A comparative study of supine traction, supine side-bending radiographs, and supine MRI to determine coronal flexibility in degenerative lumbar scoliosis patients.
The purpose of this study was to compare curve correction in degenerative lumbar scoliosis using supine traction radiographs, supine side-bending radiographs, and supine MRI. A prospective analysis of Cobb angles from patients diagnosed with degenerative lumbar scoliosis who underwent supine traction radiography (TR), side-bending radiography (SB), and supine MRI. The Cobb angles at thoracic (T), thoracolumbar/lumbar (TL/L), and lumbosacral (LS) levels were measured, and the curve correction in percentages compared with standing AP radiography was calculated as corrective flexibility. Differences in curve correction were analyzed. In total, 33 patients with an age range of 50-80 years were eligible for inclusion. Traction radiography provided the greatest accuracy in curve correction, with a significant difference from side-bending radiography and supine MRI in T, TL/L, and LS levels (P < 0.001). The difference between side-bending radiography and supine MRI in TL/L and LS levels was not significant (P = 0.721, P = 0.654, respectively). A moderate correlation was found between the corrective flexibility of TR and SB at the T level (0.563, P = 0.001), a strong correlation was observed between the corrective flexibility of TR and SB at the TL/L level (0.709, P < 0.001), and at the TL/L level, a moderate correlation was identified between TR and supine MRI corrective flexibility (0.425, P = 0.014). Traction radiographs significantly outperformed side-bending radiographs and supine MRI in terms of access curve flexibility in degenerative lumbar scoliosis.


Applications of rib sparing technique in internal mammary vessels exposure of abdominal free flap breast reconstructions: a 12-year single-center experience of 215 cases.
Internal mammary vessels (IMVs) are widely used recipient vessels in abdominal free flap breast reconstructions. Rib sparing technique is an alternative method with less damage in IMVs exposure. This study aims to investigate the factors influencing the selection of IMVs, as well as analyze the applicability and related factors of rib sparing technique in abdominal breast reconstruction. Medical records of 215 patients who underwent abdominal free flap reconstruction from November 2006 to December 2017 in Fudan University Shanghai Cancer Center (FUSCC) were analyzed. Intercostal space (ICS) was measured from preoperative chest computed tomography scan. Factors influencing the choice of recipient vessels and rib sparing were analyzed. Surgery time, hospitalization and complications were assessed. Among all 218 flaps, 172 flaps used IMVs as the recipient vessels while 46 used other vessels. patients with immediate reconstruction (P=0.005) and axillary lymph nodes dissection (ALND) (P<0.001) were less likely to use IMVs. Patients' body mass index (BMI) and radiotherapy history showed no statistically significant differences between the two groups (P=0.338 and 0.811). In IMVs group, 62% cases used rib sparing technique. Compared with rib resection group, patients with rib sparing were taller (P=0.047) and with a wider ICS (2.65±0.54 vs. 2.25±0.38 cm, P<0.001). Rib sparing group had a shorter surgery and postoperative hospitalization time, as well as a lower complication rate, but the differences were not statistically significant (P=0.120, 0.450 and 0.612). IMVs were used more frequently as the recipient vessels in abdominal free flap breast reconstructions, especially when axillary operation was not performed at the same time. Rib sparing technique had the potential to decrease surgery time, hospitalization days and complications rate. It could be applied in most of the patients with IMVs exposure, particularly in taller patients and patients with a wider ICS. Preoperative chest computed tomography scan can be used to assess the ICS width to provide operational suggestions.


Continuous similarity analysis in patient populations.
Decreased movement symmetry is associated with injury risk and accelerated disease progression. Methods to analyze continuous data either cannot be used in pathologic populations with abnormal movement patterns or are not defined in terms easily incorporated into clinical care. The purpose of this study was to develop a method of describing symmetry and movement quality in continuous time-series data that results in scores that can be readily incorporated into clinical care. Two scores were developed: (1) the symmetry score (SS) which evaluates similarities in time-series data between limbs and (2) the closeness-to-healthy score (CTHS) which evaluates the similarity of time-series data to a control population. Kinetic and kinematic data from 56 end-stage unilateral ankle arthritis (A-OA) patients and 56 healthy older adults, along with 16 anterior cruciate ligament reconstruction (ACLR) patients and 16 healthy young adults were used to test the ability for SS and CTHS to differentiate between healthy and patient groups. Unpaired t-tests, Cohen's D effect sizes, and receiver-operating-curve analyses assessed group differences [SPSS, V27, α = 0.05]. Patients had worse SS than controls and A-OA patients had worse CTHS compared to controls. SS had strong predictive capability, while the predictive capability of CTHS varied. Combined with clinically accessible data collection methods, the SS and CTHS could be used to evaluate patients' baseline movement quality, assess changes due to disease progression, and during recovery. Results could be utilized in clinical decision making to assess surgical intervention urgency and efficacy of surgical interventions or rehabilitation protocols to improve side-to-side limb symmetry.


Detection of hepatitis B surface antigen with the miniature centrifugal fast analyzer. A modified reversed passive hemagglutination procedure.
A modified reversed passive hemagglutination test for the detection of hepatitis B surface antigen HBsAg is described. Sera and reagent cells coated with antibody to HBsAg (anti-HBs) are loaded separately into the rotor of a miniature centrifugal fast analyzer. The rotor is centrifuged briefly to transfer the components into its cuvettes. After mixing, the suspensions are allowed to stand at room temperature for 30 min, following which the rotor is again centrifuged and the absorbance of each cuvette is monitored. Cells suspended in serum containing HBsAg leave the light path more rapidly than cells suspended in sera free of antigen. The magnitude of change in absorbance varies directly with the concentration of the antigen. In 45 sera tested by the conventional V-plate technique, findings were as follows: 21 positive, 19 false positive and 5 negative. The automated procedure unequivocally differentiated the 21 positives; results for the false positive and negative specimens were identical and clearly distinguishable from the positive results. The automated procedure enhances specificity, offers equivalent sensitivity, and results that are quantitative and objective.


Development and application of a radioimmunoassay of the new progestagen gestodene.
A radioimmunoassay for the determination of gestodene (17-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one) in human plasma is described with regard to procedure, specificity, accuracy and reproducibility. Antiserum was raised against gestodene-3-O-(carboxymethyl)oxime-BSA in rabbits and [9,11-3H]-gestodene tracer was used with a specific radioactivity of 2.16 TBq/mmol. The final antiserum dilution was 1: 200,000. RIA was performed according to routine methods using diethylether plasma extracts and the charcoal separation technique. Cross-reactivity of antiserum with cortisol, 17 beta-estradiol, progesterone, testosterone and ethinylestradiol was less than 0.03%; levonorgestrel exhibited a 5% cross-reactivity. No cross-reactivity with metabolites of gestodene or ethinylestradiol was found. Accuracy and precision of the assay were tested using human plasma samples spiked with 1, 5 and 10 ng/ml gestodene. Accuracy was within 94 to 104% of the nominal values. Within-assay and between-assay coefficients of variation were in the range of 4.7-6.5% and 10.3-13.1%, resp. This RIA was used to follow plasma gestodene levels after single oral administration of 75 micrograms of gestodene combined with 30 micrograms ethinylestradiol as tablet and coated tablet in a cross-over design in 6 female test subjects. Plasma gestodene levels were equivalent after both treatments.


Resonance Raman study on mutant cytochrome P-450 obtained by site-directed mutagenesis.
Resonance Raman spectra were observed for the threonine-301 to serine or valine mutant as well as the wild type of rabbit liver microsomal cytochrome P-450 [laurate(omega-1)-hydroxylase] (P-450(omega-1], which were prepared through site-directed mutagenesis. The high-spin marker resonance Raman (RR) bands became similarly stronger for all the P-450s examined in the oxidized form upon addition of laurate, and the RR spectra in the higher frequency region of the oxidized, reduced and CO-adduct forms did not distinctly differ among the P-450s examined. Nevertheless, the Fe-CO stretching mode (vFe-CO) of the CO adduct exhibited an upshift for the valine mutant, suggesting positional proximity of Thr-301 to bound CO like Thr-252 of P-450cam, in agreement with the expectation from the sequence analysis. The vFe-CO band was shifted to higher frequency upon binding of normal alkyl fatty acids with C10 or longer alkyl chain but little affected by binding of shorter fatty acids.


Ribonucleotide reductase association with mammalian liver mitochondria.
Deoxyribonucleoside triphosphate pools in mammalian mitochondria are highly asymmetric, and this asymmetry probably contributes to the elevated mutation rate for the mitochondrial genome as compared with the nuclear genome. To understand this asymmetry, we must identify pathways for synthesis and accumulation of dNTPs within mitochondria. We have identified ribonucleotide reductase activity specifically associated with mammalian tissue mitochondria. Examination of immunoprecipitated proteins by mass spectrometry revealed R1, the large ribonucleotide reductase subunit, in purified mitochondria. Significant enzymatic and immunological activity was seen in rat liver mitochondrial nucleoids, isolated as described by Wang and Bogenhagen (Wang, Y., and Bogenhagen, D. F. (2006) J. Biol. Chem. 281, 25791-25802). Moreover, incubation of respiring rat liver mitochondria with [(14)C]cytidine diphosphate leads to accumulation of radiolabeled deoxycytidine and thymidine nucleotides within the mitochondria. Comparable results were seen with [(14)C]guanosine diphosphate. Ribonucleotide reduction within the mitochondrion, as well as outside the organelle, needs to be considered as a possibly significant contributor to mitochondrial dNTP pools.


Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry.
The role of urinary metabolic profiling in systems biology research is expanding. This is because of the use of this technology for clinical diagnostic and mechanistic studies and for the development of new personalized health care and molecular epidemiology (population) studies. The methodologies commonly used for metabolic profiling are NMR spectroscopy, liquid chromatography mass spectrometry (LC/MS) and gas chromatography-mass spectrometry (GC/MS). In this protocol, we describe urine collection and storage, GC/MS and data preprocessing methods, chemometric data analysis and urinary marker metabolite identification. Results obtained using GC/MS are complementary to NMR and LC/MS. Sample preparation for GC/MS analysis involves the depletion of urea via treatment with urease, protein precipitation with methanol, and trimethylsilyl derivatization. The protocol described here facilitates the metabolic profiling of ∼400-600 metabolites in 120 urine samples per week.


Changes in coagulation factors in postmenopausal women on ethinyl oestradiol.
Coagulation factors II, VII, X, VII + X complex and anti-thrombin III were measured in 10 postmenopausal women before, during and after a four-month course of 20 microgram daily of ethinyl oestradiol, taken three weeks in four. Factors VII, X and VII + X complex rose significantly during treatment but only factor X levels were significantly elevated at the end of the four-month treatment period. There was no change in factor II or anti-thrombin III levels. These effects on coagulation factors during ethinyl oestradiol therapy are, in general, similar to those found during treatment with conjugated equine oestrogens and oestradiol valerate in a previous study from the same laboratory. It seems likely that equipotent doses of ethinyl oestradiol and 'natural' oestrogens have similar effects on these coagulation factors.


Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement.
Preferences and cravings for sweet high-fat foods observed among obese and bulimic patients may involve the endogenous opioid peptide system. The opioid antagonist naloxone, opioid agonist butorphanol, and saline placebo were administered by intravenous infusion to 14 female binge eaters and 12 normal-weight controls. Eight of the binge eaters were obese. During infusion, the subjects tasted 20 sugar/fat mixtures and were allowed to select and consume snack foods of varying sugar and fat content. Naloxone reduced taste preferences relative to baseline in both binge eaters and controls. Total caloric intake from snacks was significantly reduced by naloxone in binge eaters but not in controls. This reduction was most pronounced for sweet high-fat foods such as cookies or chocolate. No consistent effects on taste preferences or food intakes were observed with butorphanol. Endogenous opioid peptides may be involved in mediating taste responses and preferences for palatable foods, notably those rich in sugar and fat.


Hypermethylation of two CpG sites upstream of CASP8AP2 promoter influences gene expression and treatment outcome in childhood acute lymphoblastic leukemia.
DNA hypermethylation of Caspase 8 associated protein 2 (CASP8AP2) and its role in childhood acute lymphoblastic leukemia (ALL) is unclear. We analyzed methylation status of CpG sites upstream of CASP8AP2 gene in 86 children with ALL by bisulfite sequencing and quantitative PCR. Methylation percentage of two CpG sites at positions of -1189 and -1176 was inversely correlated with mRNA expression (Spearman correlation: -0.333, P=0.002). High methylation was associated with the existence of minimal residual disease (MRD) at day 78 (P=0.035), The patients in high methylation group had a poor treatment outcome. The combination of methylation level and MRD at day 33 might improve current risk stratification.


Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas.
This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers. Patients (n = 47) received weekly i.t. injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule. A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection-site pain (each 15%). MIW815 was rapidly absorbed from the injection site with dose-proportional PK, a rapid terminal plasma half-life (approximately 24 minutes), and high interindividual variability. One patient had a partial response (PR; Merkel cell carcinoma); two patients had unconfirmed PR (parotid cancer, myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation. MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study; however, evidence of systemic immune activation was seen.


Synthesis of 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide, a new [18F]fluorinated analogue of valdecoxib, as a potential radiotracer for imaging cyclooxygenase-2 with positron emission tomography.
Fluoroalkyl and fluoroaryl analogues of valdecoxib were found to possess potent inhibitory activities against cyclooxygenase-2 comparable to that of the parent valdecoxib. Among them, the fluoromethyl analogue was chosen for 18F-labeling. Thus, 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide (approximately 2000 Ci/mmol at end of synthesis) was synthesized by [18F]fluoride-ion displacement of the corresponding tosylate in approximately 40% decay-corrected radiochemical yield within approximately 120 min from end of bombardment.


Identification of candidate genes associated with resistance against race 0 of Colletotrichum lentis in Lens ervoides.
Resistance to anthracnose caused by the fungal pathogen Colletotrichum lentis was explored through transcriptome sequencing over a period of 24 to 96 h post-inoculation (hpi) of the partially resistant recombinant inbred lines (RIL) LR-66-528 and susceptible LR-66-524 of the crop wild relative Lens ervoides population LR-66. The development of infection vesicles and primary hyphae by C. lentis were significantly higher on susceptible RIL LR-66-524 compared to partially resistant LR-66-528 at 24 and 48 hpi, but exponential trends in fungal growth were observed between 24 to 96 hpi in both RILs. Comparison of inoculated with mock-inoculated samples revealed 3091 disease responsive genes, among which 477 were differentially expressed between the two RILs. These were clustered into six expression clusters with genes that had either high or low expression in one of the RILs. Differentially expressed genes (DEGs) were functionally annotated and included genes coding LRR and NB-ARC domain disease resistance proteins, protein detoxification, LRR receptor-like kinase family proteins, and wall-associated Ser/Thr Kinases. DEGs were compared to genes in previously published anthracnose resistance QTLs mapped in LR-66 and revealed 22 DEGs located in 3 QTLs. Expression of 21 DEGs was validated using RT-qPCR confirming expression trends in RNA-seq.


Activation of Multiple Eph Receptors on Neuronal Membranes Correlates with The Onset of Traumatic Optic Neuropathy.
Optic neuropathy (ON) is a major cause of irreversible blindness, yet the molecular determinants that contribute to neuronal demise have not been fully elucidated. Several studies have identified 'ephrin signaling' as one of the most dysregulated pathways in the early pathophysiology of ON with varied etiologies. Developmentally, gradients in ephrin signaling coordinate retinotopic mapping via repulsive modulation of cytoskeletal dynamics in neuronal membranes. Little is known about the role ephrin signaling played in the post-natal visual system and its correlation with the onset of optic neuropathy. Postnatal mouse retinas were collected for mass spectrometry analysis for Eph receptors. Optic nerve crush (ONC) model was employed to induce optic neuropathy, and proteomic changes during the acute phase of neuropathic onset were analyzed. Confocal and super-resolution microscopy determined the cellular localization of activated Eph receptors after ONC injury. Eph receptor inhibitors assessed the neuroprotective effect of ephrin signaling modulation. Mass spectrometry revealed expression of seven Eph receptors (EphA2, A4, A5, B1, B2, B3, and B6) in postnatal mouse retinal tissue. Immunoblotting analysis indicated a significant increase in phosphorylation of these Eph receptors 48 hours after ONC. Confocal microscopy demonstrated the presence of both subclasses of Eph receptors in the inner retinal layers. STORM super-resolution imaging combined with optimal transport colocalization analysis revealed a significant co-localization of activated Eph receptors with injured neuronal processes, compared to uninjured neuronal and/or injured glial cells, 48 hours post-ONC. Eph receptor inhibitors displayed notable neuroprotective effects after 6 days of ONC injury. Our findings demonstrate the functional presence of diverse Eph receptors in the postnatal mammalian retina, capable of modulating multiple biological processes. Pan-Eph receptor activation contributes to the onset of neuropathy in ONs, with preferential activation of Eph receptors on neuronal processes in the inner retina following optic nerve injury. Notably, Eph receptor activation precedes neuronal loss. We observed neuroprotective effects upon inhibiting Eph receptors. Our study highlights the importance of investigating this repulsive pathway in early optic neuropathies and provides a comprehensive characterization of the receptors present in the developed retina of mice, relevant to both homeostasis and disease processes.


Effect of age on exercise-induced alterations in cognitive executive function: relationship to cerebral perfusion.
Regular exercise improves the age-related decline in cerebral blood flow (CBF) and is associated with improved cognitive function; however, less is known about the direct relationship between CBF and cognitive function. We examined the influence of healthy aging on the capability of acute exercise to improve cognition, and whether exercise-induced improvements in cognition are related to CBF and cortical hemodynamics. Middle cerebral artery blood flow velocity (MCAv; Doppler) and cortical hemodynamics (NIRS) were measured in 13 young (24±5 y) and 9 older (62±3 y) participants at rest and during cycling at 30% and 70% of heart rate range (HRR). Cognitive performance was assessed using a computer-adapted Stroop task (i.e., test of executive function cognition) at rest and during exercise. Average response times on the Stroop task were slower for the older compared to younger group for both simple and difficult tasks (P<0.01). Independent of age, difficult-task response times improved during exercise (P<0.01), with the improvement greater at 70% HRR exercise (P=0.04 vs. 30% HRR). Higher MCAv was correlated with faster response times for simple and difficult tasks at rest (R(2)=0.47 and R(2)=0.47, respectively), but this relation uncoupled progressively during exercise. Exercise-induced increases in MCAv were similar and unaltered during cognitive tasks for both age groups. In contrast, prefrontal cortical hemodynamic NIRS measures [oxyhemoglobin (O(2)Hb) and total hemoglobin (tHb)] were differentially affected by exercise intensity, age and cognitive task; e.g., there were smaller increases in [O(2)Hb] and [tHb] in the older group between exercise intensities (P<0.05). These data indicate that: 1) Regardless of age, cognitive (executive) function is improved while exercising; 2) while MCAv is strongly related to cognition at rest, this relation becomes uncoupled during exercise, and 3) there is dissociation between global CBF and regional cortical oxygenation and NIRS blood volume markers during exercise and engagement of prefrontal cognition.


[Treatment characteristics of patients with the initial manifestations of failure of the cerebral blood supply at a sanatorium].
A comparative evaluation is presented of the efficacy of complex treatment in health resort conditions of cerebral circulatory insufficiency associated with vertebrogenic cervicoalgia. Treatment included climatic factors, diet, exercises, radon baths, massage, acupuncture and supplementation of this complex by manual therapy and electric stimulation of muscles of the collar system. Inclusion of manual therapy and electric stimulation allowed to improve treatment results.


Data on a new neurorehabilitation approach targeting functional recovery in stroke patients.
Robotic-assisted devices are known to positively affect the recovery of one specific motor effector after stroke. However, it has widely been reported that the functional status of patients is only partially ameliorated after application of this kind of advanced treatment. Here, data about the effect of a new rehabilitation approach has been described in a large population of stroke patients. We sought to validate an integrated rehabilitation system for stroke (IRSS) patients, which is composed of a set of robotic-assisted tools aimed at recovering the entire body. We evaluated the motor recovery in 84 stroke patients equally divided into experimental and control groups to assess the difference between IRSS approach and conventional rehabilitation treatment. We found that IRSS induced a significant improvement as measured by functional neurological scales, such as the barthel index and functional independence measure. The data provided in this article will assist therapists and physicians working for developing new rehabilitation protocols more focused on a holistic functional recovery approach. The data are available at Mendeley Data, https://doi.org/10.17632/wptmgm7zk2.1.


The role of dissolved carbon dioxide and whole bile in the in vitro activation of Taenia taeniaeformis oncospheres.
Dissolved carbon dioxide was deemed not to be an important factor in the activation of Taenia taeniaeformis oncospheres. Rabbit bile was found to provide the most appropriate whole bile for in vitro activation of oncospheres.


Unusual chromosome 7 aberrations in a case of eosinophilic myeloproliferative syndrome.
A patient with myeloproliferative syndrome with marked eosinophilia was found to have unusual karyotypic abnormalities, including monosomy for the short arm and part of the long arm of chromosome #7 in cultured bone marrow cells. These abnormalities have never been reported previously. The role of chromosome #7 deletions in the genesis of leukemic disorders is discussed.


Neuropeptides in Alzheimer type dementia.
Five neuropeptides (cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), neurotensin (NT) and substance P (SP)) were measured in 14 brain areas (4 cortical areas, hippocampus, amygdala, 3 striatal areas, 2 thalamic areas and 3 subcortical areas-- septum, substantia innominata and hypothalamus) in 12 brains with neuropathologically confirmed Alzheimer type change and in 13 control brains. Choline acetyltransferase (CAT) activity was assessed in 6 of these areas. Levels of SRIF, but not those of the other peptides, were reduced in several cortical areas in Alzheimer-type dementia (ATD). The distribution and magnitude of the reduction in SRIF were less than that of CAT activity and the temporal cortex was the only region in which there was a significant relationship between CAT and SRIF deficits. Peptide levels were unchanged in hippocampus, amygdala, thalamus, hypothalamus and striatum (except for an increase in SP in the putamen). SRIF levels were increased in substantia innominata in ATD. NT and SRIF were significantly, and VIP and SP non-significantly, reduced in the septum in ATD. Thus, apart from these alterations in the septum, SRIF was the only neuropeptide for which major changes were identified and these did not follow either the pattern of neuropathological change (e.g. in amygdala and hippocampus) or of CAT deficits (e.g. in substantia innominata).


The pathologist's perspective on vitreous opacities.
Vitreous opacities are diverse in nature. Many underlying diseases are sight-threatening and several are also lethal. This review presents the pathologist's perspective of vitreous opacities, correlates laboratory findings with the underlying disease and recommends safe methods for handling specimens. An aetiological classification of vitreous opacities is also proposed. A gentle fixative such as Cytolyt or HOPE-fixation is required, unless delivery of the vitreous biopsy specimen to the laboratory can be guaranteed within two hours. Cells and other material are precipitated onto slides or into cell blocks by centrifugation. Light microscopy with the May-Grunewald Giemsa stain is enhanced, as necessary, by the use of special stains, such as Congo red for amyloid, Perl's for iron, Periodic Acid-Schiff for microorganisms, and several others. Immunocytological methods enable cell typing, using labels such as CD3 for T-cells in reactive inflammation; CD20 for B-cells in retinal lymphoma; CD34 and myeloperoxidase for myeloid leukaemic cells. The polymerase chain reaction enhances the identification of organisms in endophthalmitis and of immunoglobulin rearrangements in lymphoma. Acquired vitreous opacities can be classified according to their aetiology as: genetic; inflammatory non-infectious; inflammatory infectious; inflammatory iatrogenic; degenerative, traumatic; neoplastic and idiopathic. Non-diagnostic vitreous biopsies, unfortunately, still do occur with the main causes of failure including small sample size; sampling error; inadequate fixation; and leakage from container during transport. Vitreous biopsy can profoundly influence the outcome in patients with vitreous opacities. Success depends on close collaboration between clinicians, pathologists and microbiologists. Vitreous samples require proper handling and expert application of a wide range of specialized techniques.


Cultivation of three-dimensional cartilage-carrier-constructs under reduced oxygen tension.
Three-dimensional cartilage-carrier-constructs were produced according to a standard protocol from chondrocytes of an adult mini-pig. Experiments with different oxygen concentrations (21, 10 and 5%, v/v O(2)) were performed and the constructs were compared qualitatively and quantitatively. The appearance of the cartilage obtained under reduced oxygen tension seemed to be closer to native cartilage with respect to shape of the cells, distribution of the cells within the matrix, smoothness of the surface, etc. The thickness of the cartilage formed by free swelling was always in the same range as for native cartilage (approximately 1mm). Qualitatively the most stable attachment of the cartilage on top of the carrier was found for 10% O(2) (v/v). Especially at 5% O(2) (v/v) the attachment between cartilage and carrier was not sufficient. The constructs generated at lower oxygen tensions had a significantly higher amount of glycosaminoglycan per DNA, but still significantly less when compared to native cartilage. Furthermore, the cultivated cartilage contained a large amount of collagen type II. The experiments proved the applied concept for generation of cartilage-carrier-constructs and the usefulness of cultivation under reduced oxygen tension.


Functional characterization and specific effects of various peptides on enzymatic activity of a DPP-III homologue from goat brain.
The purified dipeptidyl aminopeptidase from goat brain showed several characteristics similar to DPP-III although it possesses a dissimilar molecular weight and different inhibition behavior. The enzyme was found to be inhibited by metallochelators and thiol inhibitors which could be reversed by introducing metals and thiols, respectively. The enzyme activity is also significantly affected by DMSO and ethanol. It was found to be highly sensitive to even very low concentration of urea. The inhibitory potency of several dipeptides and bioactive peptides on this enzyme was investigated to characterize its active site. The highest potency was observed for the dipeptides having aromatic and bulky side chains such as Phe-Met, Leu-Arg, Met-Arg, Trp-Met and Leu-Trp.


Sepsis indicators in acute pancreatitis.
Twenty-one routine clinical and laboratory data in 161 patients with necrotizing pancreatitis (NP) undergoing surgical treatment were analyzed. The necrotic tissue at operation was bacterially infected in 41% of the patients. The goal of the study was to evaluate whether there was any special clinical feature in cases of an infection. The parameters were recorded during 48 h after admission as well as during 48 h before operation, and the frequencies submitted to both a univariate and a multivariate analysis (logistic regression model). In the period after admission, patients with infected necrosis significantly more often had a rectal temperature greater than 38.5 degrees C (p = 0.001). Before operation (i.e., after maximum conservative treatment), four findings were significantly related to an infection: rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, hematocrit less than 35% (all p = 0.0001), and paO2 less than 60 mm Hg (p = 0.001). The multivariate analysis, which calculates and quantifies the mutual influence of factors, showed a combination of three findings (rectal temperature greater than 38.5 degrees C, base excess greater than -4 mmol/L, and hematocrit less than 35%) to be related to necrosis infection before operation. All three criteria in a patient imply a probability of infection of 83%. It is noteworthy that the sepsis indicators were equally distributed in patients with focal, extended, or subtotal/total infected necrosis, but correlated with the necrosis extent in sterile necrotizing pancreatitis. Moreover, all parameters not related to the pancreatic infection [e.g., hyperglycemia, hypocalcemia, rise of lactic dehydrogenase (LDH), and the white blood cell count] correlated with the three necrosis categories.


COVID-19 Preparedness Among Emergency Departments: A Cross-Sectional Study in France.
The aim of this study was to evaluate hospital and emergency department (ED) preparedness in France facing the coronavirus disease 2019 (COVID-19) rapid growth epidemic-phase, and to determine the link between preparedness and responsiveness. In this cross-sectional study, from March 7 to March 11, 2020, all heads of ED departments in France were contacted to answer an electronic survey, including 23 questions. Quality, Organization, Training, Resources, Management, Interoperability, and Responsiveness were evaluated by calculating scores (10 points). Multivariate analysis of variance was used to compare scores. Spearman's correlation coefficient and multifaceted regression analysis were performed between Responsiveness and dimensions scores. A total of 287 of 636 French EDs were included (45.1%). Calculated scores showed (median): Quality 5.38; Organization 6.4; Training 4.6; Resources 4.13; Management 2.38; Interoperability 4.0; Responsiveness 6.25; seasonal influenza score was 5. Significant differences between scores as a function of hospital and ED main characteristics were found. Furthermore, we found significant correlations (P < 0.01) between Responsiveness and all preparedness dimensions. Organization (adjusted-R2 0.2897), Management (aR2 0.321), and Interoperability (aR2 0.422) were significantly associated with Responsiveness. Preparedness in all its dimensions is low, indicating vulnerability. Preparedness and responsiveness face a certain and ongoing risk are close linked, and that Organizational, Management, and Interoperability dimensions are main determinants.


Gore-Tex grafts for replacement of the superior vena cava.
In an effort to evaluate polytetrafluoroethylene (Gore-Tex) as a replacement for large veins, tubular grafts of the material were substituted for the precava in 33 mongrel dogs weighing 15 to 30 kg. Thirteen dogs had grafts 10 cm long by 12 mm wide with a 15-to 30 micron pore size; 15 dogs had grafts of the same length and width from 90-micron pore size material; and 5 dogs had grafts 5 cm long by 12 mm wide, of 90-micron pore size Gore-Tex. The effect of Gore-Tex tubes with and without spiral support and the differences in anatomical positions of the grafts were evaluated in terms of patency. Dogs were killed if a venogram showed occlusion of the graft. Twelve dogs survived 90 days; the longest survivor was killed at eleven months. At postmortem examination, the graft was patent but extremely narrow at the atrial end. Modification in the fabrication of Gore-Tex may eliminate factors contributing to graft failure; experiments longer than 90 days are necessary to evaluate Gore-Tex as a large vein replacement material. The 90-micron pore size material used in this experiment was unsuitable as a canine venous substitute.


Postural changes with aging in tetraplegia: effects on life satisfaction and pain.
(1) To measure kyphosis and scoliosis in individuals with tetraplegia; (2) to examine the relation between kyphosis and scoliosis and years since injury; and (3) to determine the association between kyphosis and scoliosis and measures of pain, depression, and life satisfaction. Cross-sectional, case-control study. University medical center and a free-standing university-affiliated rehabilitation hospital. (1) Ten individuals with tetraplegia I to 3 years postinjury (NT); (2) 10 individuals with tetraplegia 10 to 20 years postinjury (OT); and (3) 10 control individuals (C) matched to the other subjects on the basis of age, height, and weight. Radiographic measurements of kyphosis and scoliosis taken in a seated position, pain as measured by the short form of the McGill Pain Questionnaire (SF-MPQ), depression as measured by the Center for Epidemiological Studies-Depression Scale (CES-D), and life satisfaction as measured by the Life Satisfaction Index Assessment (LSIA) and the Craig Handicap Assessment and Reporting Technique (CHART). No significant differences were seen between the OT and NT groups with respect to age, height, or weight. In addition, no significant differences were found between the NT and OT groups with respect to measures of kyphosis and scoliosis. Individuals with tetraplegia had significantly higher (p < .05) measures of kyphosis (42 + 16.0 ) and scoliosis (14 degrees +/-9.2 degrees) than the C subjects (kyphosis, 32 degrees +/- 7.9 degrees ; scoliosis, 5 degrees+/-3.8 degrees). No correlation was found between scores on the SF-MPQ and degree of kyphosis or scoliosis. Significant differences were seen between the NT and OT groups on both CES-D (NT, 15.2+/-8.1; OT, 5.8+/-5.5) and LSIA (NT, 9.9+/-2.8; OT, 14.4+/-2.9). This study indicates that seated kyphosis and scoliosis develop early in individuals with tetraplegia and may not be progressive. No association was seen between pain and kyphosis or scoliosis in this relatively young sample (mean age of OT and NT combined, 34.8 years). Future research is needed to determine whether pain becomes a problem in individuals with significant kyphosis or scoliosis as they age.


Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma-data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin's Lymphoma Study Group).
In elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61-65 years, 66-70 years, 71-75 years, and 76-80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76-80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.


Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system.
The embryonic neuroepithelium of Drosophila gives rise to the central nervous system. We have studied the mutant phenotype and expression of a gene, single-minded (sim), which is involved in generating a specific region of this neuroepithelium. In sim mutant embryos, a subset of neuronal and nonneuronal precursor cells lying along the midline fail to emerge with the rest of the neuroepithelium. We have identified the sim transcription unit and have shown by in situ hybridization to embryos that the sim gene is expressed specifically in the midline neuroepithelium. Both the mutant phenotype and the temporal and spatial expression of transcripts suggest that the sim gene plays a key role in the emergence of this subset of cells along the midline of the developing central nervous system.


Recombinant growth hormone therapy in children with short stature in Kuwait: a cross-sectional study of use and treatment outcomes.
Recombinant Growth hormone (rGH) therapy is approved in many countries for treatment of short stature in a number of childhood diagnoses. Despite the increasing body of international literature on rGH use, there is paucity of data on rGH use in Kuwait and the broader Middle-East which share unique ethnic and socio-cultural backgrounds. This study aimed to describe the pattern of use and treatment outcomes of rGH therapy in Kuwait. This is a cross-sectional retrospective review of children treated with rGH in the Department of Pediatrics, in a major hospital in Kuwait between December 2013 and December 2014. Data were extracted using standard data extraction form and the response to rGH therapy was defined as a gain of ≥ 0.3 standard deviation score (SDS) of height per year. A total of 60 children were treated with rGH in the center. Their Median (Interquartile) age at rGH initiation was 9.0 (6.2, 10.7) years. The most common indications for rGH therapy were Growth Hormone Deficiency (GHD) 23 (38.3 %), Idiopathic Short Stature (ISS) 12 (20.0 %) and Small for Gestational Age (SGA) 9 (15.0 %). After excluding patients with TS, no significant differences were found in gender of those who received rGH therapy in all indications combined or in each group (p ≥ 0.40). At 1-year follow-up, children in all groups had median height SDS change of ≥ 0.3 SDS except for children with ISS. Age at rGH initiation was negatively associated with 1-year treatment response, Adjusted odds ratio (AOR) 0.56 (95 % CI: 0.04-1.49); p = 0.011). GHD is the most common indication of rGH therapy. All indications except for ISS showed significant 1-year treatment response to therapy. Treatment outcomes in patients with ISS should be further investigated in Kuwait. Younger age at initiation of rGH therapy was independently associated with significant response to therapy suggesting the importance of identifying children with short stature and prompt initiation of rGH therapy.


Efficient and inducible production of human interleukin 6 in Chinese hamster ovary cells using a novel expression system.
High level and inducible production of human interleukin 6 (hIL-6) was achieved using a novel expression system in Chinese hamster ovary (CHO) cells. In this system, the transcription of hIL-6 gene under the control of PhCMV*-1 promoter composed of tetracycline operator sequences and a minimal promoter is activated by a chimeric transactivator (tTA) composed of tetracycline repressor and transactivating domain of VP16 protein of herpes simplex virus. The transcription of tTA gene, which is also under the control of PhCMV*-1 promoter, is activated by itself via a positive feedback cycle. The expression of both genes is further enhanced by potentiating the VP16 transactivating domain of tTA transactivator with pX protein of hepatitis B virus. In the presence of tetracycline, the tTA transactivators can not bind to PhCMV*-1 promoter, therefore, the expression of hIL-6 and tTA gene is suppressed, and the pX will not activate basal transcription. In the absence of tetracycline, tTA transactivators bind to PhCMV*-1 promoter and activate efficient transcription of hIL-6 and tTA gene, and the transcription is further enhanced by pX via VP16 transactivating domain. Using this strategy, we isolated a clone (UX1) producing hIL-6 at a rate about 1425 ng/10(6) cells/day. Furthermore, the hIL-6 production is stringently regulated by tetracycline. This results suggested a novel strategy to establish highly efficient, inducible and cell type independent recombinant protein production system by using an artificial promoter to recruit transactivators and coactivators which can synergistically activate transcription.


Cytoprotective effects of hesperetin and hesperidin against amyloid β-induced impairment of glucose transport through downregulation of neuronal autophagy.
This study investigated whether flavonoids, such as hesperetin and hesperidin, inhibited amyloid β (Aβ)-impaired glucose utilization through regulating cellular autophagy in insulin-stimulated neuronal cells. In this study, we used a toxic Aβ1-42 peptide to impair insulin-stimulated glucose utilization in Neuro-2A cells, and this study also hypothesized that Aβ-induced autophagy might be emerging as a key process regulating neuronal glucose uptake. Additionally, hesperetin and hesperidin were used to test the neuroprotective effect against Aβ-induced impairment of glucose utilization. Our data found that Aβ-stimulated autophagy activation promoted the phenomenon of impairment of neuronal energy metabolism, including glucose uptake, glucose transporters (GLUTs), and insulin signaling cascades. In this study, confocal images of autophagy punctate further confirmed that downregulation of Aβ-stimulated autophagy could increase insulin-stimulated neuronal glucose uptake. Moreover, treatment with hesperetin and hesperidin improved Aβ-impaired glucose utilization by inhibiting Aβ-induced autophagy in neuronal cells. These findings suggest that downregulation of autophagy may be one of the approaches to control the impairment of energy metabolism leading to neuronal injury in the early development of Alzheimer's disease, and hesperetin or hesperidin may be a potential agent in the preventing of Alzheimer's disease progression.


The revised Cochrane risk of bias tool for randomized trials (RoB 2) showed low interrater reliability and challenges in its application.
The objective of the study is to assess the interrater reliability (IRR) and usability of the revised Cochrane risk of bias tool for randomized trials (RoB 2). This is a cross-sectional study. Four raters independently applied RoB 2 on the primary outcome of a random sample of individually randomized parallel-group trials (randomized controlled trials (RCTs)). We calculated the Fleiss' kappa for multiple raters, the time needed to complete the tool, and discussed the application of RoB 2 to identify difficulties and reasons for disagreement. A total of 70 outcomes from 70 RCTs were included. IRR was slight for overall judgment (IRR 0.16, 95% confidence interval (CI) 0.08-0.24); individual domain analysis gave IRR as moderate for "randomization process" (IRR 0.45, 95% CI 0.37-0.53), slight for "deviations from intended intervention" for RCTs assessing the effect of the assignment to an intervention (IRR 0.04, 95% CI -0.06 to 0.14), fair for those assessing the effect of adhering (IRR 0.21, 95% CI 0.11-0.31), and fair for the other domains, ranging from 0.22 (95% CI 0.14-0.30) for "missing outcome data" to 0.30 (95% CI 0.22-0.38) for "selection of reported results". Mean time to apply the tool was 28 minutes (standard deviation 13.4) per study outcome. The main difficulties were due to poor knowledge of the subject matter of primary studies, new terminology, different approaches for some domains compared with the previous tool, and way of formulating signaling questions. RoB 2 is a detailed and comprehensive tool but difficult and demanding, even for raters with substantial expertise in systematic reviews. Calibration exercises and intensive training are needed before its application, to improve reliability.


Renal artery occlusion in pediatric blunt abdominal trauma--decreasing the delay from injury to treatment.
The cases of seven children treated from 1980 through 1991 with blunt renal artery injuries were reviewed to determine (1) if computed tomography alone could eliminate the need for intravenous pyelography (IVP) or arteriography (ART); and (2) the causes of management delays. The diagnosis of arterial occlusion was suggested by the lack of renal contrast enhancement in six patients with CT scans and in two patients with IVP. In three patients ART was merely confirmatory. The diagnosis was suggested by IVP or CT scan within a mean of 4.7 hours of injury, but ART added an additional mean 2.3 hours to the diagnostic workup. There was an additional 3.9-hour average delay in the operating room before revascularization. Six patients underwent revascularization. Four had minimal function by postoperative renal scans. Renal artery occlusion is rapidly detected by contrast-enhanced CT scanning without IVP or ART. The time period from diagnosis to revascularization must be expedited to improve renal outcome.


Low-temperature strategy to synthesize highly ordered mesoporous silicas with very large pores.
By employing a novel low-temperature synthetic pathway, highly ordered cubic mesoporous materials with hitherto the largest pores (up to 27 nm) and unit cells (up to 44 nm) have been successfully obtained.


Diabetes remission following metabolic surgery: is GLP-1 the culprit?
The parallel occurrence of improved glucose tolerance and increased glucagon-like peptide 1 (GLP-1) response to meal intake following metabolic surgery (MS) demonstrated in several studies has led to the notion that GLP-1 is the culprit for the impressive rates of remission of type 2 diabetes mellitus (T2DM) following MS. In this article, we critically review current evidence supporting this view. Recent studies specifically designed to elucidate a causative role of GLP-1 in the antidiabetic effects of MS call into question GLP-1 as a key player for T2DM outcome following MS procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy in morbidly obese subjects. Whether GLP-1 plays a more prominent role in the remission of T2DM following MS in subjects with moderate obesity warrants further studies. Appraisal of the mechanisms involved in the amelioration of hyperglycemia following MS is a priority, as it could help in the battle against the current combined epidemics of obesity and T2DM.


Comparison of verbal and visual analogue scales for measuring the intensity and unpleasantness of experimental pain.
Although the multidimensional nature of pain is now well recognized, there are, nevertheless, very few quantitative tests to measure the separate dimensions of pain and little data concerning their relative sensitivity. The present study compares 2 currently available methods, verbal descriptor and visual analogue scales. Eight subjects rated painful and near-painful heat stimuli by using visual analogue scales for intensity or unpleasantness and by choosing the most appropriate phrases from lists of intensity or unpleasantness descriptors. In the intensity dimension, the relationship between perception and stimulus temperature was essentially identical whether calculated from the visual analogue or verbal descriptor scales. However, data derived from the verbal descriptor scales revealed that subjects rated the painful temperatures as relatively more intense than unpleasant; this difference could not be detected using the visual analogue scales. These results confirm that both visual analogue and verbal descriptor techniques successfully quantify sensory intensity and affective aspects of pain, but that verbal descriptors may provide the more sensitive tool for separating intensity and unpleasantness.


Dose-dependent phorbol ester facilitation or blockade of hippocampal long-term potentiation: relation to membrane/cytosol distribution of protein kinase C activity.
We have proposed that the translocation/activation of protein kinase C (PKC) in synergism with a Ca2+-mediated event plays an essential role in hippocampal long-term potentiation (LTP). In a previous study, we saw no effect of PKC-activating phorbol esters alone on baseline responses, although it has been reported by others to enhance synaptic transmission. To resolve this discrepancy, we investigated the dose-response to phorbol esters of both baseline and potentiated granule cell responses elicited with perforant path stimulation. It was confirmed that iontophoretic ejection of phorbol ester to the dentate hilus, which alone had no effect on baseline responses, prolonged the persistence of potentiation produced by 2 trains of 400 Hz stimulation. These data support the proposed synergistic model in which the effects of phorbol ester and high frequency stimulation together produce a long-lasting potentiation of synaptic activation. A similar synergism was observed with ejection of a lower dose of phorbol ester into the perforant path synaptic zone in the molecular layer. Higher doses delivered to the synaptic zone without 400 Hz stimulation were sufficient to enhance baseline synaptic responses, but these doses inhibited the initial potentiation induced with 2 trains of 400 Hz stimulation delivered immediately after ejection. There was at times a slowly developing enhancement observed after the initial blockade. Thus, induction of a persistent synaptic enhancement was observed without initial potentiation. Measurement of PKC activity in membrane and cytosol indicated that PKC activation is only associated with the persistence phase of LTP. In contrast, there was no change in PKC subcellular distribution associated with the blockade of initial potentiation by higher doses of PDBu.


Does CUD measure interhemispheric transfer time? The allocation of attention influences the Poffenberger effect.
A simple reaction time (SRT) difference between responses to visual stimuli presented ipsilaterally and contralaterally to the responding hand, known as the Poffenberger effect or the crossed-uncrossed difference (CUD), has been commonly interpreted as a measure of interhemispheric transfer time (IHTT). However, the validity of this interpretation and the measure's reliability have been debated. The present study aimed at obtaining reliable evidence of the influence of spatial attention on the CUD, which would provide an argument against the classical interpretation of CUD. To meet the high statistical power requirements, over 100 thousand SRTs in total were collected from 12 participants. The task had three stimulus presentation conditions differing in the degree of stimulus location uncertainty: blocked (no uncertainty), randomized (full uncertainty), and mixed (25% uncertainty). The results showed robust effects of location uncertainty, proving spatial attention's contribution to the CUD. Further, we observed a strong visual-field asymmetry reflecting the right hemisphere specialization in target detection and spatial reorienting. Lastly, despite exceptional reliability of the component SRT measures, the CUD reliability was still too low to justify using this measure as an index of individual differences.


Prepregnancy Obesity and Risks of Stillbirth.
We examined the association of maternal obesity with risk of stillbirth, focusing on whether the pattern of results varied by gestational age or maternal race-ethnicity or parity. Analyses included 4,012 stillbirths and 1,121,234 liveborn infants delivered in California from 2007-2010. We excluded stillbirths due to congenital anomalies, women with hypertensive disorders or diabetes, and plural births, to focus on fetuses and women without these known contributing conditions. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI). Separate models were run for stillbirths delivered at 20-23, 24-27, 28-31, 32-36, 37-41 weeks, relative to liveborn deliveries at 37-41 weeks. For stillbirth at 20-23 weeks, RRs were elevated for all race-ethnicity and parity groups. The RR for a 20-unit change in BMI (which reflects the approximate BMI difference between a normal weight and an Obese III woman) was 3.5 (95% CI 2.2, 5.6) for nulliparous white women and ranged from 1.8 to 5.0 for other sub-groups. At 24-27 weeks, the association was significant (p<0.05) only for multiparous non-Hispanic whites; at 28-31 weeks, for multiparous whites and nulliparous whites and blacks; at 32-36 weeks, for multiparous whites and nulliparous blacks; and at 37-41 weeks, for all groups except nulliparous blacks. The pattern of results was similar when restricted to stillbirths due to unknown causes and somewhat stronger when restricted to stillbirths attributable to obstetric causes. Increased risks were observed across all gestational ages, and some evidence of heterogeneity of the associations was observed by race-ethnicity and parity.


Combination of high-resolution ultrasound-guided perivascular regional anesthesia of the internal carotid artery and intermediate cervical plexus block for carotid surgery.
All previously documented regional anesthesia procedures for carotid artery surgery routinely require additional local infiltration or systemic supplementation with opioids to achieve satisfactory analgesia because of the complex innervation of the surgical site. Here, we report a reliable ultrasound-guided anesthesia method for carotid artery surgery. High-resolution ultrasound-guided regional anesthesia using a 12.5-MHz linear ultrasound transducer was performed in 34 patients undergoing carotid endarterectomy. Anesthesia consisted of perivascular regional anesthesia of the internal carotid artery and intermediate cervical plexus block. The internal carotid artery and the nerves of the superficial cervical plexus were identified, and a needle was placed dorsal to the internal carotid artery and directed cranially to the carotid bifurcation under ultrasound visualization. After careful aspiration, local anesthetic was spread around the internal carotid artery and the carotid bifurcation. In the second step, local anesthetic was injected below the sternocleidomastoid muscle along the previously identified nerves of the intermediate cervical plexus. The necessity for intra-operative supplementation and the conversion rate to general anesthesia were recorded. Ultrasonic visualization of the region of interest was possible in all cases. Needle direction was successful in all cases. Three to five milliliters of 0.5% ropivacaine produced satisfactory spread around the carotid bifurcation. For intermediate cervical plexus block, 10 to 20 mL of 0.5% ropivacaine produced sufficient intra-operative analgesia. Conversion to general anesthesia because of an incomplete block was not necessary. Five cases required additional local infiltration with 1% prilocaine (2-6 mL) by the surgeon. Visualization with high-resolution ultrasound yields safe and accurate performance of the block. Because of the low rate of intra-operative supplementation, we conclude that the described ultrasound-guided perivascular anesthesia technique is effective for carotid artery surgery.


Economic Burden of Herpes Zoster and Post-Herpetic Neuralgia in Adults 60 Years of Age or Older: Results from a Prospective, Physician Practice-Based Cohort Study in Kushiro, Japan.
Herpes zoster has a high incidence rate among people aged ≥ 60 years and can lead to serious complications such as post-herpetic neuralgia. There are currently no data on the economic burden of herpes zoster and post-herpetic neuralgia in Japan, and the objective of this study was to address this gap. A total of 412 patients aged ≥ 60 years diagnosed with herpes zoster were recruited. Demographic, clinical, and healthcare resource utilization data on patients with herpes zoster or post-herpetic neuralgia collected via case report forms were used to estimate direct medical cost. Data obtained from a questionnaire survey among patients with herpes zoster/post-herpetic neuralgia were used to estimate transportation cost and productivity loss. The mean number of outpatient visits was 5.7. Prescription medications were the main cost driver accounting for 60% of the direct medical cost. The mean direct medical and total herpes zoster-related costs per patient were ¥43,925 and ¥57,112, respectively, and were higher in patients with post-herpetic neuralgia than in those with herpes zoster without complications. Direct medical cost represented 77%, productivity loss 19%, and transportation cost 4% of the total. This is the first study of the economic burden of herpes zoster and post-herpetic neuralgia in Japan and it demonstrated substantial direct medical cost as a result of the multiple outpatient visits and prescription medications required. These findings provide baseline data for possible future economic evaluations of new herpes zoster/post-herpetic neuralgia interventions. This cost analysis is part of a prospective, physician practice-based cohort study conducted between June 2013 and February 2015 in Kushiro, Japan (Clinicaltrials.gov identifier NCT01873365, registered on 6 June, 2013).


Biocompatibility effects of indirect exposure of base-metal dental casting alloys to a human-derived three-dimensional oral mucosal model.
The study employed a three-dimensional (3D) human-derived oral mucosal model to assess the biocompatibility of base-metal dental casting alloys ubiquitous in fixed prosthodontic and orthodontic dentistry. Oral mucosal models were generated using primary human oral keratinocyte and gingival fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions were exposed to oral mucosal models for increasing time periods (2-72h). Analysis methodologies (histology, viable cell counts, oxidative stress, cytokine expression and toxicity) were performed following exposure. Ni-based alloy immersion solutions elicited significantly decreased cell viability (P<0.0004) with increased oxidative stress (P<0.0053), inflammatory cytokine expression (P<0.0077) and cellular toxicity levels (P<0.0001) compared with the controls. However, the Ni-free Co-Cr-based alloy immersion solutions did not elicit adverse oxidative stress (P>0.4755) or cellular toxicity (P<0.2339) responses compared with controls. Although the multiple analyses highlighted Ni-Cr base-metal alloy immersion solutions elicited significantly detrimental effects to the oral mucosal models, it was possible to distinguish between Ni-Cr alloys using the approach employed. The study employed a 3D human-derived full-thickness differentiated oral mucosal model suitable for biocompatibility assessment of base-metal dental casting alloys through discriminatory experimental parameters. Increasing incidences of Ni hypersensitivity in the general population warrants serious consideration from dental practitioners and patients alike where fixed prosthodontic/orthodontic dental treatments are the treatment modality involved. The novel and analytical oral mucosal model has the potential to significantly contribute to the advancement of reproducible dental medical device and dental material appraisals.


Properties of component X of rat heart pyruvate dehydrogenase complex.
Pyruvate dehydrogenase complex was purified from rat heart. A new component(mol.wt; 52,000) was found in the purified complex in addition to well known three component enzymes. This component(referred to as component X) was acetylated with [2-14C] pyruvate in the absence of CoA as well as lipoate acetyltransferase. The anti-lipoate acetyltransferase antibody reacted with component X and lipoate acetyltransferase, suggesting that component X shows homology with lipoate acetyltransferase in protein structure. cDNA for lipoate acetyltransferase was isolated from rat liver cDNA library in lambda gt 11. cDNA for lipoate acetyltransferase recognized two kinds of mRNAs of 3.5 Kb and 2.5 Kb.


Pre-eruptive varicella encephalitis and cerebellar ataxia.
Varicella-related neurologic symptoms usually appear during or following the exanthem. Pre-eruptive neurologic manifestations are extremely rare. We report a 6-year-old boy who developed encephalitis, characterized by drowsiness and left-sided hyperactive deep tendon reflexes and cerebellar ataxia, both of which antedated the exanthem by 16 days. The diagnostic and public health implications are discussed.


Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis.
Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.


Staphylococcus aureus-Derived PSMα Peptides Activate Neutrophil FPR2 but Lack the Ability to Mediate β-Arrestin Recruitment and Chemotaxis.
Formyl peptide receptor 2 (FPR2) is a G protein-coupled pattern recognition receptor sensing both mitochondrial- and bacterial-derived formylated peptides, including the PSMα toxins secreted by community-associated methicillin-resistant Staphylococcus aureus strains. Similar to many other FPR2 agonistic peptides, nanomolar concentrations of both PSMα2 and PSMα3 activate neutrophils to increase the cytosolic concentration of Ca2+ and release NADPH oxidase-derived reactive oxygen species. In addition, the PSMα peptides induce FPR2 homologous desensitization, actin polymerization, and neutrophil reactivation through a receptor cross-talk mechanism. However, in contrast to conventional FPR2 agonistic peptides, including the host-derived formyl peptide MCT-ND4, we found that the PSMα peptides lacked the ability to recruit β-arrestin and induce neutrophil chemotaxis, supporting the previous notion that β-arrestin translocation is of importance for cell migration. Despite the lack of β-arrestin recruitment, the PSMα peptides induced an FPR2-dependent ERK1/2 phosphorylation and internalization. Furthermore, structure-activity relationship analysis with PSMα2 derivatives revealed critical roles of the first 3 aa linked to N-fMet as well as the C terminus of PSMα2 in promoting FPR2 to recruit β-arrestin. In summary, our data demonstrate a novel neutrophil activation pattern upon FPR2 sensing of PSMα peptides, signified by the ability to induce increased intracellular Ca2+, ERK1/2 phosphorylation, internalization, and NADPH oxidase activity, yet lack of β-arrestin recruitment and neutrophil chemoattraction. These novel features adopted by the PSMα peptides could be of importance for S. aureus virulence and might facilitate identification of new therapeutic strategies for treating S. aureus infections.


Pulmonary vein stenosis mimicking interstitial lung disease.
Pulmonary vein stenosis (PVS) is a rare condition, often difficult to diagnose and associated with poor prognosis at advanced stages. Lung parenchymal abnormalities are indirect evidence of PVS and can manifest as multifocal opacities, nodular lesions, unilateral effusions, and interstitial septal thickening. These can lead to erroneous diagnoses of airway disease, pneumonia, malignancies or interstitial lung disease. This review summarizes the current literature about the approach to, evaluation and management of these patients. Our case report demonstrates that PVS is an under-recognized complication of cardiovascular surgery and should be considered in all patients presenting with respiratory symptoms after a cardiac procedure.


Predicting chemical bioavailability using microarray gene expression data and regression modeling: A tale of three explosive compounds.
Chemical bioavailability is an important dose metric in environmental risk assessment. Although many approaches have been used to evaluate bioavailability, not a single approach is free from limitations. Previously, we developed a new genomics-based approach that integrated microarray technology and regression modeling for predicting bioavailability (tissue residue) of explosives compounds in exposed earthworms. In the present study, we further compared 18 different regression models and performed variable selection simultaneously with parameter estimation. This refined approach was applied to both previously collected and newly acquired earthworm microarray gene expression datasets for three explosive compounds. Our results demonstrate that a prediction accuracy of R(2) = 0.71-0.82 was achievable at a relatively low model complexity with as few as 3-10 predictor genes per model. These results are much more encouraging than our previous ones. This study has demonstrated that our approach is promising for bioavailability measurement, which warrants further studies of mixed contamination scenarios in field settings.


Is therapeutic lying contradictory to person-centred care? Toward understanding the connection.
There is a lack of clarity about therapeutic lying in the context of everyday dementia care. This study provides conceptual clarity on how the term is used and considers the concept in relation to person-centred care. Rodgers' (1989) evolutionary framework of concept analysis was employed. A systematic multiple database search was conducted and supplemented with snowballing techniques. Data were analysed thematically through an iterative process of constant comparison. This study highlighted that therapeutic lying is intended to be used in the person's best interests for the purpose of doing good. However, its potential for doing harm is also evident. Its use in the literature has increased with the general trend towards becoming more accepted in the discourse. A continuum emerged depending on the degree to which a lie departs from the truth. Emerging guidelines were also evident as to when a lie could or could not be justified. The term therapeutic lying, was contrasted with aspects of person-centred care and was found to be problematic. We conclude that there may be more pragmatic ways of constructing language around the care of people with dementia which could be less stigmatising.


Uveitis in Gaucher disease.
Chronic uveitis has been previously reported in a patient with Gaucher's disease and improved with enzyme replacement therapy. This report describes the course of uveitis in two other patients with type I Gaucher's disease. Observational case reports. Review of all patients in a large referral clinic for Gaucher's disease for incidence of uveitis. Two patients with uveitis among 527 patients (0.4%) were found. Each had a different clinical outcome from the other and from the patient cited in the literature. Both patients have mild Gaucher's disease, but one patient has uveitis well controlled for 10 years solely by local corticosteroids, whereas the other has suffered progression of uveitis despite enzyme replacement therapy.


Pelvic floor dysfunction distress is correlated with quality of life, but not with muscle function.
To analyze the relationship between the symptoms of pelvic floor dysfunction (PFD) and quality of life (QoL), as well as the function of the pelvic floor muscle (PFM) in women with urinary incontinence (UI). A cross-sectional study conducted in two centers in Brazil (Northeast and Southeast regions) with women with stress urinary incontinence (SUI) and mixed urinary incontinence (MUI). Data on pelvic floor symptoms, discomfort and impact on QoL were collected using the Pelvic Floor Distress Inventory-short form (PFDI-SF-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) instruments. PFM function was assessed by palpation (PERFECT scale) and manometry. Pearson's correlation test, analysis of variance (ANOVA) and the Student's t test were used to discriminate the differences, adopting a significance level of 5%. A total of 72 women participated in the study (mean age 51.7 ± 11.9 years). The presence and discomfort of pelvic floor symptoms (PFDI-SF-20) were correlated with QoL (PFIQ-7) (r = 0.52, p < 0.001). Deficits in PFM function (power and pressure) were observed, however, there was no correlation between these with the presence and discomfort of the pelvic floor symptoms (PFDI-SF-20). Greater discomfort due to PFD symptoms were correlated with a worse QoL. However, the relationship between symptoms and PFM function was not significant. These results reinforce the need to assess the aspects of activity and participation which compose functionality and QoL, and not only the PFM functions in women with UI.


Electroconvulsive therapy modulates critical brain dynamics in major depressive disorder patients.
Electroconvulsive therapy (ECT) is widely considered as an effective and fast-acting option for treating patients with major depressive disorder (MDD). However, the neural basis underlying this powerful therapy remains uncertain. Recent studies have suggested that the healthy brain may operate near a critical state, which may reflect a balance between neuronal excitation and inhibition. In the present study, we investigated whether there are any changes regarding criticality in MDD and, if so, whether ECT can reverse them. Critical dynamics analyses were performed on resting-state functional magnetic resonance imaging (rs-fMRI) data collected from 39 MDD patients and 38 healthy controls (HCs). We found that compared with HCs, MDD patients, especially those who responded positively to ECT, tended to have smaller average avalanch sizes and lower branching ratios, suggesting a sub-critical state, at both the whole-brain and functional network levels. Importantly, ECT effectively corrected such anomalies, accompanied by enhanced degree centrality and functional connectivity of high-degree nodes located in the networks including the default-mode and the frontoparietal networks. These results indicate that ECT can modulate large-scale brain dynamics of MDD patients to be closer to criticality. Our study sheds new light on the pathology of MDD and the network mechanism by which ECT influences treatment.


Evaluation of CO2-induced azole-based switchable ionic liquid with hydrophobic/hydrophilic reversible transition as single solvent system for coupling lipid extraction and separation from wet microalgae.
The utilization of microalgae as bioenergy source was limited by the excessive cost and energy consumption during the process of lipid extraction and separation. CO2-induced switchable ionic liquids (S-ILs) with reversible hydrophobic-hydrophilic conversion were synthesized and applied for lipid extraction and separation. The reversible transition mechanism of switchable IL is due to the formation of carbamate. The novel approach based on S-ILs was developed for lipid extraction from wet microalgae, which coupled microalgae cell disruption, lipid extraction, separation, and solvent recovery process without additional solvents. The highest lipid extraction efficiencies from wet microalgae were obtained by C6DIPA-Im, and the lipids were recovered from the extraction phase by simply bubbling CO2. Furthermore, C6DIPA-Im maintained more than 83.6 ± 3.6% of its initial lipid extraction efficiency after recycling five times. The S-IL based extraction and separation method provides a new strategy for sustainable bioenergy production.


Structure and absolute stereochemistry of the anticancer agent EBC-23 from the Australian rainforest.
EBC-23 (2), a prostate anticancer agent, was isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforest. Extensive NOE experiments enabled the relative stereochemistry of the proposed EBC-23 (2) structure to be determined. Total synthesis of both enantiopodes over nine linear steps, involving challenging RCM and spiroacetal cyclizations, confirmed the gross structure and relative and absolute stereochemistry.


The influence of stabilizer and bioadhesive polymer on the permeation-enhancing effect of AT1002 in the nasal delivery of a paracellular marker.
Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential. Thus, this paper focused on the susceptibility of AT1002 for identifying additives to minimize the instability of AT1002, and the permeation-enhancing effect of AT1002 when co-administered with a bioadhesive polymer. The stability study showed that AT1002 were unstable in neutral to basic pH conditions and with increasing incubation time, and 5% dextrose and the 1% mixture of amino acids (arginine, cysteine, glycine) significantly minimized the instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the intranasal study of a paracellular marker, the administration of mannitol with AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17-fold increases in C(max) and AUC(0-360min) in the presence of carrageenan over the control. Thus, the addition of carrageenan as a bioadhesive polymer and dextrose as a stabilizer together with AT1002 may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents.


Preformulation stability of Spantide II, a promising topical anti-inflammatory agent for the treatment of psoriasis and contact dermatitis.
Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin-1 receptor (NKR-1) and blocks inflammation associated with substance P. The anti-inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N-methyl-2-pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high-performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40 degrees C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable alpha-helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine-proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate-ethanol, ethanol-water, ethanol and N-methyl-2-pyrrolidone. The results of this study indicate that ethyl oleate-ethanol (1:1) and ethanol-water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II.


Electrophoretic study of keratin polypeptides in chemically-induced oral carcinomas in the hamster.
Comparison was made of the electrophoretic keratin polypeptide patterns of normal hard palate epithelia from three hamsters and of eight palatal squamous cell carcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Keratin polypeptides from normal epithelia had a molecular weight range of about 48,000 to 70,000. In the tumour extracts, the large polypeptides (above 61,000) found in the normal epithelia were absent, but the majority of other small polypeptides below 61,000 were expressed. Three as yet undefined polypeptides, in the range of 40,000 to 70,000, were detected in tumour extracts, but not in extracts of normal palatal mucosa. The keratin polypeptide electrophoretic alterations in carcinomas of hamster palatal mucosa are similar to those reported for extra-oral carcinomas in other animal species.


[Studies on the orthology of epiphysis cerebri in cattle (Bos taurus var. domesticus L.)].
The pineal organ from 20 cattle (10 week-old female calfs, from one year to several years of age male and female cattle) were investigated with histological and histochemical methods. Carbohydrats are evident in a insignificant quantity in the parenchyma cells. The content of lipids is very high according to the age of the cattle the quantity varying. Proteins are evident only in small quantities. The content of ribonucleic acid is equally high in the cytoplasma of the parenchyma cells.


Limb arterial injuries associated with limb fractures: clinical presentation, assessment and management.
Review of limb arterial injuries associated with limb fractures. Retrospective study. University Hospital. The clinical presentation, assessment and management of 25 patients with upper (seven) and lower (18) limb arterial injuries associated with limb bone fractures has been retrospectively reviewed. Five patients presented with life threatening injuries and classic signs of acute limb ischaemia, 15 patients had an obvious limb arterial injury, and 5 presented with a suspected limb arterial injury. The site of arterial damage was: superficial femoral (4); popliteal (11); tibioperoneal trunk (3); anterior tibial (4); posterior tibial (3); peroneal (2); axillary (1); brachial (5); radial (4); and ulnar artery (4). The types of arterial repair were: autogenous vein interposition or bypass grafting (17); P.T.F.E. (2); end-to-end anastomosis (14); and ligation (8). The popliteal vein was injured in six cases, repaired in four and ligated in two; the superficial femoral vein was injured in four cases, repaired in three and ligated in one; and the axillary vein was injured in one case and was ligated. Primary nerve repair was employed in six out of seven injured nerves. Skeletal fixation preceded vascular repair in 21 patients and in four a Javid shunt was used. Intraoperative fasciotomy was performed in 12 out of 18 patients with lower limb ischaemia. Completion arteriography revealed residual thrombi in the distal foot of four patients, in whom intraarterial thrombolysis was effective. During the follow-up period of 1.5 to 2 years, the upper and lower limb preservation rate was 100 and 89%, respectively. The upper limb function was judged excellent in five patients, good in one and fair in one. In the lower limbs it was excellent in 11 patients, good in three, fair in one and poor in one. To ensure life and functional limb salvage of patients with devastating vascular injuries, a well organised multidisciplinary approach is necessary.


Postthoracotomy paravertebral analgesia: will it replace epidural analgesia?
Thoracotomy is associated with significant acute postoperative pain and a high incidence of development of chronic pain. Thoracic epidural analgesia has long been standard treatment for postthoracotomy pain, but recently there has been increased interest in alternative regional techniques, particularly paravertebral analgesia. This article compares the analgesic efficacy, side effects, complications of, and contraindications for thoracic epidural and paravertebral analgesia techniques and discusses their effects on the development of chronic postthoracotomy pain. This information will allow a more considered choice of analgesic technique after thoracotomy.


Real-life use of apremilast for the treatment of psoriasis in patients with oncological comorbidities: a retrospective descriptive multicentre study in France.
Systemic treatment options for psoriasis are limited for patients with recent neoplasia. We report the real-life use of apremilast (APR) in patients with psoriasis and recent cancer. We conducted a retrospective, multicentre study in five hospitals and among 120 private dermatologists in the north of France from January 2015 to May 2021. We included patients treated with APR for psoriasis and suffering from an active cancer or who had been diagnosed with a cancer or treated for a cancer within the last five years. We included 23 patients diagnosed with a cancer, on average 2.6 years before the introduction of APR for psoriasis. In most patients, APR was specifically chosen due to oncological history. At 16±8 weeks, 55% (n=11/20) of patients had achieved PASI 50 score, 30% (n=6/20) PASI 75, 5% (n=3/20) PASI 90 and 37.5% (n=3/8) of them had a significant improvement in quality of life. Non-serious adverse events were observed in 65.2% (n=15/23) of patients (diarrhoea in 39%), resulting in discontinuation of treatment for 27.8%. The average duration of treatment was 303.8±252.4 days. For four patients, a recurrence or a progression of cancer was recorded during APR treatment. In our patients with both psoriasis and cancer, APR improved quality of life, with a good safety profile. A larger study, matched for type, stage and treatment of underlying cancer, would be necessary to draw further conclusions about the oncological safety of APR.


Fluoride releasing and enamel demineralization around orthodontic brackets by fluoride-releasing composite containing nanoparticles.
Fluoride-containing materials have been suggested to control enamel demineralization around orthodontic brackets during the treatment with fixed appliances. The improvement of their properties has been made through innovations, such as the application of nanotechnology by incorporation of nanofillers. This in vitro study evaluated the capacity of fluoride releasing and enamel demineralization inhibition of fluoride-releasing nanofilled cement around orthodontic brackets using an artificial caries biofilm model. Forty bovine enamel discs were selected by evaluating surface microhardness and randomized into four groups (n = 10): non-fluoride-releasing microfilled composite, fluoride-releasing microfilled composite, resin-modified glass ionomer cement (RMGI), and fluoride-releasing nanofilled composite (FN). After brackets bonding in each disc, the specimens were subjected to a cariogenic challenge through a Streptococcus mutans biofilm model. After the experimental period, the biofilm formed around the brackets was collected for fluoride analysis and the mineral loss around the brackets was determined by integrated demineralization via cross-sectional microhardness measurement at 20 and 70 μm from the bracket margin. Additionally, samples of each group were subjected to energy-dispersive X-ray spectroscopy (EDX) analysis examined under a scanning electron microscopy (SEM). ANOVA followed by Tukey test were applied for fluoride concentration and mineral loss data, respectively. At both distances, only RMGI statistically differed from the other groups presenting the lowest demineralization, although there was a trend to a lower demineralization of enamel around brackets in FN group. Similar condition was found to fluoride concentration and EDX/SEM analysis. Under the cariogenic exposure condition of this study, the fluoride-releasing nanofilled material had similar performance to fluoride-releasing microfilled materials. The presence of nanofillers in the fluoride-releasing materials studied did not promote further benefits against caries lesion development around brackets and presented inferior demineralization inhibition than the resin-modified glass ionomer material.


[Brachytherapy in combination with function-preserving surgery. An interdisciplinary challenge].
A multimodal, interdisciplinary approach known as intensity-modified brachytherapy is a promising alternative for patients with advanced head and neck cancer infiltrating the orbita and skull base. An 87-year-old man presented with a recurrence of squamous cell carcinoma of the medial corner of the left eye that had been locally resected and irradiated by external beam radiotherapy multiple times. The cancer was resected with preservation of the eye with close margins, implantation of afterloading catheters, and reconstruction of the defect with a median forehead flap. The patient was irradiated with a total radiation dose of 30 Gy IMBT. After 1 year, there was no evidence of locoregional recurrence. The background of this therapeutic process and analysis of the current literature regarding this interdisciplinary treatment of head and neck cancer infiltrating the orbita and skull base are discussed based on this case report.


[D2 pancreas-preserving lymphadenectomy in tumors of the upper third of the stomach].
The technique of the D2 pancreas preserving lymphoadenectomy in gastric cancer surgery is described. The technique allows the complete clearing of the node stations n. 11,10 without pancreatic tail resection, which avoids major complications.


Successful treatment of placenta accreta spectrum disorder using management strategy of serial uterine artery embolization combined with standard weekly and a 8-day methotrexate/folinic acid regimens at 7 weeks of gestation.
We describe our experience with serial uterine artery embolization (UAE) combined with standard weekly methotrexate and a eight-day methotrexate/folinic acid (MTX/FA) treatment regimen in the management of placenta accreta spectrum (PAS) disorder at 7 weeks of gestation. A 38-year-old woman, gravida 2 para 0, with a history of myomectomy, was referred for ultrasound (US) evaluation due to suspected cervico-isthmic pregnancy. Transvaginal US image showed a viable embryo with a disproportionately bigger placenta encircling the fetus and completely covering the internal os of the cervix at 7 weeks of gestation. Color Doppler imaging revealed diffuse intraplacental and periplacental vascularity. Patient chose to terminate the pregnancy but attempted to preserve the uterus for future fertility following counseling. Serial UAE procedures were performed using Gelfoam and metallic microcoils. Two courses of a standard weekly MTX and a eight-day MTX/FA treatment regimen were administered to accelerate placental regression. The beta-hCG gradually decreased to a normal level, and an ultimate resolution of the PAS disorder was observed at 110 days after treatment. Early diagnosis of the PAS disorder could result in better obstetric outcome through earlier intervention using serial UAE combined with standard weekly and a eight day MTX//FA regimen in the first trimester of pregnancy.


The in vitro wear behavior of experimental resin-based composites derived from a commercial formulation.
To investigate the short- and long-term in vitro wear resistance of experimental resin-based composites (RBCs) derived from a commercial formulation. Six experimental RBCs were manufactured by manipulating the monomeric resin composition and the filler characteristics of Grandio (Voco GmbH, Cuxhaven, Germany). The Oregon Health Sciences University (OHSU) oral wear simulator was used in the presence of a food-like slurry to simulate three-body abrasion and attrition wear for 50,000, 150,000 and 300,000 cycles. A three-dimensional image of each wear facet was created and the total volumetric wear (mm(3)) and maximum wear depth (μm) were quantified for the RBC and antagonist. Statistical analyses of the total volumetric wear and maximum wear depth data (two- and one-way analyses of variance (ANOVA), with Tukey's post hoc tests where required) and regression analyses, were conducted at p=0.05. Two-way ANOVAs identified a significant effect of RBC material×wear cycles, RBC material and wear cycles (all p<0.0001). Regression analyses showed significant increases in the total volumetric wear (p≤0.001) and maximum wear depth data (p≤0.004) for all RBCs with increasing wear cycles. Differences between all RBC materials were evident after ≥150,000 wear cycles and antagonist wear provided valuable information to support the experimental findings. Wear simulating machines can provide an indication of the clinical performance but clinical performance is multi-factorial and wear is only a single facet. Employing experimental RBCs provided by a dental manufacturer rather than using self-manufactured RBCs or dental products provides increased experimental control by limiting the variables involved.


Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck : First clinical experience with vismodegib for locally advanced disease.
Definitive radiotherapy and vismodegib, an oral inhibitor of the hedgehog pathway, are both established treatment options for locally advanced basal cell carcinomas (BCC). Both have shown good results in local tumor control; however, the effects concerning advanced tumors are often not of a lasting nature and to date no systematic data about the combination of the two modalities are available. We retrospectively analyzed four patients who received vismodegib and radiotherapy in combination. Radiation doses varied between 50.4 Gy and 66.0 Gy. Three patients had recurrent BCC. One patient had locoregional lymph node involvement. Vismodegib was taken once a day (150 mg) during the entire time of irradiation and beyond upon instructions of the attending dermatologist. In three cases a persistent complete response was observed, in one case the tumor remained stable for approximately 6 months until further tumor progression was documented. The combined therapy was well tolerated in all cases. No exceptional side effects pointing at a drug-radiation interaction were observed. The combination of vismodegib and radiation seems feasible and the initial results are promising. In our cohort, there was no increase in unexpected side effects. Further research is needed to evaluate the significance of this combined therapy.


Physico-chemical properties of prostaglandins and related pharmacological compounds. A theoretical study on conformational related activity.
Thromboxane A2, prostaglandin H2, a series of chemically stable cyclic endoperoxide analogues (U 46619, U 44069, ONO 11113, 9, 11, diazo PGH2 and SQ 26655) and different isomers of SQ 26655 were analysed for their spatial configuration by conformational analysis in a simulated membrane-water interface environment with a "structure tree" procedure already described for prostaglandins, leukotrienes and lipoxins. The conformers derived from the structure tree and with a high probability of existence are presented. A new method allows one to visualize the surface charge density of the calculated molecules. The spatial configuration and the surface charge density of each molecule are compared to their known order of competition binding to the putative TXA2/PGH2 receptor of platelets. The conformational and charge density analysis merely shows that the different stereochemistry of these molecules lead to spatial conformation, that mimics (agonists), or that are far from (antagonists) the TXA2/PGH2 conformation.


Comparative distribution and excretion of carboplatin and cisplatin in mice.
The comparative distribution and excretion of Carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II, CBDCA, JM8) and cisplatin have been investigated in Balb C- mice following i.v. administration of the maximally tolerated doses (MTDs) of the compounds. Although the concentrations of platinum in the plasma and tissues during the alpha-phase were much higher for Carboplatin than for cisplatin, reflecting the difference in the doses used (4 vs 80 mg/kg), the tissue-to-plasma ratios were similar. During the beta-phase (1-10 days), however, both the platinum concentrations and the ratios were found to be similar for most tissues when cisplatin and Carboplatin were compared. The platinum concentrations and the tissue-to-plasma ratios of the spleen, brain, muscle, testes, ovary and bile, on the other hand, were consistently higher (two- to sixfold) after Carboplatin than after cisplatin. The highest ratios (greater than 20) were found in the kidney, liver, spleen (after Carboplatin only) and skin at 6 days after treatment. Comparison of the two compounds showed that the half-lives of platinum in the plasma and tissues during both the alpha- and beta-phases were similar, except for the spleen, in which a nine-fold greater t1/2 beta was recorded for Carboplatin than for cisplatin. The main route of excretion for the two complexes is via the kidneys, with 52% of cisplatin and 93% of Carboplatin being excreted during the first 3 days. The major part of this, however, is excreted within the 1st day. These results indicate that, although there are quantitative differences, the distribution and excretion profiles are similar for Carboplatin and cisplatin.