Reduction of genistein clastogenicity in Chinese hamster V79 cells by daidzein and other flavonoids.
A broad spectrum of health benefits has been ascribed to soy products. These products contain soy protein and relatively high levels of polyphenolic compounds known as flavonoids. While they are the most likely candidates for biological activity, flavonoids as a class, and of specific interest, genistein, are well known to be genotoxic due to their ability to "poison" cellular DNA topoisomerase II (topo II) resulting in stable chromosome breakage and mutation and raising questions about the long term health effects associated with chronic flavonoid exposure. Interestingly, some flavonoids, such as biochanin, galangin and daidzein, are catalytic topo II inhibitors (not poisons) and actually antagonize the clastogenicity of topo II poisons. It is shown in the present paper that flavonoids possessing catalytic topo II inhibitory activity, strongly antagonize the clastogenicity of genistein in Chinese hamster V79 cells. Importantly, one of these, daidzein, is a major constituent of marketed soy products. It is conjectured that the potential human clastogenic risk of soy products containing genistein might be mitigated or abolished due to the presence of daidzein or other flavonoids in those products.


LncRNA MIAT correlates with immune infiltrates and drug reactions in hepatocellular carcinoma.
Long non-coding RNA (lncRNA) is a kind of important molecules involved in the formation of immune landscape in tumor microenvironment. However, there are few studies on the relationship between lncRNA and immunomodulatory regulation of hepatocellular carcinoma (HCC). In this study, we combined with single cell transcriptome sequencing and TCGA data to analyze the relationship between lncRNA MIAT and immune cells in HCC. TIMER database analysis indicated that the expression of MIAT in HCC was negatively correlated with tumor purity, positively correlated with the number of immune cells such as B cells, T lymphocytes and macrophages, and positively correlated with the expression of immune checkpoint molecules such as PD-1, PD-L1 and CTLA4. Analysis of single cell sequencing data of immune cells in HCC showed that MIAT was mainly distributed in tumor, and enriched in FOXP3+CD4+T cells and PDCD1+CD8+, GZMK+CD8+T cells, indicating that MIAT may be involved in the immune escape process of HCC. Besides, through the construction of transcription factor (TF) regulatory network, MIAT-TF-mRNA, we found that the interaction of MIAT and TFs may affect the immune microenvironment of LIHC by regulating the expression of target genes JAK2, SLC6A6, KCND1, MEIS3 or RIN1; LncMAP and CARE analysis showed that MIAT was highly related to the sensitivity of many anticancer drugs, especially sorafenib. In addition, the effect of MIAT on PD-L1 and its relationship with sorafinib were verified in clinical specimens and cells. This study made a meaningful attempt to reveal the immune escape mechanism and to find the effectiveness of targeted drugs in patients with HCC.


Expression profiles of seven glutathione S-transferase (GST) genes from Venerupis philippinarum exposed to heavy metals and benzo[a]pyrene.
Glutathione S-transferases (GSTs) are phase II enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. In this study, we reported the cloning and molecular characteristics of seven genes of the GST family (VpGSTS1, VpGSTS2, VpGSTS3, VpGSTO, VpGSTMi, VpGSTM and VpGSTR) from Venerupis philippinarum together with mRNA tissue distribution patterns and temporal expression profiles in response to cadmium, copper and benzo[a]pyrene (B[a]P) exposures. The deduced amino acid sequences of VpGSTs showed high similarities to counterparts of other species that clustered into the same clades in the phylogenetic analysis. At basal levels of tissue expression, most VpGSTs were highly expressed in hepatopancreas compared with other tissues. All VpGSTs showed differential response profiles depending on the concentrations of various toxicants and exposure times. More notably, the expressions of VpGSTS2 and VpGSTS3 transcripts were significantly up-regulated in hepatopancreas from Cu and B[a]P-exposed animals, indicating that these two sigma VpGSTs were highly sensitive to Cu and B[a]P exposure. However, the expressions of VpGSTM and VpGSTR were significantly induced by Cu or B[a]P exposure, respectively. These findings suggested the role of VpGSTS2, VpGSTS3, VpGSTM and VpGSTR in defense against oxidative stress and highlighted their potential as biomarkers to Cu or B[a]P exposure.


Preparation and Characterization of Super-Absorbing Gel Formulated from κ-Carrageenan-Potato Peel Starch Blended Polymers.
κ-carrageenan is useful for its superior gelling, hydrogel, and thickening properties. The purpose of the study was to maximize the hydrogel properties and water-absorbing capacity of κ-carrageenan by blending it with starch from potato peels to be used as safe and biodegradable water-absorbent children's toys. The prepared materials were analyzed using FTIR and Raman spectroscopy to analyze the functional groups. Results showed that there was a shift in the characteristic peaks of starch and κ-carrageenan, which indicated their proper reaction during blend formation. In addition, samples show a peak at 1220 cm-1 corresponding to the ester sulfate groups, and at 1670 cm-1 due to the carbonyl group contained in D-galactose. SEM micrographs showed the presence of rough surface topology after blending the two polymers, with the appearance of small pores. In addition, the presence of surface cracks indicates the biodegradability of the prepared membranes that would result after enzymatic treatment. These results are supported by surface roughness results that show the surface of the κ-carrageenan/starch membranes became rougher after enzymatic treatment. The hydrophilicity of the prepared membranes was evaluated from contact angle (CA) measurements and the swelling ratio. The swelling ratio of the prepared membranes increased gradually as the starch ratio increased, reaching 150%, while the water-uptake capacity increased from 48 ± 4% for plain κ-carrageenan to 150 ± 5% for 1:2 κ-carrageenan/starch blends. The amylase enzyme showed an effective ability to degrade both the plain κ-carrageenan and κ-carrageenan/starch membranes, and release glucose units for up to 236 and 563, respectively. According to these results, these blends could be effectively used in making safe and biodegradable molded toys with superior water-absorbing capabilities.


Repair of bone defect by using vascular bundle implantation combined with Runx II gene-transfected adipose-derived stem cells and a biodegradable matrix.
A large hurdle in orthopedics today is the difficulty of dealing with the non-union of fractured bones. We therefore evaluated the effects of runt-related transcription factor II (Runx II), a factor used to create gene-modified tissue-engineered bone, combined with vascular bundle implantation for repairing segmental bone defects. Adenovirus Runx II gene (Ad-Runx II)-modified rabbit adipose-derived stem cells (ADSCs) were seeded onto polylactic acid/polycaprolacton (PLA/PCL) scaffolds to construct gene-modified tissue-engineered bone. The following four methods were used for repair in rabbit radial-defect (1.5 cm long) models: gene-modified tissue-engineered bone with vascular bundle (Group A), gene-modified tissue-engineered bone (Group B), non-gene-modified tissue-engineered bone with vascular bundle (Group C), and PLA/PCL scaffolds only (Group D). X-ray, histological examination, biomechanics analysis, and micro-angiography were conducted 4, 8, and 12 weeks later to determine angiogenesis and osteogenesis. The volume and speed of production of newly formed bones in Group A were significantly superior to those in other groups, and de-novo vascular network circulation from the vessel bundle through newly formed bone tissue was observed, with the defect being completely repaired. Group B showed a slightly better effect in terms of speed and quality of bone formation than Group C, whereas the bone defect in Group D was replaced by fibrous tissue. The maximal anti-bending strength in Group A was significantly higher than that in the other groups. Runx II gene therapy combined with vascular bundle implantation thus displays excellent abilities for osteoinduction and vascularization and is a promising method for the treatment of bone non-union and defect.


'New roles are no replacement'.
Nursing associates and apprentices should not replace registered nurses, the chief executive of NHS England has told senior nurses and midwives.


Reduction of ferric iron by acidophilic heterotrophic bacteria: evidence for constitutive and inducible enzyme systems in Acidiphilium spp.
To compare the abilities of two obligately acidophilic heterotrophic bacteria, Acidiphilium acidophilum and Acidiphilium SJH, to reduce ferric iron to ferrous when grown under different culture conditions. Bacteria were grown in batch culture, under different aeration status, and in the presence of either ferrous or ferric iron. The specific rates of ferric iron reduction by fermenter-grown Acidiphilium SJH were unaffected by dissolved oxygen (DO) concentrations, while iron reduction by A. acidophilum was highly dependent on DO concentrations in the growth media. The ionic form of iron present (ferrous or ferric) had a minimal effect on the abilities of harvested cells to reduce ferric iron. Whole cell protein profiles of Acidiphilium SJH were very similar, regardless of the DO status of the growth medium, while additional proteins were present in A. acidophilum grown microaerobically compared with aerobically-grown cells. The dissimilatory reduction of ferric iron is constitutive in Acidiphilium SJH while it is inducible in A. acidophilum. Ferric iron reduction by Acidiphilium spp. may occur in oxygen-containing as well as anoxic acidic environments. This will detract from the effectiveness of bioremediation systems where removal of iron from polluted waters is mediated via oxidation and precipitation of the metal.


A systematic review of social determinants of health in pediatric organ transplant outcomes.
Equitable access to pediatric organ transplantation is critical, although risk factors negatively impacting pre- and post-transplant outcomes remain. No synthesis of the literature on SDoH within the pediatric organ transplant population has been conducted; thus, the current systematic review summarizes findings to date assessing SDoH in the evaluation, listing, and post-transplant periods. Literature searches were conducted in Web of Science, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature databases. Ninety-three studies were included based on pre-established criteria and were reviewed for main findings and study quality. Findings consistently demonstrated disparities in key transplant outcomes based on racial or ethnic identity, including timing and likelihood of transplant, and rates of rejection, graft failure, and mortality. Although less frequently assessed, variations in outcomes based on geography were also noted, while findings related to insurance or SES were inconsistent. This review underscores the persistence of SDoH and disparity in equitable transplant outcomes and discusses the importance of individual and systems-level change to reduce such disparities.


Microvascularization and expression of VEGF and its receptors in recurring meningiomas: pathobiological data in favor of anti-angiogenic therapy approaches.
We studied expression of molecules of the vascular endothelial growth factor (VEGF) pathway and its relation to vascularization, cell proliferation and patient outcome in recurring non-anaplastic meningioma. We studied 29 tumor specimens of 8 patients with recurring meningiomas and of 8 age- and gender-matched control patients with non-recurring meningiomas (including meningothelial, transitional, fibroblastic and atypical subtypes) using immunohistochemistry and in-situ hybridization. VEGF protein, VEGF-mRNA, VEGF receptor (VEGFR)-1 mRNA, VEGFR-2 mRNA and hypoxia-inducible factor (HIF)-1-α protein were expressed in 27/29 (93%), 20/27 (74%), 9/27 (33.3%), 12/27 (44.4%) and 5/29 (17.2%) specimens, respectively. VEGFR- 2 mRNA expression was found in 6/8 tumors extracted at first operation in patients with recurring tumors and in none of the control cases (p = 0.007). Microvessel density (MVD) and Ki-67 index values were generally higher in meningiomas with expression of angiogenic factors. The association of high Ki-67 index values with VEGF-mRNA expression was significant (p = 0.04). Time to recurrence was shorter in patients with high MVD than in patients with low MVD (p = 0.027). High MVD correlates with unfavorable prognosis in our series of recurring meningioma. VEGF and its receptors are frequently expressed in meningiomas and seem important for tumor growth and recurrence. Thus, anti-VEGF therapy in aggressive meningioma seems rational from a pathobiological point of view.


The auricular surface as age indicator in a modern Greek sample: A test of two qualitative methods.
The auricular surface is often found very well preserved, thus age-related changes in this anatomical area can be important for any set of human remains that require identification under different taphonomic conditions. This study tests the Buckberry and Chamberlain (2002) and Schmitt et al. (2005) methods in predicting the age of individuals in a documented sample from Crete, Greece. Both methods were used to record changes on the auricular surface in a mixed-sex sample of 74 individuals, directly as well as through photographs, by two independent observers. Cohen's kappa and intra class correlation coefficients (ICC) were used in order to assess inter-observer and intra-observer agreement. Results showed than none of the methods predicted age with sufficient accuracy, as high error rates were recorded. The Schmitt et al. (2005) method performed better, mainly because the age ranges it uses are broader. Scoring through photographs does not seem to introduce bias in predicting age, as demonstrated by the high intra-observer agreement rates. Inter-observer agreement was also high. The low intra- and inter-observer error rates suggest that the poor performance of both methods in the Cretan sample is not due to a lack of clarity in the description of the morphological changes recorded on the auricular surface; rather it should be attributed to a poor correlation between these changes and age at death in our material.


Editorial Commentary: Shoulder Arthroscopy With Epinephrine Diluted Saline-Irrigation Fluid.
The addition of epinephrine to irrigation fluid aims to improve visual clarity during shoulder arthroscopy. A potential benefit is shorter operative time. Intra-articular procedures received the greatest benefit, although bleeding within the subacromial space is typically more problematic for shoulder arthroscopists.


Safety and Efficacy of Testosterone Therapy on Musculoskeletal Health and Clinical Outcomes in Men: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
Age-related declines in muscle and bone, alongside a shift toward greater adiposity, contribute to falls and fracture risk. Testosterone is osteogenic, myogenic, and catabolic to fat. As such, we examined the effects of testosterone therapy on musculoskeletal health and clinical outcomes in men. Electronic databases (Medline, Embase, Web of Science, Central) were systematically searched for randomized controlled trials (RCTs) reporting on the effects of testosterone therapy versus placebo on any primary outcome (bone density, muscle mass, fat mass, muscle strength/physical performance) or secondary outcome (falls, fractures, disability, adverse events) in men (≥18 years). A random effects meta-regression examined the effects of testosterone on prespecified outcomes. One thousand seven hundred twenty-eight men across 16 RCTs were included (mean age: 77.1 ± 7.6 years). Baseline mean serum testosterone ranged from 7.5 ± 0.3 to 18.9 ± 1.2 nmol/L. Compared to placebo, 6 months of testosterone therapy increased hip bone density and total lean mass, but effects for handgrip and total fat mass did not reach statistical significance. No significant effects of testosterone therapy on musculoskeletal outcomes were evident at 12 months. The limited number of RCTs reporting on adverse events/clinical outcomes, and the low incidence of these events across RCTs, prohibited statistical comparisons. After 6 months, testosterone effectively increases hip bone density and total lean mass in men, but its effects are unclear for lumbar spine bone density and handgrip strength. Further, RCTs are needed to clarify the safety and efficacy of testosterone on musculoskeletal health and clinical outcomes.


Prevalence and significance of gallium-67 uptake in the heart after open-heart surgery.
Radioactive gallium-67 (Ga-67) has been shown to accumulate within areas of pericardial inflammation. The present study estimated prospectively the prevalence and clinical significance of Ga-67 uptake in the heart in 62 patients 10 to 16 days after open-heart surgery. Of 62 patients studied, markedly diffuse Ga-67 uptake was detected in 21 (34%) and focal or mild diffuse uptake in 23 (37%). Results were negative in 18 (29%). Nine patients with a negative scan result (50%) had received corticosteroid therapy before imaging, whereas only 2 patients with a positive scan result (5%) were receiving steroids. The erythrocyte sedimentation rate and C-reactive protein level were both higher in patients with Ga-67 uptake compared with those with a negative scan result (p less than 0.01 in both). No other clinical, echocardiographic or electrocardiographic indicators of postpericardiotomy syndrome were related to Ga-67 uptake. No patient developed cardiac tamponade or constrictive pericarditis during the 12-week follow-up and the Ga-67 scan results did not predict the occlusion of coronary artery bypass grafts. Thus, pericardial inflammation manifested as Ga-67 uptake is a common finding after open-heart surgery and appears to be a benign condition.


"Spontaneous" endothelial injury in the rat caudal artery.
Numerous spontaneous lesions, characterized principally by a gap in the internal elastic lamina, form with age in the caudal artery of the young, male Wistar rat. Such newly formed lesions were studied, with special reference to the state of the endothelium, using three techniques: "en face" examination of silver-stained caudal artery, [3H]thymidine autoradiography, and light and electron microscopy. In many, but perhaps not all cases, areas of endothelium are damaged or removed either simultaneously or shortly after the formation of the break in the internal elastic lamina and some underlying smooth muscle cells are damaged. Polymorphonuclear cells and monocytes are attracted to the site of injury. A repair process rapidly ensues including rapid regeneration of the endothelium and proliferation of smooth muscle cells in the underlying media and of some adventitial fibroblasts. This process results in the restitution of the endothelial monolayer and the laying down of one or several layers of longitudinal smooth muscle and collagen and elastic fibers in the subendothelial space. This demonstration of naturally occurring damage to fairly large areas of endothelium and the events which occur in the repair process is of interest in view of the "response-to-injury" theory of atherogenesis; observations are discussed in the light of previous studies performed on experimentally removed endothelium.


A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group.
Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P < 0.001). Mortality was 48.4, 48.6, and 52.1 percent, respectively (P = 0.638), up to the time of discharge from the intensive care unit and 62.3, 61.7, and 63.8 percent (P = 0.875) at six months. Among patients who survived, the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups. No differences in mortality among the three groups were found for any diagnostic category. A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates: 44.8, 40.4, and 39.0 percent, respectively (P = 0.478). Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients.


Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia.
Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia. Amyloid-β (Aβ) 1-42, total tau (t-tau), phosphorylated tau, Aβ40 , Aβ38 , beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), neurogranin (ng), phosphorylated neurofilament heavy-chain, and α-synuclein (α-syn) CSF levels were analyzed in 319 subjects, among whom 57 also underwent an amyloid PET scan. We also analyzed longitudinal clinical data from 239 subjects. Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels. These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.


Roles of illumination on distribution of phosphorus in Chlorella vulgaris under mixotrophic cultivation.
Phosphorus (P) is a non-substitutable resource and global reserves of phosphate rock are limited. In this study, phosphorus recovery by Chlorella vulgaris, and the effects of different light intensities (2000 Lux, 5000 Lux, 8000 Lux, 12,000 Lux) on the phosphorus distribution in the soluble microbial product (SMP), extracellular polymeric substance (EPS) and intracellular polymeric substance (IPS) were analyzed. The results showed that the 5000 Lux was the optimum light intensity for P uptake and transformation by Chlorella vulgaris under mixotrophic cultivation. At the light intensity of 5000 Lux, the P uptake rate was 100% after 32 days of cultivation, and the concentration of intracellular organic phosphorus (OP) was 5.77 mg P/L. Moreover, EPS was the main P pool when inorganic phosphorus (IP) was depleted in bulk solution. Phosphorus recovery by microalgae is an important solution to treat P-containing wastewater.


Lack of effect of a selective vasopressin V1A receptor antagonist SR 49,059, on potentiation by vasopressin of adrenoceptor-mediated pressor responses in the rat mesenteric arterial bed.
The vasopressin receptor subtype involved in the enhancement by vasopressin of adrenoceptor-mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries. [Arg8]vasopressin (1-10 nM) dose-dependently increased the perfusion pressure and enhanced the pressor response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 nM of [Arg8]vasopressin up to 4 and 3 fold, respectively. During prolonged exposure (45 min) the direct vasoconstrictor effect of [Arg8]vasopressin (10 nM) rapidly declined whereas the potentiation of methoxamine-induced vasoconstriction was maintained. The selective vasopressin V1A receptor antagonist SR 49,059 (1-3 nM) and the non-selective V1A/B and oxytocin receptor antagonist [deamino-Pen1,Tyr(Me)2,Arg8]vasopressin (15-45 nM) inhibited the direct vasoconstrictor action of [Arg8]vasopressin but had no effect on the enhancement of the pressor response to methoxamine or electrical stimulation. The V1B receptor agonist [deamino-Cys1,beta-(3-pyridyl)-D-Ala2,Arg8]vasopressin (100-1000 nM) and the V2 receptor agonist [deamino-Cys1,D-Arg8]vasopressin (1-10 nM) were devoid of any pressor activity and did not potentiate methoxamine-evoked vasoconstriction. In contrast, [1-triglycyl,Lys8]vasopressin (100 - 1000 nM) potentiated the methoxamine responses without per se inducing vasoconstriction. In arteries precontracted with methoxamine (7.5 microM) pressor responses to [Arg8]vasopressin (3-10 nM) were not inhibited by a dose of SR 49,059 (3 nM) which abolished the peptide's vasoconstrictor effect under control conditions. These data show that the direct vasoconstrictor effect of [Arg8]vasopressin is mediated by V1A receptors while the enhancement of adrenoceptor-mediated pressor responses is insensitive to V1A, V1B, and oxytocin receptor antagonists and is not mimicked by selective agonists of V1B and V2 receptors. In conclusion, an unusual interaction of vasopressin with V1A receptors, or even the existence of a novel receptor subtype, has to be considered.


Effects of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women.
The purpose of this study was to investigate the effects of 12 weeks of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women. Twenty healthy middle-aged women were recruited for this study. Several measurements were performed pre and post exercise training, including: body weight and composition, peak oxygen consumption (peak VO2), energy intake after the single bout of exercise, and the release of gut hormones with fasting and after the single bout of exercise. Exercise training resulted in significant increases in acylated ghrelin fasting levels (from 126.6 ± 5.6 to 135.9 ± 5.4 pmol/l, P < 0.01), with no significant changes in GLP-1 (from 0.54 ± 0.04 to 0.55 ± 0.03 pmol/ml) and PYY (from 1.20 ± 0.07 to 1.23 ± 0.06 pmol/ml) fasting levels. GLP-1 levels post exercise training after the single bout of exercise were significantly higher than those pre exercise training (areas under the curve (AUC); from 238.4 ± 65.2 to 286.5 ± 51.2 pmol/ml x 120 min, P < 0.001). There was a tendency for higher AUC for the time courses of PYY post exercise training than for those pre exercise training (AUC; from 519.5 ± 135.5 to 551.4 ± 128.7 pmol/ml x 120 min, P = 0.06). Changes in (delta) GLP-1 AUC were significantly correlated with decreases in body weight (r = -0.743, P < 0.001), body mass index (r = -0.732, P < 0.001), percent body fat (r = -0.731, P < 0.001), and energy intake after a single bout exercise (r = -0.649, P < 0.01) and increases in peak VO2 (r = 0.558, P < 0.05). These results suggest that the ability of exercise training to create a negative energy balance relies not only directly on its impact on energy expenditure, but also indirectly on its potential to modulate energy intake.


Whole fetal liver transplantation--a new approach to cell therapy.
We recently developed a novel rat model for liver repopulation, heterografting of microliver slices, aimed at overcoming the limitations inherent in both whole liver and hepatocyte transplantations. The aim of the present study was to evaluate the potential of whole fetal liver transplantations to survive and differentiate within the adult liver, using the adult liver slice transplantation model. Embryonic day 14 whole fetal livers from dipeptidyl peptidase IV+/+ wild-type Fischer 344 rats were transplanted into the livers of dipeptidyl peptidase IV-/- mutant rats. Adult hepatic markers, dipeptidyl peptidase IV, albumin, glycogen, and proliferation cell nuclear antigen- proliferation cell nuclear antigen (PCNA) were assessed in the transplanted liver tissue by immunohistochemistry. Two groups of 9 rats each were transplanted with 3 fetal livers per recipient. Two months later the rats were sacrificed and the markers were detected in the transplanted tissues. In conclusion, the results of this study raise the possibility that fetal liver transplantation could serve as a model for genetic metabolic liver diseases.


Notes on the history of SocialScienceResearch: In celebration of its 50th anniversary.
This paper reports a first look at the founding of Social Science Research, providing a few key signposts but keenly aware that a full history must await recovery of many additional documentary materials. The journal was founded by James S. Coleman and Peter H. Rossi, who had trained at Columbia, taught at Chicago, and founded the interdisciplinary Department of Social Relations at Johns Hopkins. The Coleman-Rossi vision statement embeds three key ideas: (1) quantitative theoretical work and quantitative empirical work are close and constant partners; (2) quantitative theoretical work and quantitative empirical work each require special methods; and (3) crossing disciplinary lines spurs the growth of knowledge. The first issue of Social Science Research appeared in 1972. Then as now, SSR welcomed papers that may be too innovative or too technical (or too long or too short) for other journals, inclusive of papers that cross traditional disciplinary lines. Examination of the first four volumes (1972-1975) reveals a beautiful realization of the founders' vision - a collection of rigorous quantitative papers from across the social sciences, pushing frontiers in both theory and empirics and in both substance and methods. There is innovation and creativity - and a touch of the playfulness that accelerates the growth of knowledge.


An all-optical quantum gate in a semiconductor quantum dot.
We report coherent optical control of a biexciton (two electron-hole pairs), confined in a single quantum dot, that shows coherent oscillations similar to the excited-state Rabi flopping in an isolated atom. The pulse control of the biexciton dynamics, combined with previously demonstrated control of the single-exciton Rabi rotation, serves as the physical basis for a two-bit conditional quantum logic gate. The truth table of the gate shows the features of an all-optical quantum gate with interacting yet distinguishable excitons as qubits. Evaluation of the fidelity yields a value of 0.7 for the gate operation. Such experimental capability is essential to a scheme for scalable quantum computation by means of the optical control of spin qubits in dots.


Mass transfer properties of gases in fluorocarbons.
The solubility and diffusion coefficient of oxygen and carbon dioxide were measured in both the pure and emulsified of two fluorocarbons, perfluorotributylamine and perfluorobutyl perfluorotetrahydrofuran. The solubility coefficient and the diffusivity of oxygen in the pure form of the fluorocarbons decreased with decreasing partial pressure of Oxygen (PO2), but the solubility coefficient and the diffusivity of carbon dioxide were independent of its partial pressure. The solubility and diffusion of oxygen in the emulsified form of the fluorocarbons followed the pattern expected from the behavior of oxygen in the pure fluorocarbon. The experimental results suggest that there exists a physical and/or chemical interaction between oxygen and the fluorocarbons, and this interaction is more pronounced at partial pressures below 150 mm Hg. Comparisons of the oxygen content in the fluorocarbon emulsions with that in whole blood show that at PO2 of 760 mm Hg, the oxygen content in the fluorocarbon emulsions is approximately one-half that in whole blood, but at PO2 of 50-150 mm Hg, the oxygen content in the emulsions decreases to values which are less than one-tenth that of whole blood.


Quantification and localization of EEG interictal spike activity in patients with surgically removed epileptogenic foci.
To demonstrate if interictal spike activity was localized within the resected area in surgically treated epilepsy patients; and if there is correspondence between the degree of localization and improvement after surgery. We analyzed long-term EEGs from 34 patients. Interictal spikes were grouped in clusters and averaged according to morphology and topography. The relative contribution of each cluster to the total number of spikes in each patient was estimated. Dipole and distributed EEG source localization of each cluster was made. The percentage of spike activity localized within the site of resection (SR) during the onset was estimated. The relationship between the percentage of activity within SR and the surgery outcome was assessed. Fourteen patients had 90-100% of spikes within SR, 9 had 50-89%. Most patients with more than 50% of activity localized within SR were seizure free, while the 5 patients who had all activity localized outside SR were not seizure free. Localization of clusters containing the largest quantity of interictal spikes during onset generally corresponded to the likely location of the epileptogenic cortex. Computer-assisted EEG source localization with our methodology can be a useful adjunct for the evaluation of candidates for epilepsy surgery.


Implications for Health Management Through an Analysis of Changes in Life Patterns of Generation Z College Students Experiencing the COVID-19 Pandemic: A Qualitative Study.
This study examines the radical changes in the everyday life patterns of Gen Z college students and their health-related perceptions in the online era. Twelve Korean college students in their 20s attending online classes were included in this study. Online video interviews were conducted between September 2021 and January 2022, and content analysis was performed on the one-on-one interview transcripts. Four main categories and ten subcategories were derived from the data analysis: (1) living in a mobile world, (2) new lifestyle transcending time and space and adaptation to the change, (3) expansion of the meaning of health, and (4) interest in health and health management. Gen Z college students have quickly adapted to the convenience of a non-face-to-face lifestyle, and their perceptions about health and methods of health management have also changed accordingly. Correspondingly, for the new generation of university students, providing customized health care that reflects the lifestyle of using mobile devices and includes self-management areas is necessary.


Laminin alters cell shape and stimulates motility and proliferation of murine skeletal myoblasts.
Proliferating skeletal myoblasts show multiple specific responses to laminin, one of the major glycoprotein components of basement membranes. Using MM14Dy myoblasts, a myogenic cell strain derived from a normal adult mouse skeletal muscle, we show in this study that substrate-bound laminin but not other matrix proteins such as collagens or fibronectin specifically and rapidly induces the outgrowth of cell processes, resulting in bipolar, spindle-shaped cells. This effect is independent from the presence of collagens or serum, and was also observed in primary cultures of fetal mouse skeletal myoblasts. The outgrowth of cell processes on laminin is associated with a dramatic stimulation of cell motility: MM14 myoblasts migrate about five times faster on laminin than on fibronectin. In another series of experiments the effect of laminin and fibronectin on thymidine uptake and proliferation of myoblasts was tested. On top of a type I collagen substrate which was provided to ensure complete adhesion even at low doses of laminin or fibronectin, laminin stimulated myoblast proliferation and incorporation of [3H]thymidine in a dose-dependent manner. The stimulation is two- to threefold higher than on dishes coated with equivalent amounts of fibronectin and is observed both in the presence and in the absence of serum. These results suggest that laminin, a major component of the muscle basal lamina, may be actively involved in the development and regeneration of skeletal muscle.


Olfactory Function in Latino Farmworkers: Subclinical Neurological Effects of Pesticide Exposure in a Vulnerable Population.
We compared olfactory function in pesticide-exposed Latino farmworkers and nonfarmworkers to explore its use as a subclinical indicator of neurological pesticide effects. We recruited 304 current farmworkers and 247 nonfarmworkers. All completed odor identification (14 odors) and threshold tests (16 concentrations of n-butanol) using a well-established methodology. Farmworkers reported significantly greater lifetime pesticide exposure. Performance on both olfactory tests declined with age. Odor identification performance did not differ between groups. For odor threshold, farmworkers needed significantly higher concentrations to detect the odor. Results were unchanged when adjusted for sex, age, and smoking. Olfactory function differences between farmworkers and nonfarmworkers suggest possible neurological effects. Because declining olfactory function is an early symptom of Parkinson disease and related conditions, it is a possible subclinical indicator of neurodegenerative disease in this vulnerable worker population.


Perceptual change in response to a bistable picture increases neuromagnetic beta-band activities.
The purpose of the present study was to examine by whole-head magnetoencephalography (MEG) brain oscillatory responses related to visual perceptual change of short-term duration in the absence of morphologic change. Twenty healthy volunteers participated in this study. We used three pictures: a bistable picture with ambiguous contours that could represent two different objects ('target') and two preceding pictures that were clear representations of either object ('face' or 'saxophone'). Two types of stimulus conditions were created, the 'face-target' (F-T) condition and the 'saxophone-target' (S-T) condition, and data acquisition was performed mainly during presentation of the 'target' picture. Time-frequency analysis was performed by means of fast Fourier transform. All subjects reported that they perceived the 'target' picture predominantly as a 'face' regardless of the preceding picture. We suspect that perceptual change occurred more frequently in the S-T condition than in the F-T condition. We found significantly greater synchronization in the beta (14-30-Hz) frequency band, ranging from 250 to 450ms predominantly over the occipital and parietal regions, after stimulus alternation for the S-T condition than for the F-T condition. Results of the present study show that the change in beta-band activity reflects a change in visual perception.


Prognostic value of translocation t(11;18) in tumoral response of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type to oral chemotherapy.
To determine the impact of translocation t(11;18) on response to oral alkylating agents in gastric mucosa-associated lymphoid tissue lymphoma (GML). Fifty-three patients with a GML were studied. Helicobacter pylori-positive patients (n = 34) received anti-H pylori treatment and H pylori-negative patients (n = 19) or patients who failed to respond to anti-H pylori treatment received oral alkylating agents. t(11;18) was detected by reverse transcription polymerase chain reaction from frozen gastric biopsies. t(11;18) was detected in 32% of patients. It was more prevalent in H pylori-negative as compared with H pylori-positive patients (12 of 19 v five of 34 patients; P = .0005). Among 31 H pylori-eradicated patients, t(11;18) was detected in three patients, all of whom experienced treatment failure, and it was absent in 28 patients: 21 patients (75%) were in remission and seven patients (25%) experienced treatment failure (P = .03). Among 21 patients who received an alkylating agent, t(11;18) was detected in 12 patients: five patients (42%) were in remission and seven patients (58%) experienced treatment failure. t(11;18) was absent in nine patients: eight patients (89%) were in remission and one patient (11%) experienced treatment failure by the end of treatment. Four patients in remission relapsed during follow-up (median, 7 years): they all had t(11;18). Durable remission was obtained in eight (89%) of the nine patients without t(11;18) versus one of the 12 patients (8%) with t(11;18) (P = .0003). Presence of t(11;18) in GML is predictive of resistance to oral alkylating agents, with less than 10% of durable remission at long-term follow-up.


Myocardial Infarction Complications After Surgery in Vietnam: Estimates of Incremental Cost, Readmission Risk, and Length of Hospital Stay.
Myocardial infarction is a considerable burden on public health. However, there is a lack of information about its economic impact on both the individual and national levels. This study aims to estimate the incremental cost, readmission risk, and length of hospital stay due to myocardial infarction as a post-operative complication. We used data from a standardized national system managed by the Vietnam Social Insurance database. The original sample size was 1,241,893 surgical patients who had undergone one of seven types of surgery. A propensity score matching method was applied to create a matched sample for cost analysis. A generalized linear model was used to estimate direct treatment costs, the length of stay, and the effect of the complication on the readmission of surgical patients. Myocardial infarction occurs most frequently after vascular surgery. Patients with a myocardial infarction complication were more likely to experience readmission within 30 and 90 days, with an OR of 3.45 (95%CI: 2.92-4.08) and 4.39 (95%CI: 3.78-5.10), respectively. The increments of total costs at 30 and 90 days due to post-operative myocardial infarction were 4,490.9 USD (95%CI: 3882.3-5099.5) and 4,724.6 USD (95%CI: 4111.5-5337.8) per case, while the increases in length of stay were 4.9 (95%CI: 3.6-6.2) and 5.7 (95%CI: 4.2-7.2) per case, respectively. Perioperative myocardial infarction contributes significantly to medical costs for the individual and the national economy. Patients with perioperative myocardial infarction are more likely to be readmitted and face a longer treatment duration.


A prospective survey of postoperative nausea and vomiting with special regard to incidence and relations to patient characteristics, anesthetic routines and surgical procedures.
We performed a prospective study on 421 patients subjected to routine general-, orthopaedic-, urologic-, gynecological and paediatric surgery to estimate the current incidences of nausea and vomiting during the first 24 hours after surgery. The overall incidences of postoperative nausea or vomiting were 17% and 28%, respectively. Postoperative emetic symptoms were not related to age in adults. Women had more often emetic symptoms than men (P < 0.01). In general, opiate premedication was more frequently associated with postoperative nausea and vomiting than benzodiazepines (P < 0.01), but in otherwise comparable subgroups of patients undergoing major surgery, this difference was not confirmed. Balanced general anaesthesia caused more nausea (23%) and vomiting (53%) than face-mask anaesthesia (13% and 15%, respectively) or regional blocks (12% and 7%, respectively) (P < 0.001). There was a positive correlation between the duration of anaesthesia and the incidence of postoperative emetic symptoms (P < 0.001). The incidences of postoperative nausea and vomiting after abdominal surgery were 23% and 58% respectively. Corresponding figures for orthopaedic surgery were 25% and 34%, other kinds of extra-abdominal surgery 18% and 32% and for laparoscopy 21% and 25%. After minor gynecological-, urological- and paediatric surgery the incidences were less than 20%. In conclusion female gender, balanced anaesthesia, lengthy duration of anaesthesia, and abdominal and orthopaedic operations appeared to be most frequently associated with postoperative emetic symptoms.


Serial examination of serum IL-8, IL-10 and IL-1Ra levels is significant in neonatal seizures induced by hypoxic-ischaemic encephalopathy.
We investigated changes in the levels of significant cytokines in relation to neonatal seizures, a pattern of cytokine concentrations serially and the severity of brain insult. The hypoxic-ischaemic encephalopathy-induced seizure group consisted of 13 patients, and another 15 normal newborns were enrolled as a control group. All of the initial samples were obtained within the first 24 h of admission, and the second samples were obtained between 48 and 72 h in both groups. Only the third samples were taken in the seizure group on the 5th day. During neonatal seizures, the levels of most cytokines increased within 24 h, and, in particular, the levels of interleukin (IL)-8 significantly increased (P < 0.05). After 48-72 h of seizure onset, the levels of most cytokines decreased, especially, IL-1Ra; however, IL-8 and IL-10 remained increased (P < 0.05). During the prognosis, one patient who was diagnosed with quadriplegic cerebral palsy at 6 months of age presented extreme elevation of IL-1beta, IL-1Ra, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha in the initial sample, reflecting the severity of brain damage. A significant increase in IL-8 may serve as a biomarker for earlier detection of brain damage in neonatal seizure, if detected within 24 and 48-72 h of the seizure.


N-WASP Guides Cancer Cells toward LPA.
The actin remodeling factor N-WASP is best known as an Arp2/3 complex activator in processes like endocytosis, extracellular matrix degradation, and host-pathogen interaction. In this issue of Developmental Cell, Juin et al. establish a novel trafficking function for N-WASP in driving lysophosphatidic acid-dependent chemotaxis and metastasis of pancreatic cancer cells.


Burn injuries in Port Harcourt, Nigeria.
The pattern of burn injuries in Port Harcourt, Nigeria is presented for the first time. Ninety-two patients were studied and 43 (46.74 per cent) of them were children in the 0-5 years age range. Thirty-seven of the children in this group suffered from scalds and six from flame burns. Petrol fire was the commonest cause of flame burns. The overall mortality was 26.09 per cent and the majority of deaths occurred in burns covering over 50 per cent of the total body surface area. Improved parental supervision of children, in particular toddlers, a more reliable public power supply system, a ban on carrying petrol in open containers in the streets and public enlightenment campaigns are advocated by the authors as preventive measures.


Delayed skin hypersensitivity as indicator of T-cell function in three population groups.
Immunological differences between a rural under-developed black population with a low incidence of rheumatoid arthritis, and living according to old traditional ways have been compared with an urban black and urban Caucasian population with a high incidence of the disease. A delayed skin hypersensitivity test for cell-mediated immunity with seven antigens and control was used. The rural group showed a statistically significant inhibition of cell-mediated immunity with 37% showing an anergic response. A matched Caucasian group showed a more marked response while an urban black group occupied an intermediate position. The 37% anergic response in our rural group was seen despite the fact that they were very healthy and their immune systems resisted multiple parasitic and infective onslaughts. From this data interpretation of an anergic response to multiple skin antigen tests in peoples from under-developed populations must be approached with great caution. Whether this altered cell-mediated immunity plays a role in the low incidence of rheumatoid arthritis in under-developed peoples is still speculative.


Distribution of the interstitial cells of Cajal in the human anorectum.
The interstitial cells of Cajal are proposed to have a role in the control of gut motility. The aim of this study was to establish the distribution of interstitial cells of Cajal in the wall of the normal human anorectum. Interstitial cells of Cajal express the proto-oncogene c-kit. Interstitial cells of Cajal were identified in the colon by immunohistochemical staining, using a rabbit polyclonal anti-c-kit antibody. Anorectal tissue was obtained at surgical resection for carcinoma of the colorectum. Density of interstitial cells of Cajal was graded. Statistical analysis was performed using chi2 tests. In the longitudinal and circular muscle layers of the rectum interstitial cells of Cajal were seen in the bulk of the muscle layer. In the intermuscular plane interstitial cells of Cajal encased the myenteric plexus. Interstitial cells of Cajal were found at the inner margin of the circular muscle and in association with neural elements of the submuscular plexus. Within the internal anal sphincter interstitial cells of Cajal were infrequently scattered among the muscle fibres. The density of interstitial cells of Cajal in the internal anal sphincter was significantly lower than that observed in the circular muscle layer of the rectum (P = 0.014). In conclusion, interstitial cells of Cajal are evenly distributed in the layers of the muscularis propria of the rectum, but have a lower density in the internal anal sphincter.


A comparison of robotic versus laparoscopic distal pancreatectomy: Propensity score matching analysis.
The aim of this study was to assess the perioperative and pathologic outcomes of robotic distal pancreatectomy compared with a laparoscopic approach. A total of 121 robotic distal pancreatectomies and 992 laparoscopic distal pancreatectomies were retrospectively evaluated, comparing the demographic, perioperative and pathologic outcomes. After 1:2 propensity score matching (PSM) with 11 demographic variables, the factors were analysed again. Following PSM, 104 robotic distal pancreatectomy patients were compared with 208 laparoscopic distal pancreatectomy patients. The operation time and proportion of spleen preservation were not different between the groups. The rates of open conversion were lower, whereas the hospital costs were higher in the robotic group. Other perioperative outcomes and pathologic factors did not differ between the groups. Although robotic distal pancreatectomy is more expensive, this operation is feasible, with a higher probability of proceeding with the planned operation and with low open conversion rate.


[Custom-fit kinematic alignment in total knee arthroplasty using PSI. The story of ShapeMatch technology].
The story of ShapeMatch® custom-fit cutting guides for primary total knee arthroplasty (TKA) is special compared to other available techniques. First, it was the first such patient-specific instrument (PSI) on the market. Second, the underlying philosophy of kinematic alignment is unique compared to other competitors. Finally, it is the only PSI technique that has been withdrawn from the market. The objective of this paper is to summarize the history of the ShapeMatch® technology and to review the current literature regarding clinical evidence for kinematically aligned TKA. In the recent literature, faster rehabilitation, better knee function and higher patient satisfaction are described for kinematically aligned TKA compared to conventional alignment. However, there is also evidence for inaccuracies by using the PSI technology as a possible cause of treatment failures. Due to those problems, this technology was recalled from the market. As an alternative method to achieve kinematic alignment in TKA, manual as well as computer-assisted techniques are currently under development and are discussed here.


Cytochrome P-450 dependent metabolism of testosterone in rat skin.
The incubation of microsomes of whole skin, dermis and epidermis with 14C testosterone in the presence of NADPH resulted in the formation of 6 beta-, 7 alpha- and 16 alpha-testosterone. Maximum enzyme activity occurred in epidermal microsomes followed by dermis and whole skin. Epidermal testosterone hydroxylase activity required NADPH and oxygen and was found to be inhibited by SKF 525A and metyrapone. Our data strongly suggest that testosterone is metabolized by the cytochrome P-450 dependent monooxygenase in skin and provides the first evidence for an endogenous substrate for cytochrome P-450 in this tissue. The formation of several hydroxylated products further suggests the existence of multiple isozymes of cytochrome P-450 in rat skin. These studies provide additional evidence that target tissues may modulate their hormone levels by enzyme pathways that are locally regulated.


Fenestration of a Papyrus PK covered stent to recover the occluded left main bifurcation after sealing a left main perforation during a CTO procedure.
Covered stents are indicated for coronary perforations, but they may seal off major side branches in that process. We report the successful sealing of an ostial left main perforation, induced by a guide catheter in the course of a retrograde approach to treat a chronic total occlusion (CTO) of the right coronary artery (RCA) in a 76year old woman with prior CABG. The implanted Papyrus covered stent, however, overlapped the left main bifurcation and occluded the non-grafted circumflex artery (CX) resulting in acute ischemia. Through a double lumen catheter advanced over the wire located in the left anterior descending coronary artery (LAD) territory, a stiff recanalization wire could be advanced from the side-port to penetrate the stent membrane towards the CX. This was successfully achieved, and after subsequent dilatation, a drug-eluting stent was implanted in Culotte-fashion from the CX to the left main with subsequent kissing-balloon dilatation. The clinical symptoms subsided immediately, and the RCA was finally recanalized in antegrade parallel wire technique. No periprocedural infarct was observed during 48h of follow-up before discharge. At clinical follow-up of 6months the patient is symptom-free.


New data on psychological traits and sleep profiles of patients affected by nocturnal eating.
Nocturnal eating behavior is shared by patients affected by a parasomnia, sleep-related eating disorder (SRED), and several eating disorders such as night eating syndrome (NES) and binge-eating disorder (BED); however, the differential clinical features of these patients have been poorly studied, with persisting difficulties in defining the borders between these pathologies. The aim of this study was to evaluate polysomnographic and personality characteristics of nocturnal eaters to further differentiate the syndromes. During a period of six months, consecutive patients complaining of nocturnal eating were asked to participate to the study. Twenty-four patients who were found to eat during the polysomnographic recording (PSG) study, and gender-matched control subjects were included. All subjects underwent a full-night video-PSG study and a psychometric assessment including the Eating Disorder Inventory (EDI-2), the self-rating Bulimic Investigatory Test-Edinburgh (BITE), the Temperament and Character Inventory (TCI), and the Barratt Impulsivity Scale (BIS). Nocturnal eaters showed a mild reduction in sleep efficiency and duration due to a moderate sleep fragmentation, whereas the percentage of each sleep stage was not significantly affected. Nocturnal eaters scored higher at many subscales of the EDI-2, at the BITE symptoms subscale, and at the BIS attentional impulsivity subscale. The psychological characteristics found in our patients with NES seem to be typical for patients affected by eating disorders, and support the hypothesis that the nocturnal behavior of these individuals is due to an eating disorder; however, specific traits also allow differentiation of NES from BED.


Psychiatric Management, Administration, and Leadership: a Continuum or Distinct Concepts?
To clarify the relationship between the concepts of management, administration, and leadership in psychiatry. The authors provide a review of the conceptual evolution of administrative psychiatry and develop operational definitions of these three domains. Based upon their experiences, they discuss relevant core competencies and personal attributes. The authors found that the terms psychiatric management, psychiatric administration, and psychiatric leadership are often used interchangeably, yet they each have a different and distinct focus. Additionally, some in the field consider the concepts overlapping, existing on a continuum, while others draw distinct conceptual boundaries between these terms. Psychiatrists in leadership positions function in all three domains. While these are distinct concepts, the authors recommend that administrative psychiatrists integrate all three in their everyday work. The authors suggest the distinctions among these concepts should inform training and identify core competencies related to these distinctions. Mentoring should focus on the practical integration of the concepts of management, administration, and leadership in administrative psychiatry. The authors present a cohesive framework for future development of a curriculum for education and research.


A postsynaptic inhibitory histamine H2-receptor in the mouse isolated vas deferens.
The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 microM depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [3H]-NA evoked by field stimulation or by high K+ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H2-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca2+ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg2+ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H2-receptor. The stimulation of H2-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca2+ required for contraction by depressing the influx of Ca2+.


Comprehensive cloning of patient-derived 9022-bp amplicons of hepatitis C virus.
The instability of recombinant clones accommodating large or full-length viral genomes is frequently a technical challenge in RNA virus research. In an attempt to establish a rapid plasmid-based reverse genetics system that utilizes long RT-PCR technique (LRP), similar difficulty was encountered in the cloning of 9022-bp LRP amplicon. All HCV genotype 1a strains used for LRP cloning showed a remarkable difference in terms of cloning stability. Subsequent analysis revealed the predictive value of phylogenetic positions in determining the cloning stability. Putative Escherichia coli promoters on the HCV genome might be responsible for such cloning difference. An exhaustive exploration, testing nearly one hundred cloning protocols, did not reveal a general approach that can achieve stable cloning for all HCV 1a strains. The selection of appropriate strains, guided by phylogenetic analysis, appears to be necessary prior to the construction of infectious HCV 1a clones. These observations are not only valuable for potentially establishing an HCV 1a cell culture model but also have general implications for other RNA viruses due to concern about cloning instability.


Antimicrobial susceptibility of ceftolozane-tazobactam against multidrug-resistant Pseudomonas aeruginosa isolates from Melbourne, Australia.
We collected 163 clinical Pseudomonas aeruginosa isolates at a tertiary hospital specialising in adult cystic fibrosis (CF) and lung transplantation (LTx) in Melbourne, Australia, to explore the activity of ceftolozane-tazobactam (C/T) in populations at high-risk for antimicrobial resistance. Of these, 144 (88.3%) were collected from sputum, and 19 (11.7%) from bronchoalveolar lavage. Most (85.3%) were derived from patients with cystic fibrosis and included a subset of patients that had undergone LTx. These isolates were tested against 11 antibiotics, including C/T, using Sensititre plates for broth microdilution (BMD) testing. Sixty (36.8%) isolates were classified as multidrug resistant (MDR) and 32 (19.6%) were extensively drug resistant (XDR). Overall, 133/163 (81.6%) isolates were susceptible to C/T. For MDR and XDR isolates, 88.3% and 28.1% were C/T susceptible, respectively. Among the non-MDR/XDR isolates, 100% remained susceptible to C/T. Comparisons of C/T susceptibility were made using BioMérieux Etests and Liofilchem MIC test strips (MTS). Categorical agreement to BMD was >93% for both test strips, but essential agreement to BMD was slightly higher with Etest (89.0%) compared to Liofilchem (74.8%). In conclusion, C/T retained activity against most MDR and over a quarter of XDR P. aeruginosa isolates from complex patients with CF and post-LTx.


Assessing the safety benefits of an advanced vehicular technology for protecting pedestrians.
This paper proposes a methodology to quantify the safety benefits of an active hood lift system (AHLS) for protecting pedestrians. AHLS works by lifting up the hood of a vehicle to obtain the space to absorb the impact energy before the pedestrian's head hits the hood in pedestrian-vehicle collision. The safety benefit is defined as the number of pedestrian lives saved by the AHLS. Both actual accident data analysis and simulation experiments were conducted to develop a probabilistic pedestrian fatality model based on the head injury criteria (HIC). Then, the fatality model was further applied to estimate the safety benefit. Analysis results revealed that the 95% confidence interval of the number of pedestrian lives saved by the AHLS was between 32.8 and 83.6 pedestrians. It is believed that the proposed methodology could be further applied in evaluating other vehicular technologies for traffic safety. In addition, the outcomes of this study would be effectively utilized in establishing relevant traffic safety policies.


The Use of Total Cervical Occlusion along with McDonald Cerclage in Patients with Recurrent Miscarriage or Preterm Deliveries.
To study the fetal outcome with the use of McDonald cerclage and total cervical occlusion in women with recurrent mid-trimester miscarriages or preterm deliveries, as well as complications of total cervical occlusion in the women. Prospective descriptive observational study on patients with two or more mid-trimester miscarriages, deliveries before 36 weeks, or patients who have experienced failure of transvaginal cerclage. Twenty-six women were studied. Of these, 92% delivered at term. Two women delivered at 33 and 35 weeks, respectively. There was one neonatal death. Take home baby rate was 96.2%. There was no serious maternal morbidity among the patients. The addition of external cervical OS occlusion to McDonald cerclage could improve fetal outcome in women with recurrent mid-trimester miscarriages and preterm deliveries.


New approaches for treatment of systemic lupus erythematosus.
Each of the new approaches to treating SLE offers some hope in the ongoing effort to respond effectively to the challenges of this debilitating and often lethal condition. Research is extremely active and promises to accelerate as more is learned.


Role of fungal burden in risk stratification of HIV-negative patients with Pneumocystis pneumonia: A 12-year, retrospective, observational, multicenter cohort.
This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP). This was a retrospective analysis of the characteristics associated with 30-day mortality in patients who were positive for P. jirovecii using polymerase chain reaction in bronchoalveolar lavage fluid between 2006 and 2017 in a multicenter cohort from Central Norway. The fungal burden was indicated by the cycle threshold (CT) values from semiquantitative real-time polymerase chain reaction targeting the β-tubulin gene. We included 170 patients with proven or probable PCP. The all-cause 30-day mortality was 18.2%. After adjusting for host characteristics and premorbid corticosteroid use, a higher fungal burden was associated with a higher risk of dying: adjusted odds ratio 1.42 (95% confidence interval 0.48-4.25) for a CT value 31-36, increasing to odds ratio 5.43 (95% confidence interval 1.48-19.9) for a CT value ≤30 compared with patients with a CT value ≥37. The Charlson comorbidity index (CCI) improved the risk stratification: patients with a CT value ≥37 and CCI ≤2 had a 9% mortality risk compared with 70% among those with a CT value ≤30 and CCI ≥6. Comorbid cardiovascular disease, solid tumors, immunological disorders, premorbid corticosteroids, hypoxemia, abnormal leukocyte counts, low serum albumin, and C-reactive protein ≥100 were also independently associated with 30-day mortality. The sensitivity analyses did not suggest selection bias. Fungal burden may improve the risk stratification of patients without HIV-negative patients with PCP.


Effect of different alcoholic-alkaline treatments on physical and mucoadhesive properties of tapioca starch.
Alcoholic-alkaline treatment (AAT) is a physical modification method for the production of granular cold water swelling starch and should be optimized for each starch source. The main objective of this research was to investigate physical and mucoadhesive properties of tapioca starch (TS) modified by different AATs. Improvement of cold-water absorption, solubility, rheological properties at low temperatures, clarity, freeze-thaw stability, and mucoadhesion was positively correlated with the alkali amount and reaction temperature and negatively correlated with ethanol content. Morphological studies demonstrated different degrees of swelling, birefringence loss, and surface wrinkling of granules depending on modification degree. Starch pastes, modified in a higher degree, showed a change from rheopexy to thixotropy and from translucency to turbidity over time. The highest quality along with maintaining granular integrity was obtained by treating starch (10 g) with 30 g alkaline solution (2.5 M) and 110 g aqueous ethanol (40%) at 25 °C. The characteristics of this sample were higher than those of corn counterpart except for viscosity, consistency, and freeze-thaw stability and were almost similar to those of thermally gelatinized TS (TGTS). Therefore, this AA-modified TS can be an alternative for TGTS in instant and heat-sensitive foods and delivery of bioactives as a mucoadhesive polymer.


Performance characteristics of a gamma camera over a wide range of energies.
The problem of choosing which collimator to use for imaging a new isotope has been approached by collecting resolution and sensitivity data for a selected group of isotopes. These have been chosen to be readily available and to have generally a single gamma-ray only. Resolution and sensitivity plots for a low energy collimator and a high energy collimator are presented and their use with several isotopes of interest is discussed. The interpretation of recommedations in the literature on the choice of collimators for newly introduced isotopes would be considerably simpler if data in this format were commonly available.


An atypical bilateral trifurcation of recurrent laryngeal nerve.
Thyroidectomy is a frequently performed surgery for benign and malignant conditions. Nevertheless, one of the most critical complications of thyroidectomy is recurrent laryngeal nerve (RLN) injury leading to vocal cord paralysis. A thorough knowledge of the anatomical variations of RLN and ligation of the related vessels close to their distal branches is critical to avoid injury. Here, we report the first case of bilateral trifurcation of recurrent laryngeal nerve (RLN) in a 40-year old woman with multinodular goitre. Total thyroidectomy was performed and RLN was preserved bilaterally. Followed by a precise dissection, fine branches were traced penetrating the larynx. We did not observe any further post-operative complications and patient was discharged with desired outcomes. Anatomical variations of the RLN include-bifurcations, trifurcations, relation of RLN with inferior thyroid artery (ITA) and presence of non-recurrent laryngeal nerve. Only RLN dividing at a distance greater than 5 mm (branching point distance) before its entry into the larynx beneath the cricothyroid are said to bifurcate or trifurcate. Approximately 25% of nerves show branching [71%-unilateral and 18%-bilateral bifurcation]. Incidence of unilateral trifurcations have been noted be 0.9% and the rates of bilateral trifurcation and the divisions of the branches is yet to be ascertained. This is the first report of a bilateral trifurcation of RLN, detected in patient with multinodular goitre and hence warrants a precise analysis of variations of the RLN in patients undergoing thyroidectomy, which is critical to prevent RLN injury.


The Volunteer Dementia and Delirium Care (VDDC)© program: An exploration of perceived barriers and enablers to implementation in an acute and subacute metropolitan hospital.
To explore the perceived barriers and enablers to the implementation of the Volunteer Dementia and Delirium© program from the perspective of key stakeholders in a metropolitan hospital network. Focus groups and interviews with hospital staff, volunteers, patients and caregivers. Deductive analysis was conducted for the Behaviour Change Wheel (COM-B) domains, and inductive thematic analysis for emerging themes. Utilising the skills and knowledge of volunteers, making the program available to all patients, and recognising that volunteers will improve the care experience for patients were identified as enablers. Threats to volunteer safety, difficulty in defining roles and responsibilities of volunteers, volunteer attrition and availability and supervision of volunteers were perceived as barriers to implementation. To enhance the implementation of the program into a metropolitan setting, strategies addressing the identified barriers and enablers need to be developed.


Enzymatic activity on sandy beaches of the Ligurian Sea (NW Mediterranean).
Enzymatic activity was measured on two beaches of the Ligurian Sea (NW Mediterranean) during late spring and summer 2003. The detected activities (leucine aminopeptidase, beta-glucosidase, alpha-glucosidase, and beta-N-acetylglucosaminidase) were related to the available organic substrates (proteins and carbohydrates) and to the bacterial community (expressed in terms of abundance, biomass, and frequency of cell division). The very low chlorophyll a concentrations (never higher than 40 ng g(-1)) suggested that heterotrophic microorganisms play a major role in the beach ecosystem. Enzymatic activities devoted to organic matter degradation were lower in the emerged part of the beaches and higher in the sites covered, permanently or temporarily, by seawater, suggesting that sea action enlivens the degradation processes. Leucine aminopeptidase ranged from 0.26 to 13.02 nmol g(-1)h(-1), and beta-glucosidase (the most expressed glycolytic enzyme) from 0.03 to 4.51 nmol g(-1)h(-1). Strong changes in the proteolytic/glycolytic activity ratio were observed, with a sudden rise in glycolysis during summer, leading to ratio values from about 30 down to 1. Thus, beaches were identified as preferential degradation sites, where very refractory compounds such as cellulose may also be efficiently processed.


[An early switch from intravenous to oral antibiotics is equally effective as the standard intravenous therapy in severe community acquired pneumonia].
To compare an early switch from intravenous to oral antibiotics with the standard intravenous therapy in patients admitted to hospital with severe community acquired pneumonia. Multicentre randomised prospective trial with follow-up at 28 days. Patients with severe pneumonia who were admitted to hospital were randomised for 7 days intravenous antibiotic therapy (control group) or for an early switch to oral antibiotic therapy after 3 days of intravenous antibiotic therapy (intervention group). An intention-to-treat analysis was performed. The primary outcome measure was clinical cure. The length of hospital stay was a secondary outcome measure. Out of the 302 patients included in the trial, data was analysed from 265 patients. The mortality rate in the intervention group did not differ significantly from that of the control group (mean difference: 2%; 95% CI: -3-8). After 28 days, 83% of the patients in the intervention group and 85% in the control group were clinically cured (mean difference: 2%; 95% CI: -7-10). The length of hospital stay was 1.9 days shorter in the intervention group (95% CI: 0.6-3.2 days). An early switch from intravenous to oral antibiotics in patients admitted to hospital for severe community acquired pneumonia is safe and reduces the length of hospital stay by approximately 2 days.


Cell shape characterization, alignment, and comparison using FlowShape.
The shape of a cell is tightly controlled, and reflects important processes including actomyosin activity, adhesion properties, cell differentiation, and polarization. Hence, it is informative to link cell shape to genetic and other perturbations. However, most currently used cell shape descriptors capture only simple geometric features such as volume and sphericity. We propose FlowShape, a new framework to study cell shapes in a complete and generic way. In our framework a cell shape is represented by measuring the curvature of the shape and mapping it onto a sphere in a conformal manner. This single function on the sphere is next approximated by a series expansion: the spherical harmonics decomposition. The decomposition facilitates many analyses, including shape alignment and statistical cell shape comparison. The new tool is applied to perform a complete, generic analysis of cell shapes, using the early Caenorhabditis elegans embryo as a model case. We distinguish and characterize the cells at the seven-cell stage. Next, a filter is designed to identify protrusions on the cell shape to highlight lamellipodia in cells. Further, the framework is used to identify any shape changes following a gene knockdown of the Wnt pathway. Cells are first optimally aligned using the fast Fourier transform, followed by calculating an average shape. Shape differences between conditions are next quantified and compared to an empirical distribution. Finally, we put forward a highly performant implementation of the core algorithm, as well as routines to characterize, align and compare cell shapes, through the open-source software package FlowShape. The data and code needed to recreate the results are freely available at https://doi.org/10.5281/zenodo.7778752. The most recent version of the software is maintained at https://bitbucket.org/pgmsembryogenesis/flowshape/.


Treatment of Pauwels type III femoral neck fracture with medial femoral neck support screw: a biomechanical and clinical study.
A femoral neck fracture is currently one of the most common types of fracture in clinical practice. The incidence continues to increase due to traffic accidents, trauma, and osteoporosis. This research includes a biomechanical study and a clinical retrospective study. In the biomechanical studies, three groups' effects (Control Group: 3CCS, DHS group, and study Group: 3CCS + mFNSS group) were compared by vertical compression tests, torsion tests, and fatigue tests. All the data were collected and analyzed. We subsequently performed a retrospective analysis of 131 patients with femoral neck fractures. The operative time, intraoperative blood loss, quality of postoperative fracture reduction, and follow-up observation of fracture healing, screw retreatment rates and fixation failure rates, as well as femoral head necrosis rates and hip function in two groups with 3CCS and 3CCS + mFNSS were compared. By the biomechanical study, we found that 3CCS + Mfnss group were biomechanically superior to 3CCS group and superior to the DHS group in terms of resistance to torsion. However, it was less effective than the DHS group in compressive strength and fatigue resistance. In terms of clinical application, 3CCS + mFNSS group was found to have lower screw retreatment rates and femoral head necrosis rates, and to have better fracture healing rates than group with 3CCS, indicating that medial support screws can effectively resist the vertical shear forces of fracture ends and promote the stability and healing of fracture ends, as well as to reduce the incidence of postoperative complications.


Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM.
Although AIMP3/p18 is normally associated with the multi-tRNA synthetase complex via its specific interaction with methionyl-tRNA synthetase, it also works as a tumor suppressor by interacting with ATM, the upstream kinase of p53. To understand the molecular interactions of AIMP3 and the mechanisms involved, we determined the crystal structure of AIMP3 at 2.0-angstroms resolution and identified its potential sites of interaction with ATM. AIMP3 contains two distinct domains linked by a 7-amino acid (Lys57-Ser63) peptide, which contains a 3(10) helix. The 56-amino acid N-terminal domain consists of two helices into which three antiparallel beta strands are inserted, and the 111-amino acid C-terminal domain contains a bundle of five helices (Thr64-Tyr152) followed by a coiled region (Pro153-Leu169). Structural analyses revealed homologous proteins such as yeast glutamyl-tRNA synthetase, Arc1p, EF1Bgamma, and glutathione S-transferase and suggested two potential molecular binding sites. Moreover, mutations at the C-terminal putative binding site abolished the interaction between AIMP3 and ATM and the ability of AIMP3 to activate p53. Thus, this work identified the two potential molecular interaction sites of AIMP3 and determined the residues critical for its tumor-suppressive activity through the interaction with ATM.


Babesia microti: prolonged survival of salavarian piroplasms in nymphal Ixodes dammini.
We determined how long Babesia microti survive in the salivary glands of nymphal Ixodes dammini. Of those ticks held at 21 C, the proportion with demonstrable piroplasms decreased from 95%, prior to 20 weeks post-larval-feeding (p-l-f), to less than 80% at 42 weeks p-l-f. Similarly, the number of infected acini decreased significantly. Nymphal I. dammini were kept alive for as long as 1 year, by transferring them to 4 C, at 20 weeks p-l-f. The proportion of infected ticks at 52 weeks p-l-f was less than half of the proportion of infected nymphs examined prior to 20 weeks p-l-f, and only 1/6 as many acini were infected. Ultrastructural observations of salivary glands from ticks at 44 weeks p-l-f revealed that B. microti parasites in older ticks remain in the sporoblast meshwork phase; such parasites rarely differentiated into sporozoites. Degenerating parasites containing autophagic vacuoles were also observed in older ticks.


Adrenalectomy stimulates the formation of initial atherosclerotic lesions: reversal by adrenal transplantation.
Long-term changes in the secretion of immunosuppressive adrenal-derived glucocorticoid hormones influence cardiovascular disease risk. Here we determined the consequences of changes in adrenal steroid metabolism for the development of atherosclerotic lesions in mice. Atherosclerosis-susceptible low-density-lipoprotein (LDL) receptor knockout mice were subjected to adrenalectomy (ADX) or a control (SHAM) operation and subsequently fed an atherogenic diet for 4 weeks. Atherogenic diet feeding raised plasma corticosterone levels in SHAM mice, but not adrenalectomized mice, resulting in an 83% lower (P<0.01) corticosterone level in adrenalectomized mice. Adrenalectomy was associated with a respectively 22% and 29% lower plasma level of cholesterol and triglycerides. In contrast, white blood cell counts were increased 2-fold (P<0.01) in adrenalectomized mice, which could be attributed to a significant 2.1- to 2.6-fold rise in lymphocyte (P<0.05) and monocyte (P<0.05) numbers. Probably as a result of the enhanced systemic inflammatory status, adrenalectomy was associated with a higher susceptibility for diet-induced atherosclerosis (321±18×10(3) μm(2) for ADX vs 240±31×10(3) μm(2) for SHAM; P<0.05) not withstanding the lowered cholesterol levels. Restoring adrenocortical steroid secretion - but not adrenal medulla function - and the associated downstream glucocorticoid receptor signaling in adrenalectomized mice through adrenal transplantation induced a reversal of the adrenalectomy-associated rise in white blood cell numbers, plasma monocyte chemoattractant protein 1 (MCP-1) levels, and atherosclerotic lesion development (lesion size in transplanted mice: 258±34×10(3) μm(2); P<0.05 vs ADX). In conclusion, our studies show that adrenal-derived steroids protect against the development of initial atherosclerotic lesions in LDL receptor knockout mice.


Comparison of the neurotoxicities between volatile organic compounds and fragrant organic compounds on human neuroblastoma SK-N-SH cells and primary cultured rat neurons.
These are many volatile organic compounds (VOCs) that are synthesized, produced from petroleum or derived from natural compounds, mostly plants. Fragrant and volatile organic compounds from plants have been used as food additives, medicines and aromatherapy. Several clinical and pathological studies have shown that chronic abuse of VOCs, mainly toluene, causes several neuropsychiatric disorders. Little is known about the mechanisms of neurotoxicity of the solvents. n-Octanal, nonanal, and 2-ethyl-1-hexanol, which are used catalyzers or intermediates of chemical reactions, are released into the environment. Essential oils have the functions of self-defense, sterilization, and antibiosis in plants. When volatile organic compounds enter the body, there is the possibility that they will pass through the blood-brain barrier (BBB) and affect the central nervous system (CNS). However, the direct effects of volatile organic compounds on neural function and their toxicities are still unclear. We compared the toxicities of n-octanal, nonanal and 2-ethyl-1-hexanol with those of five naturally derived fragrant organic compounds (FOCs), linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and n-phenethyl alcohol. MTT assay of human neuroblastoma SK-N-SH cells showed that the IC50 values of linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and phenethyl alcohol were 1.33, 2.3, >5, >5, and 2.39 mM, respectively, and the IC50 values of toluene, n-octanal, nonanal and 2-ethyl-1-hexanol were 850, 37.2, 8.31 and 15.1 μM, respectively. FOCs showed lower toxicities than those of VOCs. These results indicate that FOCs are safer than other compounds.


Acinetobacter cumulans sp. nov., isolated from hospital sewage and capable of acquisition of multiple antibiotic resistance genes.
We studied the taxonomic position of six phenetically related strains of the genus Acinetobacter, which were recovered from hospital sewage in China and showed different patterns of resistance to clinically important antibiotics. Whole-genome sequencing of these strains and genus-wide phylogeny reconstruction based on a set of 107 Acinetobacter core genes indicated that they formed a separate and internally cohesive clade within the genus. The average nucleotide identity based on BLAST and digital DNA-DNA hybridization values between the six new genomes were 97.25-98.67% and 79.2-89.3%, respectively, whereas those between them and the genomes of the known species were ≤78.57% and ≤28.5%, respectively. The distinctness of the strains at the species level was also supported by the results of the cluster analysis of the whole-cell protein fingerprints generated by MALDI-TOF MS. Moreover, the strains displayed a catabolically unique profile and could be differentiated from the phylogenetically closest species at least by their inability to grow on d,l-lactate. A total of 18 different genes were found in the six genome sequences which encode resistance to seven classes of antimicrobial agents, including clinically important carbapenems, oxyimino-cephalosporins, or aminoglycosides. These genes occurred in five different combinations, with three to 10 different genes per strain. We conclude that the six strains represent a novel Acinetobacter species, for which we propose the name Acinetobacter cumulans sp. nov. to reflect its ability to acquire and cumulate diverse resistance determinants. The type strain is WCHAc060092T (ANC 5797T=CCTCC AB 2018119T=GDMCC 1.1380T=KCTC 62576T).


A framework for a streamline-based probabilistic index of connectivity (PICo) using a structural interpretation of MRI diffusion measurements.
To establish a general methodology for quantifying streamline-based diffusion fiber tracking methods in terms of probability of connection between points and/or regions. The commonly used streamline approach is adapted to exploit the uncertainty in the orientation of the principal direction of diffusion defined for each image voxel. Running the streamline process repeatedly using Monte Carlo methods to exploit this inherent uncertainty generates maps of connection probability. Uncertainty is defined by interpreting the shape of the diffusion orientation profile provided by the diffusion tensor in terms of the underlying microstructure. Two candidates for describing the uncertainty in the diffusion tensor are proposed and maps of probability of connection to chosen start points or regions are generated in a number of major tracts. The methods presented provide a generic framework for utilizing streamline methods to generate probabilistic maps of connectivity.


The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary.
Fluorescence in situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescence in situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines.


Glowing podocytes in living mouse: transgenic mouse carrying a podocyte-specific promoter.
Green fluorescence protein (GFP) has been utilized as a marker of gene expression due to the great advantage in its simple and quick detectability. We generated transgenic mice carrying a GFP cDNA under the control of a beta-actin/beta-globin promoter (CX promoter) and cytomegalovirus enhancer. The green luminescence derived from GFP was apparent in skeletal muscle, pancreas, heart and kidney, but not in other tissues. The GFP expression in the kidney was localized in podocytes. Moreover, in situ hybridization of GFP showed that the transcriptional level was highly active in the podocytes. These results suggested that the glowing green fluorescence would be a useful in vivo marker of podocyte in these transgenic lines in the physiological and pathophysiological state, and that the CX promoter could allow a podocyte-specific expression of a molecule of interest in kidney.


Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response. A comparative study.
Surgery is the standard treatment of rectal cancer after neoadjuvant therapy. Some authors advocate a nonoperative management (NOM) after complete clinical response (cCR) following chemoradiotherapy (CRT). We compare our results with NOM to standard resection in a retrospective analysis. Rectal adenocarcinomas submitted to NOM after CRT between September 2002 and December 2013 were compared to surgical patients that had pathological complete response (pCR) during the same period. Endpoints were Overall Survival (OS), Disease Free Survival (DFS), Local Relapse (LR) and Distant Relapse (DR). Forty-two NOM patients compared to 69 pCR patients operated after a median interval of 35 weeks after CRT. NOM tumors were distal (83.3% vs 59.4%, p = 0.011), less obstructive (26.2% vs 54.4%, p = 0.005) and had a lower digital rectal score (p = 0.024). Twelve (28.0%) recurrences in NOM group and eight (11.5%) in the surgical group occurred after a follow-up of 47.7 and 46.7 months respectively. Isolated LR occurred in five (11%) NOM patients and one (1.4%) in the surgical group. Four (80%) LR were surgically salvaged in NOM group. No difference in OS was found (71.6% vs 89.9%, p = 0.316) but there was a higher DFS favoring surgical group (60.9% vs 82.8%, p = 0.011). Distal tumors had worse OS compared to proximal tumors in surgical group (5-year OS of 85.5% vs 96.2%, p = 0.038). The NOM achieved OS comparable to surgical treatment and spared patients from surgical morbidity but it resulted in more recurrences. This approach cannot be advocated routinely and controlled trials are warranted.


[Comparison of the effectiveness of quadruple salvage regimen for Helicobacter pylori infection according to the duration of treatment].
At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.


Ageing effects on flash visual evoked potentials (FVEP) recorded from parietal and occipital electrodes.
The effects of ageing on flash visual evoked potentials (FVEP) recorded from 6 posterior parietal and occipital sites were studied in a sample of 73 healthy subjects of between 20 and 86 years of age. Latencies of components P1, N1 and P2, and amplitudes of components P1 and P3 increased linearly with age at all emplacements. The results obtained from occipital electrodes are in line with previous reports and additionally show that i) the effects of age constantly increase over time, and ii) age affects not only the early but also the later components (> 150 ms) of the FVEP. The overall pattern of results suggests that elderly subjects show slower transmission of visual information and deficiencies in the inhibitory regulation of activity generated during the arrival of repetitive non-attended visual stimulation. The findings with parietal electrodes show that ageing effects are more marked at these emplacements than at occipital electrodes. Furthermore, this raises the question of a possible differential involvement of primary and nonprimary visual cortex by age, but this hypothesis can only be explored with high-intensity multichannel recordings and dipolar modelling.


Concurrent activation of hippocampal glycine and polyamine sites of the N-methyl-D-aspartate receptor synergistically reverses working memory deficits in rats.
Intrahippocampal administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.18 microg/side) significantly increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors by intrahippocampal MK-801 was significantly attenuated by concurrent infusion of D-cycloserine (1.0 microg/side) or spermidine (10 microg/side), agonists of the glycine and polyamine modulatory sites on the NMDA receptor/channel complex, respectively. Combined injection of the behaviorally ineffective doses of 0.1 microg/side D-cycloserine and 0.32 microg/side spermidine synergistically reduced intrahippocampal MK-801-induced increase in working memory errors. The combination of D-cycloserine and spermidine also synergistically attenuated the increase in working memory errors resulting from intrahippocampal injection of the muscarinic acetylcholine receptor antagonist scopolamine (3.2 microg/side). These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine and polyamine sites can synergistically compensate deficiency of hippocampal NMDA and muscarinic receptor-mediated neurotransmission involved in working memory function.


Lesion of the amygdala on the right and left side suppresses testosterone secretion but only left-sided intervention decreases serum luteinizing hormone level.
The effect of right- and left-sided intra-amygdaloid injection of kainic acid on the hypothalamo-hypophyseal-testicular axis was studied in rats. Both right- and left-sided injection of the neurotoxin into the amygdala resulted in a significant decrease in basal testosterone secretion in vitro of both testes and in serum testosterone concentration. In addition, left-sided administration of kainic acid significantly suppressed serum luteinizing hormone level, while right-sided intervention did not alter this parameter. The results of the present study provide further evidence on the involvement of the amygdala in the control of testicular steroidogenesis. Furthermore, the observations suggest functional asymmetry of the amygdala concerning the mechanism of suppressed testosterone secretion.


[Analysis of gene complexes predisposing to coronary atherosclerosis].
The following seven polymorphic marker loci of genes responsible for predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus responsible for angiotensin-converting enzyme insertion/deletion polymorphism for the presence or absence of the Alu insertion in the gene; the F13, PLAT, and APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci responsible for point mutations in methylenetetrahydrofolate reductase and those in angiotensinogen, respectively, and the NOS3 locus controlling the number of tandem repeats in the nitric oxide synthase gene. These loci are located on different chromosomes and encode products involved into various metabolic pathways leading to CAS. In the populations studied, significant differences between healthy subjects and patients predisposed to cardiovascular diseases were revealed with regard to the above seven markers. The 174M allele (T174M polymorphism in the ACE gene) was significantly associated with coronary atherosclerosis. It was found that specific gene combinations are involved in the CAS development and determine variation in the pathogenetically important quantitative traits.