The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein.
The molecular basis of the three major alleles (Fy(a)/Fy(b)/Fy) of the Duffy (FY) blood group system has recently been established but the Fy(x) phenotype associated with weak expression of the Fy(b) and other FY antigens is poorly understood. In the Fy(x) genes of five unrelated British and Swedish donors with the Fy(a+b+weak) phenotype we found two missense mutations predicting amino acid changes Arg89Cys and Ala100Thr in the FY glycoprotein. The same mutations were found in two Fy(a-b+weak) samples from individuals of Swedish and Algerian origin. Their red blood cells showed a marked decrease in Fy(b), Fy3 and Fy6 expression measured by routine serology and flow cytometry. The rare FY genotypes Fy(x)Fy(x) and Fy(x)Fy were confirmed by family studies and DNA sequencing. Screening by allele-specific primer PCR (ASP-PCR) for these mutations among 100 Caucasian and 100 Black random blood donors indicated allele frequencies of 2.5% and 0% respectively. Ala100Thr alone was present in 33% of the Caucasians (but none of the Blacks) with no weakening of FY expression. A novel allele at the FY locus associated with the Fy(x) phenotype was studied. Mistyping of this weak Fy(b) antigen in clinical transfusion medicine may lead to delayed haemolytic transfusion reactions in immunized patients. A potential role for genomic typing is proposed.


Cognitive deficits triggered by early life stress: The role of histone deacetylase 1.
Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive deficits found in neurodegenerative disorders and age-related memory decline. However, the role of HDACs in stress-induced cognitive deficits has not been investigated. In the stress-susceptible mouse strain Balb/c, early life stress triggers a persistent decrease in HDAC expression in the forebrain neocortex, including reduced expression of class I HDACs. The same mice show pronounced cognitive deficits in adulthood, namely deficits in working memory and attention set-shifting. Here we show that these mice also exhibit reduced association of HDAC1 with promotor III of the brain-derived neurotrophic factor (Bdnf) gene, and that cognitive testing leads to abnormally increased Bdnf mRNA expression. A pharmacological reduction of Bdnf-tropomyosine kinase B receptor signaling effectively reverses the cognitive deficits, indicating that enhanced transcriptional activation of the Bdnf gene contributes to their emergence. In contrast to Balb/c mice, C57Bl/6 mice only develop attention set-shifting deficits when raised by Balb/c foster mothers during the time the pups are exposed to early life stress. HDAC1 levels at Bdnf promotor III are unaltered in such C57Bl/6 mice, although they exhibit decreased levels of HDAC1 at the promotor of the early-growth response gene 2 (Egr2) and abnormally increased Egr2 mRNA expression after cognitive testing. Hence, contrary to the beneficial effects of HDAC inhibition in neurodegenerative diseases, the reduced HDAC1 levels at promotors of distinct plasticity-associated genes predispose animals exposed to early life stress to enhanced expression of these genes upon cognitive challenge, an effect that negatively influences cognitive task performance.


Scintigraphic evaluation of sarcomata in children and adults by Ga67 citrate.
Gallium-67 scans were performed on 32 patients with adult and childhood sarcomata as part of clinical staging studies. Gallium-67 scans proved to be highly accurate in assessing sites of disease in patients with malignant schwannoma, Ewing's sarcoma, and rhabdomyosarcoma. Gallium-67 scans were inaccurate in determining sites of disease in patients with other types of sarcomata. It is concluded that Gallium-67 scanning is a useful adjunct to clinical staging in selected patients with sarcomata.


Curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis.
Necroptosis was reported as one backup way of programmed cell death when apoptosis was blocked, and the receptor interacting protein 1 was considered as the key necroptosis regulator protein. Here, we report the neuroprotective effects of curcumin which attenuates necroptosis. Primary cortical neurons were cultured and were injured by ferrous chloride, z.vad.fmk was applied to block apoptosis, curcumin was administrated to protect neurons, necrostatin-1 was applied to inhibit necroptosis if needed. Cell viability was measured by detecting lactate dehydrogenase activity in lysates of surviving cells, and assessed by cell counting kit-8. The expression of receptor interacting protein 1 was detected by immunoblot and immunofluorescence. Results showed that necroptosis mainly occurred in the concentrations of ferrous chloride ranging from 100 to 200μM, curcumin attenuated necroptosis in a dose-dependent manner. Furthermore, curcumin decreased expression of receptor interacting protein 1 in a dose- and time-dependent manner. Taken together, these findings suggest that curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis.


Surface phenotypes of human peripheral blood mononuclear cells from patients with gastrointestinal carcinoma.
Peripheral blood mononuclear cells (PBMC) from 40 patients with gastrointestinal carcinoma (GIC), 13 patients with primary carcinoma in other localizations(non-GIC), and from 57 apparently healthy donors were isolated by Ficoll-Paque gradient centrifugation. The separated cells were stained with several monoclonal antibodies and subjected to analysis on a fluorescence-activated cell sorter. A decreased percentage of PBMC expressing T cell antigens was noted amongst GIC patients, and was mainly due to a reduction of the Leu 2a subset, thus, leading to an increase in the Leu 3a/Leu 2a ratio from 1.4 to 2.1 Non-GIC patients had decreased numbers of both T helper and suppressor cells. Amongst PBMC from GIC and non-GIC patients a statistically increased percentage of cells expressed LeuM 2 (P less than 0.001), LeuM 3 (P less than 0.001), OKM 1 (P less than 0.005), VEP 9 (P less than 0.001), and HLA-DR (P less than 0.001) antigens compared to healthy controls. The percentage of cells bearing these monocyte/macrophage antigens correlated well with the number of cells having monocyte morphology, stained for non-specific esterase, phagocytosed latex particles, and expressed Fc IgG receptor. Our results demonstrate clearly that tumor-bearing patients have an increased relative number of monocytes. The data suggest that cells of the macrophage lineage may be involved in defense mechanisms and changes of the immune system evoked by various tumors.


Simulation and design of shaped pulses beyond the piecewise-constant approximation.
Response functions of resonant circuits create ringing artefacts if their input changes rapidly. When physical limits of electromagnetic spectroscopies are explored, this creates two types of problems. Firstly, simulation: the system must be propagated accurately through every response transient, this may be computationally expensive. Secondly, optimal control: circuit response must be taken into account; it may be advantageous to design pulses that are resilient to such distortions. At the root of both problems is the popular piecewise-constant approximation for control sequences in the rotating frame; in magnetic resonance it has persisted since the earliest days and has become entrenched in the commercially available hardware. In this paper, we report an implementation and benchmarks of recent Lie-group methods that can efficiently simulate and optimise smooth control sequences.


Unexpected presentation of accessory breast: vulvar accessory breast tissue: a case report.
The accessory breast is composed of residual glandular mammary tissue that persists after normal embryonic development. The entity is so rare that it is easily neglected in the diagnosis of disease. We report a 24-year-old virgin Persian woman with a left-sided vulvar mass and no pain or discomfort until shortly before her presentation at our department. Ectopic breast tissue in the vulva was diagnosed. We performed wide local resection of the lesion. Pathological investigation of the lesion confirmed the presence of ectopic breast tissue with secretory changes. She had no specific developmental abnormalities and had no relevant family history. She was followed up for 10 months and had recovered fully by this time. Accessory breast tissue should be considered as a diagnosis when a mass is seen along the embryonic milk line, especially if the clinical findings reveal changes in the mass accompanied by changes in sex hormones.


DNA Polymerases Divide the Labor of Genome Replication.
DNA polymerases synthesize DNA in only one direction, but large genomes require RNA priming and bidirectional replication from internal origins. We review here the physical, chemical, and evolutionary constraints underlying these requirements. We then consider the roles of the major eukaryotic replicases, DNA polymerases α, δ, and ɛ, in replicating the nuclear genome. Pol α has long been known to extend RNA primers at origins and on Okazaki fragments that give rise to the nascent lagging strand. Taken together, more recent results of mutation and ribonucleotide incorporation mapping, electron microscopy, and immunoprecipitation of nascent DNA now lead to a model wherein Pol ɛ and Pol δ, respectively, synthesize the majority of the nascent leading and lagging strands of undamaged DNA.


A detailed mechanism of degradation behaviour of biodegradable as-ECAPed Zn-0.8Mg-0.2Sr with emphasis on localized corrosion attack.
In this study, advanced techniques such as atom probe tomography, atomic force microscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy were used to determine the corrosion mechanism of the as-ECAPed Zn-0.8Mg-0.2Sr alloy. The influence of microstructural and surface features on the corrosion mechanism was investigated. Despite its significance, the surface composition before exposure is often neglected by the scientific community. The analyses revealed the formation of thin ZnO, MgO, and MgCO3 layers on the surface of the material before exposure. These layers participated in the formation of corrosion products, leading to the predominant occurrence of hydrozincite. In addition, the layers possessed different resistance to the environment, resulting in localized corrosion attacks. The segregation of Mg on the Zn grain boundaries with lower potential compared with the Zn-matrix was revealed by atom probe tomography and atomic force microscopy. The degradation process was initiated by the activity of micro-galvanic cells, specifically Zn - Mg2Zn11/SrZn13. This process led to the activity of the crevice corrosion mechanism and subsequent attack to a depth of 250 μm. The corrosion rate of the alloy determined by the weight loss method was 0.36 mm·a-1. Based on this detailed study, the degradation mechanism of the Zn-0.8Mg-0.2Sr alloy is proposed.


Dual Cross-Linked Fluorinated Binder Network for High-Performance Silicon and Silicon Oxide Based Anodes in Lithium-Ion Batteries.
In next generation lithium-ion batteries (LIBs), silicon is a promising electrode material due to its surprisingly high specific capacity, but it suffers from serious volume changes during the lithiation/delithiation process which gradually lead to the destruction of the electrode structure. A novel fluorinated copolymer with three different polar groups was synthesized to overcome this problem: carboxylic acid, amide, and fluorinated groups on a single polymer backbone. Moreover, a dual cross-linked network binder was prepared by thermal polymerization of the fluorinated copolymer and sodium alginate. Unlike the common chemical cross-linked network with a gradual and nonreversible fracturing, the dual cross-linked network which combines chemical and physical cross-linking could effectively hold the silicon particles during the volume change process. As a result, excellent electrochemical performance (1557 mAh g-1 at a 4 A g-1 current density after 200 cycles) was achieved with this novel reversible cross-linked binder. Further research studies with regard to the influences of fluorine and acrylamide content were conducted to systematically evaluate the designed binder. Moreover, with the help of new binder, the silicon/graphite and silicon oxide/graphite electrode exhibit superb cycle performance with capacity fade rate of 0.1% and 0.025% per cycle over 200 and 700 cycles, respectively. This novel and unsophisticated design gives a result for fabrication of high-performance Si based electrodes and advancement of the realization of practical application.


Determination of lead and cadmium in seawater using a vibrating silver amalgam microwire electrode.
Silver amalgamated electrodes are a good substrate to determine lead (Pb) and cadmium (Cd) in seawater because they have properties similar to mercury but without the free mercury (Hg). Here a silver amalgamated microwire (SAM) electrode is optimised for the determination of Pb and Cd in coastal waters and uncontaminated ocean waters. The SAM was vibrated during the deposition step to increase the sensitivity, and electroanalytical parameters were optimised. The Hg coating required plating from a relatively concentrated (millimolar) solution, much greater (500×) than used for instance to coat glassy carbon electrodes. However, the coating on the ex situ amalgamated electrode was found to be stable and could be used for up to a week to determine trace levels of Pb in seawater of natural pH. The limit of detection square-wave ASV (50 Hz) using the pre-plated SAM electrode was 8 pM Pb using a 1-min plating time at pH 4.5. The limit of detection in pH 2 seawater was 4 pM using a 5-min plating time, and it was 12 pM using a 10-min plating time at natural pH in the presence of air, using a square-wave frequency of 700 Hz. The vibrating SAM electrode was tested on the determination of Pb in reference seawater samples from the open Atlantic (at the 20 pM level), Pacific, and used for a study of Pb in samples collected over 24 h in Liverpool Bay (Irish Sea).


Humoral immunity and lymphocyte subpopulations in patients with dilated cardiomyopathy.
The incidence of serum organ and non-organ specific autoantibodies, the peripheral blood lymphocyte blastogenic response to phytohaemagglutinin, concanavalin A and pokeweek mitogen, and the surface markers of peripheral T and B lymphocytes were studied in 15 patients affected by coronary artery disease and in 21 patients with dilated cardiomyopathy. In the latter group there was a significantly impaired blastogenic response to concanavalin A with respect to both the normal control group and patients with coronary artery disease (P less than 0.01). The percentage of peripheral blood lymphocytes with cytotoxic/suppressor activity was also reduced in patients with dilated cardiomyopathy in comparison to normal subjects and patients with coronary artery disease (P less than 0.01 and P less than 0.05, respectively). These data may reflect an in vivo defect in suppressor cell function in patients with dilated cardiomyopathy.


Increasing donor-recipient weight mismatch in pediatric orthotopic heart transplantation does not adversely affect outcome.
The aim of the study was to show the effect of heart transplant donor-recipient weight mismatch on mortality, right-ventricular (RV) failure, and medium-term control of systemic blood pressure. From 2000 to 2008 inclusive, 161 patients undergoing orthotopic heart transplantation at our unit were retrospectively analyzed. The cohort was divided into three groups of similar size depending on the tertile ranges of the donor-recipient weight ratio. Median follow-up was 4.81 years. Donor-recipient body weight ratio was analyzed with respect to intubation time, time in intensive care unit (ITU), development of RV failure, medium-term survival, and freedom from medium-term hypertension. The median age was 115 months (23 days to 18 years), at a median weight of 26.9 kg (3-88 kg) at transplant. Median donor-recipient weight ratio was 1.61 (0.62-3.25). Mean intubation time was 448 h (SD 749.2), mean time in the ITU 302.7 h (SD 617.8). On linear regression, these were not related to donor-recipient weight ratio. A total of 38 patients (23.6%) developed postoperative RV failure. Nearly one-fifth (18.9) of patients in the lowest tertile group developed RV failure. In the middle tertile group, 24.5% developed RV failure and 28.8% in the upper tertile of weight mismatch, although this was not statistically significant (p = 0.48). On survival analysis, there was a higher mortality among those with the lowest tertile of mismatch (log-rank p = 0.04), but there was no difference in midterm survival on condition of survival to discharge (log-rank p = 0.14). There was also no association between weight ratio and freedom from medium-term hypertension as measured on serial 24-h ambulatory blood pressure monitoring (log-rank p = 0.39). There were nine patients in whom the weight mismatch was 3 or greater. There was no association between this 'extreme' mismatch group and either midterm mortality (p = 0.76) or freedom from hypertension (p = 0.62), but this was associated with the need for postoperative extracorporeal membrane oxygenator (ECMO) support (p < 0.01). Our current policy involves accepting a maximum donor-recipient weight ratio of 3. These encouraging findings cautiously justify this policy, in an era when marginal donors are increasingly sought.


Forest management devolution: gap between technicians' design and villagers' practices in Madagascar.
In the 1980s, tropical forest-management principles underwent a shift toward approaches giving greater responsibilities to rural people. One argument for such a shift were the long-term relations established between rural people and their natural resources. In Madagascar, a new law was drawn up in 1996 (Gelose law), which sought to integrate rural people into forest management. A gap was observed between the changes foreseen by the projects implementing the Gelose law and the actual changes. In this article, we use the concept of the social-ecological system (SES) to analyze that gap. The differences existing between the planned changes set by the Gelose contract in the village of Ambatoloaka (northwest of Madagascar) and the practices observed in 2010 were conceptualized as a gap between two SESs. The first SES is the targeted one (i.e., a virtual one); it corresponds to the designed Gelose contract. The second SES is the observed one. It is characterized by the heterogeneity of forest users and uses, which have several impacts on forest management, and by very dynamic social and ecological systems. The observed SES has been reshaped contingent on the constraints and opportunities offered by the Gelose contract as well as on other ecological and social components. The consequences and opportunities that such an SES reshaping would offer to improve the implementation of the Gelose law are discussed. The main reasons explaining the gap between the two SESs are as follows: (1) the clash between static and homogeneous perceptions in the targeted SES and the dynamics and heterogeneity that characterize the observed SES; and (2) the focus on one specific use of forest ecosystems (i.e., charcoal-making) in the targeted SES. Forest management in the observed SES depends on several uses of forest ecosystems.


Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study.
The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined. We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants. A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development. Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose. This study is retrospective in nature. Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy.


Changes in soil micronutrients along a temperature gradient in northern China.
How climate warming affected terrestrial ecosystems received considerable attention. Soil micronutrients play a vital role in regulating the growth of all living organisms and thus make a significant contribution to plant production. However, the responses of soil micronutrients to climate warming still remained unclear. While soil sampling along a temperature gradient could reveal the long-term influence of climate warming on soil nutrient dynamics, the variations of soil micronutrients with temperature might be interfered by the effect of precipitation due to the collinearity between temperature and precipitation. Moreover, changes in soil micronutrients over broad geographical scale could be affected by soil texture. Hence, this study conducted a soil investigation across a temperature transect along the 400 mm isohyet in northern China to examine the responses of soil micronutrients to changing temperature and soil texture when the effect of precipitation was minimized. We observed that soil copper (Cu), manganese (Mn) and zinc (Zn) contents all decreased along the temperature gradient. Soil Cu, Mn and Zn contents were positively correlated with soil clay and silt contents and negatively correlated with soil sand content. Temperature and soil texture together accounted for 72.0 % of the variations in soil micronutrient contents. Temperature and soil texture individually explained 10.4 % and 48.0 %, and their shared variation explained 13.6 % of the variations in soil micronutrient contents. Moreover, soil parent material also exerted an effect on soil micronutrient contents. Our results suggested that climate warming might cause a decrease in soil micronutrient contents.


A novel dansyl-based fluorescent probe for highly selective detection of ferric ions.
A novel dansyl-based fluorescent probe was synthesized and characterized. It exhibits high selectivity and sensitivity towards Fe(3+) ion. This fluorescent probe is photostable, water soluble and pH insensitive. The limit of detection is found to be 0.62 μM. These properties make it a good fluorescent probe for Fe(3+) ion detection in both chemical and biological systems. Spike recovery test confirms its practical application in tap water samples.


Masking mechanisms applied to thin-film coatings for the manufacturing of linear variable filters for two-dimensional array detectors.
We propose a method for manufacturing linear variable interference filters for two-dimensional (2D) array detectors, based on the use of correcting masks combining both rotation and translation movements of the masks and substrates. The major advantage of this method is its capability to produce several identical filters in a single run. 20 mm x 20 mm samples were manufactured with a wavelength ratio almost equal to 2 along the thickness gradient direction. In agreement with calculations, the measured uniformity perpendicular to the gradient is about 99.8% along 20 mm.


Diurnal changes in salmon GnRH secretion in the brain of masu salmon (Oncorhynchus masou).
The day-night changes of salmon GnRH (sGnRH), which is secreted from various brain regions, were analyzed in maturing and matured masu salmon (Oncorhynchus masou). In maturing males, the levels of sGnRH secreted from the olfactory bulb (OB), terminal nerve (TN), and ventral telencephalon and preoptic area (VT+POA) were all significantly higher during midnight than daytime. However, the contents of sGnRH in the pituitary gland during midnight were not higher than those during daytime. In maturing females, the levels of sGnRH secreted from the VT+POA were higher during midnight than daytime, and the contents of sGnRH in the pituitary gland were also higher during midnight. In matured fish, the levels of sGnRH secreted from the OB, TN and VT+POA during midnight were significantly higher than those during daytime. There were also no significant differences in the contents of sGnRH in the pituitary gland. These results suggest that a short photoperiod may be involved in diurnal secretion rhythms of sGnRH in various brain regions and the pituitary gland.


A social and demographic study of Tibetan refugees in India.
The social and demographic characteristics of approximately 65,000 Tibetan refugees in India were determined from data collected 1994-1996. Approximately 55,000 refugees were living in 37 settlements widely distributed around India. The remaining 10,000 refugees were monks living in monasteries associated with some of the settlements, mostly in the south of India. In the settlements, a community-based surveillance system was established and data were collected by trained community health workers in house to house visits. In the monasteries, data were collected by the community health workers in monthly interviews with a designated liaison monk at each monastery. These data indicated little immigration of new civilian refugees in the past 10 years into the settlements but a steady influx of new monks into the monasteries. The age distribution in the settlements showed a prominent mode in the 15-25 year age range, a declining birth rate, and an increasing proportion of elderly. In general, refugees born in India were educated through secondary school, while refugees born in Tibet were often illiterate. The principle occupations were education involving 27% (including students), farming, 16%. and sweater selling, 6.5%; another 6.5% were too young or too old for employment, and only 2.4% were unemployed. The overall crude birth rate was determined to be relatively low at 16.8/1000. although this may underestimate the true figure. Infant mortality varied from 20 to 35/1000 live births in the different regions. Child vaccination programs cover less than 50% of the population. The burden of illness in this society was mainly characterized by diarrhoea. skin infections, respiratory infections, fevers, and, among the elderly. joint pains and cardiovascular problems. Although calculated death rates were unrealistically low, due to under-reporting, causes of death, derived from "verbal autopsies", were mainly cancer, tuberculosis, accidents, cirrhosis and heart disease in order of decreasing frequency. Overall, the sociodemographic and health characteristics of this population appear to be in transition from those typical of the least developed countries to those typical of middle income and more affluent societies.


Fat mass measured by DXA varies with scan velocity.
To study the influence of scan velocities of DXA on the measured size of fat mass, lean body mass, bone mineral content and density, and total body weight. The subjects were 71 healthy white adults, 38 women and 33 men. The mean age was 41.7 +/- 13.5 years and body mass index was 28.6 +/- 5.6 kg/m(2). The subjects were scanned consecutively in slow, medium, and fast scan mode by a Lunar DPX-IQ DXA scanner. Throughout the body mass index and sagittal height ranges, scanned lean body mass significantly decreased with higher scan velocity and lean body mass was 2.7% lower in fast than in medium mode (p < 0.0001). In contrast, fat mass, percentage of body fat, and bone mineral contents were higher with increasing scan velocity. Areas not analyzed by the scanner, so called blue spots, increased with scan velocity and sagittal height, and their presence significantly enhanced the error. Body weight estimated by DXA in slow mode was -0.8% lower than scale weight in the women (p < 0.001) and -0.2% in men (not significant), and the difference was greater with increasing scan velocity. Scan velocity significantly influences the measured fat mass size, lean body mass, bone mineral content, and body weight. To obtain the most accurate results, slow mode is preferable and fast scans should be avoided. Future studies should report and take scan velocity into consideration.


The activity of tyrosine 3-monooxygenase is usually suppressed by an endogenous factor in brain.
Tyrosine 3-monooxygenase activity of the crude extract from rat striatum had a sharp pH optimum at pH 5.6 and showed almost no activity at pH 7 and higher. When the crude extract was adjusted to pH 5.2, the resulting precipitate showed high activity in the pH range of 6 to 7.5. Incubation of the acid-precipitated fraction with the acid-soluble fraction resulted in a remarkable decrease in the enzyme activity, as assayed at a neutral pH. These findings suggest that there is an endogenous factor inhibiting the activity of tyrosine 3-monooxygenase in rat brain.


Sutureless anastomoses using magnetic rings in canine liver transplantation model.
In the first posttransplant month, the most frequent complications are due to technical problems related to complex vascular and bile duct reconstructions during the operation. Moreover, despite great improvements in suturing technique and materials, severe organ ischemia-reperfusion caused by time-consuming hand suturing is still an important factor in graft survival. During the operation, severe hypotension, hypoxic acidosis, hyperkalemia, and renal dysfunction may occur during the anhepatic phase due to the prolonged venous clamping time required for hand suturing. Therefore, hand suturing is a handicap in the development of further advancements in liver transplantation. In this study, we aimed to test a new "mechanical installation method" for rapid vascular reconstruction. The magnetic pinning-ring device was developed consisting of paired magnetic rings coated with titanium oxide and embedded in a polypropylene shell. The rings were equipped with alternately spaced holes and titanium pins. Forty adult mongrel dogs were randomly divided into groups: A (n = 16), all vascular and bile duct reconstruction by magnetic ring without venous bypass; B (n = 16), all vascular and bile duct reconstruction by hand suturing with venous bypass; C (n = 8), sham transplantation group, transection of all vessels and common bile duct followed by anastomosis with the magnetic rings without liver transplantation. From groups A and B, dogs were randomly selected as donors (n = 8) or recipients (n = 8) of liver transplantations. We recorded operation time, vascular and bile duct anastomosis time, anhepatic time, administration of supplemental fluids during operation, and survival; blood samples were collected for the detection of liver damage (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and tumor necrosis factor α level. Patency was confirmed using ultrasound scans at various time points as late as 24 wk after surgery. Angiography was used to evaluate the anastomoses formed with magnetic rings. In group C, gross observation, histologic staining, and scanning electron microscopy were used to evaluate the vessels and bile ducts 12 wk postoperatively. In group A, the total operation time, inferior vena cava, and portal vein anastomosis times were significantly shortened, and the anhepatic phase was reduced to about one-fifth that of group B, which was a significant difference between the two groups (P < 0.01). The mean total operative time was 2.54 ± 0.45 h. In order to maintain adequate blood pressure, the mean fluid volume infused was 800.56 ± 60.56 mL in the recipients of group A, which was lower than that in group B (2241.67 ± 390.78 mL, P < 0.01). Use of a pressor agent in group A was unnecessary. After operation, five of eight animals in group A survived more than 7 d after operation. The main cause of death was acute rejection. Only three of eight animals in group B survived more than 1 wk after operation due to chronic anastomotic bleeding, kidney failure, heart failure, and gastrointestinal bleeding. There was a statistically significant difference (P < 0.01) between the short-term survival rate in the two groups (75.0% versus 37.5%). The ALT (1544.46 ± 286.27) U/L and AST (1710.74 ± 252.27) U/L levels after operation in the animals with hand suturing were significantly higher than those in the sutureless group (ALT = 1116.41 ± 210.55 U/L; AST = 1176.95 ± 248.25) U/L after reperfusion (P < 0.01). The serum tumor necrosis factor α levels (45.56 ± 10.78) ng/L in group B were significantly higher than those of group A (26.64 ± 10.84) ng/L after reperfusion (P < 0.01). Re-endothelialization was confirmed in all vessels in group C, with neither formation of aneurysms nor thickening of the vascular wall noted after 12 wk. The bile duct anastomoses also healed well. The magnetic pinning-ring device offers a simple, fast, reliable, and efficacious technique for nonsuturing vascular and bile duct anastomoses. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of tissue. Application of the magnetic ring anastomosis technique can effectively reduce the complications caused by hand suturing, and can reduce the extent of ischemia-reperfusion injury, leading to smoother operations and improved prognosis.


Robotic Takedown of Internal Mammary Artery to Prevent Occlusion From Bars During Nuss Pectus Repair.
The Nuss procedure for repair of pectus excavatum involves the placement of substernal support bars that remain in place for 2 to 3 years. There are concerns about occlusion of the internal mammary artery due to the intrathoracic bars. It would be optimal to preserve one or more internal mammary arteries with the pectus repair. This report describes a 28-year-old man with severe symptomatic pectus excavatum who underwent Nuss repair. Robotic left internal mammary artery takedown was performed at the intercostal spaces planned for Nuss bars to prevent occlusion or damage from the bars.


Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus
Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.


Temporal trends in the incidence of post-dural puncture headache following labor neuraxial analgesia in the United States, 2006 to 2015.
Labor neuraxial analgesia utilization has increased in the United States (U.S.) but its impact on maternal safety is unknown. This study analyzed the temporal trends in the incidence of post-dural puncture headache (PDPH) in obstetrics. Data for vaginal or intrapartum cesarean deliveries came from the National Inpatient Sample 2006-2015, a U.S. 20% representative sample of hospital discharge records. The outcome was PDPH (ICD-9-CM codes 349.0 and 03.95) categorized into (1) PDPH coded without epidural blood patch (EBP), and (2) PDPH coded with EBP. Temporal trends in incidence were described using the percent change between 2006 and 2015 and its 95% confidence interval (CI). Of the 29 011 472 deliveries studied, 86 558 (29.8 per 10 000; 95% CI: 29.3 to 30.2) recorded a diagnosis of PDPH, including 34 019 without EBP (11.7 per 10 000; 95% CI 11.4 to 12.0) and 52 539 with EBP (18.1 per 10 000; 95% CI 17.8 to 18.4). A significant decrease in the incidence of PDPH was observed from 31.5 per 10 000 in 2006 to 29.2 per 10 000 in 2015 (-7.5%; 95% CI -2.2 to -0.5; P=0.001). The decrease in the incidence of PDPH was significant irrespective of the presence of EBP. The decrease was observed in the three categories of hospitals examined (rural, urban non-teaching, and urban teaching). During the study period, the reported incidence of PDPH in the U.S. has decreased modestly. Intervention programs are needed to address this persistent and preventable cause of maternal morbidity.


Eyelid hook injury - A preventable domestic injury.
The aim of this report is to describe the presentation and management of eyelid injury resulting from the hook of a rubber string. A seven-year-old boy presented with pain of the right upper eyelid. A rubber string with metal hook ends, snatched his right eye from below. The hook pierced through his upper eyelid from the conjunctival surface and remained in situ. However, there was no globe laceration noted. Removal was performed by reverse-tracking of the hook through the wound. The wound was stitched with 6'0 Vicryl sutures. Healing was excellent with minimal scarring.


New clinical criteria for the assessment of liver involvement in Hodgkin's disease.
The hepatic involvement in Hodgkin's disease, histologically verified in 133 patients who underwent laparotomy or laparoscopy, proved to be singly related to the following clinical findings: result of the liver isotopic scan, liver and/or spleen enlargement, serum albumin less than or equal to 3.5 g/dl, GOT and/or GPT greater than or equal to 20 mU/ml, serum alkaline phosphatase (SAP) greater than or equal to 210 mU/ml, BSP retention at 45 min greater than or equal to 6.5% and ESR greater than or equal to 51 mm at 1 hr. Such clinical findings were jointly evaluated and further selected by means of a logistic discriminant analysis, and the simplest function with the best discriminant ability between involved and non-involved liver was made by liver scan, spleen enlargement, BSP retention and GOT (89.5% of correct diagnoses). Since the Ann Arbor clinical criteria for liver involvement showed correct diagnoses in 69-80% of the cases, more reliable criteria can be proposed. So, liver involvement is highly probably (a) when three or more of the five variables indicated above are abnormal, or (b) when a markedly abnormal liver scan is associated with alteration of at least one of the other four parameters: otherwise liver will be non-involved.


Reoperation after initial treatment of endometriosis with conservative surgery.
One hundred and fifty-three patients with pelvic endometriosis met the study criteria of inferility, tissue diagnosis, treatment with conservative surgery, and adequate follow-up. The extent of disease was classified according to Acosta and and associates. Pregnancy rates were 10 to 100% in various subclassifications of patients; these pregnancy rates were related to the extent of disease and the existence of concurrent inferitility factors. One hundred and seventeen patients were followed up for three years. Reoperation in this group was carried out in 28 patients for recurrent pain and/or persistent infertility. Each patient had diagnostic laparoscopy preceding relaparotomy. The reoperation rate was 40.6% in those patients who remained infertile, whereas this rate was only 3.7% in those patients who conceived following initial operation. The incidence of conception after a second conservative procedure was 12%. However, an equal number of patients in this group required total abdominal hysterectomy as a third procedure for control of recurrent pain. Thus, repeat conservative surgery should play a secondary role in the treatment of patients with infertility and recurrent endometriosis.


A comparison of the learnability of manual sign and Blissymbolics with nonhandicapped adults.
Although advocates exist for teaching either Blissymbolics or manual sign to language-impaired students, relatively few empirical data exist on the learnability of the two systems. The present study compared the learning of a list of 20 Blissymbols and comparable ASL signs in a controlled paired-associate (P-A) paradigm. Blissymbols were learned significantly faster than manual sign particularly in early learning trials. Results are discussed in terms of the memory requirements of the two systems and their relationship with sign/symbols learning.


Occupational therapy entry-level education in Australia: which path(s) to take?
There has been an increase in the number of occupational therapy educational programmes offered in Australia over recent years. Although universities offer bachelor, masters and graduate-entry masters programmes, there is a push to consider phasing out occupational therapy bachelor degrees. The aim of this study was to identify advantages and disadvantages associated with current and future credentials needed for entry into the profession. This article reviews current literature and other issues concerning entry-level occupational therapy education. The underlying issues are complex and require great consideration as a profession. As a profession we need to take charge of our destiny before governments, universities and other stakeholders/professions determine the basic level of entry for our profession.


Body Mass Index and Dental Caries: A Systematic Review.
This review was undertaken to analyze the relationship between body mass index (BMI) and dental caries with the available literature evidence. The articles were searched from Medline/PubMed and Journal of Web published between 2005 and 2016. Out of the 146 references obtained, 16 articles in English language were read in full, which fulfilled the inclusion criteria after assessing by Down and Black criteria. No consensus was reached in the relationship between BMI and dental caries in the present review due to varied associationsHow to cite this article: Shivakumar S, Srivastava A, Shivakumar GC. Body Mass Index and Dental Caries: A Systematic Review. Int J Clin Pediatr Dent 2018;11(3):228-232.


Association study of functional genetic variants of innate immunity related genes in celiac disease.
Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD) pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1alpha, IL-1beta, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT) that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. The TDT analysis for IL-1alpha, IL-1beta, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Our results suggest that the analysed polymorphisms of IL-1alpha, IL-1beta, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.


Kinetics of insulin receptor internalization and recycling in adipocytes. Shunting of receptors to a degradative pathway by inhibitors of recycling.
The kinetics of receptor internalization and recycling was directly determined in adipocytes by measuring 125I-insulin binding to total, intracellular, and cell-surface insulin receptors. In the absence of insulin 90% of all receptors were on the cell-surface and 10% were intracellular. Insulin (100 ng/ml) rapidly altered this distribution by translocating surface receptors to the cell-interior through a temperature and energy dependent process. Surface-derived receptors were seen within cells as early as 30 s and accumulated intracellularly at the rate of approximately 20,000/min (t 1/2 = 2.7 min). After 6 min the size of the intracellular receptor pool plateaued (for up to 2 h), with 30% of surface receptors residing within the cell. This plateau was due to the attainment of an equilibrium between receptor uptake and recycling, since removal of insulin (to stop receptor uptake) was followed by both a rapid depletion of intracellular receptors and a a concomitant and stoichiometric reappearance of receptors on the cell-surface. Receptors were efficiently recycled, with little or no net loss observed even after 4 h of insulin treatment; however, recycling could be partially inhibited (approximately 10%) by several agents (e.g. chloroquine and Tris). Tris treatment of adipocytes in the presence of insulin led to 50% loss of surface and total receptors at 2 and 4 h, respectively. Since chloroquine prevented the decrease in total receptors, but not the loss of surface receptors, it appears that Tris impairs recycling by diverting a portion of incoming receptors to a chloroquine-inhibitable degradative site. From these results we conclude that: 1) insulin triggers endocytotic uptake of insulin-receptor complexes; 2) internalized receptors are then rapidly reinserted into the plasma membrane, and the receptors can traverse this recycling pathway within 6 min; 3) prolonged recycling does not normally result in measurable receptor loss, but when receptors are prevented from recycling, they become trapped intracellularly and are shunted to a chloroquine-sensitive degradative pathway; and 4) chloroquine and Tris are only partially effective inhibitors of receptor recycling.


Acute organophosphorus insecticide poisoning in Sri Lanka.
Records of 92 cases of acute organophosphorus (OP) insecticide poisoning were analysed. Of the patients 91% were under 30 years of age and 86% were males. The common agents were Dimethoate, Methamidophos, Malathion, Monocrotophos and Fenthion. Poisoning was due to ingestion with suicidal intent in the majority. In addition to the acute cholinergic features, the other important manifestations were delayed onset respiratory paralysis and delayed polyneuropathy. The overall mortality was 18%.


Bedside ultrasonography for acute gallstone disease: a diagnostic accuracy study of surgical registrars and emergency medicine physicians.
Acute gallstone disease, primarily biliary colic and acute cholecystitis, represents a significant burden on surgical services. Prolonged waiting times for ultrasonography to confirm a diagnosis contributes to inefficiency and delays surgery. Bedside ultrasound offers an opportunity for clinicians make a diagnosis more promptly and streamline acute surgery. This study evaluated the reliability of bedside ultrasound performed by clinicians following local training and a trial of its introduction into clinical practice. This was a prospective inter-rater reliability study of bedside ultrasound scans performed on patients referred for suspected acute gallstone disease. Results were compared with a formal ultrasound scan in the radiology department. Inter-rater agreement for the finding of gallstones and the imaging diagnosis of acute cholecystitis was assessed. A total of 124 patients underwent bedside ultrasound scan, 87 (70.2%) performed by surgical registrars. Mean patient age was 48 years (range 19-92 years) with 95 females (76.6%). Inter-rater reliability for the finding of gallstones showed strong agreement with kappa 0.85 (95% confidence interval 0.76-0.95) whereas for the imaging diagnosis of acute cholecystitis there was a minimal agreement with kappa 0.37 (95% confidence interval 0.18-0.56). Sensitivity and specificity for the finding of gallstones on bedside ultrasound was 93% and 92%, respectively. Bedside ultrasound is accurate for the finding of gallstones, but the imaging diagnosis of acute cholecystitis is more challenging. There remains the potential for this to improve the efficiency of surgical assessment in suspected acute gallstone disease and this supports the ongoing provision of bedside ultrasound in surgical services.


Activated carbons from KOH-activation of argan (Argania spinosa) seed shells as supercapacitor electrodes.
Activated carbons were prepared by KOH-activation of argan seed shells (ASS). The activated carbon with the largest surface area and most developed porosity was superficially treated to introduce oxygen and nitrogen functionalities. Activated carbons with a surface area of around 2100 m(2)/g were obtained. Electrochemical measurements were carried out with a three-electrode cell using 1M H(2)SO(4) as electrolyte and Ag/AgCl as reference electrode. The O-rich activated carbon showed the lowest capacitance (259 F/g at 125 mA/g) and the lowest capacity retention (52% at 1A/g), due to surface carboxyl groups hindering electrolyte diffusion into the pores. Conversely, the N-rich activated carbon showed the highest capacitance (355 F/g at 125 mA/g) with the highest retention (93% at 1A/g), due to its well-developed micro-mesoporosity and the pseudocapacitance effects of N functionalities. This capacitance performance was among the highest reported for other activated carbons from a large variety of biomass precursors.


Symmorphosis and skeletal muscle V̇O2 max : in vivo and in vitro measures reveal differing constraints in the exercise-trained and untrained human.
The concept of symmorphosis postulates a matching of structural capacity to functional demand within a defined physiological system, regardless of endurance exercise training status. Whether this concept applies to oxygen (O2 ) supply and demand during maximal skeletal muscle O2 consumption (V̇O2 max ) in humans is unclear. Therefore, in vitro skeletal muscle mitochondrial V̇O2 max (Mito V̇O2 max , mitochondrial respiration of fibres biopsied from vastus lateralis) was compared with in vivo skeletal muscle V̇O2 max during single leg knee extensor exercise (KE V̇O2 max , direct Fick by femoral arterial and venous blood samples and Doppler ultrasound blood flow measurements) and whole-body V̇O2 max during cycling (Body V̇O2 max , indirect calorimetry) in 10 endurance exercise-trained and 10 untrained young males. In untrained subjects, during KE exercise, maximal O2 supply (KE Q̇O2max ) exceeded (462 ± 37 ml kg(-1) min(-1) , P < 0.05) and KE V̇O2 max matched (340 ± 22 ml kg(-1) min(-1) , P > 0.05) Mito V̇O2 max (364 ± 16 ml kg(-1) min(-1) ). Conversely, in trained subjects, both KE Q̇O2max (557 ± 35 ml kg(-1) min(-1) ) and KE V̇O2 max (458 ± 24 ml kg(-1) min(-1) ) fell far short of Mito V̇O2 max (743 ± 35 ml kg(-1) min(-1) , P < 0.05). Although Mito V̇O2 max was related to KE V̇O2 max (r = 0.69, P < 0.05) and Body V̇O2 max (r = 0.91, P < 0.05) in untrained subjects, these variables were entirely unrelated in trained subjects. Therefore, in untrained subjects, V̇O2 max is limited by mitochondrial O2 demand, with evidence of adequate O2 supply, whereas, in trained subjects, an exercise training-induced mitochondrial reserve results in skeletal muscle V̇O2 max being markedly limited by O2 supply. Taken together, these in vivo and in vitro measures reveal clearly differing limitations and excesses at V̇O2 max in untrained and trained humans and challenge the concept of symmorphosis as it applies to O2 supply and demand in humans.


UFT and its metabolite gamma-butyrolactone (GBL) inhibit angiogenesis induced by vascular endothelial growth factor in advanced cervical carcinoma.
The aim of this study was to evaluate the potential role of UFT and its metabolite gamma-butyrolactone (GBL) for inhibition of angiogenesis induced by vascular endothelial growth factor (VEGF) in advanced cervical carcinoma by the determination of serum GBL and VEGF, and by immunohistochemical staining to assess VEGF protein expression, before and after UFT therapy. The subjects were 35 patients with an advanced cervical carcinoma and five healthy volunteers between 2002 and 2003 at Hiroshima University Hospital, under informed consent. The patients received two courses of oral fluoropyrimidine (UFT) therapy at a dose of 600 mg/day for 5 and 2 days off treatment. Serum GBL and VEGF was measured before and after UFT therapy by the gas chromatography mass spectrometry and ELISA-kit in 22 patients and five healthy volunteers, respectively. Immunohistochemical detection of VEGF protein was done in 35 cervical cancers. Results The mean serum GBL level before and after UFT therapy was 21.9 +/- 2.3 and 79.3 +/- 6.2 ng/ml, respectively, and it was significantly increased after UFT administration (P < 0.0001). The mean serum VEGF level before and after UFT therapy was 95.3 +/- 28.1 and 67.5 +/- 11.2 pg/ml, respectively, and it was decreased by UFT administration. In 20 out of 33 (66.6%) patients who were detected with VEGF protein, VEGF protein expression was decreased by UFT therapy. The Delta GBL value (GBL after UFT--GBL before UFT therapy) showed a significant inverse correlation with Delta VEGF value (VEGF after therapy--VEGF before therapy) (r2 = 0.940). Our findings suggest that UFT and its metabolite GBL inhibit angiogenesis induced by VEGF to have an antitumor effect on cervical cancer.


A case of 21q-syndrome with half normal SOD-1 activity.
A male Japanese infant was found to have a chromosomal aberration of del(21)(qter leads to q22.1-2) and decreased superoxide dismutase (SOD) activity in erythrocytes and polymorphonuclear and mononuclear leukocytes. The cuprozinc enzyme (SOD-1) level was 40-50% of normal, while the cyanide-insensitive manganese enzyme (SOD-2) activity was within the normal range. Determination of SOD activity in blood cells is a valuable method of classification of the syndrome.


Current Status of Development of Methods to Assess Effects of Cumulative or Aggregated Underwater Sounds on Marine Mammals.
There are no standards for assessment of the cumulative effects of underwater sound. Quantitative assessments typically consider a single source, whereas qualitative assessments may include multiple sources but rarely identify response variables. As a step toward understanding the cumulative effects of underwater sound, we assessed the aggregated sounds of multiple sources received by migrating bowhead whales (Balaena mysticetus). The quantitative method models the sound field from multiple sources and simulates movement of a population through it. The qualitative method uses experts to assess the responses of individuals and populations to sound sources and identify the potential mechanisms. These methods increase the transparency of assessments.


B-cell Non-Hodgkin Lymphomas with Plasmacytic Differentiation.
B-cell non-Hodgkin lymphomas with plasmacytic differentiation are a diverse group of entities with extremely variable morphologic features. Diagnostic challenges can arise in differentiating lymphoplasmacytic lymphoma from marginal zone lymphoma and other low-grade B-cell lymphomas. In addition, plasmablastic lymphomas can be difficult to distinguish from diffuse large B-cell lymphoma or other high-grade lymphomas. Judicious use of immunohistochemical studies and molecular testing can assist in appropriate classification.


Effects of iris pigmentation on response of ocular pressure to timolol.
Timolol ophthalmic solution effectively reduced mean intraocular pressure (IOP) in Negro and Caucasian patients with chronic open angle glaucoma and untreated IOP of 22 mm Hg or higher. No differences in pressure lowering response were observed among the races although the Negroes required somewhat higher timolol concentrations to produce similar reductions from baseline IOP. Negro patients also appeared to have a more severe disease as indicated by the number of prior antiglaucoma drugs required and the untreated (baseline) pressures. An unexpected finding was the significantly greater number of Caucasians with dark irides who were discontinued from therapy because of inadequate pressure reduction.


Changes in endocrine profiles during ovsynch and ovsynch plus norprolac treatment in Murrah buffalo heifers at hot summer season.
The aim of this study was to compare the changes in hormonal profiles during ovsynch and ovsynch plus norprolac treatment in Murrah buffalo heifers following timed artificial insemination (TAI) at stressful summer months, through intensive endocrine analysis. The norprolac (an anti-prolactin drug) at the dose rate of 10.0 mg/animal /day effectively suppressed the level of prolactin upto 30 hours. The hormones quantified in blood plasma samples collected before, during and after ovsynch and ovsynch plus norprolac treatment were LH, prolactin, progesterone, estradiol-17beta and total estrogens. The plasma prolactin and progesterone concentrations were negatively correlated (r = - 0.24) during summer estrous cycle, which indicated prolactin-induced suppression of progesterone secretion through poor luteal development. The ovsynch treatment reduced the incidence of anestrous from 45% before treatment to only 18% after treatment. The norprolac induced prolactin suppression improved the efficiency of ovsynch treatment upto 100% cyclicity after treatment in comparison to 36% acyclicity before treatment. In both the treatments 45% and 55% of animal became pregnant after TAI, respectively. The high prolactin secretion contributed to poor fertility by lowering gonadal hormones (estradiol-17beta, total estrogens and progesterone) production in summer months. This finding of endocrine changes suggests that ovsynch protocol for estrus synchronization has potential application for improvement of fertility in repeat breeding buffaloes even during extreme summer months through suppression of prolactin secretion.


Systemic metastasis from primary intracranial germinoma: a case report and literature review.
A case of systemic haematogenous metastasis occurring post-operatively from a primary suprasellar intracranial germinoma is reported. While local invasion and direct spread associated with surgical incision and shunt procedures are well known, haematogenous metastasis of these tumours is extremely rare. Problems associated with establishing this diagnosis are discussed.


Clinical presentations of Hepatitis E: A clinical review with representative case histories.
Hepatitis E virus (HEV) typically causes an acute, self-limiting hepatitis and is among the commonest cause of such presentations. Hepatitis E viral infection is also increasingly recognized as a cause of chronic hepatitis amongst the immunocompromised, particularly amongst solid organ transplant recipients. Chronic HEV infection remains an underdiagnosed disease and chronic infection can lead to rapidly progressive liver fibrosis and cirrhosis. This review examines current understanding of the HEV. We illustrate typical clinical presentations, management strategies [(based upon guidelines from both the British Transplant Society (BTS) and European Association for the study of liver (EASL)] and outcomes of HEV infection in different cohorts of patients by highlighting select transplant and non-transplant patient cases, from one of the largest tertiary Hepatology centres in Europe.


Digital Holographic Microscopy to Assess Cell Behavior.
Digital holographic microscopy is an imaging technique particularly well suited to the study of living cells in culture, as no labeling is required and computed phase maps produce high contrast, quantitative pixel information. A full experiment involves instrument calibration, cell culture quality checks, selection and setup of imaging chambers, a sampling plan, image acquisition, phase and amplitude map reconstruction, and parameter map post-processing to extract information about cell morphology and/or motility. Each step is described below, focusing on results from imaging four human cell lines. Several post-processing approaches are detailed, with an aim of tracking individual cells and dynamics of cell populations.


Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?
To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.


Influence of ethyl acetate extract and quercetin-3-methyl ether from Polygonum amphibium on activation lymphocytes from peripheral blood of healthy donor in vitro.
The influence of an ethyl acetate extract from Polygonum amphibium L. and quercetin-3-methyl ether isolated from them were examined on the human immune system. The investigations were made on peripheral blood mononuclear cells from healthy donors. The cells were stimulated by plant extract and quercetin-3-methyl ether in 24 h culture and analysed inflow cytometry. The following mice monoclonal antibody anti human activate markers were used: anti HLA-DR PE, anti CD25 FITC, anti CD69 FITC and anti CD71 FITC. The level of Interleukine-2 in blood serum and in culture supernatants was measured by ELISA method. Ethyl acetate extract from Polygonum amphibium caused the rise in the number of CD25 and HLA-DR positive lymphocytes and increased the expression of CD25 and CD71 antigens. The level of IL-2 was increasing for the duration of the culture, independently from the presence of stimulators. Besides quercetin-3-methyl ether, from herb of Polygonum amphibium L., trans-taxifolin, quercetin and kaempferol were isolated The structure of the isolated compounds was determined by spectroscopic (UV, (1)H NMR, (13)C NMR and CI-MS) methods.


Investigating the Safety of Multiple Body Contouring Procedures in Massive Weight Loss Patients.
Deformities after massive weight loss are usually severe and affect many parts of the body, negatively impacting patients' social and intimate lives. A common request of patients after massive weight loss is to treat more than one anatomical area in one surgical procedure. Advantages include a single recovery period, lower surgical costs, and faster patient satisfaction. Disadvantages may include increased need for blood transfusions, longer hospital stay, and increased risk of common complications. The main objective of the study is to compare operative risk, hospital length of stay, complication rate, and patient satisfaction in MWLP according to the number of surgical procedures performed in the same surgical setting. This is a retrospective case-control study of 653 MWLP who underwent multiple contouring procedures simultaneously in a single surgical procedure. All patients underwent surgery between 2016 and 2020. The patients studied were divided into 4 groups according to the number of anatomical areas operated on. A total of 1254 body contouring procedures were included in the study. Follow-up time ranged from 13 to 41 months, with a mean of 17 months. The mean age in the study was 33 years old. Women accounted for 78% of the studied population and men accounted for 22%. The overall complication rate (major and minor) was 105 cases (16.07%) in all groups CONCLUSION: Patient satisfaction was highest in patients who underwent 2-3 procedures within the same surgical setting compared to patients who underwent +3 procedures. Nevertheless, this is clinically insignificant. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Characterization and distribution of a phospholipase A2 activity from adult rabbit lung.
A phospholipase A2 activity was characterized in adult rabbit lung. This activity was calcium- and deoxycholate-dependent and displayed an alkaline pH optimum. Km and Vmax were 0.176 mM and 256.8 pmoles/min./mg protein respectively. The microsomal fraction displayed the highest enzymatic specific activity; the lowest activity was present in the cytosol. Yet this latter fraction accounted for the majority of the total activity. Although the specific activity was high within the lamellar body fraction this compartment contained only approximately 2% of the total activity. Phospholipase A2 activity was inhibited by bromophenacyl bromide, chlorpromazine and mepacrine in decreasing order of effectiveness. Treatment of the microsomes with increasing concentrations of NaC1 indicated that the lung phospholipase A2 activity was relatively loosely bound to the microsomal membranes and was maximally removed with salt at a concentration only slightly higher than physiological. Addition of calmodulin to the enzyme assay did not significantly alter hydrolysis of labelled phosphatidylcholine.


Early detection of lung inflammation: exploiting T1-effects of iron oxide particles using UTE MRI.
At high magnetic fields diagnostic proton MRI of the lung is problematic, because of fast T2* relaxation. The application of superparamagnetic contrast agents and the exploitation of the corresponding T2* effect is inefficient with conventional MRI methods, which limits the early detection of lung diseases. However, a simple theoretical treatment shows that in the lung, by the use of ultra-short echo time sequences, T2* effects can be neglected while T(1) shortening effects can be used for signal detection. In our study, we have applied a theoretically and experimentally optimized 3D ultra-short echo time sequence to lung phantoms and to a mouse model of lung inflammation, which was induced by systemic bacterial infection. Following the systemic application of very small superparamagnetic iron oxide nanoparticles, a significant signal increase in the lung of infected animals was detected already at 24 h postinfection, compared to control mice (17%, P < 0.001). Iron accumulation in the lung parenchyma as consequence of the host immune response was histologically confirmed. By conventional T2*- and T(2)-weighted imaging, neither structural changes nor formation of substantial edema were observed.


A concise pathway to synthesize a novel class of pyrido(2,3-d)pyrimidine-C-β-D-glycosides.
A concise pathway to synthesize a novel class of nine different pyrido(2,3-d)pyrimidine-C-β-d-glycosides is reported. Formation of Michael adduct as an intermediate followed by heterocyclization are the key steps and the products were characterized by different spectral studies. β-Anomeric forms of C-glycosides were assigned from 1H NMR spectroscopy.


Propensity score matching analysis of the impact of Syntax score and Syntax score II on new onset atrial fibrillation development in patients with ST segment elevation myocardial infarction.
New-onset atrial fibrillation (NOAF) is a common complication in the setting of ST segment elevation myocardial infarction (STEMI), and worsened short/long-term prognosis. Several clinical parameters have already been associated with NOAF development. However, relationship between NOAF and coronary artery disease (CAD) severity in STEMI patients is unclear. This study evaluates the relationship between NOAF and CAD severity using Syntax score (SS) and Syntax score II (SSII) in STEMI patients who were treated with primary percutaneous coronary intervention (pPCI). We enrolled 1,565 consecutive STEMI patients who were treated with pPCI. Patients with NOAF were compared to patients without NOAF in the entire study population and in a matched population defined by propensity score matching. Patients with NOAF had significantly higher SS and SSII than those without, both in the matched population (18.6 ± 4 vs 16.75 ± 3.6; p < .001 and 42 ± 13.4 vs 35.1 ± 13.1; p < .001, respectively), and in all study population (18.6 ± 4 vs 16.5 ± 4.6; p < .001 and 42 ± 13.3 vs 31.5 ± 11.9; p < .001 respectively). SSII, compared to its components, was the only independent predictor of NOAF (OR: 1,041 95% CI: 1.015-1.068; p = .002). In the long-term follow-up, all-cause long-term mortality was significantly higher in patients with NOAF than those without NOAF (23.3% vs. 11%; p = .032). This is the first study to comprehensively examine the relationship between NOAF development and CAD severity using SS and SSII. We demonstrated that, in STEMI patients, high SSII was significantly related to NOAF and was an independent predictor of NOAF. Furthermore, patients with NOAF were associated with poor prognosis.


Appendico-ileo-vesical fistula.
Appendico-vesical fistula is a rare condition. In total, 109 cases, most secondary to appendicitis, have been reported in the English-language literature. We report the first case, to our knowledge, of appendico-ileo-vesical fistula secondary to appendiceal diverticulitis. An enterovesical fistula was diagnosed by urine culture, cystoscopy, and computed tomography. The locations of enteric opening sites were demonstrated by barium enema and colonoscopy. Ileocecal resection and fistulectomy with primary reconstruction were performed. We believe that accurate pre- and intra-operative diagnosis is essential for cure. This case demonstrates the importance of barium enema and colonoscopic examinations in the diagnosis and treatment of complicated enterovesical fistula.


Seagrasses and seagrass habitats in Pacific small island developing states: Potential loss of benefits via human disturbance and climate change.
Seagrasses provide a wide range of services including food provision, water purification and coastal protection. Pacific small island developing states (PSIDS) have limited natural resources, challenging economies and a need for marine science research. Seagrasses occur in eleven PSIDS and nations are likely to benefit in different ways depending on habitat health, habitat cover and location, and species presence. Globally seagrass habitats are declining as a result of anthropogenic impacts including climate change and in PSIDS pressure on already stressed coastal ecosystems, will likely threaten seagrass survival particularly close to expanding urban settlements. Improved coastal and urban planning at local, national and regional scales is needed to reduce human impacts on vulnerable coastal areas. Research is required to generate knowledge-based solutions to support effective coastal management and protection of the existing seagrass habitats, including strenghened documentation the socio-economic and environmental services they provide. For PSIDS, protection of seagrass service benefits requires six priority actions: seagrass habitat mapping, regulation of coastal and upstream development, identification of specific threats at vulnerable locations, a critique of cost-effective restoration options, research devoted to seagrass studies and more explicit policy development.


Macrophage glycolipid receptors for human migration inhibitory factor (MIF): differentiated HL-60 cells exhibit MIF responsiveness and express surface glycolipids which both bind MIF and convert nonresponsive cells to responsiveness.
The human promyelocytic leukemia line HL-60 when treated with a phorbol diester (TPA) differentiates into cells (HL60-TPA) that respond to human migration inhibitory factor (MIF). Unresponsive HL-60 cells became responsive to MIF when preincubated with a glycolipid-enriched preparation extracted from HL60-TPA cells, human monocytes, human macrophage-like (U937) cell line, or with the purified glycolipid receptor for MIF from guinea pig peritoneal macrophages. Human blood monocytes exhibited an increased response to MIF when preincubated with glycolipids from HL60-TPA and U937 cells but not from HL-60 cells. Finally, glycolipids from HL60-TPA cells but not from HL-60 cells were able to reversibly bind MIF when covalently coupled to agarose. These studies suggest that TPA induces the differentiation of HL-60 cells into MIF-responsive cells through the expression of a glycolipid receptor for MIF.


Outcomes in adulthood after neurosurgical treatment of brain tumors in the first 3 years of life: long-term follow-up of a single consecutive institutional series of 97 patients.
Long-term outcome for children who underwent surgery for brain tumors in the first 3 years of life is not well-known. We performed a retrospective study on surgical morbidity, mortality rate, academic achievement, and work participation in children below 3 years of age who underwent primary tumor resection for a brain tumor in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Long-term survivors were defined as with a survival from primary diagnosis of 20 years or more. Ninety-seven consecutive children were included. No patient was lost to follow-up. Gross total resection was achieved in 67 children during the primary procedure, 25 had subtotal resections, and 5 had only partial resection. The 20-year survival figures for the 46 children with high-grade tumors was 33%, and the corresponding figures for 51 patients treated for low-grade tumors was 82%. Five of the 57 20-year-survivors died 21, 29, 30, 30, and 41 years, respectively, following primary surgery. Fifty of the 52 long-term survivors had a Barthel Index (BI) of 100, while the remaining two had a BI of 40. Twelve patients were long-term survivors after treatment for HG tumors (26%), while 40 of the 51 patients treated for LG tumors (78%) were alive. Thirty-two of the 52 long-term survivors were in full-time work and 29 of them after treatment for LG tumors. Another 10 were in part-time work, while the last 10 individuals had no working capacity. Survival is better for patients with low-grade tumors compared with those with high-grade tumors. The functional level of long-term survivors is affected by adjuvant therapy and radiotherapy in particular. Neurosurgical intervention in itself is safe and plausible for pediatric brain tumor patients below 3 years of age. However, there should be a focus on potential late affects, and survivors should be followed by knowledgeable clinical staff for the neoplastic disease as well as for potential side effects. In this consecutive series, a 33% 20-year survival for children treated for HG tumors and 82% for patients with LG tumors was observed. The patients with LG tumors who had been treated with surgical resection without any adjuvant therapy showed a good clinical outcome as adults, and two-thirds of them were in full-time work.


H+ coupled transport of orally active cephalosporins lacking an alpha-amino group across brush-border membrane vesicles from rat small intestine.
The effect of an inwardly directed H+ gradient' on the transport characteristics of ceftibuten, cefixime and analogues of ceftibuten in rat intestinal brush-border membrane vesicles have been investigated. In the presence of a transmembrane H+ gradient, ceftibuten and its analogues exhibited a peak to equilibrium overshoot and an accumulation in the vesicles against the concentration gradient. However, the uptake of cefixime and S-1006 [(6R, 7R)-(7-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-8-oxo- 3- carbamoyloxy-methyl-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxyl ic acid), which lacks a carboxyl group at position 4 of carboxyethylidene structure, exhibited no overshoot, although the equilibrium uptake was increased by a H+ gradient. The equilibrium uptake was dependent on the pH of the final incubation medium and the H+ gradient. These data suggested that the orally active cephalosporins were transported into rat intestinal brush-border membrane by the transmembrane H+ gradient and the pH of the medium.


Prognostic value of left atrial volume in asymptomatic organic mitral regurgitation.
Basal left atrial volume (LAV) indexed to body surface area (LAVI) predicts adverse events in patients with organic mitral regurgitation, but information is lacking regarding change in left atrial volume during follow-up. One hundred forty-four asymptomatic patients (mean age, 71 ± 12 years; 66% women; mean ejection fraction, 66 ± 4.8%) with moderate to severe mitral regurgitation were prospectively included, with a median follow-up period of 2.76 years (interquartile range, 1.86-3.48 years). Fifty-four patients (37.50%) reached the combined end point of dyspnea and/or systolic dysfunction. Both basal and change in LAV were independently associated with the combined end point on multivariate analysis: for basal LAVI ≥ 55 mL/m(2), odds ratio, 2.26 (95% confidence interval, 1.04-4.88; P = .038), and for change in LAV ≥ 14 mL, odds ratio, 7.32 (95% confidence interval, 3.25-16.48; P < .001), adjusted for effective regurgitant orifice area and deceleration time. Combined event-free survival at 1, 2, and 3 years was significantly less in patients with basal LAVI ≥ 55 mL/m(2) (75%, 58%, and 43%) than in those with basal LAVI < 55 mL/m(2) (95%, 89%, and 77%) (log-rank test = 15.38, P = .0001). The incidence of the combined end point was highest (88%) in patients with basal LAVI ≥ 55 mL/m(2) and change in LAV ≥ 14 mL. Measurement of basal LAV and its increase during follow-up predict an adverse course in patients with moderate and severe asymptomatic mitral regurgitation. Hence, its assessment could be incorporated into the currently used algorithm for risk stratification and decision making in this group of patients.


Bioengineering of the Human Neural Stem Cell Niche: A Regulatory Environment for Cell Fate and Potential Target for Neurotoxicity.
Human neural stem/progenitor cells of the developing and adult organisms are surrounded by the microenvironment, so-called neurogenic niche. The developmental processes of stem cells, such as survival, proliferation, differentiation, and fate decisions, are controlled by the mutual interactions between cells and the niche components. Such interactions are tissue specific and determined by the biochemical and biophysical properties of the niche constituencies and the presence of other cell types. This dynamic approach of the stem cell niche, when translated into in vitro settings, requires building up "biomimetic" microenvironments resembling natural conditions, where the stem/progenitor cell is provided with diverse extracellular signals exerted by soluble and structural cues, mimicking those found in vivo. The neural stem cell niche is characterized by a unique composition of soluble components including neurotransmitters and trophic factors as well as insoluble extracellular matrix proteins and proteoglycans. Biotechnological innovations provide tools such as a new generation of tunable biomaterials capable of releasing specific signals in a spatially and temporally controlled manner, thus creating in vitro nature-like conditions and, when combined with stem cell-derived tissue specific progenitors, producing differentiated neuronal tissue structures. In addition, substantial progress has been made on the protocols to obtain stem cell-derived cell aggregates such as neurospheres and self-assembled organoids.In this chapter, we have assessed the application of bioengineered human neural stem cell microenvironments to produce in vitro models of different levels of biological complexity for the efficient control of stem cell fate. Examples of biomaterial-supported two-dimensional and three-dimensional (2D and 3D) complex culture systems that provide artificial neural stem cell niches are discussed in the context of their application for basic research and neurotoxicity testing.


Protocol for mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation.
Damage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients. The aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation. The SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15-30% = mild, >30% significant). The location and category of induced errors was marked in each subject's individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles). Mapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation. Mapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions.


Regulation of targeting determinants in interorganelle communication.
The field of interorganelle communication is now established as a major aspect of intracellular organisation, with a profusion of material and signals exchanged between organelles. One way to address interorganelle communication is to study the interactions of the proteins involved, particularly targeting interactions, which are a key way to regulate activity. While most peripheral membrane proteins have single determinants for membrane targeting, proteins involved in interorganelle communication have more than one such determinant, sometimes as many as four, as in Vps13. Here we review the targeting determinants, showing how they can be relatively hard to find, how they are regulated, and how proteins integrate information from multiple targeting determinants.


Disease Progression and Sphingolipids and Neurofilament Light Chain in Early Idiopathic Parkinson's Disease.
Parkinson's disease(PD) lacks a biomarker for disease progression. To analyze how cerebrospinal fluid (CSF), glucosylceramide (GlcCer), sphingomyelin (SM), or serum neurofilament light chain (NfL) associate with progression of PD in a retrospective cohort, we used linear mixed-model regressions between baseline biomarkers and change in dopamine transporter brain-imaging (DaTscan©), Montreal cognitive assesment (MoCA), or global composite outcome (GCO) score. In 191 PD patients, biomarkers were not associated with DaTscan or MoCA change over 2.1 years. Higher baseline GlcCer/SM ratio and serum-NfL nonsignificantly associated with increase in GCO score. Results do not support a role for CSF-sphingolipid/serum-NfL to predict cognitive and DaTscan progression in early-PD. Potential prediction of global clinical change warrants further study.


12-Acylindolo[1,2-c]quinazolines by palladium-catalyzed cyclocarbonylation of o-alkynyltrifluoroacetanilides.
6-Trifluoromethyl-12-acylindolo[1,2-c]quinazolines are prepared in high yield through the palladium-catalyzed reaction of bis(o-trifluoroacetamidophenyl)acetylene with aryl or vinyl halides and triflates. The reaction, which tolerates a variety of important functional groups, probably involves the formation of a 3-acyl-2-(o-trifluoroacetamidophenyl)indole intermediate, followed by its cyclization to the indoloquinazoline product. [reaction: see text]


[Comparing group educational intervention to individual and self-learning in COPD].
Chronic obstructive pulmonary disease (COPD) is considered a public health issue which affects 10.2% of Spanish population between 40 and 80 years of age. Many patients do not perform well the inhalation technique. Error rates vary between 50-80% depending on the device under study. These values haven been proven to decrease with educational interventions. To ascertain whether a group educational intervention is superior to an individual intervention or to a conventional approach in these patients as regards quality of life measured by means of the total score of the COPD Assessment Test (CAT),of adherence to treatment, exacerbations and hospitalizations. A multicenter, multidisciplinary cluster-randomized controlled clinical trial with three branches (conventional intervention, individual intervention and group intervention) in a cohort of COPD-patients. Sociodemographic data and risk factors were collected and several questionnaires were completed (CAT, BODEx, Barthel, Lawton y Brody). A descriptive analysis of qualitative and quantitative variables and a multiple linear regression were conducted. 149 patients of average age 69.08 (SD 1.26). Significant differences were observed in CAT in the different intervention groups according to the level of severity on BODEx. The rate of patients performing well the inhalation technique was significantly lower at the beginning of the study and the number of exacerbations was lower after the intervention. Last year's exacerbations were linearly related to post-intervention suffering. Better results are obtained using the traditional and individual interventions. There is a decrease in number of exacerbations, hospitalizations, CAT score and post-intervention inhalation technique.


Reactions of granulocytic lineage of hemopoiesis and mechanisms of their development in combined treatment with adriablastin and taxotere.
We studied myelotoxic effects of adriablastin and taxotere combination on granulocytic lineage cells and processes of their recovery in patients with stage III-IV breast cancer. Intensive maturation of granulocytic CFU provided regeneration of the hemopoiesis even under conditions of reduced proliferative activity of these cells, which, in turn, led to accumulation of mature and immature neutrophilic granulocytes in the bone marrow and improved reserve capacities of the neutrophil pool in the bone marrow.


Targeting a TAF to make muscle.
In a recent issue of Molecular Cell, Deato et al. (2008) elucidate the basis by which the muscle-specific activator MyoD recruits the core transcription machinery to the promoter of a key regulatory gene involved in myogenic differentiation.


Laryngeal hibernoma: case series of a rare tumor.
Hibernomas are rare, benign tumors of brown adipose tissue uncommonly found in the head and neck. A review of the English-language literature was conducted for this study. We present a series of 2 laryngeal hibernomas treated with transoral laser microsurgical resection at a tertiary referral center over a period of 18 years. Only 2 cases of laryngeal hibernoma have been previously described in the literature. Two additional cases were encountered at our institution. Preoperative imaging demonstrated a well-circumscribed neoplasm with fat density compatible with lipoma, but internal heterogeneity and vascularity seen in the context of liposarcoma. Transoral laser microsurgical resection was successfully performed in each case. Despite unique radiographic features, hibernomas are difficult to distinguish from well-differentiated liposarcoma and lipoma variants without pathologic correlation. Complete surgical resection is indicated. In our experience, transoral laser microsurgical excision of laryngeal hibernomas is a safe, effective treatment modality with little associated morbidity.


Enchytraeid numbers, biomass and respiratory metabolism in a beech woodland - Wytham Woods, Oxford.
The mean annual population density of enchytraeids in the litter and upper 6 cm of soil was found to be 14,590 m-2. Mean individual weights approximated 116, 158 and 151 μg wet wt. in the litter, 0-3 cm and 3-6 cm strata respectively. The mean biomass was estimated to be 1.908 g wet wt m-2. Vertical migration was shown to occur, the upward migration in late Autumn was a response to temperatures in the litter being temporarily higher than those of the 0-3 cm stratum. As a result of upward vertical migration and possibly recruitment, numbers reached a maximum in the litter during Winter. On an annual basis the litter, 0-3 and 3-6 cm strata contained 41.43, 46.44 and 12.12% respectively of the extracted enchytraeids. The equivalent biomass values were 33.18, 52.46 and 14.36%. Total numbers and biomass revealed a general picture of high values in late Autumn to Winter which gradually decreased through Spring and Summer except for a minor peak in May-June. The annual oxygen consumption of the enchytraeids approximated 4.285 l O2 m-2 yr-1 (≡20.461 kcal≡85.610 kJ) and accounted for 1.63% of the total soil metabolism. A production/biomass (P/B) ratio of 4.93 was estimated as was a net population efficiency of 32%. For this site the contribution by enchytraeids to total soil respiration is about one-third that of the earthworms and an order of magnitude greater than that of the nematodes.


Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.
Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc.


Broca's Aphemia: The Tortuous Story of a Nonaphasic Nonparalytic Disorder of Speech.
Broca coined the neologism "aphemia" to describe a syndrome consisting of a loss of the ability to speak without impairment of language and paralysis of the faciolingual territories in actions unrelated to speech, such as protruding the tongue or pursing the lips. Upon examining the brains of patients with aphemia, Broca concluded that the minimum possible lesion responsible for aphemia localized to the posterior left inferior frontal gyrus and lower portion of the middle frontal gyrus. A review of Broca's writings led us to conclude that (a) Broca localized speech, not language, to the left hemisphere, (b) Broca's aphemia is a form of apraxia, (c) Broca's aphemia is not, therefore, a terminological forerunner of aphasia, and (d) Broca was an outspoken equipotentialist concerning the cerebral localization of language. Broca's claim about the role of the left hemisphere in the organization of speech places him as the legitimate forebear of the two most outstanding achievements of Liepmann's work, namely, the concepts of apraxia and of a left hemisphere specialization for action.


High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases.
Patients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM. Transcript levels of hypoxia-adaptive genes (such as PDK isoenzymes) were assessed in the tissue of healthy liver, corresponding CRLM, healthy colon mucosa and corresponding tumour. Uni- and multivariate analyses were performed. Responses to chemotherapy upon up- or down-regulation of PDK4 were studied in vitro. PDK4 expression within healthy liver tissue was associated with increased overall survival and liver function following surgical resection of CRLM. This association was enhanced in patients with NC. PDK4 expression in CRLM tissue did not correlate with overall survival. Up-regulation of PDK4 increased the resistance of hepatocytes and colon cancer cells against chemotherapy-induced toxicity, whereas knockdown of PDK4 enhanced chemotherapy-associated cell damage. Our findings suggest that up-regulated PDK4 expression reduces hepatic chemotherapy-induced oxidative stress and is associated with improved postoperative liver function in patients undergoing multimodal treatment and resection of CRLM.


TIN2 deficiency leads to ALT-associated phenotypes and differentiation defects in embryonic stem cells.
Telomere integrity is critical for embryonic development, and core telomere-binding proteins, such as TIN2, are key to maintaining telomere stability. Here, we report that homozygous Tin2S341X resulted in embryonic lethality in mice and reduced expression of Tin2 in the derived mouse embryonic stem cells (mESCs). Homozygous mutant mESCs were able to self-renew and remain undifferentiated but displayed many phenotypes associated with alternative lengthening of telomeres (ALT), including excessively long and heterogeneous telomeres, increased ALT-associated promyelocytic leukemia (PML) bodies, and unstable chromosomal ends. These cells also showed upregulation of Zscan4 expression and elevated targeting of DAXX/ATRX and H3K9me3 marks on telomeres. Furthermore, the mutant mESCs were impeded in their differentiation capacity. Upon differentiation, DAXX/ATRX and PML bodies disassociated from telomeres in these cells, where elevated DNA damage was also apparent. Our results reveal differential responses to telomere dysfunction in mESCs versus differentiated cells and highlight the critical role of TIN2 in embryonic development.


Bacterial Colonisation of Suction Cannulas in Orthopaedic Surgery.
Osteoarticular infections represent a major complication in orthopaedic surgery. The aim is to identify the percentage of suction cannulas colonised and to determine the relationship between the time they are used in surgery and the colonisation of these cannulas. Descriptive and prospective study that analysed 546 suction cannulas used in clean orthopaedic surgery in a trauma centre, between November 2017 and March 2018. The distal end of the cannula was cultured to determine the colonisation rate. 7.3% of the cultured cannulas were positive for pathogens, the most frequent being Staphylococcus epidermidis at 27.5%. In addition, an association was found between colonisation and the length of time the cannula was used. The possibility of colonisation of cannulas used for between 60minutes or more, is greater than those used for less than 60minutes; between 60 and 90minutes the possibility is twice as high OR= 2.2 (CI:95% 1.1 - 4.1) and in cannulas used for more than 90minutes it is 8 times higher OR= 8.49 (CI:95% 1.77 - 40.86). The colonisation rate of cannulas is lower than reported in the literature. The longer the cannula is used in surgery increases the risk of their colonisation. Follow-up studies are being considered to determine whether suction cannula colonisation is associated with increased postoperative infection.