Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells.
Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1+CD8+T cells. We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.


Mitochondrial mRNA polymorphisms in different Arabidopsis accessions.
In our analysis of 5' and 3' end formation in plant mitochondria, we compared the major transcript ends of all mitochondrial protein-coding genes between the three Arabidopsis (Arabidopsis thaliana) accessions Columbia (Col), C24, and Landsberg erecta (Ler). Differences between transcript patterns were found for seven genes. For atp6-2, no transcripts at all were detected in Ler. This and further analyses suggest that the atp6-2 gene arrangement is absent from the mitochondrial DNA of this accession. All other transcript polymorphisms are attributed to variations at the 5' termini and were consistently observed in all tissues investigated. mRNA phenotyping of reciprocal Col/Ler, Col/C24, and Ler/C24 F(1) hybrids revealed the differing transcript patterns of ccmC to be inherited maternally, suggesting these to arise from differences in the mitochondrial DNA. Biparental inheritance was observed for the polymorphic transcripts of nad4, nad9, ccmB, and rpl5, indicating these differences to be caused by nuclear-encoded trans-factors. Deviant transcript patterns were tested in further accessions and were found in at least three additional accessions. Detailed examination of the nad4 and the nad9 transcripts demonstrates that the respective polymorphisms affect the major mRNAs of these genes. This study shows that natural genetic variation in Arabidopsis can also affect mitochondrial mRNA end processing. These variations can now be used to identify the nuclear genes responsible, as well as the mitochondrial cis-elements required, for 5' end generation of mitochondrial transcripts.


Acute fluoride toxicity from ingesting home-use dental products in children, birth to 6 years of age.
This paper analyzes reports to the American Association of Poison Control Centers (AAPCC) of suspected overingestion of fluoride by children younger than 6 years of age between 1989 and 1994, and estimates the probably toxic amounts of various home-use fluoride products in children younger than 6 years of age. Annual incidence rates of reported fluoride exposures attributed to dietary supplements, toothpaste, and rinses were calculated. Probably toxic amounts of each product were calculated using the frequently cited dose of 5 mg/kg. Children younger than 6 years of age accounted for more than 80 percent of reports of suspected overingestion. While the outcomes were generally not serious, several hundred children were treated at health care facilities each year. A 10 kg child who ingests 50 mg fluoride (10.1 g 1.1% NaF gel; 32.7 g 0.63% SnF2 gel; 33.3 g 1,500 ppm F toothpaste; 50 g 1,000 ppm F toothpaste; and 221 mL 0.05% NaF rinse) will have ingested a probably toxic dose. Overingestion of fluoride products in the home is preventable. Dentists and other health care providers should educate parents and child care providers about the importance of keeping fluoride products out of reach of children. Manufacturers should be encouraged by the ADA and the FDA to use child-resistant packaging for all fluoride products intended for use in the home.


Profile of ipilimumab and its role in the treatment of metastatic melanoma.
Melanoma is an immunogenic cancer. However, the ability of the immune system to eradicate melanoma tumors is affected by intrinsic negative regulatory mechanisms. Multiple immune-modulatory therapies are currently being developed to optimize the immune response to melanoma tumors. Two recent Phase III studies using the monoclonal antibody ipilimumab, which targets the cytotoxic T-lymphocyte antigen (CTLA-4), a negative regulator of T-cell activation, have demonstrated improvement in overall survival of metastatic melanoma patients. This review highlights the clinical trial data that supports the efficacy of ipilimumab, the immune-related response criteria used to evaluate clinical response, and side-effect profile associated with ipilimumab treatment.


Doxepin inhibits CYP2D6 activity in vivo.
Doxepin is a tricyclic antidepressant formulated as a mixture of E-(trans) and Z-(cis) stereoisomers. Cytochrome P450 2D6 (CYP2D6) catalyzes the hydroxylation of E-doxepin and E-N-desmethyldoxepin stereospecically. There is evidence that tricyclic antidepressants might inhibit CYP2D6 activity but there is no data about the influence of doxepin on CYP2D6. Eleven patients diagnosed with depression according to ICD-10 criteria were included in the study. After wash-out period, before doxepin treatment, sparteine metabolic ratio (MR1) was assessed. After 2-weeks of doxepin treatment, MR2 was estimated. Sparteine and its metabolites were determined in urine by gas chromatographic method of Eichelbaum et al. Based on MR1 values, 10 patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor metabolizer). During the study, after doxepin treatment, none of patients has changed phenotype status. However, MR2 values were statistically significantly higher than MR1. These results show the inhibitory effect of doxepin on CYP2D6 activity and may be of clinical value, especially in polymedicated patients treated with other CYP2D6 substrates or inhibitors.


Role of osteotomy in the treatment of slipped capital femoral epiphysis.
The treatment of severe slipped capital femoral epiphysis (SCFE) remains problematic. Treatment of most mild and moderate cases has been simplified, not by our increasing knowledge of physiology or molecular genetics, but by the advances in radiographic imaging, metallurgy, and the development of cannulated screw technology. Most centers agree that the placement of a single pin or screw across the center of the epiphysis, stabilizing the unreduced epiphysis and keeping the implant out of the joint space until physeal closure is achieved, is the most efficient and effective method for the majority of slips. Despite this knowledge and improvement in early results, the problems of avascular necrosis and chondrolysis have not been eliminated. Of more concern for patients whose severe unreduced SCFE has been pinned in situ is the secondary problem of the altered biomechanics of the lower extremity, leaving the hip in extension, the limb externally rotated and shortened. Most series show poor long-term results of realignment osteotomies; however, most series also show poor long-term results of severe slips treated by any means. These population groups are historically the same. Current radiographic imaging and implant design may eliminate most of the technical problems encountered with the accuracy and stability of realignment osteotomies, thereby allowing earlier motion, which may improve our results. The current status of realignment osteotomies is reviewed.


The effect of 1,2-indanedione, a latent fingerprint reagent on subsequent DNA profiling.
The compound 1,2-indanedione was recently introduced in our laboratory as an operational reagent for developing latent fingerprints on porous surfaces. As part of the reagent implementation, a study was carried out in order to determine whether either of the two operational 1,2-indanediones formulations interferes with further DNA profiling. Both formulations are based on HFE7100 solvent. One is acidic and the other neutral. In a controlled experiment, known donors attached stamps to envelopes by licking them. The stamped envelopes were initially treated with either one indanedione formulation or the other, and DNA was then extracted for STR typing. No differences were observed between the STR profiles obtained from treated and untreated stamps and envelopes, indicating that 1,2-indanedione does not adversely affect the extraction and subsequent amplification of the STRs examined. However, preliminary results indicate that potential DNA analysis depends on the time interval between the indanedione treatment and DNA extraction as no DNA can be recovered six days following treatment. For this reason, it is strongly recommended to extract DNA from treated items of evidence as soon as possible after indanedione treatment.


Analytical Calculations of Scattering Amplitude of Surface Plasmon Polaritons Excited by a Spherical Nanoantenna.
Since surface plasmon polaritons (SPPs) are surface waves, they cannot be excited by an incident plane wave, because free-space photons do not possess a sufficient in-plane momentum. Phase matching between the incident light and SPP can be achieved using a high-refractive-index prism, grating, or nanoantennas. In this work, we found an expression for the amplitude of SPP excited by an arbitrary 3D current distribution placed near a metal interface. The developed method is based on the well-known technique used in waveguide theory that enables finding the amplitudes of waveguide modes excited by the external currents. It reduces the SPP excitation problem to the summation of the set of emitters. As a particular example, we considered a spherical dipole nanoantenna on a metal substrate illuminated by a normally incident plane wave. The analytical calculations were in good agreement with the full-wave numerical simulations.


[Sodium and arterial hypertension --one hundred years of controversies].
Sodium chloride (salt) plays a role in the development and maintenance of high blood pressure (25% of the normotensive population are called sodium sensitive and 50% of the hypertensive people would present a significative decrease either of their blood pressure when low salt diet is applied) or of cardiovascular complications, but also of other diseases (obesity, osteoporosis, kidney stones, cancer,...) The regulation of salt balance is played by the kidneys, the function of which can be genetically (more rarely) or secondarily acquired (most often) disturbed. Salt restriction (maximum 5-6 g/d) with higher potassium intake, is now recommended. This can easier allow the lowering of the blood pressure, especially in resistant forms of hypertension. Proposed to everybody, even normotensive, it could be beneficial reducing the trend of blood pressure increase with age, but also the burden of cardiovascular complications and promoting general health. For reaching these objectives, this reduction in salt consumption needs motivated and well educated people, well labelled food products about salt content and the apprppriate help of food industries.


The impact of a managed care network on attendance, follow-up and treatment at a hepatitis C specialist centre.
Infection with the hepatitis C virus commonly occurs in patient groups who have difficulty accessing conventional medical care, reducing their chance of successful antiviral therapy. Managed care networks (MCNs) have been suggested as a mechanism of improving access to care; however, there is little evidence to support their use in patients with hepatitis C. The aim of this study was to evaluate the impact of a MCN for patients with hepatitis C. This was a retrospective cohort study of all individuals in our area who had received a positive hepatitis C antibody test between August 1994 and June 2008. The MCN introduced a new referral pathway, which included nonmedical referrals and outreach nurse-led clinics. These interventions were introduced in 2004 and evaluated in 2008. After the introduction of the MCN, the proportion of individuals who accessed care increased from 61% (280/430) to 82.4% (721/875). There was an increase in nonmedical referrals with 81 (18.3%) being directly referred from Drug Problem Services and 75 (17%) from the Prison Service. The changes to referral did not have a negative impact on treatment outcomes as the number who completed treatment increased from 66.1% (43/65) to 73.7% (98/133) and the sustained virological response increased from 50.7% (33/65) to 60.9% (81/133). This study provides evidence that the collaboration of health care professionals within a network can have a radical effect in improving access to care in a traditionally hard to reach population. This has been achieved with little additional resource, but rather working smarter with existing staff.


Selective stabilization of self-assembled hydrogen-bonded molecular capsules through π-π interactions.
Subtle noncovalent forces such as π-π interactions play an import role in the folding of biological macromolecules such as DNA and proteins. We describe here a system where such interactions on the outside of a molecular capsule trigger a selective change of its structure as a self-assembled receptor.


Curcumin-loaded apotransferrin nanoparticles provide efficient cellular uptake and effectively inhibit HIV-1 replication in vitro.
Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research. In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis. Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness.


Effects of a 12-Week Hatha Yoga Intervention on Cardiorespiratory Endurance, Muscular Strength and Endurance, and Flexibility in Hong Kong Chinese Adults: A Controlled Clinical Trial.
Objective. To examine the effects of a 12-week Hatha yoga intervention on cardiorespiratory endurance, muscular strength and endurance, and flexibility in Chinese adults. Methods. 173 adults (aged 52.0 ± 7.5 years) were assigned to either the yoga intervention group (n = 87) or the waitlist control group (n = 86). 19 dropped out from the study. Primary outcomes were changes in cardiorespiratory endurance (resting heart rate (HR) and maximal oxygen uptake (VO2max)), muscular strength and endurance (curl-up and push-up tests), and lower back and hamstring flexibility (the modified back-saver sit-and-reach (MBS) test). Results. Compared to controls, the yoga group achieved significant improvements in VO2max (P < 0.01), curl-up (P < 0.05) and push-up (P < 0.001) tests, and the MBS left and right leg tests (both P < 0.001) in both genders. Significant change was also found for resting HR between groups in women (P < 0.05) but not in men. Further analysis comparing participants between younger and older subgroups yielded similar findings, except that the older participants in the yoga group failed to improve resting HR or the curl-up test versus control. Adherence (89%) and attendance (94%) were high. No serious adverse events occurred. Conclusion. A 12-week Hatha yoga intervention has favorable effects on cardiorespiratory endurance, muscular strength and endurance, and flexibility in Chinese adults.


Compassion in jewish, christian and secular nursing. A systematic comparison of a key concept of nursing (part I).
The topos of the Compassionate God is a dominant motive of the Jewish and Christian traditions. It is relevant for nursing because it asks the nurse to imitate God so as to become God-like. Also, to think that God suffers with the suffering believers is thought to give comfort to them. Because in the western world the topos of the Compassionate God represents the basis of the ethics of compassion/caring, this piece of basic research is important for clinical practice. This study explores to what extent Jewish and Christian nursing adhered to the biblical topos of the Compassionate God at different periods and in different cultural contexts. A mixed methods approach was used. It included variations of hermeneutical text analysis as used in historical, philosophical, theological, science of religion, and nursing research. The analysis of the literary sources shows that the topos of the Compassionate God was interpreted differently in different cultural contexts. However, at all times it directed religious and secular nursing. Since the beginning of the 21(st) century it builds the core of "compassionate caring" as propagated by North American nursing science. The topos of the Compassionate God laid the foundation of the tradition of the ethics of compassion in nursing. More research is required to learn whether it also plays a role in Islamic nursing.


[Participation of bonth splenic CD(5)(+) and CD(5)(-) B lymphocytes in production of platelet glycoprotein-specific autoantibodies in chronic ITP].
To investigate the percentage of splenic CD(5)(+) B lymphocytes in chronic idiopathic thrombocytopenic purpura (IT) and the impact of splenic CD(5)(+) and CD(5)(-) B lymphocytes on the production of platelet glycoprotein (GP)-specific autoantibodies. Splenic CD(5)(+) B lymphocytes were identified by two-color flow cytometric analysis in eight patients. Four of the eight patients displayed plasma autoantibodies against both GPIIb/IIIa and GPIb/IX, and their splenic B lymphocytes were separated by Ficoll-Hypaque density gradient and sheep erythrocyte, and further purified by magnetic activate cell separation (MACS). Purified CD(5)(+) and CD(5)(-) B lymphocytes were cultured separately with or without staphylococcus aureus cowan I (SAC). GP specific autoantibodies in culture supernatants were measured by modified monoclonal antibody immobilization of platelet antigen assay (MAIPA). The percentage of splenic CD(5)(+) B lymphocytes in ITP patients was slightly higher than that in control with no statistical significance. MACS purified splenic CD(5)(+) and CD(5)(-) B lymphocytes from three out of four ITP patients produced high levels of anti-GPIIb/IIIa and anti-GPIb/IX antibodies. Culture supernatants of CD(5)(+) B lymphocytes from the other patient showed positive reaction only in GPIb/IX MAIPA. Culture supernatant of CD(5)(-)B lymphocytes from the same patient were double positive in both GPIIb/IIIa and GPIb/IX MAIPA. Both splenic CD(5)(+) and CD(5)(-) B lymphocytes produce platelet GP-specific autoantibodies in chronic ITP with similar antibody spectrum and titer, and may all play a role in the autoimmune pathogenesis of ITP.


Contrast enhancement and quantitative signal analysis in MR imaging of multiple myeloma: assessment of focal and diffuse growth patterns in marrow correlated with biopsies and survival rates.
This study describes infiltration patterns of multiple myeloma in spinal MR imaging and correlates the findings with biopsies, survival rates, and signal intensity measurements in unenhanced and enhanced studies. Fifty-three patients with multiple myeloma and 53 age-matched controls underwent MR imaging of the spine. Twenty-nine patients underwent sagittal T1-weighted spin-echo enhanced imaging and all patients underwent sagittal T1-weighted spin-echo unenhanced and opposed-phase gradient-recalled echo images, and signal intensity measurements were taken. MR imaging was correlated to marrow specimens (n = 40) and a clinical staging system. The probability of survival was also calculated. Finally, we performed qualitative visual evaluation (infiltration pattern, degree of tumor involvement) and a quantitative evaluation (marrow signal intensity ratios, contrast enhancement). Five infiltration patterns were found: normal-appearing marrow with low-grade interstitial infiltration (n = 5), focal (n = 18), diffuse (n = 12), focal and diffuse (n = 13), and salt-and-pepper (n = 5). Infiltration pattern correlated with clinical staging; all patients with normal-appearing and salt-and-pepper patterns were clinically stage I. Diffuse marrow infiltration was assessed by marrow ratios: low-grade infiltration, greater than 2.0; intermediate, 1.0-2.0; highgrade, less than 1.0. Contrast enhancement with a signal intensity increase greater than 40% indicated diffuse infiltration. In the control group, all of whom had no marrow disease, enhancement varied (mean +/- SD, 16% +/- 8.9%) but did not exceed 40%. Marrow involvement on MR images correlated significantly with clinical staging and survival (p < or = .001). MR imaging with opposed gradient-recalled echo sequences and contrast enhancement provided data that allowed us to classify infiltration patterns and to quantify diffuse marrow involvement in multiple myeloma, both of which correlated to clinical staging and biopsy. Also, the MR data was of prognostic value. Therefore, like laboratory parameters, biopsies, and radiographs, MR imaging can be a supporting pillar in staging and planning treatment of patients with multiple myeloma.


Retrobulbar hematoma in blow-out fracture after open reduction.
Retrobulbar hemorrhage, especially when associated with visual loss, is a rare but significant complication after facial bone reconstruction. In this article, two cases of retrobulbar hematoma after surgical repair of blow-out fracture are reported. In one patient, permanent loss of vision was involved, but with the other patient, we were able to prevent this by performing immediate decompression after definite diagnosis. We present our clinical experience with regard to the treatment process and method for prevention of retrobulbar hematoma using a scalp vein set tube and a negative pressure drainage system.


Translocation breakpoints are clustered on both chromosome 8 and chromosome 21 in the t(8;21) of acute myeloid leukemia.
The t(8;21)(q22;q22) is consistently associated with acute myeloid leukemia (AML) M2. Recent data have suggested that breakpoints on chromosome 21 are clustered within a single intron of a novel gene, AML1, just downstream of a region of homology to the runt gene of D melanogaster. In this report, we confirm rearrangement at the same location in at least 12 of 18 patients with t(8;21). Furthermore, we have isolated recombinant clones spanning the breakpoint regions on both the der(8) and the der(21) from one patient. By using a chromosome 8 probe derived from these clones, we show that t(8;21) breakpoints are also clustered on chromosome 8.


Does L-carnitine improve endothelial function in hemodialysis patients?
Atherosclerosis is the leading cause of death in hemodialysis patients. These patients are also very prone to L-carnitine deficiency due to kidney disease. In this clinical trial, we investigated the effect of oral L-carnitine on endothelial function of these patients. [corrected] We studied 31 adult chronic hemodialysis patients in our center and divided them into two groups. The first group (n = 20) received 1500 mg/dialysis interval (every other day) oral L-carnitine. The control group (n = 11) received placebo for one month. Ultrasonographic measurements of flow mediated dilation and carotid intima-media thickness were performed before and after one month of L-carnitine and placebo therapy. This study showed that after one month of L-carnitine or placebo therapy there was no significant improvement in flow mediated dilation (p = 0.80 and p = 0.59, respectively) or decrease in carotid intima-media thickness (p = 0.12 and p = 0.50, respectively). Our study revealed that one month of oral L-carnitine therapy did not improve endothelial function in hemodialysis patients. Long-term studies with large sample size using intravenous form and higher doses of the drug are required to clarify the questionable role of L-carnitine in hemodialysis patients.


Creating Tunable Quantum Corrals on a Rashba Surface Alloy.
Artificial lattices derived from assembled atoms on a surface using scanning tunneling microscopy present a platform to create matter with tailored electronic, magnetic, and topological properties. However, artificial lattice studies to date have focused exclusively on surfaces with weak spin-orbit coupling. Here, we illustrate the creation and characterization of quantum corrals from iron atoms on the prototypical Rashba surface alloy BiCu2, using low-temperature scanning tunneling microscopy and spectroscopy. We observe very complex interference patterns that result from the interplay of the size of the confinement potential, the intricate multiband scattering, and hexagonal warping from the underlying band structure. On the basis of a particle-in-a-box model that accounts for the observed multiband scattering, we qualitatively link the resultant confined wave functions with the contributions of the various scattering channels. On the basis of these results, we studied the coupling of two quantum corrals and the effect of the underlying warping toward the creation of artificial dimer states. This platform may provide a perspective toward the creation of correlated artificial lattices with nontrivial topology.


Effects of microgravity on growing cultured skin constructs.
Understanding the cellular, chemical, and physical responses of cells to stimuli is critical to successfully engineering tissue. The effect of culturing a living skin equivalent (LSE) in a submerged microgravity environment was investigated. LSEs were developed by culturing normal human epidermal keratinocyte (NHEK) on a submerged fibroblast and type 1 collagen gel matrix. Once formed, LSEs were brought up to the air/liquid interface, and after 4 days, the cultures were maintained in either (a) a normal air/liquid interface (S), (b) resubmerged in media (R), (c) folded on themselves to enclose the keratinized layer (F/R), or (d) cut into 2-4-mm fragments and suspended in a state of microgravity in a NASA-designed bioreactor (B). All groups were cultured for an average of 3 additional days. LSEs were processed for histologic evaluation. Skin cells were stained for cytokeratin to evaluate function. Images were digitally captured and processed for analysis. Parameters, including epithelial thickness, cellular areas, nuclear number, nuclear area, cytoplasmic area, and stained cytokeratin areas were measured. Removing the air/media interface significantly increased the number of NHEKs present in the skin; microgravity greatly enhanced this effect (p < 0.0001). No significant difference in cellular function as measured by protein expression [stained cytokeratin area (micro(2)) per cell] was found among the groups, though the ratio of nuclear area was significantly increased in all three groups as compared to the S group (p = 0.00227). In the case of the R and F/R groups, this appears due to the loss of the NHEK layer associated with those groups. Additionally, significant nuclear hypertrophy was demonstrated in the B group (p < 0.0001), and cellular hyperplasia was measured in all submerged groups as compared to static (p < 0.0001). Elimination of the air/liquid interface enhanced proliferation of keratinocytes. This effect was further enhanced in the presence of microgravity. No significant effect on cell function was noted with the use of this microgravity environment. We hypothesize that the increased epidermal contact plays a role in this proliferation. Microgravity is also associated with nuclear and cellular hypertrophy over and above that of the submersion methods.


In vitro studies of DNA damage caused by tricyclic antidepressants: a role of peroxidase in the side effects of the drugs.
Studies show that tricyclic antidepressants prescribed for migraines, anxiety, and child enuresis have numerous adverse effects in living cells. One of the undesired outcomes observed under treatment with these drugs is DNA damage. However, the mechanisms underlying damage have yet to be elucidated. We performed in vitro studies of the DNA damage caused by four tricyclic antidepressants: imipramine, amitriptyline, opipramol, and protriptyline. We focused particularly on the DNA damage aided by peroxidases. As a model of a peroxidase, we used horseradish peroxidase (HRP). At pH 7, reactions of HRP with excess hydrogen peroxide and imipramine yielded an intense purple color and a broad absorption spectrum with the maximum intensity at 522 nm. Reactions performed between DNA and imipramine in the presence of H(2)O(2) and HRP resulted in the disappearance of the DNA band. In the case of the other three drugs, this effect was not observed. Extraction of the DNA from the reaction mixture indicated that DNA is degraded in the reaction between imipramine and H(2)O(2) catalyzed by HRP. The final product of imipramine oxidation was identified as iminodibenzyl. We hypothesize that the damage to DNA was caused by an imipramine reactive intermediate.


Removal of massive subretinal organized blood clot with fragmatome.
The purpose of the study was to describe using fragmatome in removing subretinal organized blood clot in eyes of age-related macular degeneration and massive subretinal hemorrhage. This study was an interventional, consecutive case series. Patients with massive subretinal hemorrhage with total or subtotal retinal detachment from age-related macular degeneration and organized subretinal blood clot were managed by creating large retinectomy. The less organized blood was removed with vitrector. The subretinal organized blood clot was removed by fragmatome. The retina was reattached with perfluorocarbon liquid, and laser was applied at the margin of retinectomy. Silicon oil was infused at the end of surgery. All patients had subretinal blood totally or subtotally removed. The organized blood clot, which was difficult to be removed by vitrector was easily and efficiently removed by fragmatome. Visual acuity improved in all eyes, and retina was well attached under silicon oil. Fragmatome offers a more efficient way in removing organized blood clot, which will much shorten the duration of operation.


What does self-identified drug of choice tell us about individuals under community corrections supervision?
The term "drug of choice" (DOC) refers to substance abusers' preferred drug and this information often adds to the clinical picture of the patient because substance users often meet diagnostic criteria for dependence on multiple drugs. Characteristics such as age, race, marital status, and psychiatric illnesses have been shown to differentiate among individuals with different DOC preferences. However, no studies have examined DOC in the context of criminal behavior and other drug dependencies. The participants (N = 15,475) of a community corrections program, Treatment Alternatives for Safer Communities (TASC), were classified by DOC for the 4 main drugs of abuse (alcohol, marijuana, cocaine, and opioids) and each drug class was compared with the other 3 DOC using binary logistic regression. Alcohol as DOC was associated with being older, white, male, having private health insurance, being medicated for a mental health disorder, and having a criminal history of person offenses. Cocaine as DOC was associated with being older, black, female, attempting suicide, having less than a high school education, living in a shelter or with relatives, being unemployed, being uninsured, being physically and sexually abused, and committing property and court offenses but not person or substance offenses. Marijuana as DOC was associated with being younger, black, male, never being married, and committing substance but not property or court offenses. Opioids as DOC were associated with being white, female, being married, higher education, being unemployed, and being medicated for a mental health disorder. Overall, there were substantial differences between the 4 DOC groups, and the results are commensurate with expectations based on the abuse and dependency literature.


Interactions of [3H]amphetamine with rat brain synaptosomes. I. Saturable sequestration.
Previous studies have identified a saturable site of d-[3H]amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37 degrees C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. The saturation analysis and pharmacological characteristics of AMSEQ (i.e., low affinity and lack of stereospecificity) suggest that AMSEQ may be related to high dose, nonstereospecific effects of amphetamine, such as stereotypy in rats and psychosis in humans. The relative high potency of antidepressants in inhibiting AMSEQ suggests the importance of this phenomenon in the therapeutic effects of these drugs. Furthermore, the link between antidepressants and AMSEQ may provide insight into the comorbidity of major depression and drug abuse.


The prognostic value of cN-II and cN-III enzymes in adult acute myeloid leukemia.
We analyzed the expression of deoxycytidine kinase (dCK), UMP/CMP-kinase (UMP/CMP-K), nucleotide diphosphokinase (NDPK-B) and 5'-nucleotidases cN-II, cN-III, cdN and mdN by quantitative polymerase chain reaction at diagnosis in leukemic blasts from 96 patients with acute myeloid leukemia (AML) treated with ara-C. Our results show that high mRNA levels of cN-II and low mRNA levels of cN-III are correlated with a worse clinical outcome and suggest that these enzymes may have a role in sensitivity to ara-C in AML patients.


[Fungi and bacteria on air filters from heating, ventilation and air-conditioning systems: a method for determination of fungi and bacteria on air filters].
A method was developed for the determination of microorganism concentrations on air filters of HVAC systems, and the influence of different test parameters on the microbiological results was examined by considering various used air filters from several such systems. Microorganisms are detected by shaking air filter samples in fluid, where their concentration is then determined as surface cultures. Since varying the shaking time (30, 60, 90 min) had no influence on the quantitative microorganism determination, a shaking time of 60 minutes was chosen for detection of bacteria, yeasts and moulds. Incubation of blood agar plates either for 4 days at 20 degrees C +/- 2 degrees C or for 2 days at 36 degrees C +/- 1 degree C yielded identical concentrations of bacteria and yeasts. Since results obtained with malt extract agar and Czapek-Dox agar are comparable, one of the two culture media is sufficient for the quantitative determination of moulds on air filters. For statistical evaluation, the inoculation of three parallel agar plates per growth medium was found to be adequate, and the arithmetic mean and the median proved to be equivalent. Investigation on the detection rate showed that, on the average, the method developed demonstrated 80% of the microorganisms detectable on an air filter sample. Thus a simple method is available for quantitative determination of microorganisms on air filters.


Tempo is the key.
Walking flies find the source of attractive odors by changing how frequently they stop and turn in response to the smell.


Dynamic Partitioning of Synaptic Vesicle Pools by the SNARE-Binding Protein Tomosyn.
Neural networks engaged in high-frequency activity rely on sustained synaptic vesicle recycling and coordinated recruitment from functionally distinct synaptic vesicle (SV) pools. However, the molecular pathways matching neural activity to SV dynamics and release requirements remain unclear. Here we identify unique roles of SNARE-binding Tomosyn1 (Tomo1) proteins as activity-dependent substrates that regulate dynamics of SV pool partitioning at rat hippocampal synapses. Our analysis is based on monitoring changes in distinct functionally defined SV pools via V-Glut1-pHluorin fluorescence in cultured hippocampal neurons in response to alterations in presynaptic protein expression. Specifically, we find knockdown of Tomo1 facilitates release efficacy from the Readily Releasable Pool (RRP), and regulates SV distribution to the Total Recycling Pool (TRP), which is matched by a decrease in the SV Resting Pool. Notably, these effects were reversed by Tomo1 rescue and overexpression. Further, we identify that these actions of Tomo1 are regulated via activity-dependent phosphorylation by cyclin-dependent kinase 5 (Cdk5). Assessment of molecular interactions that may contribute to these actions identified Tomo1 interaction with the GTP-bound state of Rab3A, an SV GTPase involved in SV targeting and presynaptic membrane tethering. In addition, Tomo1 via Rab3A-GTP was also observed to interact with Synapsin 1a/b cytoskeletal interacting proteins. Finally, our data indicate that Tomo1 regulation of SV pool sizes serves to adapt presynaptic neurotransmitter release to chronic silencing of network activity. Overall, the results establish Tomo1 proteins as central mediators in neural activity-dependent changes in SV distribution among SV pools. Although information transfer at central synapses via sustained high-frequency neural activity requires coordinated synaptic vesicle (SV) recycling, the mechanism(s) by which synapses sense and dynamically modify SV pools to match network demands remains poorly defined. To advance understanding, we quantified SV pool sizes and their sensitivity to neural activity while altering Tomo1 expression, a putative regulator of the presynaptic Readily Releasable Pool. Remarkably, we find Tomo1 actions to extend beyond the Readily Releasable Pool to mediate the Total Recycling Pool and SV Resting Pool distribution, and this action is sensitive to neural activity through Cdk5 phosphorylation of Tomo1. Moreover, Tomo1 appears to exert these actions through interaction with Rab3A-GTP and synapsin proteins. Together, our results argue that Tomo1 is a central mediator of SV availability for neurotransmission.


Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient improves the branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia: a prospective study.
The present study aimed to elucidate the effect of switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient in patients with cirrhosis with hypoalbuminemia. Twenty-six patients with cirrhosis with hypoalbuminemia despite treatment with branched-chain amino acid granules containing 12 g of branched-chain amino acid were enrolled in the prospective study. The branched-chain amino acid-enriched nutrient and control groups were composed of 16 and 10 patients, respectively. The patients in branched-chain amino acid-enriched nutrient group switched to branched-chain amino acid-enriched nutrient mixture containing 12.2 g of branched-chain amino acid and 410 kcal with a half of it consumed as a late evening snack, and the patients in the control group continued branched-chain amino acid granules. Laboratory data related to nutrition parameter were assessed at baseline, 3 months after baseline, and at 6 months after baseline. Two patients were withdrawn; hence, nine and 15 patients in the branched-chain amino acid granules and branched-chain amino acid-enriched nutrient groups, respectively, were subjected to full analysis. Serum albumin levels and total lymphocyte counts in both groups did not change in the study period. The branched-chain amino acid-to-tyrosine ratio in the branched-chain amino acid-enriched nutrient group significantly increased from baseline to 6 months after baseline (P = 0.030), whereas that in the control group did not increase. Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrients improves branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia.


Limited role of nuclear receptor Nur77 in Escherichia coli-induced peritonitis.
Nuclear receptor Nur77 (NR4A1, TR3, or NGFI-B) has been shown to play an anti-inflammatory role in macrophages, which have a crucial function in defense against peritonitis. The function of Nur77 in Escherichia coli-induced peritoneal sepsis has not yet been investigated. Wild-type and Nur77-knockout mice were inoculated with E. coli, and bacterial outgrowth, cell recruitment, cytokine profiles, and tissue damage were investigated. We found only a minor transient decrease in bacterial loads in lung and liver of Nur77-knockout compared to wild-type mice at 14 h postinfection, yet no changes were found in the peritoneal lavage fluid or blood. No differences in inflammatory cytokine levels or neutrophil/macrophage numbers were observed, and bacterial loads were equal in wild-type and Nur77-knockout mice at 20 h postinfection in all body compartments tested. Also, isolated peritoneal macrophages did not show any differences in cytokine expression patterns in response to E. coli. In endothelial cells, Nur77 strongly downregulated both protein and mRNA expression of claudin-5, VE-cadherin, occludin, ZO-1, and β-catenin, and accordingly, these genes were upregulated in lungs of Nur77-deficient mice. Functional permeability tests pointed toward a strong role for Nur77 in endothelial barrier function. Indeed, tissue damage in E. coli-induced peritonitis was notably modulated by Nur77; liver necrosis and plasma aspartate aminotransferase (ASAT)/alanine aminotransferase (ALAT) levels were lower in Nur77-knockout mice. These data suggest that Nur77 does not play a role in the host response to E. coli in the peritoneal and blood compartments. However, Nur77 does modulate bacterial influx into the organs via increased vascular permeability, thereby aggravating distant organ damage.


Modulation of cardiac growth and development by HOP, an unusual homeodomain protein.
We have discovered an unusual homeodomain protein, called HOP, which is comprised simply of a homeodomain. HOP is highly expressed in the developing heart where its expression is dependent on the cardiac-restricted homeodomain protein Nkx2.5. HOP does not bind DNA and acts as an antagonist of serum response factor (SRF), which regulates the opposing processes of proliferation and myogenesis. Mice homozygous for a HOP null allele segregate into two phenotypic classes characterized by an excess or deficiency of cardiac myocytes. We propose that HOP modulates SRF activity during heart development; its absence results in an imbalance between cardiomyocyte proliferation and differentiation with consequent abnormalities in cardiac morphogenesis.


Lipoproteins and atherosclerosis in children: an early marriage?
Describe the relationship between serum lipoproteins and the development of atherosclerosis in young subjects aged 15-34 years, and discuss the implications for prevention of coronary heart disease. Data from gross and microscopic evaluation of aorta and coronary arterial specimens as part of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study demonstrates that by the age of 15 years, all subjects have atherosclerosis. Lipoprotein risk factors for coronary heart disease are associated with the extent and prevalence of gross aortic and coronary atherosclerosis and with the development of microscopic coronary plaques that have qualities consistent with clinically significant lesions. Association of lipoprotein risk factors with intermediate type atherosclerotic lesions becomes evident in subjects in their late teens, whereas associations with raised lesions become evident in subjects greater than 25 years of age, consistent with a transitional role of intermediate lesion in the formation of advanced plaques. Atherosclerosis begins in childhood and a significant number of young people have advanced coronary artery plaques. Early atherosclerosis is accelerated by lipoprotein risk factors. Thus, long-range prevention of atherosclerosis should begin in childhood and should include measures to control hyperlipidemia.


Conformational analysis of geometric isomers of pitavastatin together with their lactonized analogues.
Super-statins are synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is the rate-limiting enzyme responsible for the biosynthesis of cholesterol. All of the super-statins with a C=C double bond spacer between the heterocyclic and the dihydroxycarboxylic moiety that are currently on the market exist as E-isomers. To extend the understanding of conformational and thermodynamic preferences of Z-isomeric super-statin analogues, this study focused on analyzing pitavastatin and its lactonized derivatives via NMR spectroscopy and ab initio calculations. Z-isomeric pitavastatin analogues exist in solution as a pair of interconverting rotamers, where the Gibbs free energies between the major and minor rotamers are within 0.12 and 0.25 kcal mol-1 and the rotational energy barriers are between 15.0 and 15.9 kcal mol-1. The analysis of long-range coupling constants and ab initio calculations revealed that rotation across the C5'-C7 single bond is essential for generating a pair of atropisomers. The overall comparison of the results between Z-isomeric pitavastatin and rosuvastatin analogues demonstrated that the former are to some extent more flexible to attain numerous conformations. Demonstrating how structural differences between super-statin analogues induce distinctive conformational preferences provides important insight into the super-statins' conformational variability and may well improve future drug design.


Note: development of ESS Bilbao's proton ion source: Ion Source Hydrogen positive.
The Ion Source Hydrogen positive is a 2.7 GHz off-resonance microwave discharge ion source. It uses four coils to generate an axial magnetic field in the plasma chamber around 0.1 T that exceeds the ECR resonance field. A new magnetic system was designed as a combination of the four coils and soft iron in order to increase the reliability of the source. The description of the simulations of the magnetic field and the comparison with the magnetic measurements are presented. Moreover, results of the initial commissioning of the source for extraction voltage until 50 kV will be reported.


Development of the gut microbiota in healthy twins during the first 2 years of life and associations with body mass index z-score: Results from the Wuhan twin birth cohort study.
The gut microbiota undergoes rapid and vital changes to microbial community structure and the microbial-immune crosstalk during the first 3 years of life, which is thought to be involved in the pathobiology of later-life disease. Compared to single-born children, little is known about the gut microbiota of twins in early childhood. Based on the Wuhan Twin Birth Cohort study, 344 stool samples from 204 twin families were analyzed to investigate the difference in gut microbiota composition at 6, 12, and 24 months of age. Furthermore, this study evaluated the association between gut microbiota development curves and body mass index z-score (BMI_Z) curves at 6, 12, and 24 months of age. The predominant microbiota phyla identified in twins were Proteobacteria, Actinobacteriota, Firmicutes, Bacteroidota, and Verrucomicrobiota. The richness and diversity of gut microbiota increased from 6 to 24 months old (alpha diversity with p < 0.05). Beta diversity revealed 61 gut microbiota genera that were significantly different in relative abundance among the three age groups. Among the 61 gut microbiota genera, 30 distinct trajectory curves (DTCs) were generated by group-based trajectory models after log2 transformation of their relative abundance. Subsequently, Spearman correlation analysis revealed that only five gut microbiota DTC were correlated with the BMI_Z DTC. Therefore, we further examined the association between the five gut microbiota genera DTC and BMI_Z DTC using generalized estimation equation models. The results revealed a significant association between the DTC groups of Parabacteroides and that of BMI_Z (coefficient = 0.75, p = 0.04). The results of this study validated the hypothesis that the richness and diversity of gut microbiota developed with age in twins. Moreover, participants with a higher DTC of log2-transformed Parabacteroides had a higher BMI_Z DTC during the first 2 years of life. Further studies are needed to confirm the association between Parabacteroides and BMI_Z in other populations.


Helicobacter pylori eradication for peptic ulceration: an observational study in a Scottish primary care setting.
Despite being established for the treatment of peptic ulcer (PU) disease, few studies have assessed the long-term effectiveness and economic benefits of Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate the effect of community based Hp eradication for patients with chronic peptic ulcer disease requiring maintenance acid suppression. The endpoints used were the patients dyspeptic symptoms and the requirement for the prescription of maintenance acid suppression therapy. The study area covered seven general practices in the Glasgow area. Patients with previously diagnosed peptic ulcer disease receiving prescribed acid suppression therapy were invited to a dyspepsia clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive patients received Hp eradication therapy and were reviewed six weeks later. At six months a review of practice records was carried out, and two years after eradication a postal questionnaire was sent to participating patients. A total of 243 patients attended the initial clinic of which 81.9% were HRBT positive. 156 of 196 patients offered Hp eradication re-attended at six weeks. The per protocol eradication rate was 91.7%. After six months patients who had received eradication therapy were less likely to require maintenance acid suppression therapy compared with those to whom eradication was not given. Two years after treatment 76.5% of patients felt their symptoms were improved, but 42.2% were still receiving maintenance therapy. The estimated cost of treatment per month per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In conclusion we felt that community based Hp eradication for patients with chronic PU disease is effective, however it does not completely alleviate dyspepsia. Predictors of symptomatic response or of no longer requiring acid suppression therapy after two years were younger age of onset of PU disease and absence of pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication improves patients symptoms, reduces the requirement for maintenance acid suppression and is cost-effective after two years follow-up in this targeted group.


Growth pattern trajectories in boys with Duchenne muscular dystrophy.
The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD). We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.


Temporal Dynamics and Spatial Variation of Azoxystrobin and Propiconazole Resistance in Zymoseptoria tritici: A Hierarchical Survey of Commercial Winter Wheat Fields in the Willamette Valley, Oregon.
Fungicide resistance can cause disease control failure in agricultural systems, and is particularly concerning with Zymoseptoria tritici, the causal agent of Septoria tritici blotch of wheat. In North America, the first quinone outside inhibitor resistance in Z. tritici was discovered in the Willamette Valley of Oregon in 2012, which prompted this hierarchical survey of commercial winter wheat fields to monitor azoxystrobin- and propiconazole-resistant Z. tritici. Surveys were conducted in June 2014, January 2015, May 2015, and January 2016. The survey was organized in a hierarchical scheme: regions within the Willamette Valley, fields within the region, transects within the field, and samples within the transect. Overall, frequency of azoxystrobin-resistant isolates increased from 63 to 93% from June 2014 to January 2016. Resistance to azoxystrobin increased over time even within fields receiving no strobilurin applications. Propiconazole sensitivity varied over the course of the study but, overall, did not significantly change. Sensitivity to both fungicides showed no regional aggregation within the Willamette Valley. Greater than 80% of spatial variation in fungicide sensitivity was at the smallest hierarchical scale (within the transect) of the survey for both fungicides, and the resistance phenotypes were randomly distributed within sampled fields. Results suggest a need for a better understanding of the dynamics of fungicide resistance at the landscape level.


Edible oleogels as solid fat alternatives: Composition and oleogelation mechanism implications.
The growing awareness of the adverse health effects of trans-fats and saturated fats are driving researchers to seek healthy alternatives. A promising strategy to structure liquid oil, called oleogelation, has been a subject of great interest. In the development of oleogels, highly unsaturated oils can be structured through different gelation mechanisms by varying structuring agents (e.g., polymeric or low molecular weight oleogelators). Due to their potential to reduce saturated fat in food products while also providing solid texture without changing the oil's chemical composition and nutritional values, oleogels have been introduced into various products (meat, spread, and confectionary) as alternatives to traditional solid fats. However, the shortcomings of oleogels cannot be ignored, such as the softer texture and the poorer plasticity than traditional solid fat. As the physicochemical properties and functionalities of oleogels are highly dependent on their composition and structuring mechanism, it is possible to obtain a product with desirable functionality by choosing a suitable oleogelator or oil phase. Thus, comprehensive and detailed knowledge regarding the role of oleoglarors, oil phase, and oleogelation mechanism on oleogelation is needed. This review primarily focuses on published information within the last decades addressing how the composition and oleogelation mechanism affect the structure and functionality of oleogels and oleogel-based products. The factors affecting the oil gelation are summarized concerning three aspects: (i) oleogelator (chemical composition and molecular structure); (ii) oil phase (TAG composition and minor component); and (iii) oleogelation mechanism. Finally, the future perspectives toward oleogels are highlighted. This review aims to deepen the understanding of oleogelation and the rational design of oleogel-based products.


Comparative study between pap smear and visual inspection with acetic acid (via) in screening of CIN and early cervical cancer.
Cervical cancer is the second most common among women globally. In most cases of Assam, Ca Cervix is detected late due to lack of effective screening programme. To screen the patient at Gynaecology OPD at the age 18-60 yrs by doing pap smear, VIA (Visual Inspection with Acetic Acid) and to detect sensitivity and specificity for detecting CIN and early Ca Cervix. It is a cross sectional study of 300 women (18- 60 yrs) who fulfill selection criteria. The pap smear and VIA are done in these cases. In positive cases, cervical biopsy and histopathological studies are done, The sensitivity and specificity of each test are determined and compared. The positive result detected from cytology are 22, VIA was positive in 52 cases. The histology of 19 cases are suggestive of CIN and Ca Cervix. The findings were compared with other studies and evaluated. The most common finding in per speculum examination is cervical erosion. The sensitivity of VIA is 89% (versus pap smear-52%) the specificity of VIA is 87% (versus pap smear-95%). The accuracy VIA is 87% compared to pap smear-93%. The lack of effective and implementable screening programme lead to reporting of advanced cases of Ca Cervix. If detected at CIN or early Ca cervix stage, effective treatment can be provided with encouraging results. Therefore effective & implementable Ca Cervix screening need to be provided in our country.


Triple X Egyptian woman and a Down's syndrome offspring.
The 47, XXX karyotype (triple X) has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. Female patients with a sex chromosome abnormality may be fertile. In patients with a 47, XXX cell line there appears to be an increased risk of a cytogenetically abnormal child but the extent of this risk cannot yet be determined; it is probably lower in the non-mosaic 47, XXX patient than the mosaic 46, XX/47, XXX one. We describe a new rare case of triple X woman and a Down's syndrome offspring. The patient is 26 years of age. She is a housewife, her height is 160 cm and weight is 68 kg and her physical features and mentality are normal. She has had one pregnancy at the age of 25 years resulted in a girl with Down's syndrome. The child had 47 chromosomes with trisomy 21 (47, XX, +21) Figure 1. The patient also has 47 chromosomes with a triple X karyotype (47, XX, +X) Figure 2. The patient's husband (27 years old) is physically and mentally normal. He has 46 chromosomes with a normal XY karyotype (46, XY). There are neither Consanguinity between her parent's nor she and her husband.


Dietary protein, as egg albumen: effects on bone composition, zinc bioavailability and zinc requirements of rats, assessed by a modified broken-line model.
The effect of dietary protein concentration on zinc bioavailability, requirements and incorporation into bones was investigated in growing rats. Zinc requirements were determined by the broken-line method. Protein did not affect either absorption or biological half-life of 65Zn added to the diet. Zinc requirements based on weight gain or tibia zinc were generally greater when rats were fed 30% rather than 15% egg white. When fed 30% rather than 15% egg white, zinc-deficient rats gained less weight and tended to incorporate less zinc into bone, whereas zinc-adequate rats gained weight similarly and incorporated more zinc into bone. Dietary protein concentration apparently elevated the maximum amount of zinc incorporated into bones of rats fed adequate zinc. When dietary zinc was adequate (25 mg/kg diet), tibia zinc concentrations increased linearly with dietary concentrations of 15, 25, 35 and 45% egg white. When dietary zinc was adequate, higher protein diets resulted in lower tibia nitrogen, and higher tibia zinc, without substantial changes in tibia size or calcium concentration. These results indicate that high protein diets increase zinc requirements and bone zinc deposition, the latter being a consequence of altered bone zinc metabolism, rather than improved zinc bioavailability.


[Retinal detachment after surgery of the anterior segment using the pars plana approach].
Anterior segment surgery via the pars plana was done on 114 eyes with the Klöti vitreous stripper between January, 1977 and December 31, 1982. In every case the posterior capsule was removed when present and anterior or total vitrectomy was performed. None of the 114 eyes had a history of retinal detachment prior to nor at the time of anterior segment surgery. There were 37 cases of trauma in this series. Follow-up varied from 1 to 66 months with 58% of cases having a follow-up of greater than one year. There was a 10.50% post-operative retinal detachment rate (12/114 eyes). Seven detachments occurred in the 37 traumatized eyes (19.10%) versus 5 detachments in 77 non-traumatized eyes (6.49%). Of the 12 detachments, 7 presented signs of severe proliferative vitreoretinopathy (PVR) while the remaining 5 detachments appeared to be uncomplicated. No detachment was related to an iatrogenic tear and no case of PVR seemed to be related to the sclerotomy site. Successful reattachment was achieved in 3 out of 4 uncomplicated cases and 3 out of 5 cases with PVR. Vitrectomy and posterior capsulectomy are often mandatory in anterior segment problems: pupillary membranes, secondary cataracts, lens ectopiae and dislocations, vitreous wick and vitreocorneal touch. In our opinion other indications for vitrectomy and posterior capsulectomy are congenital, juvenile and post-uveitis cataracts.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of cell-cell adhesion of MDCK cells by Cdc42 and Rac1 small GTPases.
Rac1, a member of the Rho small GTPases family, has recently been shown to be involved in the regulation of cell-cell adhesion mediated by cadherin. Here we showed that Cdc42, another member of Rho family, accumulated at cell-cell contact sites. Microinjection of Rho GDI, a negative regulator of the Rho family members, into Madin-Darby canine kidney (MDCK) cells resulted in perturbation of epithelial cell morphology and of cell-cell and cell-substratum adhesions, and comicroinjection of dominant active Cdc42 or Rac1 reversed the action of Rho GDI, suggesting that the active form of Cdc42 or Rac1 is required for maintaining the cell-cell and cell-substratum adhesions. These observations suggest that Cdc42, in addition to Rac1, can regulate the cell-cell adhesion.


De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.
Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome. Genomic DNA from 13 patients with classic manifestations of NOMID/CINCA syndrome and their available parents was screened for CIAS1 mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real-time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme-linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic-adherent peripheral blood mononuclear cells. In 6 of the 13 patients, we found 6 heterozygous missense substitutions in CIAS1. Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of >900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation-positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with the recently discovered role of CIAS1 in the regulation of interleukin-1 (IL-1), we found evidence of increased IL-1beta, as well as tumor necrosis factor, IL-3, IL-5, and IL-6, but not transforming growth factor beta, in a mutation-positive patient compared with normal controls. Our data increase the total number of known germline mutations in CIAS1 to 20, causing a spectrum of diseases ranging from familial cold autoinflammatory syndrome to Muckle-Wells syndrome to NOMID/CINCA syndrome. Mutations in CIAS1 were only found in approximately 50% of the cases identified clinically as NOMID/CINCA syndrome, which raises the possibility of genetic heterogeneity. IL-1 regulation by CIAS1 suggests that IL-1 receptor blockade may constitute a rational approach to the treatment of NOMID/CINCA syndrome.


Synthesis of Trifluoromethylated Tetrasubstituted Allenes via Palladium-Catalyzed Carbene Transfer Reaction.
Herein, we report on the palladium-catalyzed synthesis of trifluoromethylated, tetrasubstituted allenes from vinyl bromides and trifluoromethylated diazoalkanes in good to excellent yield. This reaction proceeds via oxidative addition of a Pd(0) complex with vinyl bromide. Subsequent base-promoted reductive elimination generates the allene. This methodology provides an efficient strategy even on gram scale to valuable trifluoromethylated, tetrasubstituted allenes under mild reaction conditions. The allene products can be used in acid catalyzed cyclization reactions to give trifluoromethylated indene products.


Evaluation of the Determination of Dabigatran, Rivaroxaban, and Apixaban in Lupus Anticoagulant-Positive Patients.
The effect of direct oral anticoagulants (DOAC) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa, is a well-known problem and can cause both false positive and negative results. In particular, the situation in patients who develop lupus anticoagulant (LA) antibodies is highly complex. To evaluate the effectiveness of DOAC therapy in lupus-positive patients, 31 samples were enrolled in this retrospective study. All patient samples were spiked with three types of DOAC (dabigatran, DABI; rivaroxaban, RIVA; and apixaban, API) in a concentration that significantly influenced the screening test for LA and thus can mask the presence of LA. Subsequently, the DOAC was always unbound by the DOAC-Stop procedure. DOAC levels before and after binding were determined by functional assays, followed by liquid chromatography coupled with mass spectrometry (LC-MS) analysis. The determination of DOAC levels was performed by direct thrombin assay and determination of anti-Xa activity with specific calibration as functional tests for DABI and xabans (API and RIVA). To determine concentration levels of API, DABI, and RIVA, our in-house LC-MS method was used. The results of LA-positive samples show significant differences between functional tests and the LC-MS method both before and after DOAC binding. The acute findings of the presence of LA-type antibodies fundamentally affects the determination of DOAC by functional tests, and in this case, it is necessary to use LC-MS analysis to determine the true value. If patients treated with DOAC develop LA of medium and higher titers, we do not recommend checking DOAC levels with functional tests.


The incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer.
Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma. Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin. Slides were interpreted by two pathologists and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Patient demographics, clinicopathologic factors, and follow-up data were abstracted. Fifty-one patients were included in our study. Most patients had stage IA (84%) tumors of grade 2/3 histology (51%), and 11 patients (22%) received adjuvant therapy. Mean number of lymph nodes was 12.2 per patient. Of 151 lymph node paraffin blocks evaluated for pancytokeratin, only two (1.3%) had IHC-positive micrometastases. The two lymph node-positive results occurred in separate patients, leading to 3.9% of all patients in our cohort. Both micrometastatic lymph node-positive patients had adjuvant radiation therapy for uterine high-risk factors and are currently without evidence of disease at 15 and 16 months, respectively. Three lymph node-negative patients (6.1%) have developed recurrences within a median follow-up of 15 months. The incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancer and does not justify routine IHC staining. Additionally, as little evidence exists to support the clinical significance of IHC-stained micrometastases in endometrial cancer, further study is warranted.


Recent developments in population policy in Australia: the demographic setting.
"The major parties [in Australia] are moving away from an exclusive pre-occupation with immigration to a broader focus on population policy and the Minister for Immigration has expressed an implicit preference for a population of 23 million. The contributions in this section of People and Place document his concerns together with those of the shadow Minister. They also provide demographic analyses which show that the Minister's goal will be hard to achieve. This is largely because of the exceptionally high migration of the Hawke years."


The impact of intensity-modulated radiation treatment on dento-alveolar microvasculature in pharyngeal cancer implant patients.
Dental rehabilitation post-radiotherapy often requires the consideration of dental implants. However, these are tentatively prescribed due to the concern of hypovascularisation and possible osteoradionecrosis. Hence, the current study assessed the microvasculature of the dento-alveolar bone at implant sites taking into consideration the exact radiotherapy dose received to the region. Bone cores were taken from nine patients during implant treatment and compared to nine control patients. Specimens were stained using CD31 and digitalised using a high-resolution scanner for qualitative and quantitative assessment of the microvasculature. Monaco® treatment planning system was used to volume the implant site providing mean dose (Dmean ) and maximum dose (Dmax ). A total of 23 bone cores were retrieved for analysis. The cohort had a Dmean of 38.4 Gy (59.6-24.3 Gy). Qualitative analysis identified a clear reduction in the miniscule terminal capillaries and high incidence of obliterated lumens with increasing radiotherapy. Microvasculature density of irradiated patients was markedly reduced (P = .0034) compared to the control group with an inverse correlation to RT doses (P < .0001). Specifically, doses up to 30 Gy appear to preserve sufficient vascularisation (~77% in comparison with control) and tissue architecture. By contrast, exposure to higher doses 40%-61% of the micro-vessels were lost. Intensity-modulated radiotherapy doses above 30 Gy identified reduction in microvasculature which is a lower threshold than previously accepted. In pharyngeal cancer patients' doses to the jaw bones often exceed this threshold. Coupled with favourable survival in certain oropharyngeal and nasopharyngeal cancer, dental rehabilitation via implants provides a significant clinical challenge.


Inactivity of 3-methyleneoxindole as mediator of auxin action on cell elongation.
The recently reported growth-promoting ability of 3-methyl-eneoxindole was examined in order to test the hypothesis that indole-3-acetic acid acts as a growth promoter only after oxidative conversion to 3-methyleneoxindole. Methyleneoxindole was synthesized from indole-3-acetic acid and N-bromosuccinimide, and its identity was confirmed by ultraviolet absorption, infrared absorption, mass spectrometry, and melting point. Methyleneoxindole was found to lack growth-promoting activity in coleoptile and pea (Pisum sativum) stem segments. Chlorogenic acid, an inhibitor of the oxidation of indole-3-acetic acid, was found to have no inhibitory effect on growth promotion by indole-3-acetic acid. It is concluded that 3-methyleneoxindole is inactive as a growth promoter and therefore does not mediate the action of auxin on cell elongation.


Genomic insights into the evolution of the critically endangered soft-shelled turtle Rafetus swinhoei.
The 2019 death of the female Swinhoes soft-shelled turtle (Rafetus swinhoei) individual in China put this species in a dire conservation state. To avoid the loss of genetic information from the female individual and facilitate the protection and preservation of R. swinhoei, we sequenced and assembled its draft chromosome-level genome by combining BGISEQ short reads, Nanopore long reads, and Hi-C sequencing reads. We characterized its potential ZZ/ZW sex determination system. Phylogeny and divergence time analyses indicated that R. swinhoei has a close relationship with Pelodiscus sinensis, and they shared a common ancestor ~54.4 Ma. Population history analyses indicated that R. swinhoei has the lowest heterozygosity among all turtles examined, and its population size has declined dramatically over the past 10 million years. Many core genes involved in autophagy and DNA damage response, such as Rab5a and Parp1, were under positive selection and/or evolving rapidly, and these genes may make important contributions to the long lifespan and evolutionary adaptation of R. swinhoei. The loss of several tooth-related genes in turtle genomes explains the genetic basis of their toothless phenotype. This study not only provides a genomic resource for scientists to study the species using the strategy of comparative genomics, but also provides a data basis for us to find more potential R. swinhoei individuals in the wild.


On the homogeneous structure found in the system of the population of cities in Japan.
The author applies Auerbach and Zipf's rank-size rule for the population of cities to data for the nine regions of Japan for 1960, 1965, 1970, and 1975. The rule is successfully applied, and the author concludes that "the system of population of cities in Japan was so homogeneous that the distribution of the population in cities in each of the regions of this country could be described by this same rank-size rule." Some theoretical considerations concerning the rank-size rule are also discussed. (summary in JPN)


Permanency analysis on human electroencephalogram signals for pervasive Brain-Computer Interface systems.
Brain-Computer Interface (BCI) systems use some permanent features of brain signals to recognize their corresponding cognitive states with high accuracy. However, these features are not perfectly permanent, and BCI system should be continuously trained over time, which is tedious and time consuming. Thus, analyzing the permanency of signal features is essential in determining how often to repeat training. In this paper, we monitor electroencephalogram (EEG) signals, and analyze their behavior through continuous and relatively long period of time. In our experiment, we record EEG signals corresponding to rest state (eyes open and closed) from one subject everyday, for three and a half months. The results show that signal features such as auto-regression coefficients remain permanent through time, while others such as power spectral density specifically in 5-7 Hz frequency band are not permanent. In addition, eyes open EEG data shows more permanency than eyes closed data.


A Morphometric Study of the Internal Thoracic Artery and Its Branches.
The clinical importance of the internal thoracic arteries in procedures such as coronary artery bypass grafting, transverse rectus abdominis myocutaneous flaps and minimal incision direct coronary artery bypass surgery is well appreciated. The broad clinical utilization of the internal thoracic artery including the role of its branches in supplying blood to the sternum requires explicit anatomical knowledge of the vessel. The internal thoracic artery and its branches are known to exhibit morphological variations for different ethnic groups. Few studies have provided information regarding structural details and patterns of artery and its branches. The present morphometric study was conducted during year 2019. The internal thoracic artery and its branches were dissected and observed on 100 embalmed adult human cadavers of either sex (200 thoracic halves). The origin, diameter at origin and length of the artery were noted. The branching pattern and variations in branching blueprint were documented in this pioneer study. Mean length of branches of artery and mean distance between anterior intercostal arteries was quantified in this pioneer study. Sternal branches were observed in 87% instances on right side. Incidence of pericardiophrenic branches was 90% cases on left side. The origin of pericardiophrenic artery was found to be in 3rd or 4th intercostal space. The incidence of anterior intercostal arteries arising from musculophrenic artery was 73%. A detailed realization of this branching pattern would definitely allow prevention of sternal necrosis and improve prognosis in internal thoracic artery surgical mobilizations. The quantification of diameter at origin in North Indians would aid in determining central venous pressure, introducing pacemaker and administrating drugs in emergency.


Common elements in self-management of HIV and other chronic illnesses: an integrative framework.
HIV/AIDS is widely recognized as a chronic illness within HIV care, but is often excluded from chronic disease lists outside the field. Similar to other chronic diseases, HIV requires lifetime changes in physical health, psychological functioning, social relations, and adoption of disease-specific regimens. The shift from acute to chronic illness requires a self-management model in which patients assume an active and informed role in healthcare decision making to change behaviors and social relations to optimize health and proactively address predictable challenges of chronic diseases generally and HIV specifically. This article reviews literature on chronic disease self-management to identify factors common across chronic diseases, highlight HIV-specific challenges, and review recent developments in self-management interventions for people living with HIV (PLH) and other chronic diseases. An integrated framework of common elements or tasks in chronic disease self-management is presented that outlines 14 elements in three broad categories: physical health; psychological functioning; and social relationships. Common elements for physical health include: a framework for understanding illness and wellness; health promoting behaviors; treatment adherence; self-monitoring of physical status; accessing appropriate treatment and services; and preventing transmission. Elements related to psychological functioning include: self-efficacy and empowerment; cognitive skills; reducing negative emotional states; and managing identity shifts. Social relationship elements include: collaborative relationships with healthcare providers; social support; disclosure and stigma management; and positive social and family relationships. There is a global need to scale up chronic disease self-management services, including for HIV, but there are significant challenges related to healthcare system and provider capacities, and stigma is a significant barrier to HIV-identified service utilization. Recognizing that self-management of HIV has more in common with all chronic diseases than differences suggests that the design and delivery of HIV support services can be incorporated into combined or integrated prevention and wellness services.


Spatial variation in 2-methyl-4-chlorophenoxyacetic acid mineralization and sorption in a sandy soil at field level.
The phenoxyacetic acid herbicide MCPA (2-methyl-4-chlorophenoxyacetic acid) is frequently detected in groundwater beneath Danish agricultural fields. We investigated spatial variation in microbial MCPA mineralization potential in a flat agricultural field of fine sandy soil (USDA classification: Humic Dystrudept) located on the Yoldia plains of Northern Jutland, Denmark. Samples for determination of MCPA mineralization and sorption were collected from the Ap and Bs horizons at 51 sampling sites located in a 200 x 220 m grid. Spatial variation in sorption was low in both horizons (distribution coefficient, 0.36-4.16 L kg(-1)). Sorption correlated strongly with soil organic carbon content in both horizons (CV, 93 and 83%, respectively) and negatively with soil pH. [Ring-(14)C]-MCPA mineralized readily in the Ap horizon, with 49 to 62% of the (14)C-MCPA being converted to (14)CO(2) during the 67-d incubation period. With the subsoil, mineralization of (14)C-MCPA varied considerably between samples (0.5-72.8%). At neither depth was there correlation between (14)C-MCPA mineralization and sorption, soil pH, organic carbon content, clay content, number of colony-forming units (CFU), pseudomonad CFU, or any of the four microbial activity parameters measured. The presence of microbial genes encoding for the TfdA enzyme was quantified using real-time polymerase chain reaction. No correlation was found between MCPA mineralization potential and the natural background number of tfdA genes present in the soil samples. The degradation kinetics suggests that the high (14)C-MCPA mineralization rate detected in soil samples was linked to growth of the MCPA-degrading soil microbial community.


Comparative Proteomics Analysis Identifies Cdc42-Cdc42BPA Signaling as Prognostic Biomarker and Therapeutic Target for Colon Cancer Invasion.
Metastasis is one of the major causes of treatment failure in the patients with colon cancer. The aim of our study is to find key proteins and pathways that drive invasion and metastasis in colon cancer. Eight rounds of selection of cancer cells invading through matrigel-coated chamber were performed to obtain highly invasive colon cancer sublines HCT116-I8 and RKO-I8. Stable Isotope Labeling by Amino Acids in Cell Culture technology was used to identify the differently expressed proteins, and the proteomics data were analyzed by ingenuity pathway analysis. PAK1-PBD immunoprecipitation combined with Western blot were carried out to determine Cdc42 activity, and qRT-PCR and Western blot were used to determine gene expression. The functional role of Cdc42BPA and Cdc42 pathway in colon cancer invasion was studied by loss-of-function experiments including pharmacological blockade, siRNA knockdown, chamber invasion, and WST-1 assays. Human colon cancer tissue microarray was analyzed by immunohistochemistry for overexpression of Cdc42BPA and its correlation with clinicopathological parameters and patient survival outcomes. HCT116-I8 and RKO-I8 cells showed significantly stronger invasive potential as well as decreased E-cadherin and increased vimentin expressions compared with parental cells. The differently expressed proteins in I8 cells compared with parental cells were identified. Bioinformatics analysis of proteomics data suggested that Cdc42BPA protein and Cdc42 signaling pathway are important for colon cancer invasion, which was confirmed by experimental data showing upregulation of Cdc42BPA and higher expression of active GTP-bound form of Cdc42 in HCT116-I8 and RKO-I8 cells. Functionally, pharmacological and genetic blockade of Cdc42BPA and Cdc42 signaling markedly suppressed colon cancer cell invasion and reversed epithelial mesenchymal transition process. Furthermore, compared with adjacent normal tissues, Cdc42BPA expression was significantly higher in colon cancer tissues and further upregulated in metastatic tumors in lymph nodes. More importantly, Cdc42BPA expression was correlated with metastasis and poor survival of the patients with colon cancer. This study provides the first evidence that Cdc42BPA and Cdc42 signaling are important for colon cancer invasion, and Cdc42BPA has potential implications for colon cancer prognosis and treatment.


Microscopic pressure tensor for hard-sphere fluids.
The microscopic pressure tensor, which is not uniquely defined, is analyzed for a uniform hard-sphere fluid in Cartesian and spherical coordinates. Two popular definitions, one due to Irving and Kirkwood (IK) [J. H. Irving and J. G. Kirkwood, J. Chem. Phys. 18, 817 (1950)] and the other due to Harasima (H) [A. Harasima, Adv. Chem. Phys. 1, 203 (1958)], were used in this work. The IK definition is found to give the same ensemble average of the local pressure in Cartesian and spherical coordinates for a homogeneous hard-sphere system. The pressure obtained from the H definition gives, on the other hand, different results in the two coordinate systems. In Cartesian coordinates, the H pressure is identical to the IK pressure, but in spherical coordinates, the pressure depends on R (the distance from the origin). Therefore the H definition does not give a proper pressure tensor.


Pronghorn population genomics show connectivity in the core of their range.
Preserving connectivity in the core of a species' range is crucial for long-term persistence. However, a combination of ecological characteristics, social behavior, and landscape features can reduce connectivity among wildlife populations and lead to genetic structure. Pronghorn (Antilocapra americana), for example, exhibit fluctuating herd dynamics and variable seasonal migration strategies, but GPS tracking studies show that landscape features such as highways impede their movements, leading to conflicting hypotheses about expected levels of genetic structure. Given that pronghorn populations declined significantly in the early 1900s, have only partially recovered, and are experiencing modern threats from landscape modification, conserving connectivity among populations is important for their long-term persistence in North America. To assess the genetic structure and diversity of pronghorn in the core of their range, we genotyped 4,949 genome-wide single-nucleotide polymorphisms and 11 microsatellites from 398 individuals throughout the state of Wyoming. We found no evidence of genetic subdivision and minimal evidence of isolation by distance despite a range that spans hundreds of kilometers, multiple mountain ranges, and three interstate highways. In addition, a rare variant analysis using putatively recent mutations found no genetic division between pronghorn on either side of a major highway corridor. Although we found no evidence that barriers to daily and seasonal movements of pronghorn impede gene flow, we suggest periodic monitoring of genetic structure and diversity as a part of management strategies to identify changes in connectivity.


Serum markers of liver fibrogenesis, and liver histology findings in patients with chronic liver diseases.
Investigation of the relationships between the grade and stage of chronic liver diseases irrespective of their etiology using some novel serum markers of liver fibrogenesis, the "classical" serum markers of liver necro-inflammatory injury (such as transaminases), and the histomorphological evaluation of liver biopsies. Markers of liver fibrogenesis: serum metalloproteinase 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1), and N-terminal propeptide of the procollagen III (PIIINP); "liver function tests" (LFTs): bilirubin, transaminases ALT, AST; ALP, GMT; and liver morphology findings: necro-inflammatory activity, fibrosis; were studied in the series of 32, 'naive', i.e. yet untreated patients (women/men--11/21) with various CLDs: chronic viral hepatitis B or C 13 (CHB 3, CHC 10), non-alcoholic steatohepatitis 9, liver steatosis 4, primary biliary cirrhosis 5, drug-induced hepatitis. The diagnoses were based on the clinical, laboratory and liver imaging (ultrasonography) findings and confirmed by the liver biopsy. Investigation of liver fibrogenesis serum markers (PIIINP, MMP-1, TIMP-1) in patients with various CLDs has shown statistically significant correlations of these parameters with "classical" serum markers of liver necro-inflammation (ALT, AST) and the results of histomorphological evaluation of the necro-inflammatory activity (parameters NAI, MEF) and fibrosis (parameter FI) in liver biopsies. (Tab. 4, Ref. 31.)


Nonoperative Management Is as Effective as Immediate Splenectomy for Adult Patients with High-Grade Blunt Splenic Injury.
The comparative effectiveness of nonoperative management (NOM) vs immediate splenectomy (IS) for hemodynamically stable adult patients with grade IV or V blunt splenic injury (BSI) has not been clearly established in the literature. We performed a retrospective analysis of adult patients, from the 2013 to 2014 American College of Surgeons Trauma Quality Improvement Program (TQIP) Participant Use Data Files, who sustained grade IV or V BSI. Outcomes after IS vs attempted NOM were compared using propensity score analysis in order to adjust for patient- and injury-related variables. Nonoperative management was attempted in 1,489 (52.2%) of 2,746 patients who sustained grade IV or V BSI. Propensity matching techniques resulted in a cohort of 758 IS and NOM patients who were well matched for all known patient- and injury-related variables. In-hospital mortality was not different between the IS and NOM patients (11.5% vs 10.0%, p = 0.33), although IS patients had a higher incidence of infectious complications (21.4% vs 16.9%, p = 0.02). The rate of NOM failure in our sample was 20.1%. Independent predictors of failed NOM included the presence of a bleeding disorder, early blood transfusion requirement, and grade V injury. Splenic artery embolization was associated with a decreased risk of NOM failure. Patients who had failed NOM had a lower in-hospital mortality rate than IS patients (6.4% vs 16.4%, p = 0.004), but required longer hospitalization. Nonoperative management is as effective as IS for hemodynamically stable adult patients with grade IV or V BSI. The delay in operative intervention that results from failed attempts at NOM does not adversely affect the outcomes of patients who ultimately require splenectomy.


Acute gastric mucosal ulceration in septic shock. An experimental study on pathogenic mechanisms.
Intravenous infusion of live. E. coli bacteria in cats did not induce microscopic damage to the gastric mucosa within 3 hours. However, if the cats before the induction of bacteremia were given 80 mM HCl and 0.6 ml gallbladder bile/kg b.w. microscopic mucosal damage developed regularly in the corpus-fundus area of the stomach. The gastric mucosal damage was not associated with significant decrease of total gastric blood flow as measured continuously electromagnetically or decreased gastric mucosal blood flow measured early and late during sepsis using radioactively labelled microspheres. Neither was the development of gastric mucosal damage associated with reduced gastric wall collagen concentration nor in RNA, DNA concentrations or RNA/DNA ratio in the gastric mucosa.


Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus).
Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameters significantly correlated with testicular weight and volume. These observations were consistent a dependence on the testis growth on bioCG. Unfortunately, the low serum levels of bioCG were not measurable in this study. At 43 wk, the animals reached puberty. At 52 wk of age, animals attained maximum body and epididymal weights and qualitatively normal spermatogenesis, but testes continued growing, reaching a maximum of all parameters at 70 wk of age, without further major changes at the age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21, (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and (3) serum testosterone and ITAs are highly variable without any identifiable correlation with pituitary bioCG.