Black tea and theaflavins suppress various inflammatory modulators and i-NOS mediated nitric oxide synthesis during gastric ulcer healing.
The modulation of the cyclooxygenase-independent pathway by black tea (BT) and its constituent theaflavins (TFs) during their healing action against indomethacin-induced stomach ulceration in mice was investigated. On the 3(rd) day of its administration, indomethacin (18 mg/kg) induced maximum stomach ulceration, which was associated with increased myeloperoxidase (MPO) activity (93.3%, p<0.001), and inducible nitric oxide synthase (iNOS) expression (1.6-fold, p<0.001), along with augmented levels of serum nitrite (1.5-fold, p<0.001), selectins and cell adhesion molecules (CAMs), as well as reduced endothelial nitric oxide synthase (eNOS) expression (60%, p<0.001). Treatment with BT (40 mg/kg) and TF (1 mg/kg) for 3 days reversed these parameters and provided excellent (78-81%) ulcer healing. However, alterations of NOS expressions and levels of selectins and CAMs were only partially responsible for the excellent healing capacity (∼80%) of omeprazole (3 mg/kg × 3 days).


Immune islet killing mechanisms associated with insulin-dependent diabetes: three rabbit antibody-mediated islet cell cytotoxicity models.
Antibody-mediated islet cell killing mechanisms have been associated with human insulin-dependent diabetes. Several types of antibody-mediated cytotoxic mechanisms exist, but only complement-dependent antibody-mediated cytotoxicity is reported for islet killing. To evaluate further islet cytotoxic antibody mechanisms, we have studied antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity using polyclonal rabbit anti-rat islet cell immune serum and 51Cr-labelled dispersed normal rat islet target cells. Maximal immune serum-mediated islet cell specific cytotoxicity was 80% for complement-dependent antibody-mediated cytotoxicity, 40% for antibody-dependent cellular cytotoxicity and 20% for complement-augmented antibody-dependent cellular cytotoxicity. The minimum serum dilution for maximal islet cell cytotoxicity was 1:100 for complement-dependent antibody-mediated cytotoxicity, 1:10 for complement-augmented antibody-dependent cellular cytotoxicity. These data indicate a unique optimal serum dilution for each of the three antibody killing mechanisms. Immune serum-mediated cytotoxicity was more specific for rat islet target cells than macrophage target cells. That antibody mediated these cytotoxic events was documented using immune serum-derived, DEAE purified immunoglobulin G which induced killing in all three antibody assays. Both antibody-dependent cellular cytotoxicity assays appear useful for studies of human diabetes, since human non-T mononuclear cells are cytotoxic to islet cells. These results suggest that for studies of potential islet cell killing mechanisms in insulin-dependent diabetes, specific xenogeneic assays exist not only for complement-dependent antibody-mediated islet cytotoxicity, but also for antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity.


Induced pluripotent stem cell-derived extracellular vesicles overexpressing SFPQ protect retinal Müller cells against hypoxia-induced injury.
Splicing factor proline/glutamine-rich (SFPQ) is expressed in induced pluripotent stem cells (iPSCs), which are reported to orchestrate hypoxic injury responses and release extracellular vesicles (EVs). Therefore, this study sought to explore the role of iPSC-derived EVs carrying SFPQ in hypoxia-induced injury to retinal Müller cells. We induced oxygen-glucose deprivation/reoxygenation (OGD/R) in Müller cells. SFPQ was overexpressed or knocked down in iPSCs, from which EVs were extracted. Müller cells were co-cultured with EVs, and the results indicated that SFPQ protein was transferred into retinal Müller cells by iPSC-derived EVs. We identified an interaction of SFPQ with HDAC1 in retinal Müller cells. Specifically, SFPQ recruited HDAC1 to downregulate HIF-2α by regulating its acetylation. The in vitro studies suggested that iPSC-derived EVs, SFPQ or HDAC1 overexpression, or HIF-2α silencing diminished cell injury and apoptosis but elevated proliferation in retinal Müller cells. The in vivo studies indicated that iPSC-derived EVs containing SFPQ curtailed apoptosis of retinal Müller cells, thus alleviating retinal ischemia/reperfusion (I/R) injury of rat model. Taken together, iPSC-derived EVs containing SFPQ upregulated HDAC1 to attenuate OGD/R-induced Müller cell injury via downregulation of HIF-2α.


Animal behaviour: emotion in invertebrates?
Bees exposed to vigorous shaking designed to simulate a dangerous event judge ambiguous stimuli as predicting a negative outcome - a 'pessimistic' cognitive bias that is characteristic of anxious or depressed humans and other vertebrates in putative negative emotional states.


Computer simulation of subchondral bone adaptation to mechanical loading in an incongruous joint.
We hypothesized that the typically bicentric distribution of subchondral bone density (i.e., two maxima) in incongruous joints with deeper sockets could be predicted by a computer simulation employing a concavely incongruous finite-element model and current bone remodeling theory. Additional objectives were to assess the uniqueness of the solution with respect to assumed model parameters and initial conditions and to determine the relationship between contact areas, subchondral bone stress, and subchondral bone density patterns. An idealized model of the humeroulnar joint was constructed with a quantitatively realistic representation of its natural incongruity. A currently accepted remodeling theory was implemented with a finite-element code using a node-based approach. The simulation predicted a dense subchondral bone plate after application of 3,000 daily load cycles for 300 days. The pronounced bicentric distribution of subchondral mineralization emerged. The solution was virtually independent of the initial density distribution and other assumed model parameters. Furthermore, the model predicted high tensile stresses in the subchondral bone, when the joint socket was spread apart during loading. Therefore, the locations of maximal strain energy density in the subchondral bone did not correspond with areas of joint contact. The results of the bone remodeling simulations are consistent with patterns of subchondral bone density determined experimentally. Furthermore, the solutions exhibited a high degree of uniqueness, were rather insensitive to changes in cartilage stiffness, moderately sensitive to number of applied loading cycles, and highly sensitive to loading magnitude. Tensile stresses seem to play a dominant role in subchondral bone remodeling due to bending in the subchondral bone plate. Thus, we conclude that, in the case of an incongruous joints with deeper sockets, the density of the subchondral bone cannot be regarded as a direct measure of the adjacent articular pressure.


The incidence and course of perianal complications and arthralgia after intestinal resection with restoration of continuity for Crohn's disease.
The influence of bowel resection for Crohn's disease on the frequency of arthralgia and perianal manifestations was evaluated in a follow-up study of 82 patients. Arthralgia and perianal manifestations were analysed according to two separate periods: the preoperative duration of disease (4.2 +/- 3.2 years) and the postoperative duration (4.3 +/- 2.6 years). In patients operated on more than once, the time before the first and after the latest operation was included in the study. At the time of the follow-up, 19 patients suffered from recurrent disease. The frequency of arthralgia did not change after resection irrespective of whether or not there was recurrence. In patients without recurrence, however, perianal manifestations diminished after resection (P less than 0.05). In the postoperative period only 10 per cent of those without recurrence suffered from perianal lesions compared with 47 per cent of those with recurrence (P less than 0.001). If perianal lesions were in existence preoperatively, they healed spontaneously in 80 per cent of the patients without recurrence, but were still active among those with recurrence (P less than 0.001). Our results indicate that the perianal manifestations are closely connected to the inflammatory process in the intestine. On the other hand, the arthralgia seems to be independent of the inflammatory process of the bowel and may be related to a general defect of the gastrointestinal mucosa in Crohn's disease.


Assessment of preoperative accelerated radiotherapy and chemotherapy in stage IIIA (N2) non-small-cell lung cancer.
Forty patients with N2 non-small-cell lung cancer (stage IIIA), as determined by mediastinoscopy, were entered into a preoperative neoadjuvant study of chemotherapy (platinum, 5-fluorouracil, vinblastine) and accelerated radiotherapy (150 cGy twice per day for 7 days) for two cycles. Surgical resection was then performed and followed up with an additional cycle of chemotherapy and radiotherapy. All patients completed preoperative therapy. A major clinical response was seen in 87% of patients. Thirty-five patients underwent resection (one preoperative death, one refused operation, one had deterioration of pulmonary function, and two had pleural metastases). Operative mortality rate was 5.7% (2/35). Sixty percent of patients had no complications. Major complications included pulmonary emboli (three), pneumonia (two), and myocardial infarction (one). Down-staging was seen in 46% of patients, with two patients (5.7%) having no evidence of tumor in the specimen, five patients having sterilization of all lymph nodes, and nine patients having sterilization of mediastinal nodes but positive N1 nodes. Median survival of 40 patients was 28 months, with a projected 5-year survival of 43%. Patients with downstaged disease had statistically significant improved survival compared with patients whose disease was not downstaged.


Pregnancy outcome in patients with early recurrent abortion following laparoscopic tubal corneal interruption of a fallopian tube with hydrosalpinx.
To investigate the outcome of pregnancy following laparoscopic unilateral tubal fulguration of hydrosalpinges in patients with recurrent spontaneous early abortion. Prospective randomized controlled trial. University tertiary center. Thirteen patients with history of unexplained recurrent early spontaneous abortion and a unilateral hydrosalpinx diagnosed by sonography and hysterosalpingography in whom other causes of abortion were excluded. The treatment group (group I) consisted of seven women who underwent laparoscopic unilateral tubal fulguration. The control group (group II) consisted of six patients for whom no surgical intervention was performed. Continuation of pregnancy over first trimester. Six patients in the treatment group and five in the control group conceived. Five patients in the treatment group and none in the control group had pregnancy beyond the first trimester and finally reached 36-40 weeks gestational age (P=.02). Laparoscopic tubal fulguration improves pregnancy outcome in selected patients with previous recurrent early abortion and a unilateral hydrosalpinx.


Phonotaxis in flying crickets. II. Physiological mechanisms of two-tone suppression of the high frequency avoidance steering behavior by the calling song.
The effects of two-tone stimuli on the high frequency bat-avoidance steering behavior of flying crickets (Teleogryllus oceanicus) were studied during tethered flight. Similarly, the effects of two-tone stimuli on the ultrasound sensitive auditory interneuron, Int-1, which elicits this behavior, were studied using intracellular staining and recording techniques. When a low frequency tone (3-8 kHz) was presented simultaneously with an aversive high frequency tone (in a two-tone stimulus paradigm), the high frequency avoidance steering behavior was suppressed. Suppression was optimal when the low frequency tone was between 4 and 5 kHz and about 10-15 dB louder than the high frequency tone (Figs. 2, 3). Best suppression occurred when the low frequency tone-pulse just preceded or overlapped the high frequency tone-pulse, indicating that the suppressive effects of 5 kHz could last for up to 70 ms (Fig. 4). The threshold for avoidance of the bat-like stimulus was elevated when model bat biosonar (30 kHz) was presented while the animal was performing positive phonotaxis toward 5 kHz model calling song, but only if the calling song intensity was relatively high (greater than 70-80 dB SPL) (Fig. 1). However, avoidance steering could always be elicited as long as the calling song was not more than 10 dB louder than the ultrasound (Fig. 1). This suppressive effect did not require performance of positive phonotaxis to the calling song (Fig. 2) and was probably due to the persistence of the suppressive effects of the 5 kHz model calling song (Fig. 4). The requirement for relatively high intensities of calling song suggest that the suppression of bat-avoidance by the calling song is not likely to be of great significance in nature. The high frequency harmonics of the male cricket's natural calling song overlap the lower frequency range used by insectivorous bats (10-20 kHz) and are loud enough to elicit avoidance behavior in a flying female as she closely approaches a singing male (Fig. 5). The high frequency 'harmonics' of a model calling song were aversive even if presented with a normally attractive temporal pattern (pulse repetition rate of 16 pps) (Fig. 6A). When the 5 kHz 'fundamental' was added to one of the high frequency 'harmonics', in a two-tone stimulus paradigm, this complex model calling song was attractive; the high frequency 'harmonic' no longer elicited the avoidance behavior (Fig. 6) and the animals steered toward the model CS. Thus, addition of 5 kHz to a high frequency harmonic of the calling song 'masked' the aversive nature of this stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)


[Sequence analysis of the mutated genes in CTXEVC Phi and nct-CTXnew Phi genomes in Vibrio cholerae JS94484 strain].
To analyze the sequences of the mutated genes in CTX(EVC)Phi and nct-CTX(new)Phi genomes in Vibrio cholerae JS94484 strain. The mutated genes in CTX(EVC)Phi and nct-CTX(new)Phi genome were obtained by PCR, sequenced and analyzed. ig1, rstR, ig2, and ctxAB genes in CTX(EVC)Phi genome of V. cholerae strain JS94484 were highly homologous with those of standard EVC strain N16961, while ig1, rstR and ig2 genes in nct-CTX(new)Phi genome of the strain JS94484 shared low homology with those of the other 3 biotypes of V. cholerae. Considerable difference was detected in the last 60 bp of zot genes between CTX(EVC)Phi and nct-CTX(new)Phi genomes, indicating possible difference in the amino sequences of the Zot proteins encoded by these two genes. The sequence of toxin-coregulated pilus A subunit gene (tcpA) of the strain JS94484 was identical with that of strain N16961. ig1, rstR and ig2 genes of nct-CTX(new)Phigenome are of a novel type, and their functions await further investigation.


Transesophageal echocardiographic finding of left atrial appendage lobe mimicking a mass lesion.
We describe an elderly patient undergoing ablation for atrial fibrillation in whom, two-dimensional transesophageal echocardiography showed a mass-like lesion in or adjacent to left atrial appendage (LAA). This mass-like effect was produced by en face visualization of the top of a LAA lobe in the presence of a small effusion in the transverse sinus of the pericardium.


Ventricular coupling of electrical and mechanical dyssynchronization in heart failure patients.
We studied the relationships of electrical and mechanical synchronization in patients with heart failure (CHF) and various degree of ventricular conduction delays. Ninety-two CHF patients (60 +/- 13 years old, LVEF < 45%), NYHA II-III-IV, and 35 age-matched control subjects were studied with angioscintigraphic phase analysis. We measured ejection fractions (LVEF, RVEF) and calculated the total activation time for the left (TtLV) and right ventricle (TtRV), and the synchronization time between right and left ventricle (TRVLV), and between LV apex and base (Tab). Patients were divided into three groups according to QRS duration: group 1 < 120 ms (n = 28), group 2 < 150 ms (n = 23), group 3 > or = 150 ms (n = 41). In group 1: LVEF = 31.1 +/- 10.9%, RVEF = 30.1 +/- 12.6%, TtLV = 204 +/- 70 ms, TtRV = 183 +/- 61 ms, TRVLV = 7 +/- 33 ms, Tab = 29 +/- 23 ms. In group 2, these were: 27.8 +/- 9.1%, 27.8 +/- 8.8%, 227 +/- 95 ms, 248 +/- 137 ms, 35 +/- 42 ms*, and 39 +/- 53 ms respectively. In group 3: LVEF = 20.5 +/- 9.5%t, RVEF = 28.4 +/- 16.1%, TtLV = 304 +/- 155 mst, TtRV = 234 +/- 106 mst, TRVLV = 64 +/- 42 mst, and Tab = 67 +/- 48 ms*, all P < 0.001 versus controls *P < 0.05 versus G1, tP < or = 0.01 versus G1. A significant relation links QRS to both inter- and intraventricular asynchrony (TRVLV: r = 0.65; TtLL: r = 0.70, Tab: r = 0.60), and to LV function (r = 0.72); while LVEF relates more closely to intraventricular asynchrony: TtLV (r = 0.52), TtLL (r = 0.67), than to interventricular asynchrony: TRVLV (r = 0.48); P < 0.01, P < or = 0.001. In CHF patients, electromechanical and contractile alterations are coupled; regional activation may be an early parameter allowing the detection of ventricular dyssynchronization.


Robust ab initio calculation of condensed matter: transparent convergence through semicardinal multiresolution analysis.
We present the first wavelet-based all-electron density-functional calculations to include gradient corrections and the first in a solid. Direct comparison shows this approach to be unique in providing systematic "transparent" convergence, convergence with a priori prediction of errors, to beyond chemical (millihartree) accuracy. The method is ideal both for exploration of materials under novel conditions where there is little experience with how traditional methods perform and for the development and use of chemically accurate density functionals, which demand access to such precision.


Remotely Provided Open-Label Placebo Reduces Frequency of and Impairment by Allergic Symptoms.
Placebos being prescribed with full honesty and disclosure (i.e., open-label placebo [OLP]) have been shown to reduce symptom burden in a variety of conditions. With regard to allergic rhinitis, previous research provided inconclusive evidence for the effects of OLP, possibly related to a separate focus on either symptom severity or symptom frequency. Overcoming this limitation of previous research, the present study aimed to examine the effects of OLP on both the severity and frequency of allergic symptoms. In a randomized-controlled trial, patients with allergic rhinitis ( N = 74) were randomized to OLP or treatment as usual (TAU). Because of the COVID-19 pandemic, OLP was administered remotely in a virtual clinical encounter. Participants took placebo tablets for 14 days. The primary outcomes were the severity and frequency of allergic symptoms. The secondary end point was allergy-related impairment. OLP did not significantly improve symptom severity over TAU ( F (1,71) = 3.280, p = .074, η2 = 0.044) but did reduce symptom frequency ( F (1,71) = 7.272, p = .009, η2 = 0.093) and allergy-related impairment more than TAU ( F (1,71) = 6.445, p = .013, η2 = 0.083), reflecting medium to large effects. The use of other antiallergic medication did not influence the results. Although OLP was able to lower the frequency of allergic symptoms and allergy-related impairment substantially, its effects on symptom severity were weaker. The remote provision of OLP suggests that physical contact between patients and providers might not be necessary for OLP to work.


Sprint Interval Training Induces A Sexual Dimorphism but does not Improve Peak Bone Mass in Young and Healthy Mice.
Elevated peak bone mass in early adulthood reduces the risk for osteoporotic fractures at old age. As sports participation has been correlated with elevated peak bone masses, we aimed to establish a training program that would efficiently stimulate bone accrual in healthy young mice. We combined voluntary treadmill running with sprint interval training modalities that were tailored to the individual performance limits and were of either high or intermediate intensity. Adolescent male and female STR/ort mice underwent 8 weeks of training before the hind legs were analyzed for cortical and trabecular bone parameters and biomechanical strength. Sprint interval training led to increased running speeds, confirming an efficient training. However, males and females responded differently. The males improved their running speeds in response to intermediate intensities only and accrued cortical bone at the expense of mechanical strength. High training intensities induced a significant loss of trabecular bone. The female bones showed neither adverse nor beneficial effects in response to either training intensities. Speculations about the failure to improve geometric alongside mechanical bone properties include the possibility that our training lacked sufficient axial loading, that high cardio-vascular strains adversely affect bone growth and that there are physiological limits to bone accrual.


GEOGRAPHIC VARIATION OF SEXUAL DIMORPHISM IN SIZE OF SAVANNAH SPARROWS (PASSERCULUS SANDWICHENSIS): A TEST OF HYPOTHESES.
The Savannah Sparrow (Passerculus sandwichensis) is a widespread and common North American bird that shows both geographic variation and sexual dimorphism in size. I used information from 24 measurements on 1,791 individuals from 51 populations to test two hypotheses (sexual-selection and niche-partitioning) about the evolution of sexual dimorphism. Throughout their range male Savannah Sparrows are larger, on average, than females. This doubtless reflects Darwinian sexual selection, for territorial fights usually involve males, many of whom fail to obtain mates. In some parts of their range, Savannah Sparrows are commonly polygynous, whereas in others they are characteristically monogamous. Among species of American sparrows (subfamily Emberizinae) sexual size dimorphism is generally greater in polygynous species than in monogamous ones. However, I did not find a similar trend among populations of Savannah Sparrows. The amount of dimorphism in all populations of Savannah Sparrows is equivalent in magnitude to that of other species of sparrows that are commonly or regularly polygynous, and it is greater than that of other sparrow species that are characteristically monogamous. The amount of sexual dimorphism, either in overall size or in bill size, does not correlate with species diversity and does not differ between island and mainland populations. These results do not support the niche-variation hypothesis. Size dimorphism is relatively great in populations of Savannah Sparrows that are resident in southwestern salt marshes, and these birds are the only sparrow-like birds that generally breed in these marshes. Dimorphism is, in general, relatively great in marsh-dwelling species in the family Emberizidae. These species are commonly, but not always, polygynous; the mating systems of the salt-marsh Savannah Sparrows are not known. There are no significant differences in the extent of dimorphism among populations of salt-marsh sparrows, and there are few among the non-salt-marsh ones, probably reflecting conservatism in the evolution of size dimorphism.


[Atypical Lipomatous Tumour of the Hand].
Atypical lipomatous tumours (ALT) are rare semi-malignant adipose tissue tumours with the potential to transform into sarcomas. They may occur throughout the body, although the hands are very rarely involved. We present the case of a 49-year-old man with a lipomatous tumour measuring 8×4 cm at the dorsum of the right thumb. MRI demonstrated an inhomogeneous signal after contrast medium application. The tumour was excised in its entirety. Since histology confirmed the diagnosis of an ALT, the thumb was irradiated. The patient remained free of recurrence. An ALT has to be suspected if a lipomatous tumour is very large. We recommend an MRI prior to surgery in tumours larger than 5 cm. Excision should follow oncologic principles.


Axoglial interaction via the notch receptor in oligodendrocyte differentiation.
Increasing evidence has revealed that the Notch signalling pathway is one of the pivotal systems that mediate oligodendrocyte development. The Notch receptor is a type I transmembrane molecule that represents a novel cellular signalling paradigm, namely, regulated intramembrane proteolysis (RIP). The typical Notch ligands, such as Delta, Serrate/Jagged and Lag2 (DSL), promote the formation of oligodendocyte precursor cells (OPCs) and maintain them in an uncommitted stage, thus retarding oligodendrocyte appearance in the central nervous system (CNS). In contrast, our recent studies have revealed that F3/contactin, a GPI-linked neural adhesion molecule, interacts with Notch and speeds up the generation and maturation of oligodendrocytes. Considering the distinct, albeit somewhat overlapping expression patterns of F3 and DSL in the CNS, the Notch receptor appears to function ligand-dependently during oligodendrocyte development. This multipotentiality may well designate the Notch receptor as one of the therapeutic targets that one can manoeuvre to treat demyelinating diseases, such as multiple sclerosis, that is characterised by chronic myelin degeneration.


Exercise in the first week following concussion among collegiate athletes: Preliminary findings.
Our purpose was to examine the association between exercise after concussion with symptom severity, postural control, and time to symptom-resolution. Longitudinal cohort. Collegiate athletes (n = 72; age = 20.2 ± 1.3 years; 46% female) with concussion completed a symptom questionnaire at initial (0.6 ± 0.8 days post-injury) and follow-up (2.9 ± 1.4 days post-injury) evaluations, and a postural control assessment at follow-up. Participants were grouped into those who exercised in between the time of injury and the follow-up evaluation and those who did not. Decisions regarding post-concussion exercise were made by a sports medicine team consisting of a single team physician and athletic trainers. Thirteen athletes were not included in the current study, resulting in an 85% response rate. Thirteen of the athletes who completed the study exercised between evaluations (18%). There was no symptom resolution time difference between groups (median = 13 [IQR = 7-18] days vs. 13 [7-23] days; p = 0.83). Symptom ratings were similar between groups at the acute post-injury assessment (median PCSS = 18.5 [7.5-26] vs. 17 [14-40]; p = 0.21), but a main effect of group after adjusting for time from injury to assessment indicated the exercise group reported lower symptom severity than the no exercise group across both assessments (p = 0.044). The dual-task gait speed of the exercise group was higher than the no exercise group (0.90 ± 0.15 vs. 0.78 ± 0.16 m/s; p = 0.02). Athletes who were recommended aerobic exercise after concussion did not have worse outcomes than those who were not. Exercise within the first week after concussion does not appear to be associated with detrimental clinical outcomes.


The value of multiparameter 18F-FDG PET/CT imaging in differentiating retroperitoneal paragangliomas from unicentric Castleman disease.
The aim of this study was to investigate the value of multiple parameters retrieved from the FDG PET/CT studies, including SUVmax, SUVmean, SUVpeak, MTV, TLG, tumour size in differentiating retroperitoneal paragangliomas from UCD. 28 patients with solitary retroperitoneal masses who had undergone preoperative 18F-FDG PET/CT were retrospectively evaluated. Histopathology by surgical resection confirmed 17 paragangliomas and 11 UCDs. SUVmax, SUVmean, SUVpeak, MTV, TLG, and tumour size of 18F-FDG PET/CT were measured for each patient. Mann-Whitney U-test was used to assess differences in multiple parameters between paragangliomas and UCDs. The ROC curve analysis was performed to determine the differential diagnostic value of these parameters. Paragangliomas presented significantly higher SUVmax (P < 0.001), SUVmean (P = 0.001), SUVpeak (P < 0.001), and TLG (P = 0.024) than UCDs, whereas no significant difference was observed in MTV. The AUCs for differentiating paragangliomas and UCDs were 0.920, 0.888, 0.909, and 0.765 for SUVmax, SUVmean, SUVpeak, and TLG, respectively. The SUVmax cut-off of 7.75 yielded 82.4% sensitivity and 100% specificity for predicting paragangliomas. This study indicated that 18F FDG PET/CT-derived multiple metabolic parameters are useful in distinguishing between paragangliomas and UCDs. SUVmax showed the best result for the differential diagnosis of these two diseases among multiple metabolic parameters.


Evaluation of a photocatalytic reactor membrane pilot system for the removal of pharmaceuticals and endocrine disrupting compounds from water.
A photocatalytic reactor membrane pilot system, employing UV/TiO(2) photocatalysis, was evaluated for its ability to remove thirty-two pharmaceuticals, endocrine disrupting compounds, and estrogenic activity from water. Concentrations of all compounds decreased following treatment, and removal followed pseudo-first-order kinetics as a function of the amount of treatment. Twenty-nine of the targeted compounds in addition to total estrogenic activity were greater than 70% removed while only three compounds were less than 50% removed following the highest level of treatment (4.24 kW h/m(3)). No estrogenically active transformation products were formed during treatment. Additionally, the unit was operated in photolytic mode (UV only) and photolytic plus H(2)O(2) mode (UV/H(2)O(2)) to determine the relative amount of energy required. Based on the electrical energy per order (EEO), the unit achieved the greatest efficiency when operated in photolytic plus H(2)O(2) mode for the conditions tested.


The Impact of Perceived Control and Future-Self Views on Preparing for the Old Age: Moderating Influences of Age, Culture, and Context.
Preparation for age-related changes has been shown to be beneficial to adjustment in later life. However, an understanding of the factors that influence such preparations is rather limited. This study examines whether perceived control and future-self views (FSV) influence preparations for old age, and if this influence varies across ages, domains of functioning, and cultures. Assessments of perceived control, FSV, and preparations for old age in each of four different life domains (social relationships, finances, work, and health) were obtained from 1,813 adults (ages 35-85) from Germany, Hong Kong, and the United States. Future-self views partially mediated the relationship between perceived control and preparation for old age across both domains of functioning and cultures. With one exception, the association between perceived control and preparations increased with advancing age across contexts. Evidence for similar age-related moderation of the indirect effect of control through FSV was more limited. These results suggest that perceived control that is not necessarily related to aging affect FSV, which in turn influence preparing for old age. Further, our results indicate that such relationships are context- and age-specific, highlighting the importance of considering the salience and diversity of life domains and cultures.


Fibronectin.
Fibronectin is a glycoprotein consisting of repeating units of amino acids, which form domains that enable the molecule to interact with a variety of cells through both integrin and non-integrin receptors. It is encoded by a single gene, but alternative splicing of pre-mRNA allows formation of multiple isoforms that have critical roles in cell adhesion, migration and proliferation. The essential nature of fibronectin in development has clearly been demonstrated in a "knock-out" mouse model in which early lethality occurs. Fibronectin influences diverse processes including inflammation, wound repair, malignant metastasis, microorganism attachment and thrombosis. Researchers are currently developing tools, including synthetic peptides based on specific fibronectin regions. These molecules have been shown to alter processes such as lymphocyte binding in synovial tissue of rheumatoid arthritis, coronary arteriopathy in animal models of cardiac transplantation, and platelet aggregation in patients, and are thus providing important new therapeutic possibilities.


The Safety and Short-term Outcomes of Leukocyte Depleted Autologous Transfusions During Radical Cystectomy.
To examine long- and short-term outcomes using cell salvage with a commercially available leukocyte depletion filter following radical cystectomy in an oncologic population. One hundred and fifty-seven patients, 87 of whom received a cell salvage transfusion, were retrospectively identified from chart review. Ninety-day outcomes as well as long-term mortality and cancer recurrence data were collected. Chi-square, Student's t, or Mann-Whitney U tests were used as appropriate. Multivariable regressions of survival were performed with a Cox proportional-hazards model. Those who received a cell salvage transfusion did not show any differences in rate of cancer recurrence (23%) vs those who did not receive a cell salvage transfusion (24%; P = .85). There were also no differences noted in mortality rates between the 2 populations (12% vs 17%; P = .36). Furthermore, no differences were noted in postoperative complication rates, length of hospital stay, 90-day culture positive infections or readmissions (P >.05). There are no significant differences in short-term or long-term patient outcomes between those who did and did not receive an intraoperative cell salvage transfusion. Cell salvage transfusions with a leukocyte depletion filter are safe and effective methods to reduce the need for allogeneic blood transfusions while controlling for the theoretical risk of metastatic spread.


The evolution of ectoparasitism in the genus Lucilia (Diptera:Calliphoridae).
To consider the evolutionary origin of the ectoparasitic habit in the blowfly genus Lucilia (Diptera:Calliphoridae), phylogenetic analyses of mitochondrial DNA sequence data were performed for 10 species, including all the common Lucilia agents of myiasis, collected from Africa, Australasia, North America and Europe. Complementary genetic distance and parsimony analyses are used to consider inter and intraspecific relationships within the genus with reference to previous morphological work. The results support the hypothesis of independent multiple evolution of the ectoparasitic habit in Lucilia sericata, Lucilia cuprina and the Lucilia caesar/Lucilia illustris group and suggest that it has coevolved in relatively recent history along with the domestication and husbandry of sheep. The geographic differences in pathogenic importance of various species of Lucilia also suggest that there is a strong climatic influence determining which species has dominated. Lucilia cuprina has become the predominant pathogenic species in sub-tropical and warm temperate habitats (e.g., Australia and South Africa), L. sericata in cool temperate habitats (e.g., Europe and New Zealand) and L. caesar and L. illustris become more common in sheep myiasis in more northerly Palaearctic regions.


[Anatomic variations in the ethmoid sinus in patients undergoing dacryocystorhinostomy at the Hassan II de Fès Medical Center (study of 215 patients)].
Although several studies have tried to identify the causes of failure of dacryocystorhinostomy (DCR) surgery, the ethmoid sinus remains an underestimated and little described source of failure. To study anatomical relationship between the ethmoidal sinus, particularly the "Agger nasi" cell, with the lacrimal fossa in the North African population, little described in the literature. This study is based on the results of preoperative analysis of dacryo-computed tomography. Analysis of preoperative computed tomography images of patients undergoing dacryocystorhinostomy over a 7-year period from January 2011 to December 2017. Anatomical relationships were studied according to the following classification: type I: No ethmoid cells located anteriorly to the posterior lacrimal crest on transverse images; type II: ethmoidal cells extending anteriorly to the posterior lacrimal crest, but not reaching the anterior edge of the lacrimal bone; Type III: ethmoidal cells located anterior to the lacrimal bone suture. Two hundred and fifteen preoperative computed tomography images were analyzed. The morphology of the ethmoid sinus was classified as type 1 in 33.5%, type 2 in 42.32% and type 3 in 24.18%. Computed tomography analysis was symmetrical in 87.5% and asymmetrical in 12.5%. During dacryocystorhinostomy, the surgeon must take into consideration type III, which can be present in 25% of cases. In the case of surgical failure, a dacryo-CT must be performed to rule out such anterior positioning of the ethmoid cells.


Biochemical responses of Pinus pinaster trees to fire-induced trunk girdling and crown scorch: secondary metabolites and pigments as needle chemical indicators.
The biochemical responses to varying levels of localized heat damage to stems and crowns were studied in Pinus pinaster trees in Galicia, Spain. The objective was to ascertain the utility of secondary metabolites (total polyphenols. condensed tannins, astringency, free and esterified phenolic acids) and pigments (chlorophylls and carotenoids) as chemical indicators of localized fire damage. The study involved three levels of girdling by trunk heating (0%, 60%, and 75%), three levels of crown scorching (0%, 50%, and 75%), and all combinations of those trunk and crown treatment levels. Secondary metabolites and pigments were analyzed in needles before, during, and up to 8 months after fire treatments. High levels of polyphenols, condensed tannin, and pigments occurred in situations where the sole treatment was 75% crown scorching. Low levels of hydroxycinnamic acids were the result when the treatment was 75% trunk girdling. These responses occurred in the first two months after fire. Thereafter, normal values were observed. Low values of chlorophyll a/b ratio and high levels of free protocatechuic and esterified syringic acids were found to be long-term indicators of trunk girdling damage combined with crown scorching.


Factors affecting seizure outcome in Long-term epilepsy associated tumors (LEATs) in children and young adolescents.
Tumors with seizures as primary mode of presentation are collectively called Long-term epilepsy associated tumors (LEATs or Epileptomas). The overall survival is good so 'seizure outcome' becomes the primary goal rather than neuro-oncological outcome. A retrospective analysis of our surgical database (2015-19) was done to find operated patients of intra-axial brain tumors with age less than 25-years and who had presented with seizures. The mean age at presentation was 16.44 years (SD + 6.82 years). Complex partial seizures/focal unaware seizures were the most common type of seizures encountered (n = 22) with mean duration of seizures was 49.50 months (SD + 31.04 months). The most common pathology was glioneuronal tumors (GNTs) (n = 17). Gross total resection (GTR) group had a significantly better seizure outcome as compared with the Subtotal resection (STR) group (p = 0.006). Presence of focal or partial seizure was a significant factor pointing towards a better seizure control (p = 0.005). The shorter duration of symptoms, partial/focal seizures and gross total excision were predictors of a good seizure-outcome. Age of the patient and the histopathology of the tumor does not affect seizure-outcome on comparing GNTs with non GNTs.


How Can China's Recent Pension Reform Reduce Pension Inequality?
Pension inequality resulting from fragmented arrangements among different population groups - such as public sector employees, enterprise workers, rural residents, and urban informal workers - has become an essential obstacle to China's socioeconomic development. This commentary analyzes the impacts of the 2015 pension reform on the inequality within China's pension system. We claim that the unification of pension rules should be considered the greatest achievement in mitigating pension inequality. However, the integrated pension rules do not necessarily reduce gaps in pension opportunity and benefits among groups because of differentiation in their labor incomes as well as pension attributes. In addition, although the pension structures were flattened at the basic level, structural disparities exist at the supplementary level, strengthening unequal pension benefit outcomes. We argue that the 2015 pension reform enables public sector employees' privileged status to continue while enterprise employees and rural residents and urban informal workers remain at the pension system's margins.


Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study.
Therapy for ependymoma includes aggressive surgical intervention and radiotherapy administered by use of methods that keep the risk of side-effects to a minimum. We extended this treatment approach to include children under the age of 3 years with the aim of improving tumour control. Between July 11, 1997, and Nov 18, 2007, 153 paediatric patients (median age 2.9 years [range 0.9-22.9 months]) with localised ependymoma were treated. 85 patients had anaplastic ependymoma; the tumours of 122 were located in the infratentorial region, and 35 had received previous chemotherapy. Patients received conformal radiotherapy after definitive surgery (125 patients had undergone gross total, 17 near total, and 11 subtotal resection). Doses of 59.4 Gy (n=131) or 54.0 Gy (n=22) were prescribed to a 10 mm margin around the target volume. Disease control, patterns of failure, and complications were recorded for patients followed over 10 years. Overall survival, event-free survival (EFS), cumulative incidence of local recurrences, and cumulative incidence of distant recurrences were assessed. Variables considered included tumour grade, tumour location, ethnic origin, sex, age when undergoing conformal radiotherapy, total radiotherapy dose, number of surgical procedures, surgery extent, and preradiotherapy chemotherapy. After a median follow-up of 5.3 years (range 0.4-10.4), 23 patients had died and tumour progression noted in 36, including local (n=14), distant (n=15), and combined failure (n=7). 7-year local control, EFS, and overall survival were 87.3% (95% CI 77.5-97.1), 69.1% (56.9-81.3), and 81.0% (71.0-91.0), respectively. The cumulative incidences of local and distant failure were 16.3% (9.6-23.0) and 11.5% (5.9-17.1), respectively. In the 107 patients treated with immediate postoperative conformal radiotherapy (without delay or chemotherapy), 7-year local control, EFS, and overall survival were 88.7% (77.9-99.5), 76.9% (63.4-90.4), and 85.0% (74.2-95.8), respectively; the cumulative incidence of local and distant failure were 12.6% (5.1-20.1), and 8.6% (2.8-14.3), respectively. The incidence of secondary malignant brain tumour at 7 years was 2.3% (0-5.6) and brainstem necrosis 1.6% (0-4.0). Overall survival was affected by tumour grade (anaplastic vs differentiated: HR 3.98 [95% CI 1.51-10.48]; p=0.0052), extent of resection (gross total vs near total or subtotal: 0.16 [0.07-0.37]; p<0.0001), and ethnic origin (non-white vs white: 3.0 [1.21-7.44]; p=0.018). EFS was affected by tumour grade (anaplastic vs differentiated: 2.52 [1.2705.01]; p=0.008), extent of resection (gross total vs near total or subtotal: 0.20 [0.11-0.39]; p<0.0001]), and sex (male vs female: 2.19 [1.03-4.66]; p=0.042). Local failure was affected by extent of resection (gross total vs near total or subtotal: 0.16 [0.067-0.38]; p<0.0001), sex (male vs female: 3.85 [1.10-13.52]; p=0.035), and age (<3 years vs >/=3 years: 3.25 [1.30-8.16]; p=0.012). Distant recurrence was only affected by tumour grade (anaplastic vs differentiated: 4.1 [1.2-14.0]; p=0.017). Treatment of ependymoma should include surgery with the aim of gross-total resection and conformal, high-dose, postoperative irradiation. Future trials might consider treatment stratification based on sex and age.


Increased urinary cadmium excretion and its relationship to urinary N-acetyl-beta-D-glucosaminidase activity in smokers.
To assess the renal effects of low-level exposure to cadmium due to smoking we examined blood and urinary levels of cadmium and urinary excretions of N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (BMG) and metallothionein in 94 male workers aged 18-55 years. Both blood and urinary cadmium levels indicated excess exposure to cadmium caused by smoking. The urinary cadmium concentration ranged between 0.1 and 5.0 micrograms/g creatinine and increased significantly with age in the smokers. Neither urinary NAG nor BMG was increased in the smokers compared from non-smokers. A positive relationship between urinary cadmium and metallothionein was obtained not only in the smokers but also in the non-smokers. Furthermore, in the smokers urinary cadmium and metallothionein was positively related with urinary NAG. Since NAG in urine mostly originates from tubular cells by lysosomal exocytosis, the results may reflect an early cadmium effect on the lysosomal functions. Inhibitory effect of cadmium on the lysosomal degradation activities was discussed as a possible explanation of the positive relationship of urinary cadmium and metallothionein to urinary NAG.


Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.
Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.


Two distinct phenotypes of rat vascular smooth muscle cells: growth rate and Production of tumor necrosis factor-alpha.
The monoclonal theory of atherosclerosis postulates that a subpopulation of vascular smooth muscle cells (VSMCs) is selectively expanded in response to pathologic stimuli and accumulates in vascular intima. The purpose of this research was to clone VSMC, determine growth rates of the clones and their ability to release the mitogenic cytokine tumor necrosis factor-alpha (TNF-alpha). With approval of the institutional animal care and use committee, VSMCs were isolated and cultured from the thoracic aortas of three rats. To confirm that the cells in primary culture were of smooth muscle origin, they were immunostained with anti-alpha-smooth muscle-actin antibodies. Single cell-derived individual colonies with uniform appearance were surrounded by cloning rings, released with trypsin, and expanded. Growth rates of the clones were assessed by the mitochondrial dependent reduction of methyltetrazolium (MTT) to formazan after 24-hour stimulation with 10 per cent serum. Additionally, cloned cells were stimulated with 0.1, 1, 10, and 20 microg/mL lipopolysaccharide (LPS) for 24 hours, and TNF-alpha was determined in the culture medium. Data were analyzed by ANOVA. Two clones were isolated that could be divided into categories based on distinctly different morphology: 1) spindle-shaped (SP) or 2) epithelioid-shaped (EP) VSMCs. The SP clone had a growth rate that was 25 per cent higher than the EP clone (P < 0.05). Also, the SP clone had significantly higher release of TNF-alpha in response to LPS. For instance, TNF-alpha released in response to 0.1 microg/mL of LPS in the SP clone was 157 +/- 45 pg/mL versus 21 +/- 8.5 pg/mL in the EP clone (P < 0.05). Primary cultures of rat VSMCs are heterogeneous and consist of at least two morphologically distinct cell types. These clones are different in growth rate and cytokine production. It is possible that selective expansion of one of these clones contributes to formation of stenotic vascular lesions.


Forehead reconstruction with microvascular flaps: utility of aesthetic subunits.
Current literature describes the forehead as one aesthetic subunit of the face. We argue for the usefulness of aesthetic forehead subunits when microvascular flap reconstruction is required. Key to utilization of microvascular flaps for restoration of forehead subunits is an understanding of the patient population and defect characteristics most amiable to treatment. We conducted an International Review Board-approved retrospective chart review of nine consecutive patients who had undergone free flap reconstruction for large forehead defects. The patients' foreheads included one paramedian defect; one central and paramedian defect; four central, paramedian, and lateral defects; and three lateral defects. Seven patients had ulnar forearm flaps and two had anterolateral thigh flaps. The success rate was 100%. A forehead subunit classification system has been devised that provides a suitable option for cases that benefit from distant tissue replacement in a single stage, while preserving the principles of aesthetic replacement.


Factors affecting the biological response of Graphene.
Nanotechnology has gained significant importance in different fields of medical, electronic, and environmental science. This technology is founded on the use of materials at the nanoscale scale (1-100 nanometers) for various purposes, particularly in the biomedical area, where its application is growing daily due to the need of materials with advanced properties. Over the past few years, there has been a growing use for graphene and its derivative composite materials. However, different physico-chemical properties influence its biological response; therefore, further studies to explain the interactions of these nanomaterials with biological systems are critical. This review presents the current advances in the applications of graphene in biomedicine with a focus on the physico-chemical characteristics of the graphene family and their influences on biological interactions.


Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats.
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences were related to subsequent alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. TMT subgroups were created using a ratio of digging to immobility behavior during TMT exposure and rats with a ratio score < 1.0 or> 1.0 were grouped into TMT-1 (low digging/high immobility) or TMT-2 (high digging/low immobility), respectively. All male rats exposed to TMT met criteria for TMT-1, while female rats were divided into the two subgroups. In females, high digging/low immobility behavior during TMT exposure (TMT-2) was related to increased alcohol self-administration, but this was not observed in males or females that engaged in low digging/high immobility (TMT-1). These data show that individual differences in stress-reactivity can lead to lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females.


Hold your breath: Voluntary breath-holding time predicts defensive activation to approaching internal threat.
Bodily disturbances, like dyspnea, elicit responses to regain homeostasis and ensure survival. However, this life-saving function can become hyperreactive, which may lead to the emergence of psychopathology. This study investigated whether maximal voluntary breath-holding time (mvBHT), a biobehavioral marker that characterizes sensitivity to respiratory stimulation, predicts defensive mobilization to cues signaling the proximity of a mild electric shock vs. a respiratory threat (shortness of breath elicited by forced breath-holding) and the opportunity to avoid threat delivery in 60 healthy participants. While the startle reflex, a measure of defensive mobilization, generally increased with the proximity of an inevitable threat, shorter breath-holding time was specifically associated with greater startle potentiation when anticipating a respiratory threat but not an electric shock. In contrast, when both threats were avoidable, the startle reflex was comparably inhibited, irrespective of mvBHT. This study suggests that mvBHT specifically predicts hypersensitive responding to an anticipated inevitable respiratory threat.


A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice.
In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis.


Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β-amyloid load in Alzheimer's disease model.
Inducing gamma oscillations with non-invasive light flicker has been reported to impact Alzheimer's disease-related pathology. However, it is unclear which signaling pathways are involved in reducing amyloid load. Here, we found that gamma frequency light flicker increased anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing, and then physically interacted with KCC2, a neuron-specific K+ -Cl- cotransporter, suggesting that it is essential to maintain surface GABAA receptor α1 levels and reduce β-amyloid (Aβ) production. Stimulation with such light flicker limited KCC2 internalization and subsequent degradation via both tyrosine phosphorylation and ubiquitination, leading to an increase in surface-KCC2 levels. Specifically, PKC-dependent phosphorylation of APP on a serine residue was induced by gamma frequency light flicker, which was responsible for maintaining plasma membrane levels of full-length APP, leading to its reduced trafficking to endosomes and inhibiting the β-secretase cleavage pathway. The activated PKC from the gamma frequency light flicker subsequently phosphorylated serine of KCC2 and stabilized it onto the cell surface, which contributed to the upregulation of surface GABAA receptor α1 levels. Together, these data indicate that enhancement of APP trafficking to the plasma membrane via light flicker plays a critical modulatory role in reduction of Aβ load in Alzheimer's disease.


Systematic pan-cancer analysis identifies SLC35C1 as an immunological and prognostic biomarker.
GDP-amylose transporter protein 1 (SLC35C1) plays an important role in many types of cancer. Therefore, it is clinically important to further investigate the expression profile of SLC35C1 in human tumors to provide new molecular clues for the pathogenesis of glioma. In this study, we performed a comprehensive pan-cancer analysis of SLC35C1 using a series of bioinformatics approaches and validated its differential tissue expression and biological function. The results showed that SLC35C1 was aberrantly expressed in different types of tumors and significantly correlated with overall survival (OS) and progression-free interval (PFI). More importantly, the expression level of SLC35C1 was closely correlated with Tumor Microenvironment (TME), immune infiltration and immune-related genes. In addition, we found that SLC35C1 expression was also closely related to Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and antitumor drug sensitivity in various cancer types. Functional bioinformatics analysis indicated that SLC35C1 may be involved in multiple signaling pathways and biological processes in glioma. Based on SLC35C1 expression, a risk factor model was found to predict OS of glioma. In addition, in vitro experiments showed that SLC35C1 knockdown significantly inhibited the proliferation, migration and invasive ability of glioma cells, while SLC35C1 overexpression promoted proliferation, migration, invasion and colony formation of glioma cells. Finally, quantitative real-time PCR confirmed that SLC35C1 was highly expressed in gliomas.


Vasoactive intestinal peptide: a growth promoter in neuroblastoma cells.
Vasoactive intestinal peptide (VIP) is a neuromodulator, growth regulator and secretagogue for neuronal survival factors. Moreover, VIP has been suggested to be a mitogenic factor for embryonic neurons in the sympathetic nervous system. We now show that VIP had mitogenic activity in a human neuroblastoma cell line (NMB), as measured by cell number and thymidine incorporation. This mitogenic activity was dose dependent and was decreased with culture maturation. Northern blot analysis revealed VIP mRNA transcripts in this cell line suggesting an autocrine role for VIP in neurogenesis.


Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids.
High intake of fruit and vegetables may reduce the risk of osteoporosis. Carotenoids exist in abundance in these foods. This study showed the association of bone mineral density with serum carotenoids. The findings suggest that beta-cryptoxanthin and beta-carotene might provide benefits to bone health in post-menopausal female subjects. Antioxidant carotenoids are abundant in fruit and vegetables. Recent epidemiological studies show that high intakes of fruit and vegetables may reduce the risk of osteoporosis, but little is known about the association of bone mineral density (BMD) with serum carotenoids. A total of 699 subjects (222 males and 477 females) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry (DXA). The associations of serum carotenoid concentrations with the radial BMD were evaluated cross-sectionally. In male and pre-menopausal female subjects, the six serum carotenoids were not associated with the radial BMD. On the other hand, in post-menopausal female subjects, serum beta-cryptoxanthin and beta-carotene were weakly but positively correlated with the radial BMD. After adjustment for confounders, the odds ratio (OR) for the lowest quartile of BMD in the high groups (Q2-Q4) of serum beta-cryptoxanthin against the lowest quartile (Q1) was 0.45 (95% confidence interval: 0.22-0.95) in post-menopausal female subjects. However, this association was not significant after further adjusting for intakes of minerals and vitamins. Antioxidant carotenoids, especially beta-cryptoxanthin, significantly but partly associate with the radial BMD in post-menopausal female subjects.


Characterization of a novel group I F-specific RNA bacteriophage isolated from human stool.
A novel F-specific RNA bacteriophage (FRNAPH) YM1, affiliating to genogroup I (GI) of Levivirus, is isolated for the first time from human stool samples using double-layer agar plates with the Escherichia coli ATCC700891 as the host. The complete genomic sequence of YM1 is 3551 nt in length, obtained through next-generation sequencing, and contains four genes encoding for maturation protein, coat protein, lysis protein, and RNA-dependent RNA polymerase (RdRp). The genomic sequence of YM1 shares the highest similarity of 95.3% with that of a GI FRNAPH DL16 isolated from surface water of Great Bay. The YM1 possesses a non-enveloped, icosahedral virion of 23 ± 0.45 nm in diameter. One-step growth curve analysis shows that the burst time of YM1 is 30 min post-infection (p.i.) with the average burst size of 264 PFU/cell. The YM1 lyses only E. coli strains tested, revealing high host specificity. This newly discovered phage may serve as a candidate for viral indicator to monitor human enteric virus, especially norovirus, contamination in the environments.


Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ naïve TB patients in Pakistan.
Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance. Based on convenience sampling, we studied 48 MTB clinical isolates from BDQ naïve TB patients. These isolates (from our strain bank) included 38 MDR/pre-XDR/XDR (10 BDQ resistant, 8 BDQ intermediate and 20 BDQ susceptible) and 10 pan drug susceptible MTB isolates. All strains were subjected to whole genome sequencing and genomes were analysed to identify variants in Rv0678, pepQ, atpE, Rv1979c, mmpLS and mmpL5 and drug resistance associated efflux pump genes. Of the BDQ resistant and intermediate strains 44% (8/18) had variants in Rv0678 including; two reported mutations S63R/G, six previously unreported variants; L40F, R50Q and R107C and three frameshift mutations; G25fs, D64fs and D109fs. Variants in efflux pumps; Rv1273c (G462K), Rv0507c (R426H) and Rv1634c (E198R) were found to be present in drug resistant isolates including BDQ resistant and intermediate isolates. E198R in efflux pump gene Rv1634c was the most frequently occurring variant in BDQ resistant and intermediate isolates (n = 10). We found RAVs in Rv0678 to be commonly associated with BDQ resistance. Further confirmation of the role of variants in efflux pump genes in resistance is required so that they may be incorporated in genome-based diagnostics for drug resistant MTB.


Fatty liver is associated with impaired activity of PPARγ-coactivator 1α (PGC1α) and mitochondrial biogenesis in mice.
Accumulating evidence indicates that mitochondria have a key role in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a choline-deficient, ethionine-supplemented (CDE) diet. Histological studies demonstrated accumulation of fat vacuoles in up to 90% of hepatocytes in mice fed the CDE diet for 14 days. In addition, a decrease in mitochondrial levels, together with an increase in superoxide radicals' levels were observed, indicating elevation of oxidative stress in hepatocytes. ATP levels were decreased in livers from CDE-fed mice after overnight fasting. This was accompanied by a compensative and significant increase in peroxisome-proliferator-activated receptor-γ coactivator 1α (PGC1α) mRNA levels in comparison to control livers. However, there was a reduction in PGC1α protein levels in CDE-treated mice. Moreover, the expression of mitochondrial biogenesis genes nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), mitochondrial transcription factor B1 (TFB1M) and mitochondrial transcription factor B2 (TFB2M), which are all regulated by PGC1α activity, remained unchanged in fasted CDE-treated mice. These results indicate impaired activity of PGC1α. The impaired activity was further confirmed by chromatin immunoprecipitation analysis, which demonstrated decreased interaction of PGC1α with promoters containing NRF-1 and NRF-2 response elements in mice fed the CDE diet. A decrease in PGC1α ability to activate the expression of the gluconeogenic gene phosphoenol-pyruvate carboxykinase was also observed. This study demonstrates, for the first time, that attenuated mitochondrial biogenesis in steatotic livers is associated with impaired biological activity of PGC1α.


Studies on steroids. CCXIX. Separation and determination of 4-hydroxyoestriol monoglucuronides and monosulphates in biological fluids by high-performance liquid chromatography with electrochemical detection.
The separation and determination of 4-hydroxyoestriol monoglucuronides and monosulphates by high-performance liquid chromatography with electrochemical detection on a reversed-phase column has been carried out. The effects of the salt, composition and pH of the mobile phase on the resolution were investigated with a Develosil ODS-5 column. Each group of isomeric monoglucuronides and monosulphates of 4-hydroxyoestriol was efficiently resolved on this column when 0.5% sodium acetate-acetonitrile and 0.5% sodium acetate-tetrahydrofuran-acetonitrile were used as mobile phases, respectively. The use of the present method revealed that 4-hydroxyoestriol orally administered to the rat was excreted as 4-, 3-, 16-glucuronides and 4-sulphate in bile.


The Effect of Goethites on the Polymerization of Glycine and Alanine Under Prebiotic Chemistry Conditions.
After pre concentration of monomers, polymerization is the second most important step for molecular evolution. The formation of peptides is an important issue for prebiotic chemistry and consequently for the origin of life. In this work, goethite was synthesized by two different routes, named goethite-I and goethite-II. Although both samples are goethite, Far-FT-IR spectroscopy and EPR spectroscopy showed differences between them, and these differences had an effect on the polymerization of glycine and alanine. For the amino acid polymerization, three protocols were used, that resembled prebiotic Earth conditions: a) amino acid plus goethite were mixed and heated at 90 °C for 10 days in solid state, b) a wet impregnation of the amino acid in the goethite, with subsequent heating at 90 °C for 10 days in solid state, and c) 10 wet/dry cycles each one for 24 h at 90 °C. Experiments with glycine plus goethite-II, using protocols B and C, produced only Gly-Gly. In addition, for the C protocol the amount of Gly-Gly synthesized was 3 times higher than the amount of Ala-Ala. Goethite-I presented a decrease in the EPR signal, when it was submitted to the protocols with and without amino acids. It is probable the decrease in the intensity of the EPR signal was due to a decrease in the imperfections of the mineral. For all protocols the mixture of alanine plus goethite-I or goethite-II produced c(Ala-Ala). However, for wet/dry cycles, protocol C presented higher yields (p < 0.05). In addition, Ala-Ala was produced using protocols A and C. The c(Ala-Ala) formation fitted a zero-order kinetic equation model. The surface areas of goethite-I and goethite-II were 35 m2 g-1 and 37 m2 g-1, respectively. Thermal analysis indicated that the mineral changes the thermal behavior of the amino acids. The main reactions for the thermal decomposition of glycine were deamination and dehydration and for alanine was deamination.


Return to work after surgery for degenerative cervical myelopathy: a nationwide registry-based observational study.
Few studies of high quality exist on return to work (RTW) rate after surgery for degenerative cervical myelopathy (DCM). This study aims to examine the RTW rate in patients undergoing surgery for DCM. Nationwide prospectively collected data were obtained from the Norwegian Registry for Spine Surgery and the Norwegian Labour and Welfare Administration. The primary outcome was return to work, defined as being at work at a given time postoperatively without any medical income-compensation benefits. Secondary endpoints included the neck disability index (NDI) and quality of life measured by EuroQol-5D (EQ-5D). Among 439 patients operated for DCM between 2012 and 2018, 20% of the patients received a medical income-compensation benefit one year before surgery. This number increased steadily towards the operation at which timepoint 100% received benefits. By 12 months after surgery, 65% had returned to work. By 36 months, 75% had returned to work. Patients that returned to work were more likely to be non-smokers and to have a college education. They had less comorbidity, more were without benefit 1-year pre-surgery, and significantly more patients were employed at operation date. Average days of sick leave in the year before surgery were significantly less in the RTW group, and they had a significantly lower baseline NDI and EQ-5D All PROMs reached statistical significance at 12 months, in favor of the group that achieved RTW. At 12 months following surgery, 65% had returned to work. At the end of the 36-month follow-up period, 75% had returned to work, 5% less than the working percentage in the beginning of the follow-up period. This study demonstrates that a large percentage of patients return to work after surgical treatment for DCM.


Is dual morphology of rock-salt crystals possible with a single additive? The answer is yes, with barbituric acid.
Crystal face lift: barbituric acid is shown to be a new crystal-habit modifier for sodium chloride crystals. Two morphologies of salt crystals can be prepared separately with this new additive. It is of the few additives able to induce rhombic dodecahedron crystals for NaCl, and is required only a trace of amount, unlike other additives, such as glycine.


Hydrodynamics of magnetic drug targeting.
Among the proposed techniques for delivering drugs to specific locations within the human body, magnetic drug targeting surpasses due to its non-invasive character and its high targeting efficiency. Although the method has been proposed almost 30 years ago, the technical problems obstruct possible applications. It is the aim of the present work to classify the emerging problems and propose satisfactory answers. A general phenomenological theory is developed and a model case is studied, which incorporates all the physical parameters of the problem.


Acidic fibroblast growth factor prevents post-axotomy neuronal death of the newborn rat facial nerve.
The death of facial motoneurons after axotomy provides a useful tool for studying neurotrophic factors which could prevent motoneuron loss in vivo. The right facial nerve trunk before the postauricular nerve branching of newborn rats was transected at its extracranial exit, and topically treated, at the axotomy site, with either a vehicle solution containing agarose or sucralfate, or acidic fibroblast growth factor (aFGF). Acidic FGF treatment increased the survival of the facial motoneurons from 18% to 70%. These results suggest that aFGF is a neurotrophic factor for motoneurons in vivo and that this growth factor may provide a new basis for the development of treatments to prevent the loss of damaged motoneurons.


Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study.
Protein-truncating variants can have profound effects on gene function and are critical for clinical genome interpretation and generating therapeutic hypotheses, but their relevance to medical phenotypes has not been systematically assessed. Here, we characterize the effect of 18,228 protein-truncating variants across 135 phenotypes from the UK Biobank and find 27 associations between medical phenotypes and protein-truncating variants in genes outside the major histocompatibility complex. We perform phenome-wide analyses and directly measure the effect in homozygous carriers, commonly referred to as "human knockouts," across medical phenotypes for genes implicated as being protective against disease or associated with at least one phenotype in our study. We find several genes with strong pleiotropic or non-additive effects. Our results illustrate the importance of protein-truncating variants in a variety of diseases.


ATP-dependent transport for glucuronides in canalicular plasma membrane vesicles.
Using rat liver canalicular plasma membrane vesicles, it has been verified that the transport of p-nitrophenyl glucuronide (NPG) across membranes is an ATP-dependent process; the apparent Km for NPG was 20 microM. S-(2,4-dinitrophenyl)-glutathione (DNP-SG) inhibited NPG uptake dose-dependently, and NPG or testosterone glucuronide did ATP-dependent DNP-SG uptake similarly. These results suggest that transport of glucuronide is mediated by an ATP-dependent glutathione S-conjugate carrier.


Facilitation and depression of synaptic transmission in amphibian sympathetic ganglia.
There have been few reports concerning facilitation and depression in sympathetic ganglia9,17,40. In the present investigation, pairs of excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from bullfrog paravertebral sympathetic ganglia for an analysis of the site and mechanism responsible for the phenomena of facilitation and depression of ganglionic transmission. The ratio of the amplitude of the second of a depression of ganglionic transmission. The ratio of the amplitude of the second of a pair of EPSPs divided by the first was compared to the time interval between each pair of EPSPs divided by the first was compared to the time interval between each pulse. These ratios demonstrated two phases: an earlier phase of facilitation (20-500 msec pulse intervals) and a later phase of depression (500 msec-10 sec). Additional parameters-rate of rise of synaptic potentials (dV/dt), synaptic currents (EPSCs), and synaptic conductances (Gtr)-were determined and all confirmed the results obtained with EPSPs. Furthermore, the degree of facilitation or depression could be modulated by altering the extracellular concentration of calcium. On the other hand, comparison of the amplitude of pairs of presynaptic terminal spikes did not show any variability over similar stimulus intervals, nor were the amplitudes of miniature EPSPs significantly different before or after an evoked EPSP. Therefore, the processes of facilitation and depression of ganglionic transmission occur as a result of normal nerve terminal activity. The processes are occurring simultaneously, such that one or the other may predominate depending upon the interval between pulses, as well as the relative concentration of extracellular calcium.


External radiotherapy for carcinoma of the eyelid: report of 850 cases treated.
We report a retrospective series of 850 patients treated by external irradiation for carcinoma of the eyelid at Institut Curie and we compare our results with other techniques: brachytherapy and surgery. Eight hundred fifty patients were treated by external radiotherapy for carcinoma of the eyelid. None of these patients have been previously treated. All the patients were classified according to the TNM classification of (UICC). We distinguished five histological types and five clinical groups according to the site of the skin tumor. Three modalities of external radiotherapy were used: contact therapy, conventional radiotherapy, and electrontherapy. We reviewed the clinical files of the 850 patients who went regularly at follow-up visits. We report the 5-year survival results--alive with no evidence of disease: 72%; alive with progression: 2%; died from tumor progression: 0.5%; died from intercurrent disease: 19.5%; and lost to follow-up: 5%. The 5-year local control rate was 97.5%. We observed 45 failures--lymph node, metastatic, and local--and emphasize this last group by presenting the results of treatment of these local failures. We studied the complications of treatment: 2.3% of corneal complications, 2% of cataracts, and 1.4% of serious ocular complications. Our results concerning local failures and loss of the eye are comparable to those reported for other techniques involving brachytherapy or surgery. Overall, external radiotherapy is a safe and effective treatment, as it ensures a high local control rate and provides perfectly satisfactory functional and esthetic results. It seemed particularly useful to report this series in that few publications are available on this subject that, nevertheless, constitutes a topical issue.


Elevated intracranial pressure requiring decompressive craniectomy in a child with progressive primary angiitis of the central nervous system: a case report.
Elevated intracranial pressure is a potentially catastrophic complication of neurologic injury in children. Successful management of elevated intracranial pressure requires prompt recognition and therapy directed at both reducing intracranial pressure and reversing its underlying cause. A rare condition that causes elevated intracranial pressure is childhood primary angiitis of the central nervous system, which is a rare inflammatory central nervous system disease that poses diagnostic and therapeutic challenges. To our knowledge, this is the first reported case of angiography-positive progressive childhood primary angiitis of the central nervous system requiring decompressive hemicraniectomy for refractory elevated intracranial pressure in children. We report the case of a 5-year-old Saudi girl who presented to the pediatric emergency department with fever and new-onset status epilepticus. She had elevated inflammatory markers with radiological and histopathological evidence of angiography-positive progressive childhood primary angiitis of the central nervous system, complicated by elevated intracranial pressure. Despite medical management for both childhood primary angiitis of the central nervous system and elevated intracranial pressure, her neurological status continued to deteriorate and the elevated intracranial pressure became refractory. She developed right uncal, right subfalcine, and tonsillar herniation requiring decompressive hemicraniectomy with a favorable neurological outcome. Decompressive craniectomy might be considered in cases of angiography-positive progressive childhood primary angiitis of the central nervous system with elevated intracranial pressure refractory to medication. A multidisciplinary approach for the decision of decompressive craniectomy is advised to ensure patient safety and avoid possible morbidities and mortality.


Feasibility of moxifloxacin and proflavine dual fluorescence imaging for detecting gastrointestinal neoplastic lesions: A prospective study.
High-contrast and high-resolution imaging techniques would enable real-time sensitive detection of the gastrointestinal lesions. This study aimed to investigate the feasibility of novel dual fluorescence imaging using moxifloxacin and proflavine in the detection of neoplastic lesions of the human gastrointestinal tract. Patients with the colonic and gastric neoplastic lesions were prospectively enrolled. The lesions were biopsied with forceps or endoscopically resected. Dual fluorescence imaging was performed by using custom axially swept wide-field fluorescence microscopy after topical moxifloxacin and proflavine instillation. Imaging results were compared with both confocal imaging with cell labeling and conventional histological examination. Ten colonic samples (one normal mucosa, nine adenomas) from eight patients and six gastric samples (one normal mucosa, five adenomas) from four patients were evaluated. Dual fluorescence imaging visualized detail cellular structures. Regular glandular structures with polarized cell arrangement were observed in normal mucosa. Goblet cells were preserved in normal colonic mucosa. Irregular glandular structures with scanty cytoplasm and dispersed elongated nuclei were observed in adenomas. Goblet cells were scarce or lost in the colonic lesions. Similarity analysis between moxifloxacin and proflavine imaging showed relatively high correlation values in adenoma compared with those in normal mucosa. Dual fluorescence imaging showed good detection accuracies of 82.3% and 86.0% in the colonic and the gastric lesions, respectively. High-contrast and high-resolution dual fluorescence imaging was feasible for obtaining detail histopathological information in the gastrointestinal neoplastic lesions. Further studies are needed to develop dual fluorescence imaging as an in vivo real-time visual diagnostic method.


Endotoxic activity of rough organisms of Brucella species.
A rough-specific antigen extracted from the rough species Brucella ovis and lipopolysaccharide extracted from smooth Brucella abortus demonstrated equivalent levels of activity in tests for mouse lethality and limulus lysate clotting activity. Acetone-extracted whole cells of B. ovis and of B. canis and of a rough mutant of B; abortus had the same toxicity for mice, but it was not possible to extract endotoxin from B. canis by the methods used.


In vitro evaluation of dose-effects of ethanol on human osteoblastic cells.
Chronic alcoholism represents a high risk for fractures and osteopenia. Previous histomorphometric studies reported a decreased bone formation, but it has never been established whether ethanol has a direct toxic effect on osteoblasts. This present in vitro study was performed on human osteoblast cells derived from bone explants after collagenase digestion. The direct effect of ethanol was determined after 4 days of exposure to various doses, ranging from 0.01 to 5 g/l on the alkaline phosphatase (AP) activity, osteocalcin secretion and [3H]thymidine incorporation. The influence of the duration of exposure to 0.8 g/l ethanol was also determined. A significant and dose-dependent decrease in the cell proliferation was observed. AP activity was significantly decreased by high doses of ethanol (2-5 g/l). A biphasic effect of ethanol was noted on osteocalcin secretion according to the dose: it decreased at doses lower than 0.8 g/l and increased at the highest concentrations. At the dose of 0.8 g/l, whatever the duration of exposure, the decrease of the proliferation was of the same magnitude and no significant change in AP activity was observed. Significant ethanol-induced effects on osteocalcin secretion were observed only after 4 and 8 days of exposure. These data demonstrate that ethanol may have a direct toxic effect on osteoblast activity and proliferation. This could be one of the mechanisms of alcohol-induced osteopenia which has a multifactorial pathophysiology.


ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism.
To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Mutations of the H-, K-, N-ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N-ras codon 61, and one contained the mutated H-ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H-ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors.


Comparing Blind and Ultrasound-Guided Retrobulbar Nerve Blocks in Equine Cadavers: The Training Effect.
In standing ophthalmic surgery in horses, a retrobulbar nerve block (RNB) is often placed blindly for anesthesia and akinesia. The ultrasound (US)-guided RNB may have fewer complications, but the two techniques have only been compared once in equine cadavers. This study compares the techniques for success and complication rates and analyzes the effect of training on US guidance. Twenty-two equine cadavers were divided into three groups: blind RNBs were performed bilaterally in eight cadavers, US-guided RNBs were performed bilaterally in seven cadavers, and after US-guided training, blind RNBs were performed bilaterally in seven cadavers. All RNBs were performed by the same two inexperienced operators, and a combination of contrast medium (CM; 1.25 mL) and methylene blue dye (1.25 mL) were injected (2.5 mL total volume). Needle positioning in the periorbita and the distance of the CM to the optic foramen were assessed using computerized tomography (CT). Dye spreading was evaluated by dissection. In group 1, 37.5% of the injections were in the optimal central position in the periorbita; in group 2, 75% and in group 3, 71.4%. There was no significant difference between the groups regarding needle position (groups 1 and 2 p = 0.056; groups 1 and 3 p = 0.069, groups 2 and 3 p = 0.8). The mean CM distribution distance was not significantly different between all groups. Group 1 had 18.75% intraocular injections versus 0% in group 2 and 7.1% in group 3 (not significant). US guidance showed no significant increases in accuracy nor decreases in complications. However, the effects on accuracy showed a trend towards significant improvement, and larger scale follow-up studies might show significant training effects on US guidance.


Age related changes in platelet lipid composition.
Platelet lipid composition was investigated in 52 healthy subjects aged 20 to 68 years with similar dietary habits and living in a narrow geographic area in order to search possible changes referrable to aging. No significant variations were observed when platelet cholesterol, total phospholipids and different phospholipid fractions were considered, whereas cholesterol/phospholipid (C/PL) molar ratio significantly increased with aging (p less than 0.01). Moreover, a significant increase in 16:0 + 16:1 fatty acids was found in phosphatidylcholine (PC) and in sphingomyelin (SP) (r = 0.62, p less than 0.001 and r = 0.30, p less than 0.05 respectively) and a decrease in 18:2 n6 in the phospholipid fractions considered (at least p less than 0.05). These results indicate that modifications in platelet lipid composition occur with aging and that they could affect platelet functions so playing a role in the onset of atherosclerosis and in thrombotic phenomena occurring with increasing frequency in the elderly.


The microenvironment of pituitary adenomas: biological, clinical and therapeutical implications.
The microenvironment of pituitary adenomas (PAs) includes a range of non-tumoral cells, such as immune and stromal cells, as well as cell signaling molecules such as cytokines, chemokines and growth factors, which surround pituitary tumor cells and may modulate tumor initiation, progression, invasion, angiogenesis and other tumorigenic processes. The microenvironment of PAs has been actively investigated over the last years, with several immune and stromal cell populations, as well as different cytokines, chemokines and growth factors being recently characterized in PAs. Moreover, key microenvironment-related genes as well as immune-related molecules and pathways have been investigated, with immune check point regulators emerging as promising targets for immunotherapy. Understanding the microenvironment of PAs will contribute to a deeper knowledge of the complex biology of PAs, as well as will provide developments in terms of diagnosis, clinical management and ultimately treatment of patients with aggressive and/or refractory PAs.


Detection of pneumonia using free-text radiology reports in the BioSense system.
Near real-time disease detection using electronic data sources is a public health priority. Detecting pneumonia is particularly important because it is the manifesting disease of several bioterrorism agents as well as a complication of influenza, including avian and novel H1N1 strains. Text radiology reports are available earlier than physician diagnoses and so could be integral to rapid detection of pneumonia. We performed a pilot study to determine which keywords present in text radiology reports are most highly associated with pneumonia diagnosis. Electronic radiology text reports from 11 hospitals from February 1, 2006 through December 31, 2007 were used. We created a computerized algorithm that searched for selected keywords ("airspace disease", "consolidation", "density", "infiltrate", "opacity", and "pneumonia"), differentiated between clinical history and radiographic findings, and accounted for negations and double negations; this algorithm was tested on a sample of 350 radiology reports. We used the algorithm to study 189,246 chest radiographs, searching for the keywords and determining their association with a final International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis of pneumonia. Performance of the search algorithm in finding keywords, and association of the keywords with a pneumonia diagnosis. In the sample of 350 radiographs, the search algorithm was highly successful in identifying the selected keywords (sensitivity 98.5%, specificity 100%). Analysis of the 189,246 radiographs showed that the keyword "pneumonia" was the strongest predictor of an ICD-9-CM diagnosis of pneumonia (adjusted odds ratio 11.8) while "density" was the weakest (adjusted odds ratio 1.5). In general, the most highly associated keyword present in the report, regardless of whether a less highly associated keyword was also present, was the best predictor of a diagnosis of pneumonia. Empirical methods may assist in finding radiology report keywords that are most highly predictive of a pneumonia diagnosis.


Telodendrial contact of HRP-filled photoreceptors in the turtle retina: pathways of photoreceptor coupling.
Synaptic contacts of photoreceptors in the turtle retina were studied by intracellular injection of horseradish peroxidase (HRP) and electron microscopy. Both cone and rod photoreceptors radiated basal processes (telodendria) from their terminal endings. These telodendria ran laterally in the outer plexiform layer. The telodendria of cones gave rise to many fine branches that penetrated synaptic cavities of several neighboring cones. Tips of these branches terminated near the walls of synaptic cavities. Some of the telodendrial contact formed two types of basal junction: symmetrical and punctate. The distribution of cones that made telodendrial contacts with the HRP-filled cone were quantitatively investigated. Green-sensitive cones (n = 3) made telodendrial contacts with neighboring red- and blue-sensitive cones, blue-sensitive cones (n = 4) with red- and green-sensitive cones, and red-sensitive cones (n = 9) with red- and green-sensitive cones. In contrast to these cone connections, rod telodendria did not penetrate neighboring photoreceptors. Direct synaptic contacts were not found between rods and cones. Our results clarify the variety of cone couplings in turtle retina: the three chromatic classes of cones are selectively coupled by the basal junctions at the ends of telodendrial processes.


The effects of divided attention at encoding on specific and gist-based associative episodic memory.
Effects of divided attention (DA) during encoding on later memory performance are widely documented. However, the precise nature of these effects on underlying memory representations and subsequent retrieval processes has not been thoroughly investigated. Here, we examined whether DA at encoding would disrupt young adults' ability to remember associations in episodic memory at highly specific levels of representation (i.e., verbatim memory), or whether the effects of DA extend also to gist memory for associations. Two groups of participants (one under full attention, one under DA) studied face-scene pairs. The DA group simultaneously completed an auditory choice reaction-time task during encoding. Following either a short or long delay, participants were tested on their ability to discriminate intact face-scene pairs from recombined pairs that were either highly similar, less similar, or completely unrelated to originally studied pairs. The DA group performed more poorly than the full attention participants at correctly classifying most types of test pairs at both delays, and results from a multinomial-processing-tree model demonstrated that participants who encoded associations under DA experienced deficits in both specific and gist memory retrieval. We also compared the DA group to full attention older adults who were tested with the same paradigm (Greene & Naveh-Benjamin, Psychological Science, 31[3], 316-331, 2020). The DA group had lower estimates of gist retrieval than the older adults but similar estimates of verbatim memory. These results suggest that DA at encoding disrupts episodic memories at multiple levels of representation, in contrast to age-related effects, which are restricted only to the highest levels of specificity.


Antiangiogenic activity of rPAI-1(23) promotes vasa vasorum regression in hypercholesterolemic mice through a plasmin-dependent mechanism.
The antiangiogenic activity of rPAI-1(23), a truncated plasminogen activator inhibitor-1 (PAI-1) protein, induces vasa vasorum collapse and significantly reduces plaque area and plaque cholesterol in hypercholesterolemic low-density lipoprotein receptor-deficient/apolipoprotein B48-deficient mice. The objective of this study was to examine rPAI-1(23)-stimulated mechanisms that cause vasa vasorum collapse. The rPAI-1(23) protein opposed PAI-1 antiproteolytic function by stimulating a 1.6-fold increase in plasmin activity compared with the saline-treated counterpart. The increased proteolytic activity corresponded to increased activity of matrix metalloproteinase-3 and degradation of fibrin(ogen), nidogen, and perlecan in the adventitia of descending aortas. PAI-1 activity was reduced by 48% in response to rPAI-1(23); however, PAI-1 protein expression levels were similar in the rPAI-1(23)- and saline-treated hypercholesterolemic mice. Coimmunoprecipitation assays demonstrated a novel PAI-1-plasminogen complex in protein from the descending aorta of rPAI-1(23)- and saline-treated mice, but complexed PAI-1 was 1.6-fold greater in rPAI-1(23)-treated mice. Biochemical analyses demonstrated that rPAI-1(23) and PAI-1 binding interactions with plasminogen increased plasmin activity and reduced PAI-1 antiproteolytic activity. We conclude that rPAI-1(23) causes regression or collapse of adventitial vasa vasorum in hypercholesterolemic mice by stimulating an increase in plasmin activity. The rPAI-1(23)-enhanced plasmin activity was achieved through a novel mechanism by which rPAI-1(23) and PAI-1 bound plasminogen in a cooperative manner to increase plasmin activity and reduce PAI-1 activity.