey and the control group. The areas under the concentration-time curve for glucose and insulin for the entire population were significantly lower following ingestion of honey than glucose solution (P < 0.001) both at the beginning and at the end of study. CONCLUSIONS: These findings indicate that honey does not have an effect on stimulated plasma glucose and serum insulin concentrations compared with the standard glucose solution in obese prepubertal girls.

Open radical prostatectomy after transurethral resection: perioperative, functional, oncologic outcomes.

INTRODUCTION: To demonstrate any differences in the perioperative, functional and oncologic outcomes after radical retropubic prostatectomy (RRP) among those patients having previously performed transurethral resection of prostate (TURP) and those not. MATERIALS AND METHODS: A total of 35 patients were diagnosed with prostate cancer (T1a and T1b) after TURP, underwent RRP and completed a 1 year follow up (group A). They were matched with a cohort of another 35 men (group B) in terms of age, body mass index (BMI), prostatic specific antigen (PSA), Gleason score, prostate volume (before surgery), pathological stage and neurovascular bundle-sparing technique. That was a retrospective study completed between September 2011 and March 2014. RESULTS: Not a significant difference was demonstrated among the two groups of patients concerning the functional and oncologic results. On the other hand, previous prostate surgery made the operation procedure more demanding. Besides, operative time and blood loss (though not translated in transfusion rates) were higher among patients in group A. Besides, catheter removal in group A patients was performed later than their counterparts of group B. CONCLUSIONS: RRP after TURP is a relatively safe procedure and in the hands of experienced surgeons, a previously performed TURP, does not seem to compromise oncologic outcomes of the operation. Continence is preserved, though erectile function seems to be compromised compared with patients undergoing RRP without prior TURP. Moreover, defining the prostate and bladder neck margins can be challenging and the surgeon has to be aware of the difficulties that might confront.

Detection of Neuropathic Pain in End-Stage Cancer Patients: Diagnostic Accuracy of Two Questionnaires.

INTRODUCTION: Neuropathic pain is a frequent consequence of cancer pain. Quite often, in the end stage, it is difficult to discern its presence and delineate its characteristics in the context of painful cancer complications. The aim of this study was to compare the diagnostic accuracy of the Douleur Neuropathique en 4 Questions (DN4) and painDETECT questionnaires, which were translated to the patient's native language, for the diagnosis of peripheral neuropathic pain in oncology patients. METHODS: End-stage cancer patients who presented to the outpatient pain clinic were prospectively followed. At presentation, all patients completed the DN4 and painDETECT questionnaires, which had been translated to their native language, and the output was compared to the pain specialist's diagnosis of the neuropathic or non-neuropathic nature of the pain, which was considered as the gold standard. The diagnostic accuracy of both questionnaires was tested with receiver operating characteristic curves plotted from the data collected. RESULTS: Ninety patients (48.5% of 185 in total) presented with severe pain. Seventy-six had neuropathic pain (41.1%) and 109 had non-neuropathic pain. Of those with neuropathic pain, most had a mixed pain (bone or visceral in addition to neuropathic pain). The DN4 questionnaire had a sensitivity of 71.1% and a specificity of 88.7% in detecting neuropathic pain, with a cutoff value of ≥ 4, while the painDETECT questionnaire had a sensitivity of 26.3% and a specificity of 100%, with a cutoff value of ≥ 19. CONCLUSION: At standard cutoff values, the DN4 and painDETECT questionnaires, despite having been translated to the patient's native language, failed to adequately discriminate between neuropathic and non-neuropathic pain in our end-stage cancer patients.

Lapatinib with whole brain radiotherapy in patients with brain metastases from breast and non-small cell lung cancer: a phase II study of the Hellenic Cooperative Oncology Group (HeCOG).

Small molecules, mainly tyrosine kinase inhibitors, are currently used in various malignancies. Lapatinib, a dual inhibitor of EGFR/HER2 tyrosine kinases, has demonstrated effectiveness in brain metastases from HER2-overexpressing breast cancer. It also appears to sensitize EGFR-expressing cell lines to radiation. To evaluate the efficacy of lapatinib in combination with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC) and breast cancer, as assessed by volumetric analysis by MRI. 81 patients were treated with WBRT (30 Gy in ten fractions) in combination with lapatinib 1250 mg once daily, followed by lapatinib 1500 mg once daily for a total 6 weeks. 21 patients had primary breast cancer and 60 patients NSCLC. Pre- and post-treatment MRI scans in a compact disk for central volumetric assessment were available for 43 patients. 27 patients (62.8%) achieved partial response, 15 patients (34.9%) had stable disease and only one patient (2.3%) had disease progression. Response was not associated to EGFR protein expression. All 81 patients were assessed for safety. The large majority of the adverse events were mild. Eight deaths occurred, four of which were considered related to the study drugs but there were also other contributing factors. Nine cases of serious infections were observed in eight patients, but they were also receiving dexamethasone. Lapatinib in combination with WBRT in patients with brain metastases from breast cancer and NSCLC is a feasible approach that can be further studied in larger clinical trials.

Centhaquin Effects in a Swine Model of Ventricular Fibrillation: Centhaquin and Cardiac Arrest.

BACKGROUND: Centhaquin citrate is a novel agent being developed for use in the treatment of haemorrhagic shock. The aim of our study was to assess whether the administration of centhaquin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. METHODS: Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets. The animals were randomised to receive placebo plus adrenaline 0.02mg/kg (n=10, Group C) and adrenaline 0.02mg/kg plus centhaquin 0.015mg/kg (n=10, Group S). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first two hours after return of spontaneous circulation (ROSC). Survival and a neurologic alertness score were measured at 24hours after ROSC. RESULTS: A significant difference was observed in ROSC rate between the two groups, as 10 animals (100%) from Group S and 4 animals (40%) from Group C achieved ROSC (p=0.011). Systolic, diastolic, and mean aortic pressure and coronary perfusion pressure were significantly higher in Group S at the end of the second cycle of CPR. In our study, all subjects with ROSC survived for 24hours, while we observed no statistically significant differences in neurologic examination (Group C 100±0, Group S 96±12.64; p=0.527). CONCLUSION: The addition of centhaquin to adrenaline improved ROSC rates in a swine model of VF cardiac arrest.

Evolution of Gyrification in Carnivores.

The order Carnivora is a large and highly diverse mammalian group with a long and well-documented evolutionary history. Nevertheless, our knowledge on the degree of cortical folding (or degree of gyrification) is limited to just a few species. Here we investigate the degree of cortical folding in 64 contemporary and 37 fossil carnivore species. We do so by measuring the length of gyri impressions on endocranial casts. We use this approach because we have found that there is a very good correlation between the degree of cortical folding and the relative length of the gyri that are exposed on the outer surface of the hemispheres. Our results indicate that aquatic and semiaquatic carnivores have higher degrees of cortical folding than terrestrial carnivores. The degree of cortical folding varies among modern families, with viverrids having the lowest values. Furthermore, the scaling of cortical folding with brain size follows different patterns across specific carnivore families. Forty million years ago, the first carnivores had a relatively small cortex and limited cortical folding. Both the size of the cortex and the degree of cortical folding increased independently in each family during evolution.