Brief report prevalence of Echinococcus species in wild foxes in parts of Qinghai Province, China.
Echinococcosis, caused by tapeworms of the genus Echinococcus, is a zoonotic parasitic disease. Various Echinococcus spp. are endemic and distributed in the Qinghai Province of China. Currently, few studies on the prevalence of Echinococcus spp. in the wild foxes are available. Hence, the aim of the study was to evaluate the prevalence of Echinococcus spp. in wild foxes in highly endemic areas of Qinghai Province, China. A total of 600 wild canid fecal samples were collected from Yushu, Qilian and Guinan in the study region, and 521 samples were successfully molecularly identified as wild foxes (Tibetan fox: 448, red foxes: 70, corsac fox: 3). Among the wild foxes, 5.57% (29/521) tested positive for Echinococcus spp. The prevalence rates of Echinococcus spp. in wild foxes in the Yushu, Qilian and Guinan areas were 2.51%, 15.22% and 0.96%, respectively. Furthermore, sequencing analysis indicated that E. multilocularis was the most prevalent species, occurring in 4.03% (21/521) of the wild foxes. Compared to E. granulosus occurring in 0.58% (3/521) of the foxes, E. shiquicus occurred in 1.54% (8/521), and E. shiquicus was first reported with 2.17% (3/138) prevalence in the Qilian area, indicating its transmission range is expanding. The current results provide useful epidemiological data for understanding and monitoring the dissemination of Echinococcus spp. by wild foxes in Qinghai Province, China.


A study of local heating of molecules under surface enhanced Raman scattering (SERS) conditions using the anti-Stokes/Stokes ratio.
We make systematic measurements of the anti-Stokes/Stokes (aS/S) ratios using low power lasers (0.5 mW at 514 and 633 nm) of rhodamine 6G (RH6G) on dried silver colloids over a wide range of temperatures from 140 to 350 K. We show that a scan in temperature allows the extraction of the contributions to the anti-Stokes/Stokes ratio from resonance effects and heating independently, thus decoupling the two aspects of the problem.


Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice.
Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Prnp-/- mice resulted in a higher number of circulating reticulocytes, hematocrits and spleen weights in WT mice than in Prnp-/- mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Ter119+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Ter119+ cells were going through apoptosis in Prnp-/- mice than in WT mice. Plasma erythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Prnp-/- (5500 pg/ml ) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Prnp-/- animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression.


Treatable fluctuating mental impairment in a patient with Bardet-Biedl syndrome.
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by rod-cone dystrophy, polydactyly, central obesity, mental retardation, and hypogonadism. Although many organs are involved in BBS, hyperammonemia caused by portal hypertension has been reported previously in only a single patient. We describe the second such patient with BBS and hyperammonemia, associated with fluctuating mental impairment. The patient was a 17-year-old boy with BBS. Esophageal, gastric, and rectal varices and mild hepatic dysfunction started to develop at 5 years of age. A liver biopsy showed dilated portal veins with mild fibrosis in portal tract. From the age of 17 years, he often had forced laughter with apparently normal consciousness. Laboratory examinations revealed hyperammonemia (112.2mg/ml). Oral medication lowered the blood ammonia level to 69.9 mg/ml, reduced the frequency of forced laughter, and improved his IQ. Patients with BBS may have additional diseases or conditions that affect mental status, such as hyperammonemia. Physicians should explore the underlying causes of these conditions and treat such patients, who already have a compromised quality of life.


ACSS2-related autophagy has a dual impact on memory.
Autophagy is an intracellular degenerative pathway which is responsible for neuronal survival. Under the condition of nutrient deprivation, autophagy can lead to dysfunction in memory consolidation. AMPK/mTOR pathway is currently the most studied autophagy mechanism, while recently researchers have proved ACSS2 can also affect autophagy. ACSS2 is phosphorylated at Ser659 by AMPK and then forms a translocation complex with Importin α5 to translocate into the nucleus. This process interacts with TFEB, resulting in upregulated expression of lysosomal and autophagosomal genes. These upregulations inhibit synaptic plasticity and hence memory functions. On the other hand, ACSS2 is also recognized as a regulator of histone acetylation. After recruiting CBP/p300 and activating CBP's HAT activity in the nucleus, ACSS2 maintains the level of localized histone acetylation by recapturing acetate from histone deacetylation to reform acetyl-CoA, providing substrates for HAT. The increase of histone acetylation locally enhanced immediate early gene transcription, including Egr2, Fos, Nr2f2, Sgk1, and Arc, to benefit neuronal plasticity and memory in many ways.


Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental autoimmune neuritis.
The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) constitutes an effective method to selectively eliminate phagocytic cells from spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on the course of actively induced and adoptively transferred experimental autoimmune neuritis (EAN), both animal models of the human Guillain-Barré syndrome. Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis rats with bovine peripheral nerve myelin efficiently prevented clinical signs of EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN gradually also developed in Cl2MDP-liposome-treated rats, but until day 19 disease was significantly milder than in control rats injected with buffer-filled liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2-specific T cells could be suppressed even more markedly by application of Cl2MDP-liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to interference with the induction phase of this experimental disease and confirms that macrophages are important effector cells during EAN. Selective suppression of phagocytic cell function by drug-containing liposomes may hold promise as a novel treatment of demyelinating autoimmune diseases of the nervous system.


Reversal of P-glycoprotein-mediated multidrug resistance by natural N-alkylated indole alkaloid derivatives in KB-ChR-8-5 drug-resistant cancer cells.
Multidrug resistance (MDR) remains a significant challenge in cancer chemotherapy due to the overexpression of ATP-binding cassette drug-efflux transporters, namely P-glycoprotein (P-gp)/ATP-binding cassette subfamily B member 1. In this study, derivatives of N-alkylated monoterpene indole alkaloids such as N-(para-bromobenzyl) (NBBT), N-(para-methylbenzyl) (NMBT), and N-(para-methoxyphenethyl) (NMPT) moieties were investigated for the reversal of P-gp-mediated MDR in drug-resistant KB colchicine-resistant 8-5 (KB-ChR-8-5) cells. Among the three indole alkaloid derivatives, the NBBT exhibited the highest P-gp inhibitory activity in a dose-dependent manner. Further, it significantly decreased P-gp overexpression by inactivating the nuclear translocation of the nuclear factor kappa B p-50 subunit. In the cell survival assay, doxorubicin showed 6.3-fold resistance (FR) in KB-ChR-8-5 cells compared with its parental KB-3-1 cells. However, NBBT significantly reduced doxorubicin FR to 1.7, 1.3, and 0.4 and showed strong synergism with doxorubicin for all the concentrations studied in the drug-resistant cells. Furthermore, NBBT and doxorubicin combination decreased the cellular migration and showed increased apoptotic incidence by downregulating Bcl-2, then activating BAX, caspase 3, and p53. The present findings suggest that NBBT could be a lead candidate for the reversal of P-gp- mediated multidrug resistance in cancer cells.


Literacy in the health care system: a study on open heart surgery patients.
To determine if patients recovering from open heart surgery were able to read and understand written discharge instructions and further to analyze the level of difficulty of standard discharge instructions and consent forms for open heart surgery. After screening for visual acuity and efficiency, literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine test (REALM) and comprehension was tested by a post-test of five questions based on the discharge instructions. Flesch-Kincaid scores were calculated on four sets of standard written discharge instructions and consent forms. Results from the study indicated that the REALM test was more accurate than the reported grade level and that reading skills are needed to understand and comprehend information needed for post-operative care. The study further substantiated that health care facilities are not providing written instructional material that is within the reading level of the patient. Illiteracy can have a major impact in the health care system. Low reading skills can disempower and can prove to be costly for patients who are requiring health care services. Further investigation is needed on the impact of patients' reading skills on the health care system.


A revised 3-column classification approach for the surgical planning of extended lateral tibial plateau fractures.
Variable angle locking compression plates allow for lateral buttress and support of the posterolateral joint surface of tibial plateau fractures. This gives room for improvement of the surgical 3-column classification approach. Our aim was to revise and validate the 3-column classification approach to better guide the surgical planning of tibial plateau fractures extending into the posterolateral corner. In contrast to the 3-column classification approach, in the revised approach the posterior border of the lateral column in the revised approach lies posterior instead of anterior of the fibula. According to the revised 3-column classification approach, extended lateral column fractures are defined as single lateral column fractures extending posteriorly into the posterolateral corner. CT-images of 36 patients were reviewed and classified twice online according to Schatzker and revised 3-column classification approach by five observers. The intraobserver reliability was calculated using the Cohen's kappa and the interobserver reliability was calculated using the Fleiss' kappa. The intraobserver reliability showed substantial agreement according to Landis and Koch for both Schatzker and the revised 3-column classification approach (0.746 vs. 0.782 p = 0.37, Schatzker vs. revised 3-column, respectively). However, the interobserver reliability of the revised 3-column classification approach was significantly higher as compared to the Schatzker classification (0.531 vs. 0.669 p < 0.01, moderate vs. substantial agreement, Schatzker vs. revised 3-column, respectively). With the introduction of variable angle locking compression plates, the revised 3-column classification approach is a very helpful tool in the preoperative surgical planning of tibial plateau fractures, in particular, lateral column fractures that extend into the posterolateral corner. The revised 3-column classification approach is rather a practical supplement to the Schatzker classification. It has a significantly higher interobserver reliability as compared to the Schatzker classification, most likely due to the more simple nature of the revised 3-column classification approach.


Rapid Ca2+ refilling system of intracellular store(s) in human vascular endothelial cells.
Using a fura-2 method, cytosolic Ca2+ concentration [( Ca2+]i) was measured in endothelial cell monolayers from human umbilical vein. In the presence of 1.5 mM Ca2+, bradykinin (BK) induced a rapid (within 15 sec) and dose-dependent (10(-8)-10(-6) M) increase in [Ca2+]i, consisting of an initial peak and a subsequent sustained phase. The pretreatment with 3 mM EGTA for 1 min caused a significant reduction in [Ca2+]i levels both of the basal (p less than 0.05) and BK-stimulated initial peak (p less than 0.001). However, the BK-stimulated initial peak was retained in magnitude for at least 5 min under the treatment with EGTA. In contrast, the sustained phase was completely abolished by EGTA treatment. The BK-stimulated Ca2+ transient, once having been completely inhibited by ionomycin (10(-6) M) in the presence of EGTA, was rapidly (within 2 min) recovered to the untreated level by replacing it with fresh medium containing 1.5 mM Ca2+. The present results indicated that BK mobilized Ca2+ from both intracellular and extracellular space(s) and suggest the presence of an extracellular Ca2(+)-dependent rapid refilling system of intracellular Ca2+ store(s) in human vascular endothelial cells.


Pruned vine-shoots as a new enological additive to differentiate the chemical profile of wines.
For this study, Tempranillo wines were made by adding their own toasted vine-shoots (SEGs, "Shoot- Enological - Granule"). The SEGs were added in two doses (12 and 24 g/L) at three different times (before alcoholic fermentation, in the middle of alcoholic fermentation, and after fermentations) and phenolic, volatile, and mineral composition were analysed. Results showed a decrease in the total content of phenolic compounds but stilbenes, specifically trans-resveratrol, increased in all wines macerated with SEGs, as did total anthocyanins when these additives were added in the middle of fermentation. Furthermore, the ratios related to glycosylated monomeric anthocyanins were significantly higher in wines treated with SEGs. The use of SEGs did not affect the total content of volatile compounds. However, changes in terms of individual compounds resulted in an odorant series associated with SEGs, named "sweet woody", formed by compounds such as ethyl vanillate, ethyl cinnamate, and vanillin. Finally, the mineral composition of the wines was not affected using SEGs, whereby potassium was the most abundant in all the wines.


Heller myotomy versus endoscopic balloon dilatation for achalasia: A single center experience.
This study aimed to compare clinical results, symptom relief, quality of life and patient satisfaction after the 2 most common procedures for achalasia treatment: laparoscopic Heller myotomy (LHM) and endoscopic balloon dilatation (EBD).Patients treated at University Hospital of Heidelberg with LHM or EBD were included. A retrospective chart review of perioperative data and a prospective follow-up of therapeutic efficiency, Gastrointestinal Quality of Life Index (GIQLI) and patient satisfaction was conducted.Follow-up data (mean follow-up: 75.1 ± 53.9 months for LHM group and 78.9 ± 45.6 months for EBD) were obtained from 36 patients (19 LHM; 17 EBD). Eckardt score (median (q1,q3): 2 (1,4) in both groups, P = .91, GIQLI (LHM: 117 (91.5, 126) vs EBD: 120 (116, 128), P = .495) and patient satisfaction (3 (2,3) vs 3 (2,4), P = .883) did not differ between groups. Fifteen patients (78.9%) in LHM group and 11 (64.7%) in EBD group (P = .562) stated they would undergo the intervention again. All patients with EBD had at least 2 dilatations (100%), whilst only 2 patients (10.5%) had dilatation after LHM (P < .001). There were no complications after EBD, but 2 after LHM (10.5%, P = .517).Both LHM and EBD are able to control symptoms and provide similar quality of life and patient satisfaction. However, reintervention rate was higher following EBD, hence LHM provided a more sustained treatment than EBD.


Synthesis and evaluation of a new series of 1'-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4'-piperidine] derivatives as high affinity and selective histamine-3 receptor (H3R) antagonists.
A novel class of 1'-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4'-piperidine] derivatives with low nanomolar affinity for the human and rat histamine-3 receptors (H(3)Rs) are described. The spirobenzopyran piperidine ether analogs demonstrated excellent H(3)R affinity and selectivity against histamine receptor subtypes (H(1)R, H(2)R, and H(4)R), were stable in liver microsomes, and had selectivity against CYP P450 enzymes. Compounds 10, 13, 15, and 16 demonstrated high H(3)R affinity, in vitro liver microsomal stability, selectivity against CYP isoforms, moreover, these ether analogs exhibited acceptable iv pharmacokinetic (PK) properties but had poor oral exposure in rat.


Biochemical and immunological characterization of a histone variant associated with spermatogenesis in the mouse.
A chromosomal histone, H2S, specific to the mouse testis has been purified. Amino acid analysis indicated lack of cysteine and a high basic amino acid content typical of histones. Specific antibodies against histones H2S have been generated in rabbits and partially purified using (NH4)2SO4 precipitation and ion-exchange chromatography. Protein transfer experiments indicate presence of antigenically similar histones in the rat and rabbit testes but not in the guinea pig and dog testes. In addition, histone complement of somatic tissues such as lung, kidney, liver and spleen lacked antigenically similar proteins. Immunocytochemical studies using peroxidase-antiperoxidase complex indicated presence of immunoreactive cells in the seminiferous epithelium which were lacking in the interstitium. These data demonstrate histone H2S to be a unique histone associated with spermatogenesis in the mouse.


How is complementary medicine discussed in oncology? Observing real-life communication between clinicians and patients with advanced cancer.
This study aims to examine the structure of communication about complementary medicine (CM) between patients with cancer and clinicians during oncology consultations. Previously, consultations between 29 clinicians and 80 patients with advanced cancer were recorded in six hospitals in the Netherlands. The present study considers a secondary analysis. References to CM during the consultation were coded using a self-developed observational coding scheme. At least one reference to CM was observed in 35 out of 80 consultations (44 %), with a total of 73 references. In most cases, CM was initially referred to by patients. Clinicians often did not elaborate on the subject of CM. Relevant aspects related to CM (e.g., safety, effectiveness) were infrequently discussed. Both patients and clinicians showed predominantly neutral to positive attitudes towards CM. This study shows that patients are still the main initiators of discussions about CM and the topic is not consistently discussed in daily oncology practice. If exploration of patients' interest in CM or its use became routine in oncology practice, it may relieve patients of the burden of introducing the topic, decrease potential risks of CM use and increase access to evidence-based CM for all patients with cancer.


Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management.
Double heterozygosity for disease-causing BRCA1 and BRCA2 mutations is a very rare condition in most populations. Here we describe genetic and clinical data of eight female double heterozygotes (DH) for BRCA1 and BRCA2 mutations found in a cohort of 8162 German breast/ovarian cancer families and compare it with the data of their single heterozygous relatives and of the index patients of the German Consortium for Hereditary Breast and Ovarian Cancer. Furthermore, we analyze the phenotypic features of these patients with respect to age at onset of first cancer, first breast/ovarian cancer and the number of disease manifestations and compare them to that of published Caucasian female DHs and their single heterozygous female relatives. German DHs were not significantly younger at diagnosis of first breast cancer than the single heterozygous index patients of the German Consortium. However, if the data of our study were pooled with that of the literature, DHs were substantially younger at onset of first cancer (mean age 40.4 years, 95 % CI = 36.6-44.1) than their single heterozygous female relatives (mean age 51.9 years, 95 % CI = 46.8-57.0). The two groups also differed concerning the onset of first breast cancer (mean age 40.6 years, 95 % CI = 36.6-44.5 vs. 52.6, 95 % CI = 47.5-57.6). In addition, DHs had a more severe disease than their female relatives carrying a single BRCA mutation (1.4 vs. 0.6 manifestations per person). In contrast to Ashkenazi Jewish females, Caucasian DH females might develop breast cancer at an earlier age and have a more severe disease than single heterozygous BRCA mutation carriers. Therefore, DHs may benefit from more intensive surveillance programs/follow-up care and prophylactic surgery.


Sequence-specific Ni(II)-dependent peptide bond hydrolysis for protein engineering: active sequence optimization.
In previous studies we showed that Ni(II) ions can hydrolytically cleave a peptide bond preceding Ser/Thr in peptides of a general sequence RN-(Ser/Thr)-Xaa-His-Zaa-RC, where RN and RC are any peptide sequences. A peptide library screening, assisted by accurate measurements of reaction kinetics for selected peptides, demonstrated the preference for bulky and aromatic residues at variable positions Xaa and Zaa [A. Krężel, E. Kopera, A.M. Protas, A. Wysłouch-Cieszyńska, J. Poznański, W. Bal, J. Am. Chem. Soc., 132 (2010) 3355-3366]. In this work we used a similar strategy to find out whether the next residue downstream to Zaa may influence the reaction rate. Using an Ac-Gly-Ala-Ser-Arg-His-Zaa-Baa-Arg-Leu-NH2 library, with Zaa and Baa positions containing all common amino acids except of Cys, we found a very strong preference for aromatic residues in both variable positions. This finding significantly limits the range of useful Xaa, Zaa and Baa substitutions, thus facilitating the search for optimal sequences for protein engineering applications [E. Kopera, A. Belczyk-Ciesielska, W. Bal, PLoS One 7 (2012) e36350].


Combining multivariate image analysis with high-performance thin-layer chromatography for development of a reliable tool for saffron authentication and adulteration detection.
In this work, high-performance thin-layer chromatography (HPTLC) coupled with multivariate image analysis (MIA) is proposed as a fast and reliable tool for authentication and adulteration detection of Iranian saffron samples based on their HPTLC fingerprints. At first, the secondary metabolites of saffron were extracted using ultrasonic-assisted solvent extraction (UASE) which was optimized using central composite design (CCD). Next, the RGB coordinates of HPTLC images were used for estimation of saffron origin based on principal component analysis (PCA). The PCA scores plot showed that saffron samples were clustered into two clear-cut groups which was 92% matched with the geographical origins of the samples. In the next step, common plant-derived adulterants of saffron including safflower, saffron style, calendula, and rubia were investigated with MIA analysis of HPTLC images using partial least squares-discriminant analysis (PLS-DA) at 5-35% (w/w) levels. The PLS-DA results showed proper classification of saffron and adulterants with sensitivity 99.14%, specificity 96.94%, error rate 1.96% and accuracy 98.04. Also, the effect of HPTLC injection volume on the performance of the proposed strategy was evaluated. The ability of the proposed method was then investigated by analyzing two additional sample sets including mixed samples of four plant-derived adulterants and adulterated commercial samples. Sensitivity and specificity of this model were 100% which confirmed its validity.


Cytopathology of explanted intraocular lenses and the clinical correlation.
To study the cytopathological features of explanted intraocular lenses (IOLs) and correlate the features with their clinical presentation. Ocular Pathology Department, Medical and Vision Research Foundation, Sankara Nethralaya, Chennai, India. The study comprised 61 explanted IOLs (48 posterior chamber IOLs and 13 anterior chamber IOLs) removed for the following reasons: pseudophakic bullous keratopathy (36), recalcitrant uveitis (7), retinal detachment (10), endophthalmitis (5), uveitis (7), IOL subluxation (2), and painful blind eye (1). The IOLs were stained with hematoxylin and eosin using a simple cytological technique. The cytopathological features were studied and correlated with the clinical presentations. The mean time of IOL explantation was 10.1 months after surgery. Twenty-one IOLs had granulomatous and nongranulomatous inflammations and 4, nongranulomatous inflammations. One IOL had fungal filaments on the surface. Intraocular lenses can produce both granulomatous and nongranulomatous inflammation. Granulomatous inflammation was the most common in this series. The surface of IOLs explanted because of intraocular infection may show infective agents.


[Ethical issues of vaccination against Sars-CoV-2].
As a tool for public health, the vaccination policy is based on the analysis of benefits and risks. Thus, the National Consultative Ethics Committee has been at the heart of the orientations taken in terms of the deployment of the vaccination against severe acute respiratory syndrome coronavirus 2, by contributing its reflections on the associated ethical issues.


Activation of the ventral subiculum reinvigorates behavior after failure to achieve a goal: Implications for dopaminergic modulation of motivational processes.
Previous studies confirm that brief electrical stimulation of glutamatergic afferents from the ventral subiculum (vSub) can significantly enhance dopamine release in the ventral striatum for an extended duration (>20 min). However, the functional significance of this effect on motivated behavior remains to be specified. Here we tested the hypothesis that brief electrical stimulation of the ventral subiculum (20 Hz for 10 s) might increase effort expenditure for food rewards. Motivation was assessed by a progressive ratio lever pressing task, which requires continuous escalation of the numbers of lever presses to receive each subsequent sucrose pellet, eventually resulting in the failure to achieve the required ratio for a food reward. vSub stimulation at the start of a session did not affect the rate or total number of lever presses prior to reaching the "break point". In contrast, stimulation of the vSub with identical parameters on a post break point trial resulted in a significant increase in total responses. These findings demonstrate that activation of the vSub with parameters that modulate dopamine efflux in the nucleus accumbens can re-activate goal-directed behavior after failure to achieve a goal. Our data highlight a possible role for the vSub in the pathophysiology and potential treatment of motivational processes linked to psychiatric disease.


Human health risk assessment for peroxisome proliferators: more than 30 years of research.
Substances like gemfibrozil, clofibrate and fenofibrate, widely used in human care for their hypolipidemic effects, belong to a larger class of chemicals called peroxisome proliferators (PPs). PPs, by binding and activing the peroxisome proliferator-activated receptor alpha (PPARalpha), modulate gene involved in lipid homeostasis both in human and in rodent. In a different way, long term administration of PPs results in hepatocarcinogenesis only in rodent. Although the phenomenon is known since more than 30 years, the exact mechanism is not well understood and the human health risks are not established. In this mini-review is inspected the major findings done in the different species and illustrates the possible doubts for human health by the use of PPs.


Control of sturgeon sperm motility: Antagonism between K+ ions concentration and osmolality.
Spermatozoa are stored in a quiescent state in the male reproductive tract and motility is induced in response to various environmental stimuli, such as change of osmolality (general case) and a decrease of extracellular K+ in fish from Acipenseridae family. This study was aimed to investigate the relationship between osmolality and extracellular K+ concentration in controlling sperm motility in sturgeon. Pre-incubation of sturgeon sperm for 5s in hypertonic solutions of glycerol, NaCl, or sucrose (each of 335 mOsm/kg osmolality) prepares sturgeon spermatozoa to become fully motile in presence of high concentration of K+ ions (15 mM), which has previously been demonstrated to fully repress motility. Furthermore, presence of 0.5mM KCl during the high osmolality pre-incubation exposure completely prevented subsequent spermatozoa activation in a K+-rich media. Manipulating the transport of K+ ions by the presence of K+ ionophore (valinomycin), it was concluded that once an efflux of K+ ions, the precursor of sturgeon sperm motility activation, is taking place, spermatozoa then become insensitive to a large extracellular K+ concentration.


Estrogen receptor (ER)-α, β and progesterone receptor (PR) mediates changes in relaxin receptor (RXFP1 and RXFP2) expression and passive range of motion of rats' knee.
The high risk of knee injuries in female may be associated with sex-steroid hormone fluctuations during the menstrual cycle by its effect on ligaments and tendons stiffness. This study examined changes in knee range of motion in presence of estrogen and progesterone and investigated the interaction of their antagonists to relaxin receptors. Sixty WKY rats were divided into 10 different groups receiving 17β-estradiol (0.2, 2, 20 and 50 μg/kg), progesterone (4 mg/kg), estrogen receptor (ER) antagonist ICI 182/780, ERβ antagonist PHTPP, ERα antagonist MPP, and mifepristone in presence of estrogen and progesterone. Physiologic dose were injected subcutaneously 30 min before of hormone injection for 3 days consequently. Sham group received peanut oil (vehicle) also for 3 consecutive days. Following the treatment administrations, the knee range of motion and RXFP1/RXFP2 mRNA and protein expression were examined in the patellar tendon, lateral collateral ligament, and hamstring muscle. Our data showed that the knee range of motion was significantly increased in progesterone and high doses estrogen treatment but not significantly increased in low doses of estrogen treatment. The range of motion was decreased in the presence of estrogen receptor (ER) antagonist ICI 182/780, ERβ antagonist PHTPP, ERα antagonist MPP, and mifepristone, independently. Progesterone and high doses of estrogen treatment resulted in the highest range of knee laxity correlated to expression of both relaxin receptor isoforms in knee tissues. Our findings thus suggested that female subjects are more vulnerable toward non-traumatic knee injury due to estrogen and progesterone fluctuation as compared to male subjects.


Retroperitoneal cold abscess caused by mycobacteria chelonae abscessus after percutaneous nephrolithotomy in India: strategies for detection, management, and prevention in the United States.
Atypical, nontuberculous, mycobacteria (NTM) are emerging as significant pathogens in nosocomial infections. Historically, such outbreaks have been limited to developing countries, and clinicians in the United States have not been exposed to the nuances of diagnosing and treating such infections. With an increasing prevalence worldwide, all clinicians should be able to recognize and treat NTM infections. We report a case of a patient who developed a retroperitoneal cold abscess caused by NTM after percutaneous stone surgery in India. Through a comprehensive review of published reports, we offer strategies for the treatment and prevention of such outbreaks.


iCLIP data analysis: A complete pipeline from sequencing reads to RBP binding sites.
Precise knowledge on the binding sites of an RNA-binding protein (RBP) is key to understanding the complex post-transcriptional regulation of gene expression. This information can be obtained from individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) experiments. Here, we present a complete data analysis workflow to reliably detect RBP binding sites from iCLIP data. The workflow covers all steps from the initial quality control of the sequencing reads up to peak calling and quantification of RBP binding. For each tool, we explain the specific requirements for iCLIP data analysis and suggest optimised parameter settings.


Risk management for assuring safe drinking water.
Millions of people die every year around the world from diarrheal diseases much of which is caused by contaminated drinking water. By contrast, drinking water safety is largely taken for granted by many citizens of affluent nations. The ability to drink water that is delivered into households without fear of becoming ill may be one of the key defining characteristics of developed nations in relation to the majority of the world. Yet there is well-documented evidence that disease outbreaks remain a risk that could be better managed and prevented even in affluent nations. A detailed retrospective analysis of more than 70 case studies of disease outbreaks in 15 affluent nations over the past 30 years provides the basis for much of our discussion [Hrudey, S.E. and Hrudey, E.J. Safe Drinking Water--Lessons from Recent Outbreaks in Affluent Nations. London, UK: IWA Publishing; 2004.]. The insights provided can assist in developing a better understanding within the water industry of the causes of drinking water disease outbreaks, so that more effective preventive measures can be adopted by water systems that are vulnerable. This preventive feature lies at the core of risk management for the provision of safe drinking water.


Using multiple targeted therapies in oncology: considerations for use, and progress to date in breast cancer.
There has been significant progress in our basic understanding of drugs and targets in the management of breast cancer. Recent breast cancer clinical trials have examined whether combinations of drugs targeting transmembrane receptors or their downstream effectors involved in cell signal transduction can increase response rates and overcome acquired and/or de novo drug resistance compared to a single targeted agent with or without systemic chemotherapy. We reviewed published clinical trials and conference proceedings examining combinations of targeted therapies across different breast cancer subtypes. Improvements in pathological complete response (pCR) rates and progression free survival (PFS) in preoperatively treated and metastatic human epidermal growth factor 2 (HER2)-positive breast cancer, respectively, have been observed with combinations of anti-HER2 therapies given concomitantly. Promising results were also observed in estrogen receptor (ER)-positive, HER2-negative breast cancer using a mammalian target of rapamycin inhibitor with tamoxifen or an aromatase inhibitor (AI) in the preoperative setting and for patients with metastatic breast cancer that had previously progressed on endocrine therapy alone. A recent phase II trial reported a statistically significant improvement in PFS with the addition of an oral inhibitor of cyclin-dependent kinase 4/6 to letrozole compared to letrozole alone (26.1 versus 7.5 months). A phase III study is planned for early 2013. On the basis of preclinical data, clinical trials have examined combinations of hormonal agents such as fulvestrant with an AI. However, the results are conflicting. Early data indicated that poly (ADP-ribose) polymerase (PARP) inhibitors exploiting the concept of synthetic lethality would offer improved outcomes for patients with ER-negative, progesterone receptor (PR)-negative, HER2-negative breast cancer often referred to as triple negative breast cancer (TNBC); however, data in the phase III setting failed to confirm these findings but this may be because the drug was not a true PARP inhibitor. Chemotherapy continues to be the mainstay of treatment for TNBC until specific drugs and their associated targets are identified. As advances in medical technologies continue to identify multiple molecularly distinct breast cancer subgroups that are predicted to respond to combinations of targeted agents new challenges have arisen. In particular, how do we evaluate the safety and efficacy of these new drug combinations in relatively small subgroups of patients? Novel clinical trial designs will be required and increasingly regulatory agencies will require companion diagnostic tests that can identify the subgroups likely to respond to these therapies. The US Food and Drug Administration is assessing the role of pCR in breast cancer studies as a surrogate endpoint to predict clinical benefit in the accelerated drug approval process.


Significance of the simultaneous combined transcranial and endoscopic endonasal approach for prevention of postoperative CSF leak after surgery for lateral skull base meningioma.
Lateral skull base meningiomas, particularly sphenoorbital meningiomas, sometimes extend extremely widely into adjacent structures including the paranasal sinuses. For endonasal skull base reconstruction using a vascularized nasoseptal flap for prevention of postoperative cerebrospinal fluid (CSF) leak, the simultaneous combined transcranial and endoscopic endonasal approach was applied for resection of these extensive tumors. We performed a retrospective review of four patients treated with the simultaneous combined transcranial and endoscopic endonasal approach for resection of lateral skull base meningiomas. Preoperative characteristics, tumor extent, extent of resection, complications, and postoperative outcomes were analyzed. The tumor extended into the paranasal sinus, infratemporal fossa, and pterygopalatine fossa in all patients. Extracranial extension into the cavernous sinus or superior orbital fissure was detected in two and three patients, respectively. In one patient without extension into the cavernous sinus and superior orbital fissure, gross total resection was achieved, whereas in the other three patients, subtotal resection was performed, and small residual masses of the tumor remained in the cavernous sinus or superior orbital fissure to minimize the risk of postoperative ocular nerve damage. No patients experienced postoperative CSF leak. The simultaneous combined transcranial and endoscopic endonasal approach is useful for a subgroup of patients with lateral skull base meningiomas for prevention of postoperative CSF leak. Particularly in recurrent cases in which vascularized flaps from the transcranial side are likely unavailable due to prior tumor resection, this combined approach is worth considering depending on tumor extension into the paranasal sinus.


A European Competence Framework for Industrial Pharmacy Practice in Biotechnology.
The PHAR-IN ("Competences for industrial pharmacy practice in biotechnology") looked at whether there is a difference in how industrial employees and academics rank competences for practice in the biotechnological industry. A small expert panel consisting of the authors of this paper produced a biotechnology competence framework by drawing up an initial list of competences then ranking them in importance using a three-stage Delphi process. The framework was next evaluated and validated by a large expert panel of academics (n = 37) and industrial employees (n = 154). Results show that priorities for industrial employees and academics were similar. The competences for biotechnology practice that received the highest scores were mainly in: "Research and Development", '"Upstream" and "Downstream" Processing', "Product development and formulation", "Aseptic processing", "Analytical methodology", "Product stability", and "Regulation". The main area of disagreement was in the category "Ethics and drug safety" where academics ranked competences higher than did industrial employees.


Simple, sensitive method for measuring plasmin and plasminogen activity in plasma.
We describe a sensitive, simple, and rapid method for measuring plasmin and plasminogen in plasma, with fibrinogen as substrate. The assay can be done within 1 h. Plasma is diluted 20-fold with buffer and 0.1 ml (5 mul of original plasma) is incubated for 5 min at 37 degrees C, with or without 400 units of streptokinase. Then 2.0 ml of fibrinogen solution is added, the mixture again incubated (37 degrees C, 5 min), and the reaction stopped. The amount of tyrosine liberated from the fibrinogen is measured and is related to activity. This method is suitable for routine clinical work if the same batch of fibrinogen is used.


Investigating the Molecular Basis of Retinal Degeneration in a Familial Cohort of Pakistani Decent by Exome Sequencing.
To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration. A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls. We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population. We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population.


Detection of human papillomavirus (HPV) genotypes in cervico-vaginal scrapes of women with normal and abnormal cytology.
Certain types of human papillomavirus (HPV) are associated with cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The study addressed the expression and detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology by polymerase chain reaction (PCR), each woman serving as her own control. Study participants (127) were subgrouped into CIN-positive and CIN-negative, based on cytology screening, and endocervical and vaginal scrapes were collected by a gynecologist and placed immediately in saline. HPV DNA was assessed by PCR, and HPV genotypes were determined by hybridization of PCR products with type-specific biotinylated probes. Of the 127 participants, 55 tested positive and 72 tested negative for HPV DNA. While there was no difference between the two groups with regards to age or to number of pregnancies, higher numbers of smokers and of women with multiple sexual partners and abnormal cytology were seen in the HPV-positive group (P < 0.001). HPV DNA was detected in the vaginal scrapes of all HPV-positive, but in none of the HPV-negative women (sensitivity and specificity = 1.0). Furthermore, the HPV genotype was the same in vaginal and endocervical specimens in all the HPV-positive women. HPV detection by PCR, using endocervical or vaginal sampling, is a sensitive and highly specific test for the identification of HPV infection, in particular in women with cytomorphologically normal cervices.


Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes.
In cells, stimulation of protein kinase C (PKC) results in the dephosphorylation of specific residues proximal to the DNA binding domain of c-Jun, a major component of the AP-1 transcription factor. Since phosphorylation of this region of c-Jun inhibits interaction with DNA, this pathway may contribute to PKC activation of AP-1. To determine the mechanism(s) underlying this pathway, possible interactions between PKC and proteins implicated in c-Jun regulation are being investigated. Here it is shown that glycogen synthase kinase-3 beta (GSK-3 beta), a serine/threonine kinase that specifically targets the inhibitory c-Jun phosphorylation sites, is phosphorylated in vitro by particular forms of PKC (alpha, beta 1, gamma greater than beta 2; not epsilon). By contrast, the related GSK-3 alpha is not a substrate for any of these PKC isotypes. Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta.


IgG antibodies to the histone complex H2A-H2B characterize procainamide-induced lupus.
Patients treated with procainamide and other drugs commonly develop antinuclear antibodies and occasionally symptoms of lupus erythematosus. However, the pathological events which lead to clinical symptoms in some patients but only abnormal serology in others have not been established. The present study examines the incidence, amount, immunoglobulin class, and antigen-binding specificity of anti-histone and anti-denatured DNA (anti-dDNA) antibodies in three groups of patients. These comprised a prospective study of patients treated with procainamide, patients with clinical drug-induced lupus symptoms, and a group undergoing therapy for many years without any symptoms. Procainamide elicited IgG and IgM anti-dDNA antibodies concordantly. Anti-histone IgM antibodies also appeared de novo during this period but IgG anti-histone antibodies were detected less frequently. Asymptomatic patients tended to have an antibody profile consisting of highly elevated anti-dDNA, IgM antibodies reactive with all histones and IgG antibodies specific for only one or two histone classes. In contrast symptomatic patients usually had little anti-dDNA or antibodies to individual histones but had pronounced IgG antibodies to the histone complex H2A-H2B. This unique antibody was characteristics of procainamide-induced lupus and was not detected in patients whose disease was induced by hydralazine. Anti-(H2A-H2B) decreased after procainamide was discontinued, concomitant with subsidence of symptoms. The finding that autoantibodies elicited by procainamide in patients with lupus symptoms have a characteristic immunoglobulin class and specificity may be of pathogenic significance and suggests that patients susceptible to procainamide-induced lupus have a unique immune response. In addition, this information could be of diagnostic value in predicting which procainamide-treated patients will develop overt symptoms of lupus.


Microplastics in the endangered Indo-Pacific humpback dolphins (Sousa chinensis) from the Pearl River Estuary, China.
Microplastic pollution is a growing concern worldwide. Despite numerous studies showing the occurrence of microplastics in low-trophic level aquatic organisms, microplastic ingestion and contamination in cetaceans, especially those from Asian waters, has been rarely recorded. Here, we investigated stomach microplastic pollution in twelve Indo-Pacific humpback dolphins stranded along the Pearl River Estuary (PRE), China. We also compared microplastic abundances in dolphins stranded near populated urban areas (ZH, n = 6) with those stranded near rural areas (JM, n = 6). Microplastics were detected in all samples, with abundance ranging widely from 11 to 145 items individual-1 (mean ± SD, 53 ± 35.2). Major microplastics were polypropylene and polyethylene fibers, with the size mostly ranging from 1 to 5 mm and the dominant colors of white or transparent. Humpback dolphins from ZH (73 ± 36.8 items individual-1) exhibited a significantly higher average microplastic abundance than those from JM (33 ± 18.3 items individual-1, p < 0.05). In particular, the highest microplastic concentration was identified in the dolphin (SC-ZH01) stranded near the mouth of the Pearl River, whereas the dolphin (SC-JM04) collected at the rural site contained the lowest concentration of microplastics, suggesting the important influence of land-based human activities on the accumulation of microplastics in the PRE. The identification of varied microplastic polymers indicated their complex source scenarios. This study suggests that, as one of top predators in the potential microplastic food chains, this cetacean species could likely serve as an endpoint biomonitoring species of microplastic pollution in the PRE or other similar estuarine ecosystems. Our results highlight the need for more studies towards better understanding the potential impacts of microplastics on this endangered species.


Blood pressure and splanchnic nerve activity are reduced by a vagally mediated opioid action.
An enkephalin analogue, D-Ala2-Met5-enkephalinamide (DAME), caused a fall in blood pressure (BP) following right atrial administration (RA) in urethane-anesthetized rats that were also atropinized, paralyzed, and artificially ventilated. This reduction in BP was not related to opioid-induced bradycardia. At a dose of 250 micrograms/kg RA the maximum percentage change was -36.0 +/- 3.9% occurring within 10-15 s subsequent to administration. The fall in BP was blocked by both pretreatment with naloxone HCl (75-100 micrograms/kg i.v.) and bilateral cervical vagotomy. Similar hypotensive responses (-37.3 +/- 2.3%) were obtained with phenyldiguanide (PDG) (40 micrograms/kg RA), a known stimulant of pulmonary J receptors (pulmonary C fibers). However, unlike DAME, the PDG response could not be blocked by naloxone. The fall in BP. obtained with DAME and PDG, paralleled a reduction in the spike frequency of the greater splanchnic nerve activity. This reflex fall in activity did not involve supramesencephalic structures because results were similar in both urethane-anesthetized and unanesthetized midcollicular decerebrate preparations. It was concluded that opioids can act peripherally, via pulmonary opiate receptors, to inhibit central vasomotor activity and reduce BP by eliciting a pulmonary chemoreflex.


G-protein-coupled receptor signaling and the EGF network in endocrine systems.
The epidermal growth factor (EGF) network is composed of a complex array of growth factors synthesized as precursors and expressed on the cell surface. These latent growth factors are activated by cleavage and shedding from the cell surface and act by binding to various homo- and hetero-dimers of the EGF receptors (ErbBs). Although the exact molecular steps are poorly understood, ligand binding to G-protein-coupled receptors as diverse as the beta-adrenoceptors or the lysophosphatidic acid receptors leads to shedding of EGF growth factors and activation of EGF receptors. Recent observations from the pituitary and in the ovary are providing new insight into the role of this network in endocrine systems.


Mass population displacement. A global public health challenge.
Since the end of the Cold War, there has been a dramatic increase in civil conflicts resulting in approximately 50 million refugees and internally displaced civilians. The public health impact of these situations has been immense, comprising high rates of communicable diseases, elevated prevalence of acute malnutrition, and high excess mortality rates. The prevention of these adverse public health effects includes early warning and intervention; prompt supply of adequate food, water, and sanitation; measles immunization; effective management of epidemic communicable diseases; and simple and timely information systems.


Patients with schizophrenia and bipolar disorder display a similar global gene expression signature in whole blood that reflects elevated proportion of immature neutrophil cells with association to lipid changes.
Schizophrenia (SCZ) and bipolar disorder (BD) share clinical characteristics, genetic susceptibility, and immune alterations. We aimed to identify differential transcriptional patterns in peripheral blood cells of patients with SCZ or BD versus healthy controls (HC). We analyzed microarray-based global gene expression data in whole blood from a cohort of SCZ (N = 329), BD (N = 203) and HC (N = 189). In total, 65 genes were significantly differentially expressed in SCZ and 125 in BD, as compared to HC, with similar ratio of up- and downregulated genes in both disorders. Among the top differentially expressed genes, we found an innate immunity signature that was shared between SCZ and BD, consisting of a cluster of upregulated genes (e.g., OLFM4, ELANE, BPI and MPO) that indicate an increased fraction of immature neutrophils. Several of these genes displayed sex differences in the expression pattern, and post-hoc analysis demonstrated a positive correlation with triglyceride and a negative correlation with HDL cholesterol. We found that many of the downregulated genes in SCZ and BD were associated with smoking. These findings of neutrophil granulocyte-associated transcriptome signatures in both SCZ and BD point at altered innate immunity pathways with association to lipid changes and potential for clinical translation.


Euthanasia: American attitudes toward the physician's role.
This is a study of American public opinion toward euthanasia and the physician's role in performing it. The authors examine how these attributes are affected by religious affiliation, religious self-perception, political self-perception and education. The data include 8384 American respondents from years 1977, 1978, 1982, 1985 and 1988 of the General Social Survey conducted by the National Opinion Research Center. The findings suggest that highly educated, politically liberal respondents with a less religious self-perception are most likely to accept active euthanasia or suicide in the case of terminally ill patient. The data also show that Americans tend to draw a distinction between the suicide of a terminally ill patient and active euthanasia under the care of a physician, preferring to have the physician perform this role in the dying process. The tendency to see a distinction between active euthanasia and suicide was clearly affected by religious affiliation and education.


Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.
Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.


Infrequent mutations and no methylation of CDKN2A (P16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan.
CDKN2A (p16INK4A/MTS1) and CDKN2B (p15INK4B/MTS2) have recently been shown to be potent inhibitors of the cyclin D/cyclin-dependent kinase-4 complex. Both genes are candidates for the putative tumour suppressor genes located at chromosome 9p21 and are frequently inactivated in many human cancers through homozygous deletion. More recently, another reported pathway of inactivation involves loss of transcription associated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 hepatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) amplification, sequence analysis and Southern blot. Homozygous deletions of P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygous deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%). Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of these specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data suggest that the p16/MTS1 gene has a limited role in HCC. However, deletions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC.


E-learning intention material using TAM: A case study.
COVID-19 pandemic has impacted various walks of life. A critical aspect of human development is education, which has been transformed from traditional face-to-face to online education. Various researchers have studied the impact of online modes of education on the learning curve of students. This research envisions identifying the intention among students on whether to continue e-learning or revert to face-to-face mode. Factors like Perceived Usefulness, Perceived Ease of Use, and Behavioral Intention is studied through Technology Acceptance Model (TAM). To evaluate the model, structure analysis was conducted. Two hundred ninety-one students participated and responded to the questionnaire specially designed for this study. Based on the results obtained, academic motivation is positively related to Behavioral Intention, which is completely related to Perceived Usefulness and Perceived Ease of Use. Knowledge Quality and Technology Fit are other salient factors that impact the students' perceived usefulness and ease of use. On the other hand, the relationships between Information Quality and Perceived Usefulness, Perceived Ease of Use and Behavioral Intention, and Social Influence and Behavioral were not supported because of insignificant relationships.


Primary function for a chemical defense? Nicotine does not protect Datura stramonium L from UV damage.
The chemical defenses of plants are thought to play many different functional roles, all of which in some way decrease the costs of deploying the defense. However, few of these other functions have been tested with metabolites that are clearly defensive. Nicotine is a potent chemical defense with a high molar extinction coefficient in the UV, is a potent quencher of free radical pecies produced by UV absorption in vitro, and is known to increase in concentration after exposure to UV radiation. Hence this chemical defense may also function to protect against UV-induced damage. We examined nicotine's potential photoprotective role in two experiments by culturing Datura stramonium L plants in hydroponic solutions containing nicotine at two concentrations, and by exposing nicotine-containing and nicotine-free plants to UV radiation, which allowed us to manipulate nicotine contents independently of UV exposure. Plants with high levels of nicotine were not more resistant to UV-induced damage but, instead, exhibited greater decreases in photosynthetic capacity than did nicotine-free controls. Proposed multifunctional roles for chemical defenses deserve closer scrutiny.


Literal grid map models for animal navigation: Assumptions and predictions.
Many animals can navigate from unfamiliar locations to a familiar target location with no outward route information or direct sensory contact with the target or any familiar landmarks. Several models have been proposed to explain this phenomenon, one possibility being a literal interpretation of a grid map. In this paper we systematically compare four such models, which we label: Correct Bicoordinate navigation, both Target and Release site based, Approximate Bicoordinate navigation, and Directional navigation. Predictions of spatial patterns of initial orientation errors and efficiencies depend on a combination of assumptions about the navigation mechanism and the geometry of the environmental coordinate fields used as model inputs. When coordinates axes are orthogonal at the target the predictions from the Correct Bicoordinate (Target based) model and Approximate Bicoordinate model are identical. However, if the coordinate axes are non-orthogonal different regional patterns of initial orientation errors and efficiencies can be expected from these two models. Field anomalies produce high magnitudes of orientation errors close to the target, while region-wide nonlinearity leads to orientation errors increasing with distance from the target. In general, initial orientation error patterns are more useful for distinguishing between different assumption combinations than efficiencies. We discuss how consideration of model predictions may be helpful in the design of experiments.


Characterization of anti-sticking factor-II from goat epididymal plasma.
A previous study has characterized the major 47 kDa anti-sticking factor (ASF-I) from goat cauda-epididymal plasma (Roy, N., and Majumder, G.C., Biochim. Biophys. Acta, 991:114-122, 1989). This study reports the purification and characterization of ASF-II, another anti-sticking factor from the goat epididymal plasma. ASF-II was purified to apparent homogeneity by using concanavalin A-agarose affinity chromatography, DEAE-cellulose chromatography, alumina gel adsorption, and isoelectric focussing techniques. It showed a single protein band by both non-denaturing and SDS-polyacrylamide gel electrophoresis. ASF-II showed a molecular weight of 36,000 and a sedimentation constant of 2.4S. ASF-II is largely stable to heat treatment and it is a specific glycoprotein having high affinity and specificity for its anti-sticking action. At saturating concentration (1 nM) it inhibited adhesion of nearly 50% of spermatozoa to the glass surface of the haemocytometer counting chamber. Both the protein and sugar parts of the factor are essential for the anti-sticking activity since it lost its activity completely when treated with trypsin, L-fucosidase, or mannosidase. ASF-II does not coat the glass surface and it binds to spermatozoa. Data are consistent with the view that ASF-II has not been derived from the larger ASF-I molecule due to its enzymic modifications. Both ASF-I and -II had no effect on sperm forward motility as evidenced by spectrophotometric motility assays, indicating thereby the suitability of the factors to improve the existing sperm motility assays by eliminating the possibility of cell-sticking artifacts.


Active Appearance Model Induced Generative Adversarial Network for Controlled Data Augmentation.
Data augmentation is an important strategy for enlarging training datasets in deep learning-based medical image analysis. This is because large, annotated medical datasets are not only difficult and costly to generate, but also quickly become obsolete due to rapid advances in imaging technology. Image-to-image conditional generative adversarial networks (C-GAN) provide a potential solution for data augmentation. However, annotations used as inputs to C-GAN are typically based only on shape information, which can result in undesirable intensity distributions in the resulting artificially-created images. In this paper, we introduce an active cell appearance model (ACAM) that can measure statistical distributions of shape and intensity and use this ACAM model to guide C-GAN to generate more realistic images, which we call A-GAN. A-GAN provides an effective means for conveying anisotropic intensity information to C-GAN. A-GAN incorporates a statistical model (ACAM) to determine how transformations are applied for data augmentation. Traditional approaches for data augmentation that are based on arbitrary transformations might lead to unrealistic shape variations in an augmented dataset that are not representative of real data. A-GAN is designed to ameliorate this. To validate the effectiveness of using A-GAN for data augmentation, we assessed its performance on cell analysis in adaptive optics retinal imaging, which is a rapidly-changing medical imaging modality. Compared to C-GAN, A-GAN achieved stability in fewer iterations. The cell detection and segmentation accuracy when assisted by A-GAN augmentation was higher than that achieved with C-GAN. These findings demonstrate the potential for A-GAN to substantially improve existing data augmentation methods in medical image analysis.


Safety aspects of insect cell culture.
The hazards posed to the environment by the accidental release of baculovirus expression vectors can be put into perspective by the results obtained from experiments in which AcNPV was released deliberately into the field (Bishop et al., 1992). Polyhedrin positive viruses will persist in soil and on leaf surfaces for periods comprising weeks and months. However, polyhedrin negative viruses (similar to those used as expression vectors) do not survive in similar situations. In consequence, accidental release of baculovirus expression vectors poses negligible hazard. The risk of such a release will largely depend on the skill of the operators. This does not take into account the hazard posed by the recombinant product which is being made by the virus-infected insect cell. Synthesis of a mammalian-specific toxin, of course, would require particularly careful manipulation of the virus-infected cell culture.The fact that insect cell lines represent an undefined risk, in terms of carriage of adventitious agents means that their containment should be maintained at a minimum of the European containment level 2. Where the tissue of origin has a high risk of infection with human pathogens or where cells may have been used in a virus culture laboratory then appropriate testing is advisable. Careful risk assessment respecting the scale of work and whole procedures (in addition to individual assessment of agents and reagents) will ensure safe working conditions for laboratory staff. If applied properly safety procedures will also succeed in encouraging clean, efficient and well documented work procedures which are synonymous with the economical use of time and resources and good science.


[Diagnostic value of arthrography and MRI in rotator cuff tears].
To prospectively compare arthrography with MRI to determine the sensitivity and specificity in detecting rotator cuff tear. 53 shoulders were studied. All patients underwent both arthrography and MRI. The results were compared with the findings of arthroscopy or open surgery. The sensitivity in demonstrating partial-thickness tears was 70% for arthrography and 80% for MRI; the specificity was 75% for arthrography or MRI. The sensitivity in detecting full-thickness tears was 87% for arthrography and 90% for MRI, and the specificity was 100% for arthrography and 75% for MRI. The sensitivity of arthrography and MRI in detecting rotator cuff tears was identical. The specificity of arthrography in detecting full-thickness tears was higher that of MRI.


Time-resolved structure-function coupling in brain networks.
The relationship between structural and functional connectivity in the brain is a key question in systems neuroscience. Modern accounts assume a single global structure-function relationship that persists over time. Here we study structure-function coupling from a dynamic perspective, and show that it is regionally heterogeneous. We use a temporal unwrapping procedure to identify moment-to-moment co-fluctuations in neural activity, and reconstruct time-resolved structure-function coupling patterns. We find that patterns of dynamic structure-function coupling are region-specific. We observe stable coupling in unimodal and transmodal cortex, and dynamic coupling in intermediate regions, particularly in insular cortex (salience network) and frontal eye fields (dorsal attention network). Finally, we show that the variability of a region's structure-function coupling is related to the distribution of its connection lengths. Collectively, our findings provide a way to study structure-function relationships from a dynamic perspective.


Different pathways for chromosomal integration of transfected circular pSVneo plasmids in normal and established rodent cells.
The chromosomal integration of transfected circular plasmid pSV2neo molecules was investigated in normal and established mammalian fibroblasts, including two secondary cultures of normal mouse fibroblast lines, one established mouse-hamster hybrid cell line, R44, and the human fibrosarcoma line, HT1080. The physical organization of the integrated molecules was studied by restriction analysis. The results showed that whereas the normal fibroblasts predominantly integrated one head-to-tail partial dimeric molecule, the established cells predominantly integrated distinctly different molecular forms including deleted monomeres (HT1080) and various complex concatemeric molecules (R44), and frequently at more than one chromosomal site (R44). We also constructed a head-to-tail dimeric version of the plasmid, which in the case of the normal fibroblasts again integrated as a partial dimeric molecule in at least 50% of these cells. This result excluded the possibility that the normal mouse transfectants were selected for the integration of two functional neo genes. Thus, it is concluded that the distinctly different molecular forms integrated in normal and established cells demonstrate the operation of different integration pathways, the possible nature of which is discussed.


Digital twin modeling for tooth surface grinding considering low-risk transmission performance of non-orthogonal aviation spiral bevel gears.
Low-risk transmission performance including elastic deformation, loaded contact pattern, load distribution and loaded transmission error is of paramount significance to the actual manufacturing for non-orthogonal aviation spiral bevel gears. The advanced digital twin technology is introduced into tooth flank grinding. A new digital twin modeling considering low-risk transmission performances is proposed. In the modeling, low-risk transmission performance driven simulation, sensitivity analysis and robust control are developed, respectively Firstly, data-driven tooth surface modeling is developed by simulating free-form tooth surface grinding including gear tilt method and pinion double helical method. With local geometric boundary setup meshing stiffness is determined by using local Rayleigh-Ritz solution. Then, to deal with the sensitivity of gear assembly, an improved tooth contact analysis (TCA) is developed. Moreover, numerical loaded tooth contact analysis (NLTCA) is performed to build a bridge between of low-risk performances and hypoid generator parameters. The low-risk transmission performance driven control model is established by using hypoid generator parameters modification. Finally, sensitivity analysis strategy-based robust control model is solved by using Levenberg-Marquardt method for accurate hypoid generator parameters having modification amount. The provided numerical instance can verify the proposed method.


Ultimate fate and possible ecological risks associated with atrazine and its principal metabolites (DIA and DEA) in soil and water environment.
Atrazine (AT) is a triazine herbicide widely used to control weeds in several crops. De-isopropylatrazine (DIA) and de-ethylatrazine (DEA) are two of the eight primary metabolites produced by AT breakdown in soil and water. The physico-chemical properties of the soil determine their final fate. So, this study aimed to assess the function of clay loam and sandy loam soils in determining their ultimate fate and the potential ecological risks to non-target species during their persistence in soil and transportation to water bodies. The soil in pots was spiked with standard solutions of AT, DEA, and DIA at 0.3 and 0.6 mg/kg for the persistence study. The leaching potential was determined by placing soils in Plexi columns and spiking them with 50 and 100 µg standard solutions. Liquid-liquid extraction was used to prepare the samples, which were then analyzed using GC-MS/MS. The dynamics of dissipation were first-order. AT, DEA and DIA disappeared rapidly in sandy loam soil, with half-lives ranging from 6.2 to 8.4 days. AT and its metabolites had a significant amount of leaching potential. In sandy loam soil, leaching was more effective, resulting in maximal residue movement up to 30-40 cm soil depth. The presence of a notable collection of residues in leachate fractions suggests the potential for surface and groundwater contamination. In particular, DEA and DIA metabolites caused springtail Folsomia candida and earthworm Eisenia fetida to have longer and greater unacceptable risks. If the residues comparable to the amount acquired in leachate fractions reach water bodies, they could cause toxicity to a variety of freshwater fish, aquatic arthropods, amphibians, and aquatic invertebrates. Future studies should take a more comprehensive approach to evaluate ecological health and dangers to non-target species.


Crude saliva of Amblyomma cajennense sensu stricto (Acari: Ixodidae) reduces locomotor activity and increases the hemocyte number in the females of Aedes aegypti (Diptera: Culicidae).
Aedes aegypti are vector insects of arboviruses such as dengue, Zika, and chikungunya. All available vector control methods have limited efficacy, highlighting the urgent need to find alternative ones. Evidence shows that arachnids like ticks are sources of biologically active compounds. Moreover, chemical modulation of the locomotor and immune systems of vector insects can be used to control arbovirus transmission. The present study evaluated the effectiveness of crude saliva of female Amblyomma cajennense sensu stricto (s.s.) ticks in reducing locomotor activity and inducing an immune response in Ae. aegypti females. Additionally, the study evaluated the protein constitution of tick saliva. For this purpose, the crude saliva obtained from several semi-engorged A. cajennense females was used. A volume of 0.2 nL of crude tick saliva was administered to mosquitoes by direct intrathoracic microinjection. The effect of the tick's saliva on the locomotor activity of the mosquito was observed using Flybox, a video-automated monitoring system, and the hemolymph hemocyte levels were quantified by reading slides under a light microscope. The protein concentration of the crude tick saliva was 1.27 μg/μL, and its electrophoretic profile indicates the presence of proteins with a molecular weight ranging between ∼17 and 95 kDa. Microplusins, ixodegrins, cystatin, actins, beta-actin, calponin, albumin, alpha-globulins, and hemoglobin were the main proteins identified by proteomics in the saliva of A. cajennense. The microinjected saliva had low toxicity for Ae. aegypti females and significantly reduced their locomotor activity, especially in the transition between the light and dark phases. The crude tick saliva did not change the period and rhythmicity of the circadian cycle. The tick saliva significantly increased the number of hemocytes two days after injection and reduced it after five days. These results suggest that further evaluation of the biological properties of tick saliva proteins against Ae. aegypti would be of interest.


Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients.
To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir). Partially randomized, controlled, prospective trial. Single center study at tertiary care center. Sixty four patients (CD4 count 200-500 x 10(6)/l). Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2. The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed. IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group. Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.


Percutaneous revascularization of sole arch artery for severe cerebral ischemia resulting from Takayasu arteritis.
Takayasu arteritis (TA) is a rare form of inflammatory arteriopathy affecting the aorta and its major branches. Obstructive lesions of all arch vessels may lead to disabling neurologic symptoms. There is limited experience with endovascular revascularization in this situation. The present report describes immediate and follow-up results with stent-supported angioplasty of severely stenosed single patent arch arteries. Angioplasty and stent placement were performed in 10 consecutive patients with TA (age, 11-42 years; mean, 28.3 y +/- 4.1) with cerebrovascular symptoms caused by severe stenotic lesions of supraaortic (ie, carotid, vertebral, and brachiocephalic) arteries. Angioplasty was attempted in 12 stenotic lesions: carotid (n = 8), vertebral (n = 2), and brachiocephalic (n = 2). Eight lesions were discrete and four were diffuse. Balloon angioplasty and stent implantation were performed successfully in all patients. The luminal diameter increased from 0.84 mm +/- 0.6 to 5.6 mm +/- 0.7 (P < .001), and the diameter of stenosis was reduced from 81.1% +/- 6.8% to 1.7% +/- 3.3% (P < .001). No immediate procedure-related complication or neurologic deficits occurred. The symptoms improved in all patients. On follow-up (mean, 25 months +/- 7; range, 3-49 months), eight patients were asymptomatic and two patients with diffuse stenosis had recurrence of neurologic symptoms. These patients had in-stent restenosis of the carotid artery, which was successfully treated with cutting balloon angioplasty. Stent-supported angioplasty of a sole supraaortic artery in TA is safe and effective and provides good symptomatic relief in patients with multiple stenoocclusive lesions of arch arteries.


Arundinosides I-IX and graminifolosides A-B: 2R-benzylmalate and 2R-isobutylmalates derivatives from Arundina graminifolia (D.Don) Hochr. with antioxidant, cytocompatibility and cytoprotective properties.
Phytochemical investigation of the underground parts of Arundina graminifolia D.Don Hochr was conducted leading to the isolation of nine new glucosyloxybenzyl 2R-benzylmalate and two new glucosyloxybenzyl 2R-isobutylmalate derivatives. The compounds were purified using chromatographic techniques and their structures were deduced based on spectroscopic techniques including nuclear magnetic resonance and high-resolution mass spectrometry as well as comparing with previous literature. The antioxidant activities of the isolated compounds were also evaluated. The compounds showed potent antioxidant activities in the ABTS radical scavenging, DPPH radical scavenging and FRAP activities. Furthermore, the isolated compounds were observed to exert minimal cytotoxic effects against RAW 264.7 cell, suggesting biocompatibility as well as cytoprotective effects against hydrogen peroxide induced cell toxicity.


Direct observation of inhomogeneous solid electrolyte interphase on MnO anode with atomic force microscopy and spectroscopy.
Solid electrolyte interphase (SEI) is an in situ formed thin coating on lithium ion battery (LIB) electrodes. The mechanical property of SEI largely defines the cycling performance and the safety of LIBs but has been rarely investigated. Here, we report quantitatively the Young's modulus of SEI films on MnO anodes. The inhomogeneity of SEI film in morphology, structure, and mechanical properties provides new insights to the evolution of SEI on electrodes. Furthermore, the quantitative methodology established in this study opens a new approach to direct investigation of SEI properties in various electrode materials systems.


Subacute aseptic meningitis as neurological manifestation of primary Sjögren's syndrome.
Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammatory infiltration and secondary chronic dysfunction of exocrine glands. Systemic (extraglandular) manifestations of the disease occur in one-third of the patients, including a wide spectrum of peripheral and central neurological disorders. We report a case of subacute afebrile aseptic meningitis (AM) as neurological manifestation of primary SS. The neurological symptomatology presented gradual onset and progression, including diplopia, mild headache, pain and stiffness of the neck. The clinical examination pointed out xerostomia and xerophthalmia. Diagnosis of SS was confirmed by Schirmer's tear test and histopathology of the labial salivary glands. The neurological involvement was highlighted by gadolinium-enhanced magnetic resonance imaging of the brain which displayed an increased diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) analysis showed moderate pleocytosis with prevalence of polymorphonuclear leukocytes and increased protein level but no evidence of Ig intrathecal synthesis. A cycle of intravenous steroid therapy led to a complete disappearance of the neurological symptomatology and to normalization of the CSF inflammatory pattern. Given the unusual presentation of this case of AM, which resembled the characteristics of a chronic meningitis rather than those of an acute form, in patients affected by SS we must stress the importance of cephalic symptoms such as headaches and cervical stiffness (even if mild and without fever) as possible signs of central neurological involvement of the disease.


Detection and discrimination of complex sounds by pigeons (Columba livia).
Auditory scene analysis is the process by which sounds are separated and identified from each other and from the background to make functional auditory objects. One challenge in making these psychological units is that complex sounds often continuously differ in composition over their duration. Here we examined the acoustic basis of complex sound processing in four pigeons by evaluating their performance in an ongoing same/different (S/D) task. This provided an opportunity to investigate avian auditory processing in a non-vocal learning, non-songbird. These pigeons were already successfully discriminating 18.5 s sequences of all different 1.5 s sounds (ABCD…) from sequences of one sound repeating (AAAA…, BBBB…, etc.) in a go/no-go procedure. The stimuli for these same/different sequences consisted of 504 tonal sounds (36 chromatic notes×14 different instruments), 36 pure tones, and 72 complex sounds. Not all of these sounds were equally effective in supporting S/D discrimination. As identified by a stepwise regression modeling of ten acoustic properties, tonal and complex sounds with intermediate levels of acoustic content tended to support better discrimination. The results suggest that pigeons have the auditory and cognitive capabilities to recognize and group continuously changing sound elements into larger functional units that can serve to differentiate long sequences of same and different sounds.


An approach to develop two-dimensional fingerprint for the quality control of Qingkailing injection by high-performance liquid chromatography with diode array detection.
An approach was proposed to develop two-dimensional fingerprint (2D fingerprint) by means of principal component analysis (PCA) of high-performance liquid chromatography with diode array detection (HPLC/DAD) data. The approach was applied to establish 2D fingerprints of various Qingkailing injections which were produced by different manufacturers and procedures. In comparison with common one-dimensional fingerprint (ID fingerprint) at fixed wavelength, 2D fingerprint compiled additional spectral data and was hence more informative. Principal component analysis of the 2D fingerprint data was performed in this study, and it led to an accurate classification of various samples on their manufacturers and procedures. The quality of Qingkailing samples was further evaluated by similarity measures and the same results were achieved. For comparison, four conventional ID fingerprints were also applied to the quality assessment for the same samples. Finally, we demonstrated that 2D fingerprint was a more powerful tool to characterize the quality of samples, and could be used to comprehensively conduct the quality control of traditional Chinese medicines.


Minocycline protects motor but not autonomic neurons after cauda equina injury.
Conus medullaris/cauda equina injuries typically result in loss of bladder, bowel, and sexual functions, partly as a consequence of autonomic and motor neuron death. To mimic these injuries, we previously developed a rodent lumbosacral ventral root avulsion (VRA) injury model, where both autonomic and motor neurons progressively die over several weeks. Here, we investigate whether minocycline, an antibiotic with putative neuroprotective effects, may rescue degenerating autonomic and motor neurons after VRA injury. Adult female rats underwent lumbosacral VRA injuries followed by a 2-week treatment with either minocycline or vehicle injected intraperitoneally. The sacral segment of the spinal cord was studied immunohistochemically using choline acetyltransferase (ChAT) and activated caspase-3 at 4 weeks post-operatively. Minocycline increased the survival of motoneurons but not preganglionic parasympathetic neurons (PPNs). Further investigations demonstrated that a larger proportion of motoneurons expressed activated caspase-3 compared to PPNs after VRA injury and indicated an association with minocycline's differential neuroprotective effect. Our findings suggest that minocycline may protect degenerating motoneurons and expand the therapeutic window of opportunity for surgical repair of proximal root lesions affecting spinal motoneurons.


Evaluation of exercise capacity with cardiopulmonary exercise testing and BNP levels in adult patients with single or systemic right ventricles.
The aim of the study was to evaluate exercise capacity using cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP) levels in patients with single or systemic right ventricles. The study group included 40 patients (16 males) - 17 with transposition of the great arteries after Senning operation, 13 with corrected transposition of the great arteries and 10 with single ventricle after Fontan operation, aged 19-55 years (mean 28.8 ±9.5 years). The control group included 22 healthy individuals (10 males) aged 23-49 years (mean 30.6 ±6.1 years). The majority of patients reported good exercise tolerance - accordingly 27 were classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in class III. Cardiopulmonary exercise test revealed significantly lower exercise capacity in study patients than in control subjects. In the study vs. control group VO(2max) was 21.7 ±5.9 vs. 34.2 ±7.4 ml/kg/min (p = 0.00001), maximum heart rate at peak exercise (HRmax) 152.5 ±32.3 vs. 187.2 ±15.6 bpm (p = 0.00001), VE/VCO(2) slope 34.8 ±7.1 vs. 25.7 ±3.2 (p = 0.00001), forced vital capacity (FVC) 3.7 ±0.9l vs. 4.6 ±0.3 (p = 0.03), forced expiratory volume in 1 s (FEV(1)) 3.0 ±0.7 vs. 3.7 ±0.9l (p = 0.0002) respectively. Serum BNP concentrations were higher in study patients than in control subjects; 71.8 ±74.4 vs. 10.7 ±8.1 (pg/ml) respectively (p = 0.00001). No significant correlations between BNP levels and CpET parameters were found. Patients with a morphological right ventricle serving the systemic circulation and those with common ventricle physiology after Fontan operation show markedly reduced exercise capacity. They are also characterized by higher serum BNP concentrations, which do not however correlate with CpET parameters.


Epidemiological characteristics and factors influencing falls among elderly adults in long-term care facilities in Xiamen, China.
Falling in the elderly is an important social issue, especially for those who are in long-term care (LTC) facilities, in addition to being a significant economic burden. This study aims to investigate the epidemiological characteristics and identify the factors influencing falls in LTC residents.We enrolled 260 participants aged 60+ years by multistage sampling across 13 LTC facilities in Xiamen, China, in 2016. Epidemiological characteristics and falls were observed and recorded during a 12-month period using a revised FROP-Com Scale. Multiple logistic regression modeling was performed to determine the factors influencing falls.A total of 218 (83.8%) valid questionnaires were returned. 152 falls (range 1-7, mean 0.7 ± 1.3 falls/person/y) occurred in the previous year, with 69 residents (31.7%) experiencing 1 or more falls. Most participants who fell were female (71%), living in cities (85.5%), had a higher BMI (22.1 ± 4.2), and had a chronic disease (99.9%). Of all falls, 39.1% occurred in the bedroom and 26.1% in the bathroom, 58% during daytime hours between 6:00 AM and noon. Thirty-six percent of falls resulted in an injury (e.g., bruises and fractures). The principal reason for falling was due to slipping (23.2%). There were 2 interactions on fall rate between ADL and feet and footwear (OR = 3.120, P<.001; OR = 3.010, P = .007 in Models 1 and 3), and between ADL and cognitive status (OR = 4.401, P<.001; OR = 4.101, P = .005 in Models 2 and 3). Multiple regression analysis indicated that ADL, balance and gait, medical conditions, cognitive status, living environment, feet and footwear and sensory loss were factors influencing falls among elderly adults in LTC facilities.Falls occur frequently and mostly unwitnessed among elderly adults in LTC facilities, highlighting the need for more effective and individualized fall prevention. Fall efficacy enhancing programs for nursing home residents should take degree of self-care, chronic diseases, sensory loss, foot injuries, cognitive impairment, living environment, and gender into account.


Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity.
The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia. PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 μmol [100 g](-1) min(-1), p < 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 μmol [100 g](-1) min(-1), p < 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS). Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.


Visible-light mediated, oxygen-promoted regioselective cross-dehydrogenative coupling of coumarins and dimethylanilines.
Herein, we report a regioselective, photocatalytic C3 α-aminoalkylation of coumarins via a cross-dehydrogenative coupling of dimethylanilines and coumarins. Molecular oxygen was utilized as the oxidizing agent in this transformation, which exhibits a wide substrate scope and affords the products in good yields. It was established that 4-amino-substituted coumarin reacts via a different mechanism compared to coumarin derivatives that are unsubstituted at the 4-position.


[Developing the methodology of examining the lower limb veins in cosmonauts for the space medicine practice].
The article centres on development of a methodology for evaluating the function of lower limb veins of cosmonauts in microgravity. The whys and wherefores of the choice of occlusive plethysmography equipment and procedure are explained. Much place is given to arguments for the requisite body and limb positioning during venous plethysmography pre launch and on return from space flight. To minimize the gravity effect on venous blood flow, the body should be in the level position and the calf aligned with the hydrodynamically indifferent point. Determining the type of test occlusion, occlusion adjustments, venous parameters of interest, and data processing procedure constitute the methodology.


Roentgenographic evaluation of lumbar spine flexion-extension in asymptomatic individuals.
An experimental clinical study of angulatory and translational lumbar spine intervertebral motion was performed using flexion-extension radiographs obtained in the lateral plane. These "bending" films were obtained from 59 asymptomatic individuals undergoing routine pre-employment examination. Results indicate that there is 7 to 14 degrees of angulatory motion present in the lumbar spine but a large range of values exist so that norms of angulatory motion cannot be more precisely defined. There are 2 to 3 mm of translational motion present in the lumbar spine at each intervertebral level. Twenty percent of this study's asymptomatic subjects had 4 mm or more translational motion at the L4-5 interspace and at least 10% had 3 mm or greater motion at all levels except L5-S1. These results challenge conclusions based on earlier studies and call into question the use of lumbar flexion-extension bending films as a primary determinant of lumbar segmental stability.


Tricuspid atresia with double-outlet left ventricle and bilateral conus.
The first case of tricuspid atresia with a double-outlet left ventricle, l-transposition of the great arteries [S,D,L], and bilateral conus in levocardia diagnosed correctly during life is reported. This case is unique and differs from the classic double-outlet left ventricle in that there is a bilateral conus.