Ultrafast generation of hidden phases via energy-tuned electronic photoexcitation in magnetite.

Phase transitions occurring in nonequilibrium conditions can evolve through high-energy intermediate states inaccessible via equilibrium adiabatic conditions. Because of the subtle nature of such hidden phases, their direct observation is extremely challenging and requires simultaneous visualization of matter at subpicoseconds and subpicometer scales. Here, we show that a magnetite crystal in the vicinity of its metal-to-insulator transition evolves through different hidden states when controlled via energy-tuned ultrashort laser pulses. By directly monitoring magnetite's crystal structure with ultrafast electron diffraction, we found that upon near-infrared (800 nm) excitation, the trimeron charge/orbital ordering pattern is destroyed in favor of a phase-separated state made of cubic-metallic and monoclinic-insulating regions. On the contrary, visible light (400 nm) activates a photodoping charge transfer process that further promotes the long-range order of the trimerons by stabilizing the charge density wave fluctuations, leading to the reinforcement of the monoclinic insulating phase. Our results demonstrate that magnetite's structure can evolve through completely different metastable hidden phases that can be reached long after the initial excitation has relaxed, breaking ground for a protocol to control emergent properties of matter.

PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study.

BACKGROUND: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. METHODS: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. RESULTS: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. CONCLUSION: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Analysis of Postprandial Symptom Patterns in Subgroups of Patients With Rome III or Rome IV Functional Dyspepsia.

BACKGROUND & AIMS: Among patients with functional dyspepsia (FD), there is overlap in symptoms between those in the Rome III subgroups of postprandial distress syndrome (PDS) and those with epigastric pain syndrome (EPS). The Rome IV consensus proposed to incorporate all patients with postprandial symptoms into the PDS group. We aimed to evaluate the assessment of meal-related dyspepsia symptoms in patients with FD according to the Rome III vs Rome IV subdivisions. METHODS: Consecutive patients with FD referred for a gastric emptying test (n = 96) were asked to fill out the Rome III gastroduodenal questionnaire, with questions on meal-related occurrence. Study participants underwent a gastric emptying breath test, during which the intensity of dyspeptic symptoms (fullness, bloating, belching, nausea, epigastric pain, and burning) was scored before and up to 4 hours after a meal. We analyzed the association between the Rome subdivision and symptom severity and pattern during the breath test. RESULTS: According to Rome III, 10% had EPS alone, 29% PDS alone, and 61% overlapping EPS and PDS. The frequency of the symptoms reported in the Rome questionnaire associated with the intensity of the symptoms during the breath test in the PDS group and in the groups with PDS and EPS overlap, but not in the group with EPS. We adapted the definition of the PDS subgroup to include patients with meal-related non-PDS symptoms (Rome IV); this reduced the proportion of patients with overlap of EPS and PDS symptoms from 61% to 18% and in this group the association of symptoms with the meal was reduced. CONCLUSIONS: In an analysis of patients with FD, a meal induced or exacerbated symptoms in most patients. The Rome IV criteria for PDS reduce the proportions categorized as having both PDS and EPS and identify a patient group whose symptoms are associated with the meals. University hospital of Leuven study no: S55426.

Ultrafast generation and control of an electron vortex beam via chiral plasmonic near fields.

Vortex-carrying matter waves, such as chiral electron beams, are of significant interest in both applied and fundamental science. Continuous-wave electron vortex beams are commonly prepared via passive phase masks imprinting a transverse phase modulation on the electron's wavefunction. Here, we show that femtosecond chiral plasmonic near fields enable the generation and dynamic control on the ultrafast timescale of an electron vortex beam. The vortex structure of the resulting electron wavepacket is probed in both real and reciprocal space using ultrafast transmission electron microscopy. This method offers a high degree of scalability to small length scales and a highly efficient manipulation of the electron vorticity with attosecond precision. Besides the direct implications in the investigation of nanoscale ultrafast processes in which chirality plays a major role, we further discuss the perspectives of using this technique to shape the wavefunction of charged composite particles, such as protons, and how it can be used to probe their internal structure.

Laser-Induced Skyrmion Writing and Erasing in an Ultrafast Cryo-Lorentz Transmission Electron Microscope.

We demonstrate that light-induced heat pulses of different duration and energy can write Skyrmions in a broad range of temperatures and magnetic field in FeGe. Using a combination of camera-rate and pump-probe cryo-Lorentz transmission electron microscopy, we directly resolve the spatiotemporal evolution of the magnetization ensuing optical excitation. The Skyrmion lattice was found to maintain its structural properties during the laser-induced demagnetization, and its recovery to the initial state happened in the sub-µs to µs range, depending on the cooling rate of the system.

High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy.

BACKGROUND & AIMS: Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females. METHODS AND RESULTS: In 110 morbidly obese patients undergoing laparoscopic sleeve gastrectomy, hs-CRP as well as anthropometric assessment of adiposity, completed by electric bioimpedance and ultrasonography quantification of visceral fat area (VFA), were measured before and one year after surgery. As compared to males, obese female showed less severe overweight and prevalent subcutaneous fat deposition, but higher circulating hs-CRP. In obese females, hs-CRP was associated with VFA at baseline, independently of body mass index (BMI) and visceral adiposity index (OR 1.022 [95% CI 1.001-1.044]; p = 0.039). Based on decreases and increases in hs-CRP levels after surgery, two distinct subgroups of females were identified. Post-surgery decreases in hs-CRP was predominantly observed in patients with higher baseline levels of hs-CRP and associated with greater reduction of weight, BMI, fat and lean mass, VFA and visceral to subcutaneous fat ratio. Finally, we observed that high baseline values of hs-CRP were able to predict VFA reduction one-year after surgery, independently of BMI and visceral adiposity index (VAI) loss (OR 1.031 [95% CI 1.009-1.053]; p = 0.005). CONCLUSION: In obese females, hs-CRP levels might be a promising biomarker of visceral fat amount and dysfunction, in addition to predict the effectiveness of bariatric surgery in terms of loss of VFA one-year after surgery.

Three-trocar laparoscopic cholecystectomy under spinal anesthesia in a patient with asthma.

INTRODUCTION: Laparoscopy is perceived as the state-of-the-art technique for a wide variety of operations but is contraindicated by comorbidities such as respiratory diseases. We present the case of a patient affected by asthma who underwent a successful three-trocar low-pressure pneumoperitoneum under spinal anesthesia. CASE REPORT: A 58 year-old male with symptomatic gallstones had partly-controlled asthma and respiratory allergies. Potential bronchospasm was avoided by a less invasive laparoscopic technique. Under spinal anesthesia open pneumoperitoneum was achieved at the umbilicus. Two more trocars were inserted. A cholecystectomy was performed in 90 minutes keeping the patient in a supine position and the pneumopneumoperitoneum at 8 mmHg. The post-operative course was uneventful. Discharge to home occurred on day two. DISCUSSION: Laparoscopy is contraindicated in the presence of hemodynamic instability and inability of the patient to tolerate laparoscopic surgery. Asthma is caused by bronchoconstriction from a myriad possible stimuli requiring a specific anesthetic plan. Spinal anesthesia under low pressure pneumoperitoneum is a safe alternative to general anesthesia in high risk candidates. In experienced hand, a three-trocar cholecystectomy is safe and feasible. CONCLUSION: Our patient represented a challenging case due to a partly-controlled asthma. Bronchospasm under general anesthesia was prevented by spinal anesthesia to keep a spontaneous physiologic respiration, irrigation of the right subdiaphragmatic surface with lidocaine to control right shoulder pain, safe dissection by three trocars, a pneumoperitoneum at 8 mmHg, the supine position to prevent significant physiologic changes and minimize diaphragmatic irritation.

Pathophysiological Abnormalities in Functional Dyspepsia Subgroups According to the Rome III Criteria.

OBJECTIVES: The Rome III criteria proposed to subdivide functional dyspepsia (FD) into a postprandial distress syndrome (PDS) group, characterized by the presence of postprandial fullness and/or early satiety, and an epigastric pain syndrome (EPS) group, characterized by the presence of epigastric pain and/or epigastric burning. It has been suggested that different pathophysiological mechanisms underlie the symptom presentations in these subgroups that might determine treatment choices. The aim of this study was to investigate the prevalence of gastric sensorimotor dysfunction in the PDS, EPS, and overlap groups and to evaluate potential differential associations with dyspeptic symptom scores. METHODS: Consecutive FD patients fulfilling Rome III criteria were recruited and they scored frequency of dyspeptic symptoms (postprandial fullness, early satiety, nausea, bloating, epigastric pain, and epigastric burning) over the past 3 months (0-5; 1=once a month or less, 2=two or three times a month, 3=once a week, 4=several times a week, 5=every day). The cumulative symptom score was calculated by adding up the score of these dyspeptic symptoms. Based on these symptom scores, the patients were subdivided into subgroups according to the Rome III consensus: (i) PDS, characterized by postprandial fullness and/or early satiety at least several times a week, (ii) EPS, characterized by epigastric pain and/or epigastric burning at least once a week, and (iii) overlap, fulfilling the criteria for both PDS and EPS. Gastric sensitivity and gastric accommodation were measured using barostat testing, and solid gastric emptying was determined using the [14C]octanoate breath test. RESULTS: A total of 560 FD patients (165 men, age 41.8±0.7 years) were classified into PDS (n=131), EPS (n=50), and overlap (n=379) groups. The prevalence of gastric hypersensitivity, impaired gastric accommodation, and delayed gastric emptying were 37%, 37%, and 23%, respectively, without any differential distribution in Rome III subgroups (P=0.16, P=0.27, and P=0.39 respectively). Comparing the physiological parameters for these gastric sensorimotor functions, there was only a significant difference in the gastric half emptying time between subgroups, with the overlap group having a higher t1/2 (P<0.05) compared with the EPS group. In the overlap group, gastric hypersensitivity was associated with the severity of PDS symptoms (P=0.03), EPS symptoms (P=0.02), and the cumulative symptom score (P=0.02), whereas delayed gastric emptying was associated with nausea (P=0.02) and the cumulative symptom score (P=0.02). CONCLUSIONS: Except for gastric emptying in the overlap group, FD subgroups as defined by the Rome III criteria are not differentially associated with putative pathophysiological mechanisms. These observations question the utility of this classification for guiding therapeutic choices in clinical practice.

Real-Time Observation of Phonon-Mediated σ-π Interband Scattering in MgB_{2}.

In systems having an anisotropic electronic structure, such as the layered materials graphite, graphene, and cuprates, impulsive light excitation can coherently stimulate specific bosonic modes, with exotic consequences for the emergent electronic properties. Here we show that the population of E_{2g} phonons in the multiband superconductor MgB_{2} can be selectively enhanced by femtosecond laser pulses, leading to a transient control of the number of carriers in the σ-electronic subsystem. The nonequilibrium evolution of the material optical constants is followed in the spectral region sensitive to both the a- and c-axis plasma frequencies and modeled theoretically, revealing the details of the σ-π interband scattering mechanism in MgB_{2}.

High baseline C-reactive protein levels predict partial type 2 diabetes mellitus remission after biliopancreatic diversion.

BACKGROUND AND AIMS: Several studies demonstrated that surgery can improve inflammation parameters, such as C-reactive protein (CRP). Few biomarkers have been investigated to potentially predict type 2 diabetes mellitus (T2DM) remission. We aimed at determining whether pre-surgery serum CRP levels could predict T2DM remission after 3 years in patients undergoing bariatric surgery, especially biliopancreatic diversion (BPD). METHODS AND RESULTS: This study was conducted from 2007 to 2009 at the Surgical Department of the University of Genoa, Italy. Forty-four patients with T2DM undergoing BPD (n = 38) or Roux-en-Y gastric bypass (n = 6) were enrolled. The primary endpoint was to evaluate whether pre-surgery CRP levels could predict T2DM partial remission at 3-year follow-up. Secondary endpoints were to assess whether glycaemic, lipid, and inflammatory parameters modified during the follow-up. At baseline, patients with T2DM ranged from overweight to morbid obesity, had mild dyslipidaemia, and a low-grade inflammation. Bariatric surgery improved body weight, lipid and glycaemic profile both at 1- and 3-year follow-up. Pre-surgery CRP levels progressively decreased at 1- and 3-year follow-up. Among inflammatory pre-surgery parameters, only high CRP levels were shown to predict T2DM partial remission after 3 years. Multivariate analysis confirmed the predictive value of pre-surgery CRP levels independently of age, gender, type of surgery, and body mass index. CONCLUSION: Bariatric surgery, in particular BPD, improved both metabolic and inflammatory biomarkers at 1- and 3-year follow-up. Pre-surgery high CRP levels predicted 3-year T2DM partial remission, indicating a promising target population to be especially treated with BPD.

Lymph node assessment in colorectal cancer surgery: laparoscopic versus open techniques.

AIM: The aim of our study is to compare the outcomes of laparoscopic resection (LR) and open resection (OR) for colorectal cancer surgery evaluating lymph node assessment. It may be important to remove and examine an adequate number of lymph nodes because a more extensive nodal resection has been associated to higher survival rate and lower recurrences. PATIENTS AND METHODS: 150 patients (74 females and 76 males) with colorectal cancer were enrolled and analyzed from January 2006 to March 2010 in our Unit. 100 procedures were performed with traditional laparotomy and 50 procedures laparoscopically. A strict follow-up was scheduled every 1-3-6 months after surgery and, therefore, every year. RESULTS: Laparoscopic techniques require a longer operating time. 2484 total lymph nodes examined with a mean of 16,56 removed per resection in all procedures. 1632 lymph nodes were removed during open procedures and 852 removed during laparoscopy. The scheduled follow-up demonstrated that local recurrence and distant metastasis presented with no significant differences between two groups and overall survival and disease-free survival were assessed over 5 year in 80% of patients. CONCLUSIONS: According to our experience, laparoscopic colorectal surgery is safe and feasible, with better short-term outcomes and oncological adequacy comparable to open approach.

Sphenofrontal distance on three-dimensional ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation.

OBJECTIVE: To compare the distance between the sphenoid and frontal bones on three-dimensional (3D) ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation. METHODS: We acquired 3D volumes of the fetal profile from 80 normal and 30 trisomy-21 fetuses at 16-24 weeks' gestation. We used the multiplanar mode to obtain the mid-sagittal plane and measured the sphenofrontal distance as the shortest distance between the most anterior edge of the sphenoid bone and the lowest edge of the frontal bone. RESULTS: In normal fetuses, the sphenofrontal distance increased linearly with gestational age, from 15.1 mm at 16 weeks to 18.2 mm at 24 weeks. In fetuses with trisomy 21, the mean sphenofrontal distance delta value was significantly smaller than in normal cases (-3.447 mm (95% CI, -5.684 to -1.211 mm); P < 0.01). The sphenofrontal distance was below the 5(th) and 1(st) percentiles of the normal range in 29 (96.7%) and 27 (90.0%) trisomy-21 fetuses, respectively. CONCLUSIONS: The sphenofrontal distance is shorter at 16-24 weeks' gestation in fetuses with trisomy 21 than in normal fetuses. A reduction in the growth of the anterior cranial base contributes to the mid-facial hypoplasia observed in fetuses with trisomy 21. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cross-presentation in viral immunity and self-tolerance.

T lymphocytes recognize peptide antigens presented by class I and class II molecules encoded by the major histocompatibility complex (MHC). Classical antigen-presentation studies showed that MHC class I molecules present peptides derived from proteins synthesized within the cell, whereas MHC class II molecules present exogenous proteins captured from the environment. Emerging evidence indicates, however, that dendritic cells have a specialized capacity to process exogenous antigens into the MHC class I pathway. This function, known as cross-presentation, provides the immune system with an important mechanism for generating immunity to viruses and tolerance to self.

Gastroduodenal mechanisms underlying functional gastric disorders.

Functional dyspepsia (FD), a disorder thought to originate from the gastroduodenum, is one of the most prevalent functional gastrointestinal disorders. In this review, we focused on gastroduodenal mechanisms involved in the pathophysiology of FD. The roles of impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention and to luminal agents, altered mucosal integrity, low-grade inflammation and psychological stress are reviewed. The underlying pathophysiology in FD is probably multifactorial, involving a combination of several of these factors, ultimately leading to symptom pattern and severity.

Review article: Functional dyspepsia-a gastric disorder, a duodenal disorder or a combination of both?

BACKGROUND: Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach. AIM: The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms. METHODS: We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD. RESULTS: The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms. CONCLUSION: Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.

Third whole-brain radiation therapy for multiple brain metastases. Should it be considered in selected patients?

Whole brain reirradiation for the treatment of multiple brain metastases has shown promising results. However, concerns remain over the possible neurotoxic effects of the cumulative dose as well as the questionable radiosensitivity of recurrent metastases. A second reirradiation of the whole brain is ordinarily performed in our department for palliative purposes in patients presenting with multiple metastatic brain progression. For this study, an investigational third whole brain reirradiation has been administered to highly selected patients to obtain disease control and delay progression. Clinical outcomes and neurological toxicity were also evaluated.

Anisotropy of spatiotemporal decorrelation in electrohydrodynamic turbulence.

Nonlinear straining and random sweeping spatiotemporal decorrelation properties, originally introduced as the main processes for turbulent fluctuations decorrelation in usual fluid flows, have been observed experimentally in anisotropic electroconvective turbulence generated in a nematic liquid crystal under the action of an external oscillating electric field. A transition between both processes occurs when the instability is driven toward states of increasing complexity, thus showing that decorrelation mechanisms in turbulent media are more universal than naively expected. A model for both decorrelation mechanisms is introduced, its comparison with experimental results providing an estimate of the characteristic sweeping velocity.

Spatio-temporal dynamics, patterns formation and turbulence in complex fluids due to electrohydrodynamics instabilities.

The complex spatio-temporal dynamics generated by electrohydrodynamics instabilities in a nematic liquid crystal under the action of a driving oscillating electric field is investigated. Quasi-stationary convective structures which are visible at large scales are broken into chaotic patterns at higher driving voltages, thus generating small-scale structures. Scaling analysis reveals that these small-scale structures self-organize in a network of subleading structures which are reminescent of convective rolls. This network persists well inside the chaotic regimes, disappearing only at very high voltages, where stochastic dynamical scattering mode takes place.

Current standards and future strategies in immunochemotherapy of non-Hodgkin's lymphoma.

The therapeutic options for B-cell non-Hodgkin's lymphoma (NHL) have dramatically expanded with the advent of immune-based treatments. The monoclonal antibody anti- CD20 rituximab represents the best example of these advances and has quickly become incorporated into the therapeutic armamentarium for this hematological disease. In addition, other antibodies are eventually becoming part of treatment approaches to NHL. Furthermore, the role of therapeutic vaccines continues to be an important ongoing research question. Despite this success, several questions on how to optimize the use of monoclonal antibodies in NHL remain open since the best administration schedules, as well as the optimal duration of immunotherapy still have to be determined. Finally the development of resistance to treatment remains the main limit of this innovative approach, necessitating the development of strategies to circumvent resistance itself. This review will summarize the state of the art of antibody-based immunotherapy of NHL and discuss prospective approaches to improve the benefit of these treatments in patients.

Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization.

CTL recognize peptide forms of processed, foreign antigens in association with class I molecules encoded by the MHC and are usually directed against endogenously synthesized "cellular antigens," such as those expressed by virus-infected cells. In vitro studies have shown that small exogenous peptides can directly associate with class I molecules on the cell surface and mimic the target complex derived by intracellular processing and presentation. We have recently generated OVA-specific, H-2Kb-restricted CTL by immunizing C57BL/6 mice with a syngeneic tumor line transfected with the OVA cDNA. The CTL recognize the OVA transfectant E.G7-OVA and the synthetic peptide OVA258-276, but fail to recognize the native protein. We reasoned that given the potential for direct peptide/class I association observed in vitro, OVA258-276 may induce CTL after in vivo priming. However, we found that this is not the case. OVA258-276 and peptides of increasing lengths up to OVA242-276 and OVA242-285, which are all able to form the target complex in vitro, are inefficient at priming E.G7-OVA-specific CTL responses after intravenous injection. This is also true for both native and denatured OVA. In contrast to these results the synthetic peptide OVA229-276 corresponding to a peptide in a partial tryptic digestion of OVA can efficiently prime C57BL/6 mice in vivo after intravenous injection. This peptide elicits CTL that appear identical to those derived from animals immunized with syngeneic cells producing OVA endogenously. These results are discussed in terms of separate class I and class II antigen presentation pathways and the ability of only certain, exogenous antigens to enter the cytoplasmic, class I pathway.