Emission and coherent control of Levitons in graphene.

Flying qubits encode quantum information in propagating modes instead of stationary discrete states. Although photonic flying qubits are available, the weak interaction between photons limits the efficiency of conditional quantum gates. Conversely, electronic flying qubits can use Coulomb interactions, but the weaker quantum coherence in conventional semiconductors has hindered their realization. In this work, we engineered on-demand injection of a single electronic flying qubit state and its manipulation over the Bloch sphere. The flying qubit is a Leviton propagating in quantum Hall edge channels of a high-mobility graphene monolayer. Although single-shot qubit readout and two-qubit operations are still needed for a viable manipulation of flying qubits, the coherent manipulation of an itinerant electronic state at the single-electron level presents a highly promising alternative to conventional qubits.

Technical details for a robot-assisted hand-sewn esophago-gastric anastomosis during minimally invasive Ivor Lewis esophagectomy.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique. METHODS: From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines. RESULTS: The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13 days (min 7, max 37 days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum. CONCLUSION: Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results.

Anatomic features in SCAD assessed by CCT: A propensity score matching case control study.

PURPOSE: Spontaneous coronary artery dissection (SCAD) may occur in middle age population without any cardiovascular risk factor. We retrospectively evaluated anatomic features of 11 patients with SCAD using a coronary arteries computed tomography (CCT), compared to age and sex balanced patients who underwent CCT. MATERIAL AND METHODS: CCT was performed in 11 patients (7 females and 4 males) as follow-up in patients with SCAD (left anterior descending - LAD or circumflex artery - Cx) and compared, using the propensity score matching analysis, with 11 healthy patients. Several anatomic features were evaluated: Left main (LM) length, angle between descending coronary artery (LAD) and its first branch, angle between LAD and LM, distance from the annulus to RCA (a-RCA distance) and LM (a-LM distance) ostia and their ratio; ratio between LM length and length a-LM and tortuosity score of the vessel with SCAD. A fluid dynamic analysis has been performed to evaluate the effects on shear stress of vessels wall. RESULTS: LM length was significantly shorter in patients with SCAD versus healthy subjects (P=0.01) as well as LM length/a-LM (P=0.03) and the angle between LAD and the first adjacent branch was sharper (P<0.01). Tortuosity score showed a statistically significant difference between groups (P<0.001). Fluid dynamic analysis demonstrates that, in SCAD group, an angle<90 degree is present at the first bifurcation and it can be a cause of increased strain on vessel wall in patients with high tortuosity of coronary artery. CONCLUSION: Tortuosity and angle between the LAD and the adjacent arterial branch combined may determine increased shear stress on the vessel wall that increases the risk of SCAD.

Excess liver-related mortality among people with AIDS compared to the general population: an Italian nationwide cohort study using multiple causes of death.

OBJECTIVES: Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as compared to the general population (non-PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach. METHODS: A population-based, nationwide, retrospective cohort study was conducted among Italian people, aged 15-74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex- and age-standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non-PWA mortality rates. RESULTS: Among 7912 PWA (34 184 person-years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2-43.8) for all liver diseases, 131.1 (95% CI 118.3-145.0) for viral hepatitis, 29.9 (95% CI 27.0-33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1-15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15-49 years and those infected by injecting drug use. CONCLUSIONS: The high excess liver-related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users.

Toward the improvement of 3D-printed vessels' anatomical models for robotic surgery training.

Multi-Detector Computed Tomography is nowadays the gold standard for the pre-operative imaging for several surgical interventions, thanks to its excellent morphological definition. As for vascular structures, only the blood flowing inside vessels can be highlighted, while vessels' wall remains mostly invisible. Image segmentation and three-dimensional-printing technology can be used to create physical replica of patient-specific anatomy, to be used for the training of novice surgeons in robotic surgery. To this aim, it is fundamental that the model correctly resembles the morphological properties of the structure of interest, especially concerning vessels on which crucial operations are performed during the intervention. To reach the goal, vessels' actual size must be restored, including information on their wall. Starting from the correlation between vessels' lumen diameter and their wall thickness, we developed a semi-automatic approach to compute the local vessels' wall, bringing the vascular structures as close as possible to their actual size. The optimized virtual models are suitable for manufacturing by means of three-dimensional-printing technology to build patient-specific phantoms for the surgical simulation of robotic abdominal interventions. The proposed approach can effectively lead to the generation of vascular models of optimized thickness wall. The feasibility of the approach is also tested on a selection of clinical cases in abdominal surgery, on which the robotic surgery is performed on the three-dimensional-printed replica before the actual intervention.

Molecular methods for cost-efficient monitoring of HAB (harmful algal bloom) dinoflagellate resting cysts.

Cyst abundance and identity are essential for understanding and predicting blooms, and for assessing the dispersal of toxic target dinoflagellate species by natural or human mediated ways, as with ballast waters. The aim of this study was to apply rapid, specific and sensitive qPCR assays to enumerate toxic dinoflagellate cysts in sediment samples collected from Adriatic harbours. The molecular standard curves of various target species allowed obtaining the rDNA copy number per cyst. The analytical sensitivity for specific standard curves was determined to be 2 or 10 rDNA copies per reaction. The abundance varied in the range of 1-747 dinoflagellate cysts g-1 dry weight. The assays showed greater sensitivity as compared to counts by light microscopy. This qPCR method revealed a powerful tool for the quantification of cysts from toxic dinoflagellate resting stages in sediment samples from Adriatic ports.

An innovative strategy for the identification and 3D reconstruction of pancreatic cancer from CT images.

We propose an innovative tool for Pancreatic Ductal AdenoCarcinoma 3D reconstruction from Multi-Detector-Computed Tomography. The tumor mass is discriminated from health tissue, and the resulting segmentation labels are rendered preserving information on different hypodensity levels. The final 3D virtual model includes also pancreas and main peri-pancreatic vessels, and it is suitable for 3D printing. We performed a preliminary evaluation of the tool effectiveness presenting ten cases of Pancreatic Ductal AdenoCarcinoma processed with the tool to an expert radiologist who can correct the result of the discrimination. In seven of ten cases, the 3D reconstruction is accepted without any modification, while in three cases, only 1.88, 5.13, and 5.70 %, respectively, of the segmentation labels are modified, preliminary proving the high effectiveness of the tool.

Distal tibial tuberosity translation using TTA implants for the treatment of patella alta in large breed dogs. Surgical technique and clinical outcome.

INTRODUCTION: Medial patellar luxation frequently occurs in dogs resulting in lameness with increasing incidence in large breed dogs. Patella alta has been defined as a patellar ligament length to patellar length ratio that is greater than two and may predispose to patellar luxation. OBJECTIVE: To describe the surgical technique for stabilization of the distal translation of the tibial tuberosity using tibial tuberosity advancement plates and the clinical outcomes with follow-up for clinical cases of dogs. METHODS: Dogs that were presented with the complaint of patellar luxation and that were concurrently diagnosed with patella alta and were greater than 20 kg in body weight underwent surgery using a tibial tuberosity advancement plate to stabilize the osteotomy. Radiographic assessment of A:PL distance (the ratio of the proximal aspect of the patella to the femoral condyle [A] to the patellar length [PL]), L:P ratio (ratio of the length of the patellar ligament to the diagonal length of the patella), and owner assessment were obtained. RESULTS: Eleven stifles in nine dogs underwent surgical correction with a mean preoperative L:P ratio of 2.47. There were no complications and the lameness resolved clinically. The mean A:PL ratios preoperatively (2.6 ± 0.22) and postoperatively (2.1 ± 0.25) were significantly different (p = 0.0003). All owners were satisfied with the outcome and all dogs had a resolution of lameness with no recurrence of patellar luxation. CLINICAL SIGNIFICANCE: Stabilization of distal translation of the tibial tuberosity using tibial tuberosity advancement implants to correct patella alta in large breed dogs was feasible and resulted in good clinical outcome.

Correlates of muscle strength in diabetes: The study on the assessment of determinants of muscle and bone strength abnormalities in diabetes (SAMBA).

BACKGROUND AND AIMS: Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications. METHODS AND RESULTS: Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model. CONCLUSIONS: Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment.

Antiphospholipid antibodies in patients with cancer.

Antiphospholipid antibodies are generally associated with Antiphospholipid Syndrome, which can occur as a primary disorder or may be secondary to connective tissue disease or tumour. The presence of antiphospholipid antibodies in patients with tumour disease is responsible for thrombotic complications. In a population of 53 tumor patients with positive carcinoembryonic antigen CEA, carbohydrate antigen CA19.9, CA125 and CA15.3 markers, IgM and IgG anticardiolipin and antiphosphatidylinositol were detected by solid-phase immunoassays. Our results show that moderate or high levels of antiphospholipid antibodies are present in a great number of patients with CEA and CA19.9 markers, suggesting a specific association with gastroenteric tumors. By testing for antiphosphatidylinositol antibodies, many patients not evidenced by the standard anticardiolipin assay were found to be antiphospholipid-positive. The analysis of antiphosphatidylinositol antibodies as a diagnostic tool in gastroenteric cancer to highlight patients with the risk of thromboembolic complications is discussed.

Low levels of serum cholesterol/phospholipids are associated with the antiphospholipid antibodies in monoclonal gammopathy.

A decrease in cholesterol blood level, not due to a decrease synthesis by the liver, has been observed in patients suffering from tumors. In this work cholesterol blood was evaluated in patients affected by monoclonal gammopathy who were not subjected to any treatment. The blood of 25 patients were analyzed for protein and lipid content. Patients were divided according to the gamma protein content into three groups, and it was demonstrated that the group with high levels of gamma proteins presented a strong decrease in blood cholesterol and phospholipids. In these patients the presence of antibodies against phospholipids by using cardiolipin and phosphatidylinositol as antigens has also been demonstrated. The antibodies were rare in patients with a low content of gamma proteins and normal level of lipids, but the frequency was more than 80% in patients with low blood lipid levels.

Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis.

Bax is a cytosolic protein, which in response to stressing apoptotic stimuli, is activated and translocates to mitochondria, thus initiating the intrinsic apoptotic pathway. In spite of many studies and the importance of the issue, the molecular mechanisms that trigger Bax translocation are still obscure. We show by computer simulation that the two cysteine residues of Bax may form disulfide bridges, producing conformational changes that favor Bax translocation. Oxidative, nonapoptogenic treatments produce an up-shift of Bax migration compatible with homodimerization, which is reverted by reducing agents; this is accompanied by translocation to mitochondria. Dimers also appear in pure cytosolic fractions of cell lysates treated with H2O2, showing that Bax dimerization may take place in the cytosol. Bax dimer-enriched lysates support Bax translocation to isolated mitochondria much more efficiently than untreated lysates, indicating that dimerization may promote Bax translocation. The absence of apoptosis in our system allows the demonstration that Bax moves because of oxidations, even in the absence of apoptosis. This provides the first evidence that Bax dimerization and translocation respond to oxidative stimuli, suggesting a novel role for Bax as a sensor of redox imbalance.

Phenotype analysis of lymphocytes of workers with chronic benzene poisoning.

Lifetime exposure to benzene is associated to a variety of blood disorders, and except for the risk of cancer, almost nothing is known concerning health impairment in individuals who are no longer exposed. In Brazil, this exposure is one of the serious problems in workplaces, and many workers have been laid off their jobs due to this intoxication, particularly in the State of Bahia, the largest producer of benzene in Latin America, which is the area of this study. From a larger study to describe health effects and genetic polymorphisms among workers with chronic benzene poisoning (CBP), this previous specific investigation analyzes the association between CBP and the pattern of sub-populations of lymphocytes. The study was performed with a CBP group (n=24) and a control group with other occupational diseases (n=24); both were selected at the Workers Health Study Center in the State of Bahia, Brazil. Clinical and epidemiologic variables were collected from medical records and from a detailed questionnaire. The average age was similar in the two groups (51.1 and 50.7, respectively). Analyzing the mean proportions of the sub-populations of lymphocytes, statistically significant differences were found for T cytotoxic cells (TCD8) (27.9; 19.4; p=0.002) and T helper memory cell (CD4CD45RO) (31.2; 37.0; p=0.015), respectively, for the CBP group and control group. These results should be viewed with caution because of the small sample size, but they strengthen a previous impression that workers exposed to benzene have their immune system impaired, even in the long term, which may contribute to some disorders and carcinogenesis process. These workers must be strictly followed up in a medical surveillance program. Although this problem has been known for a long time, this is the first attempt to study these specific effects in Brazil.

[Contribution to the study of dental caries in 0-30-month-old infants]. / Contribuição ao estudo da cárie dentária em crianças de 0-30 meses.

This study evaluated the oral health conditions of 340 children, aged 0-30 months (21.3 +/- 5.6)--54.4% of girls and 45.6% of boys--from 20 public day nurseries of Salvador (Brazil), as to the presence of incipient carious lesions. The exam was carried out by a single examiner, who utilized a mirror, a probe and a penlight. The teeth were wiped with gauzes in order to remove the dental plaque. A questionnaire was answered by the children's parents or caretakers in order to assess information regarding knowledge on caries, caries risk factors, socioeconomic status of the family and utilization of fluoride. Two hundred and twenty-nine answered questionnaires (67.35%) were obtained. The observed lesions were classified in five stages, according to their severity (C0-C4; active/inactive). The data were analyzed using the Epi-info 6.02. The prevalence of caries was 55.3% when all stages were registered: 25% for subjects aged 0-12 months, 51.18% for subjects aged 13-24 months and 71.03% for those aged 25-30 months (chi 2 = 25.31, p < 0.01). When only active white spots were considered, 49.7% of the children were affected; 17.6% of the children presented with cavitated lesions. Among the affected children, 90.96% had lesions only on anterior teeth: 80% of the lesions were white spots and 20%, cavities. No significant difference was observed between genders. The increased amount of biofilm was positively associated with dental decay in toddlers (chi 2 = 67.61, p < 0.01), and the number of affected children increased when the sleep-time nursing habit was present (chi 2 = 0.24, p = 0.62). The prevalence of lesions increased with age and with the number of erupted teeth (chi 2 = 25.31, p < 0.01; chi 2 = 122.95, p < 0.01). Early oral health attention, diagnosis of incipient lesions, as well as educative and preventive programs to change oral hygiene and dietary habits are suggested.

Selection, characterization and x-ray structure of anti-ampicillin single-chain Fv fragments from phage-displayed murine antibody libraries.

Single-chain Fv (scFv) antibody libraries were constructed from mice immunized with an ampicillin-bovine serum albumin conjugate. Several antibodies with specificity for intact ampicillin were selected by phage display and characterized. The antibody scFv fragment aL2 binds to intact ampicillin and shows no detectable cross-reactivity with hydrolyzed ampicillin. We determined the X-ray structures of two crystal forms of w.t. aL2, which differ mainly in the side-chain conformation of Trp H109 (according to a new consensus nomenclature Kabat residue number H95) in the extremely short (three residues) CDR H3 and the presence or absence of a well-resolved molecule of 2-methyl-pentane-2,4-diol in the bottom of the binding pocket. Attempts to co-crystallize aL2 with its antigen or to diffuse ampicillin into the wild-type aL2 crystals were unsuccessful, since crystal contacts obstruct the binding pocket. However, a mutant with two point mutations near the N terminus (Gln H6 replaced by Glu and Ala H10 (Kabat H9) replaced by Gly) crystallized in a form compatible with antigen-binding. Although the mutations affect the conformation of framework I, the conformations of the binding pocket of the uncomplexed wild-type aL2 and of the mutant complex were almost identical. The structure explains the specificity of the antibody for intact ampicillin and the degree of cross-reactivity of aL2 with a wide variety of ampicillin analogs. This antibody system will be very useful as a diagnostic reagent for antibiotics use and abuse, as a model for the effect of expression of antibiotic binding molecules in Escherichia coli, and for directed evolution towards high antibiotic resistance.

The importance of framework residues H6, H7 and H10 in antibody heavy chains: experimental evidence for a new structural subclassification of antibody V(H) domains.

The N-terminal segment (FR-H1) of the heavy chain (V(H)) of antibodies shows significant conformational variability correlating with the nature of the amino acids H6, H7 and H10 (Kabat H9). In this study, we have established a causal relationship between the local sequence and the structure of this framework region and linked this relationship to important biophysical properties such as affinity, folding yield and stability. We have generated six mutants of the scFv fragment aL2, covering some of the most abundant amino acid combinations in positions H6, H7 and H10 (according to a new consensus nomenclature, Kabat H9). For the aL2 wild-type (w.t.) with the sequence 6(Q)7(P)10(A) and for two of the mutants, the X-ray structures have been determined. The structure of the triple mutant aL2-6(E)7(S)10(G) shows the FR-H1 backbone conformations predicted for this amino acid combination, which is distinctly different from the structure of the w.t, thus supporting our hypothesis that these residues determine the conformation of this segment. The mutant aL2-6(E)7(P)10(G) represents a residue combination not occurring in natural antibody sequences. It shows a completely different, unique structure in the first beta-strand of V(H), not observed in natural Fv fragments and forms a novel type of diabody. Two V(H) domains of the mutant associate by swapping the first beta-strand. Concentration-dependent changes in Trp fluorescence indicate that this dimerization also occurs in solution. The mutations in amino acids H6, H7 and H10 (Kabat H9) influence the dimerization behavior of the scFv and its thermodynamic stability. All the observations reported here have practical implications for the cloning of Fv fragments with degenerate primers, as well as for the design of new antibodies by CDR grafting or synthetic libraries.

[Characterization and distribution of Citrobacter species in a university hospital]. / Caracterización y distribución de especies de Citrobacter en un hospital universitario.

OBJECTIVE: [corrected] a) To identify Citrobacter strains following the conventional biochemical reaction of Brenner and col; b) to evaluate the sensitivity and specificity of the O'Hara's method compared with Brenner's method, and c) to determine the rate and distribution of the strains in the clinical isolates. MATERIAL AND METHODS: One hundred and twenty two clinical isolates, characterized as Citrobacter spp. were collected between May of 1994 and August of 1997. Clinical isolates included inpatients and outpatients from Hospital de Clínicas. Strains were identified following the methods of Brenner and O'Hara. RESULTS: Methods of Brenner identified 111 of 122 strains: C. freundii 59 of 111; C. koseri 18 of 111; C. werkmanii 15 of 111; C. braakii 9 of 111; C. youngae 6 of 111 and C. amalonaticus 4 of 111. O'Hara's methods identified 104 of 111 strains (94%). C. freundii was recovered most frequently from urine and feces (p Fisher < 0.026 and 0.039 respectively), while C. koseri was isolated from urine principally (p Fisher < 0.0372). CONCLUSIONS: The genus Citrobacter is an important opportunistic pathogen that can be identified in clinical microbiology laboratories using O'Hara's method.

MET(PRC) mutations in the Ron receptor result in upregulation of tyrosine kinase activity and acquisition of oncogenic potential.

Ron and Met are structurally related receptor tyrosine kinases that elicit a complex biological response leading to invasive growth. Naturally occurring point mutations activate the Met kinase in papillary renal carcinomas (MET(PRC) mutations). By site-directed mutagenesis, we generated homologous amino acid substitutions in the Ron kinase domain and analyzed the biochemical and biological properties of the mutant receptors. Among the mutations studied, D(1232)H and M(1254)T displayed transforming activity in NIH3T3 cells, inducing focus formation and anchorage-independent growth. The D(1232)H and M(1254)T substitutions resulted in increased Ron autophosphorylation both in vivo and in vitro and constitutive binding to intracellular signal transducers. Both mutations yielded a dramatic increase in catalytic efficiency, indicating a direct correlation between kinase activity and oncogenic potential. Molecular modeling of the Ron D(1232)H mutation suggests that this single amino acid substitution favors the transition of the kinase from the inactive to the active state. These data demonstrate that point mutations can confer transforming activity to the Ron receptor and show that RON is a potential oncogene.