Novel activity of RGS14 on Goalpha and Gialpha nucleotide binding and hydrolysis distinct from its RGS domain and GDI activity.
The bifunctional protein RGS14 is both a GTPase activating protein (GAP) for Gialpha and Goalphaand a guanine nucleotide dissociation inhibitor (GDI) for Gialpha. This GDI activity is isolated to a region of the protein distinct from the RGS domain that contains an additional G protein-binding domain (RBD/GL). Here, we report that RGS14 missing its RGS domain (R14-RBD/GL) binds directly to Go and Gi to modulate nucleotide binding and hydrolysis by mechanisms distinct from its defined GDI activity. In brain pull-down assays, full-length RGS14 and R14-RBD/GL (but not the isolated RGS domain of RGS14) bind Goalpha-GDP, Gialpha-GDP, and also Gbetagamma. When reconstituted with M2 muscarinic receptors (M2) plus either Gi or Go, RGS4 (which has no RBD/GL domain) and full-length RGS14 each markedly stimulates the steady-state GTPase activities of both G proteins, whereas R14-RBD/GL has little or no effect. R14-RBD/GL potentiates RGS4 GAP activity in membrane-based assays by increasing the apparent affinity of RGS4 for Gialpha and Goalpha, suggesting a cooperative interaction between the RBD/GL domain, RGS4, and Galpha. This activity of R14-RBD/GL on RGS4 is not apparent in single-turnover solution GAP assays with purified Gialpha or Goalpha, suggesting that membranes and/or receptors are required for this activity. When these findings are taken together, they indicate that regions of RGS14 outside of the RGS domain can bind inactive forms of Go and Gi to confer previously unappreciated activities that influence Galphanucleotide binding and/or hydrolysis by mechanisms distinct from its RGS domain and established GDI activity.


Distinct roles of theta and alpha oscillations in the involuntary capture of goal-directed attention.
Mechanisms of attention assign priority to sensory inputs on the basis of current task goals. Previous studies have shown that lateralized neural oscillations within the alpha (8-14Hz) range are associated with the voluntary allocation of attention to the contralateral visual field. It is currently unknown, however, whether similar oscillatory signatures instantiate the involuntary capture of spatial attention by goal-relevant stimulus properties. Here we investigated the roles of theta (4-8Hz), alpha, and beta (14-30Hz) oscillations in human goal-directed visual attention. Across two experiments, we had participants respond to a brief target of a particular color among heterogeneously colored distractors. Prior to target onset, we cued one location with a lateralized, non-predictive cue that was either target- or non-target-colored. During the behavioral task, we recorded brain activity using electroencephalography (EEG), with the aim of analyzing cue-elicited oscillatory activity. We found that theta oscillations lateralized in response to all cues, and this lateralization was stronger if the cue matched the target color. Alpha oscillations lateralized relatively later, and only in response to target-colored cues, consistent with the capture of spatial attention. Our findings suggest that stimulus induced changes in theta and alpha amplitude reflect task-based modulation of signals by feature-based and spatial attention, respectively.


[Effect of KCI additive on laser-induced soil plasma radiation].
In order to improve laser-induced breakdown spectroscopy for low-level elements testing capability, the enhancement effects of KCl additive on the emission spectra of soil samples were studied. The laser spectrum analytical system is composed of a high-energy neodymium glass laser ablating samples, a multifunctional and automatic scanning spectrometer, and a CCD data acquisition system recording plasma spectra. The electron temperature and electron density of plasmas were calculated by measuring spectral line intensity and stark broadening respectively. The experimental results showed that with the increase in the KCl additive, the spectral intensity, signal-to-background ratio, the electron temperature and the electron density all went up firstly and then down. When 15% KCl was added, the radiation intensity of plasma reached the maximum value, the spectral lines intensity of element Mn, Fe, and Ti increased by 2.23, 1.13 and 2.04 than that without additive respectively, the spectral signal-to-background ratio increased by 1.33, 0.89 and 0.94 times respectively; while the electron temperature and electron density of plasmas were heightened by 14% and 38% respectively.


Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: a case report.
Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemo-embolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.


The development of the P-CAN, a measure to operationalize the pros and cons of anorexia nervosa.
Research has suggested that a fundamental aspect of anorexia nervosa (AN) is its egosyntonic nature, the fact that it is often valued by individuals with the disorder. The current study describes the development of the P-CAN, a quantitative measure of both positive (valued) and negative aspects of AN. Items were derived from a previous qualitative study (Serpell, Treasure, Teasdale, & Sullivan. 1999. International Journal of Eating Disorders, 25, 177-186). Data from 233 women with AN were subjected to a principal components analysis. Ten subscales were identified, six describing the pros of AN and four describing the cons of the illness. The P-CAN shows good psychometric properties and should prove a useful tool for the measurement of attitudes towards AN, as well as offer insights into the maintenance of the disorder.


Space Station Biological Research Project (SSBRP) Cell Culture Unit (CCU) and incubator for International Space Station (ISS) cell culture experiments.
The CCU and Incubator are habitats under development by SSBRP for gravitational biology research on ISS. They will accommodate multiple specimen types and reside in either Habitat Holding Racks, or the Centrifuge Rotor, which provides selectable gravity levels of up to 2 g. The CCU can support multiple Cell Specimen Chambers, CSCs (18, 9 or 6 CSCs; 3, 10 or 30 mL in volume, respectively). CSCs are temperature controlled from 4-39 degrees C, with heat shock to 45 degrees C. CCU provides automated nutrient supply, magnetic stirring, pH/O2 monitoring, gas supply, specimen lighting, and video microscopy. Sixty sample containers holding up to 2 mL each, stored at 4-39 degrees C, are available for automated cell sampling, subculture, and injection of additives and fixatives. CSCs, sample containers, and fresh/spent media bags are crew-replaceable for long-term experiments. The Incubator provides a 4-45 degrees C controlled environment for life science experiments or storage of experimental reagents. Specimen containers and experiment unique equipment are experimenter-provided. The Specimen Chamber exchanges air with ISS cabin and has 18.8 liters of usable volume that can accommodate six trays and the following instrumentation: five relocatable thermometers, two 60 W power outlets, four analog ports, and one each relative humidity sensor, video port, ethernet port and digital input/output port.


Long-term outcomes of coils embolization for superior hypophyseal artery aneurysms.
Superior hypophyseal artery (SHA) aneurysms are intradural, and their rupture can result in subarachnoid hemorrhage. Considering the related surgical difficulty and anatomical restrictions, endovascular treatment (EVT) is considered the most favorable modality for SHA aneurysms; however, the long-term outcomes of EVT have rarely been reported. The study assessed the incidence of and risk factors for recurrence of SHA aneurysms after EVT as well as the correlation factors for SHA aneurysm rupture. We included 112 patients with SHA aneurysms treated with EVT at our facility between 2009 and 2020. Here, EVT included non-stent-assisted (simple or balloon-assisted) or stent-assisted coiling. Flow diverter was not included because it was barely used due to its high cost under our national insurance's limitation, and a high proportion of ruptured aneurysms in our series. Univariate and multivariate logistic regression was performed to evaluate the correlation factors for SHA aneurysm rupture, along with the incidence of and risk factors for post-EVT SHA aneurysm recurrence and re-treatment. In our patients, the mean angiographic follow-up period was 3.12 years. The presence of type IA or IB cavernous internal carotid artery (cICA) was strongly correlated with SHA aneurysm rupture. Recurrence occurred in 17 (13.4%) patients, of which only 1 (1.4%) patient had received stent-assisted coiling. All cases of recurrence were observed within 2 years after EVT. The multivariate logistic regression results showed that ruptured aneurysm and non-stent-assisted coiling were independent risk factors for aneurysm recurrence. Of the 17 cases of aneurysm recurrence, 9 (52.9%) received re-treatment. Moreover, aneurysm rupture was the only factor significantly correlated with re-treatment in multivariate logistic regression. No re-recurrence was observed when a recurrent aneurysm was treated with stent-assisted coiling. Type I cICA was common factor for aneurysm rupture. Although flow-diverter treatment serves as another suitable technique that was not compared with, coils embolization was effective treatment modality for SHA aneurysms, leading to low recurrence and complication rates, especially with stent use. All cases of recurrence occurred within 2 years after EVT; they were strongly associated with prior aneurysm rupture. Further stent-assisted coiling was noticed to prevent re-recurrence.


A two-step strategy for detecting intrauterine cytomegalovirus infection with clinical manifestations in the mother, fetus, and newborn.
We selected a high-risk group based on clinical manifestations and performed virological tests to detect intrauterine cytomegalovirus (CMV) infection. We tested the efficacy of this detection protocol in this study. We analyzed 2,309 newborns at 22 weeks or more of gestation from January 1992 to December 2000. Clinical manifestations of the mother, fetus, and newborn were used in the initial step to identify the high-risk group. For the high-risk group, if the causes of clinical manifestation remained unclear, we assayed for CMV DNA in the amniotic fluid, umbilical cord blood, or newborn urine using polymerase chain reaction (PCR) as a second step. Positive PCR results were confirmed by isolating CMV. The initial step detected 287 high-risk cases from 2,309 deliveries. In this group, 100 cases did not have reasonable explanations for the clinical manifestation. In the second-step PCR, intrauterine CMV infection was diagnosed in 10 of 100 cases (10%). The initial clinical classification reduced the proportion of cases needing laboratory investigation to 4%. Thus, our strategy detected intrauterine CMV infection in as many as 10% of high-risk patients after the first step, which is much higher than the general screening rate.


Leucocyte migration inhibition index responses of patients of amoebic liver abscess to various antigens of Entamoeba histolytica.
The whole amoebic lysate (WAL), Sephadex G-200 eluted fraction-I. (F-I), detergent dissected membrane proteins (DDMP), amoebic membrane glycoprotein (AMG) and amoebal RNA were extracted from E. histolytica. Amoebal RNA recognized 98.21% where as F-I, AMG, DDMP and WAL recognised 92.85, 91.07, 89.28 and 75% of total 56 clinically proven and amoebic serology positive amoebic liver abscess cases respectively. Intensity of recognition of individual fraction i.e., leucocyte migration inhibition index of each fraction was found to be highly significant (P < 0.001) when compared to whole amoebic lysate. This indicate the leucocyte migration inhibition index responses of patients of amoebic liver abscess to various antigenic fractions of E. histolytica with variations.


[Evaluation of venous therapy. Venous tonics, vascular protectants and thermal cures. What are the advantages for the patient?].
In the first section, the authors describe some epidemiological features and give an account of the capillary structure and the structure of different veins. They describe the venous physiology and its modulations, in order to be able to give a precise description of different venous affections: venous senescence, chronic venous insufficiency, thrombophlebitis. The particular features of these three pathologies and their action mechanisms enable the authors to envisage appropriate phleboactive therapy, and to evaluate it in advance. As far as the actual notion of evaluating these venous therapies is concerned, the authors make clear that there is no difference between thermal therapies and phleboactive allopathic therapies. They concentrate on describing a unique methodology in two stages considering the thermal establishment as a pharmaceutic laboratory and as an out-patient hospital for follow-up treatment. This therapeutic evaluation comprises two sections: preparation at the laboratory (pharmaco-clinical stage, animal experimentation) and the second stage of therapeutic clinical tests on humans. The authors define a rigorous, quantified methodology based on homogeneous samples in the framework of a computerised medical file consisting of a base and polyvalent satellites. Satellite 3, assembling the elements of the therapeutic form, deals, for example, with phlebotonics, vascular protectors and thermal cures. A detailed list of different phleboactive therapies is drawn up, making it possible to analyse their specific respective effects, and therefore to give specific prescriptions. The patient can hope for preventive measures and a cure with fewer after-effects in the context of a general, well-conducted sanitary education. The authors conclude that patients, doctors and the organizations concerned will benefit greatly from this.


Stabilization of an intermediate activation state for transducin by a fluorescent GTP analogue.
The GTP-binding protein (G protein), transducin, serves as a key molecular switch in vertebrate vision through the tight regulation of its GTP-binding (activation)/GTP hydrolytic (deactivation) cycle by the photoreceptor rhodopsin. To better understand the structure-function characteristics of transducin activation, we have set out to identify spectroscopic probes that bind to the guanine nucleotide-binding site of this G protein and maintain its ability to interact with its specific cellular target/effector, the cyclic GMP phosphodiesterase (PDE). In this study, we describe the characterization of a fluorescently labeled GTP analogue, BODIPY-FL GTPgammaS (BOD-GTPgammaS), that binds to the alpha subunit of transducin (alpha(T)) in a rhodopsin- and Gbetagamma-dependent manner, similar to the binding of GTP or GTPgammaS, with an apparent dissociation constant of 100 nM. The rhodopsin-dependent binding of BOD-GTPgammaS to alpha(T) is slow, relative to the rate of binding of GTPgammaS, particularly under conditions where rhodopsin must act catalytically to stimulate the exchange of BOD-GTPgammaS for GDP on multiple alpha(T) subunits. This reflects a slower rate of dissociation of rhodopsin and Gbetagamma from alpha(T)-BOD-GTPgammaS complexes, relative to their rates of dissociation from alpha(T)-GTPgammaS. The binding of BOD-GTPgammaS occurs without a change in the intrinsic tryptophan fluorescence of alpha(T), indicating that only a subtle movement of the Switch 2 domain on alpha(T) accompanies the binding of this GTPgammaS analogue. Nevertheless, the BOD-GTPgammaS-bound alpha(T) subunit is able to bind with high affinity to the recombinant, purified gamma subunit of PDE (gamma(PDE)) labeled with 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid (IAEDANS (K(d) approximately 13 nM)), as well as bind to and stimulate the activity of PDE, albeit less efficiently compared to alpha(T)-GTPgammaS. Taken together, these findings suggest that the binding of BOD-GTPgammaS to transducin causes it to adopt a distinct conformation that appears to be intermediate between the inactive and fully active states of alpha(T), and this fluorescent nucleotide analogue can be used as a reporter group to characterize the interactions of alpha(T) in this conformational state with its biological target/effector.


Formal comment on "Systematic review of the predictors of statin adherence for the primary prevention of cardiovascular disease".
Statins have been prescribed for primary prevention of cardiovascular disease (CVD) for nearly 3 decades. Throughout this period key opinion leaders in the field have been dismayed by the high rate of non-adherence of patients to follow their statin regimen. Hope et al., [1] have addressed this issue by providing a systematic review of research on predictors of statin adherence for primary prevention of CVD. However, their review does not address the ongoing debate as to whether statin treatment is warranted for primary prevention of CVD, nor does it adequately address concerns regarding adverse effects of statins. We have therefore written a commentary which provides a broader perspective on the benefits versus harms of statin therapy. Our perspective of the literature is that non-adherence to statin treatment for primary prevention of CVD is justified because the meager benefits are more than offset by the extensive harms.


[Children's development after placental dysfunction (author's transl)].
Katamnestic neurological and electroencephalographic studies were performed on a group of 6 to 11 year old children who had been born in the years of 1960 to 1966 with the signs of placental dysfunction. Of a total of 288 children (2,8% of the deliveries at the department of obstetrics & gynecology of the Cologne university) 177 were analized katamnestically and 152 uncerwent a clinical examination. For comparison a group of 384 children were studied who had been born in the same years spontaneously from vertex presentation after a maximum duration of labour of 16 hours. At the time of delivery these children were mature and eutrophic. 133 children of this group were studied katamnestically and 114 underwent clinical examination. The katamnestic studies showed that the group with symptoms of placental dysfunction differed in their development from the control group: these children learned later to sit, to walk, to speak, to dress without help, and to control urination. No differences were found in the ability to write and to read or in their results at school. However a larger percentage of the control group was found to attend a higher educational institution. No differences were found in the incidence of disease or behavioral abnormalities. Sleeping problems and lact concentration were more often observed in the group of children with symptoms of placental dysfunction. The general clinical examination showed no differences between the two groups. The applied different tests to examine grow movements were performed less perfect in a higher percentage by the children born with signs of placental dysfunction. Even greater differences were found in testing the voluntery skilled movements. The electroencephalogram of children of both groups showed a normal basic activity, a distinct blocking effect and a significant activation upon hyperventilation. An abnormal and pathological EEG was however significantly more often found in children born with symptoms of placental dysfunction. The results of the examination of the individual children and the combination of these results in the groups of symptoms showed that children with signs of placental dysfunction demonstrated a significantly higher incidence of symptoms. It was furthermore obvious that these symptoms were not singular but part of a complex disturbance which was manifested in the obstetrical characteristics as well as in the katamnesis and in the clinical examination. Thus, these studies have demonstrated a higher rate of morbidity in children with placental dysfunction in addition to the known high perinatal mortality. This points the necessity of an early prepartual diagnosis in particular in pregnancies with predisposition, in order to reduce not only the perinatal mortality but also to avoid the described complications in children born after placental dysfunction.


Gynecologic cancers.
In conclusion, significant advances have been made in ovarian cancer. Specifically, these relate to the success of paclitaxel and platinum-based regimens. The appropriate scheduling, dosing, and the selection of carboplatin vs cisplatin remains controversial. The role of interval debulking surgery is still investigational and we remain cautiously optimistic as to its long-term benefit. The progress in the delivery of chemotherapy to patients with cervical carcinoma, endometrial carcinoma, vaginal carcinoma, and vulvar carcinoma has been slowed by the paucity of prospective-randomized trials. Although numerous single institution non-randomized trials show promising regimens, they lack significant power and appropriate study design to prove meaningful. Our goals in the future should be to try to enter most of these patients into national collaborative studies where significant conclusions can be made because of appropriate study design and adequate patient numbers.


Bioaccessibility of Ba, Cu, Pb, and Zn in urban garden and orchard soils.
Exposure of young children to toxic metals in urban environments is largely due to soil and dust ingestion. Soil particle size distribution and concentrations of toxic metals in different particle sizes are important risk factors in addition to bioaccessibility of these metals in the particles. Analysis of particle size distribution and metals concentrations for 13 soils, 12 sampled from urban gardens and 1 from orchard found that fine particles (<105 μm) comprised from 22 to 66% by weight of the tested soils, with Ba, Cu, Pb and Zn generally at higher concentrations in the finer particles. However, metal bioaccessibility was generally lower in finer particles, a trend most pronounced for Ba and Pb. Gastric was higher than gastrointestinal bioaccessibility for all metals except Cu. The lower bioaccessibility of Pb in urban garden soils compared to orchard soil is attributable to the higher organic matter content of the garden soils.


Endoscopic carpal tunnel pressure measurement: a reliable technique for complete release.
Carpal tunnel syndrome is diagnosed by clinical symptoms, Tinel's sign, Phalen's test and electromyography. Carpal tunnel pressure measurement can also aid in the precise identification of excessive pressure sites that indicate locations for release. In this study, pressure measurements made during endoscopic carpal tunnel release at 5 points were significantly higher anywhere in the carpal tunnel than outside the tunnel and decreased markedly after release. We concluded that our measurement technique can improve the reliability of endoscopic carpal tunnel release by decreasing the likelihood of missing any nerve entrapment sites.


Synthesis of 7 alpha- and 7 beta-spermidinylcholesterol, squalamine analogues.
Stereoselective synthesis of squalamine dessulfates analogues, 7 alpha and 7 beta-N-[3N-(4-aminobutyl) aminopropyl]aminocholesterol are reported, using 7 alpha and 7 beta-aminocholesterol as a key intermediate. It's the first example in which the position of spermidine is modified at the steroid ring. These molecules showed a comparable antibacteria and fungi activities to squalamine. Then, they have a cytotoxic activity on a human non-small cell bronchopulmonary carcinoma line (NSCLC-N6).


Two-year interferon therapy with or without ribavirin in chronic delta hepatitis.
The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.


A novel salt- and organic solvent-tolerant phosphite dehydrogenase from Cyanothece sp. ATCC 51142.
Phosphite dehydrogenase (PtxD) is a promising enzyme for NAD(P)H regeneration. To expand the usability of PtxD, we cloned, expressed, and analyzed PtxD from the marine cyanobacterium Cyanothece sp. ATCC 51142 (Ct-PtxD). Ct-PtxD exhibited maximum activity at pH 9.0°C and 50°C and high stability over a wide pH range of 6.0-10.0. Compared to previously reported PtxDs, Ct-PtxD showed increased resistance to salt ions such as Na+, K+, and NH4 +. It also exhibited high tolerance to organic solvents such as ethanol, dimethylformamide, and methanol when bound to its preferred cofactor, NAD+. Remarkably, these organic solvents enhanced the Ct-PtxD activity while inhibiting the PtxD activity of Ralstonia sp. 4506 (Rs-PtxD) at concentrations ranging from 10% to 30%. Molecular electrostatic potential analysis showed that the NAD+-binding site of Ct-PtxD was rich in positively charged residues, which may attract the negatively charged pyrophosphate group of NAD+ under high-salt conditions. Amino acid composition analysis revealed that Ct-PtxD contained fewer hydrophobic amino acids than other PtxD enzymes, which reduced the hydrophobicity and increased the hydration of protein surface under low water activity. We also demonstrated that the NADH regeneration system using Ct-PtxD is useful for the coupled chiral conversion of trimethylpyruvic acid into L-tert-leucine using leucine dehydrogenase under high ammonium conditions, which is less supported by the Rs-PtxD enzyme. These results imply that Ct-PtxD might be a potential candidate for NAD(P)H regeneration in industrial applications under the reaction conditions containing salt and organic solvent.


Cavernous hemangioma of the liver: detection with single-photon emission computed tomography.
The roles of single-photon emission computed tomography (SPECT) and planar imaging with technetium-99m-labeled red blood cells in the diagnosis of cavernous hemangioma of the liver were evaluated. The study group consisted of 26 consecutive patients referred for evaluation of liver lesions. A total of 23 cavernous hemangiomas were found, all of which showed decreased or normal flow and delayed uptake of the radiotracer. SPECT demonstrated 13 hemangiomas that were not detected with planar imaging; both modalities demonstrated the other ten lesions. Lesions that were not cavernous hemangiomas showed either normal (n = 6) or increased (n = 4) flow; none had delayed increased uptake on either planar or SPECT images. SPECT with labeled red blood cells is an accurate method for the detection of cavernous hemangiomas of the liver and is more sensitive than planar imaging in depicting small lesions.


Tuning optoelectronic response of lateral core-alloyed crown nanoplatelets: type-II CdSe-CdSe1-xTex.
We present a theoretical study showing that the exciton emission in the CdSe-CdSe1-xTexcore-alloyed crown heterostructure results from the tunable quasi-type II to pure type II behavior by adjusting the Te to Se ratio. We suggest that the direct crown exciton or interface indirect exciton or a dual emission can be tuned due to the altered conduction band offset. We also found that these different emissions are red-shifted with increasing the nanoplatelets (NPLs) monolayer (ML) thickness due to the quantum confinement effect. The double exciton emission develops caused by the band bowing effect occurring in the alloyed crown. The band bowing is originated from the difference between the bonding nature of the Se and Te orbitals with the Cd orbitals in the conduction band edge states. We also found that the band bowing is sensitive on the alloyed-crown ML thickness and the in-plane strain due to hybridization magnitude between the cation (Cd) and anion (Se, Te). Our results are in accord with the available experimental data. We propose the CdSe-CdSe1-xTexcore-alloyed crown NPLs as a promising contender for the near-infrared-emitting heterostructures preparation used for light-harvesting applications.


CTRP9 decreases high glucose‑induced trophoblast cell damage by reducing endoplasmic reticulum stress.
C1q/TNF‑α‑related protein 9 (CTRP9) is downregulated in gestational diabetes mellitus (GDM) and may exert a protective effect against GDM, although its mechanism of action is yet to be elucidated. To investigate the specific role of CTRP9 in GDM, the human placental trophoblast cell line HTR8/SVneo was treated with high glucose (HG) to simulate the environment of GDM in vitro. The effects of CTRP9 on the HTR8/SVneo cells and endoplasmic reticulum (ER) stress were analyzed before and after CTRP9 overexpression using reverse transcription‑quantitative PCR and western blotting. The results obtained demonstrated that CTRP9 alleviated ER stress in the trophoblast cell line. After treating with the ER‑stress inducer tunicamycin, cell viability was investigated by performing Cell Counting Kit‑8, TUNEL and western blotting assays, which revealed that CTRP9 increased the activity of HTR8/SVneo cells induced by HG through the alleviation of ER stress. Subsequently, ELISA and western blotting assay results demonstrated that CTRP9 inhibited HG‑induced inflammation of the HTR8/SVneo cells by the reduction in ER stress. Finally, the detection of reactive oxygen species, nitric oxide (NO) synthase and NO levels confirmed that CTRP9 inhibited the oxidative stress of HTR8/SVneo cells induced by HG through the reduction of ER stress. Collectively, the results of the present study suggested that CTRP9 may decrease trophoblast cell damage caused by HG through the suppression of ER stress, and therefore, CTRP9 may potentially be a therapeutic target in the treatment of GDM.


A pilot study on the applicability of thromboelastometry in detecting brain tumour-induced hypercoagulation.
Patients with intracranial tumours have an increased risk of venous thromboembolism, particularly during the first month after neurosurgery. A proposed explanation for this increased risk, are procoagulant tumour-derived substances, such as tissue factor, usually measured in peripheral blood. The aim of the present study is to investigate whether a rotational thromboelastometry (ROTEM) can measure the procoagulative activity of tumour tissue. The study included 21 patients who were undergoing a craniotomy and complete tumour resection after written consent and ethical approval were obtained. Tumour tissue was biopsied during surgery and used for in vitro spiking of patients own citrated whole blood. Blood samples with or without spiking were analyzed with ROTEM using different activating reagents. ROTEM clotting time significantly decreased (p < .001), indicating a hypercoagulative response on clot initiation that was strongest for glioma tumours. However, ROTEM clot formation time was significantly prolonged (p < .001), which was an opposite response that indicated poor initial clot propagation. ROTEM maximum lysis was increased in the tumour tissue-spiked samples (p < .001), indicating a strong fibrinolytic activity in brain tumour tissue. Tissue extracts from intracranial tumours have both procoagulant and fibrinolytic effects that are detectable with ROTEM. Glioma tumours had the strongest hypercoagulative response in our in vitro model. Larger studies are necessary to test the clinical relevance and accuracy of tumour extract spiked viscoelastic tests to predict the individual patient risk for developing a thrombotic complication.


Novel hydroxamates potentiated in vitro activity of fluconazole against Candida albicans.
A set of 12 novel hydroxamate compounds (NHCs), structurally designed as inhibitors of histone deacetylase (HDAC) enzyme, were synthesized at our facility. These were adamantane derivatives with N-hydroxyacetamide as pharmacophore, and each of these compounds was tested for potentiating activity on fluconazole. The concentration of fluconazole which completely inhibited (concentration of complete inhibition [CCI]) the growth of Candida albicans ATCC 90028 and C. albicans ATCC 64550 was determined by micro-dilution method in the absence and presence of NHCs. The CCI of fluconazole without the NHC combination was 64 μg/ml and 1024 μg/ml against C. albicans ATCC 90028 and C. albicans ATCC 64550, respectively. The majority of the NHCs potentiated the fluconazole activity markedly as CCI of fluconazole against C. albicans ATCC 90028 reduced to 0.25 μg/ml. Similarly, CCI of fluconazole against C. albicans ATCC 64550 reduced to 4-8 μg/ml in combination with majority of NHCs while the best activity was displayed by the compound 1 with a reduction of CCI to 0.5 μg/ml. The study results revealed the potential usage of hydroxamate derivatives, structurally designed as HDAC inhibitors to enhance the activity of fluconazole against C. albicans.


Biomechanical modeling and design optimization of cartilage myringoplasty using finite element analysis.
The purpose of this study was to determine the acoustic transfer characteristics of cartilage for optimal cartilage myringoplasty. In order to do so, we developed a cartilage plate/tympanic membrane-coupled model using finite element analysis. Cartilage specimens of the tragus were obtained from fresh human cadavers, and the parameters of the tragus were determined by curve fitting and cross-calibration. A cartilage plate was used to repair an eardrum perforation, and the new coupled tympanic membrane-cartilage complex was loaded into our 3-dimensional biomechanical model of the middle ear for analysis. Our results show that first the beta-damping value of the cartilage plate depends on frequency. The value of beta damping was close to 3 x 10(-4) s at lower frequencies and 5 x 10(-6) s at higher frequencies. Secondly, reducing cartilage thickness leads to an improvement of its acoustic transfer qualities. From an acoustics point of view, the 0.1- to 0.2-mm cartilage plate seems to be most preferable with regard to tympanic membrane vibration. Furthermore, thicknesses of 0.2 mm at lower frequencies and 0.1 mm at higher frequencies were regarded as good compromises between sufficient mechanical stability and low acoustic transfer loss.


Simultaneous determination of N-butylscopolamine and oxazepam in pharmaceutical formulations by first-order digital derivative spectrophotometry.
A simple method has been developed for the simultaneous determination of N-butylscopolamine bromide and oxazepam in pharmaceutical formulations using first-order digital derivative spectrophotometry. Acetonitrile was selected as the solvent in which both compounds showed well-defined bands. Both analytes showed good stability in this solvent when solutions of the analytes were exposed to light and temperatures between 20 degrees and 80 degrees C. The simultaneous determination of both drugs was performed by the zero-crossing method at 226.0 and 257.0 nm for N-butylscopolamine and oxazepam, respectively. The linear range of determination was found to be 2.5 x 10(-7) to 8.0 x 10(-5) mol/L for N-butylscopolamine and 7.1 x 10(-8) to 8.0 x 10(-5) mol/L for oxazepam. A very good level of repeatability (relative standard deviation) of 0.2% was observed for N-butylscopolamine and oxazepam. The ingredients commonly found in pharmaceutical formulations do not interfere. The proposed method was applied to the determination of these drugs in pharmaceutical formulations (capsules).


Pheochromocytoma and myocardial infarction.
Pheochromocytomas are rare chromaffin cell tumors, 90% of which arise from the adrenal glands. Pheochromocytomas presenting with true myocardial infarction are even more rare. We report a 76-year-old man who had a previously undiagnosed pheochromocytoma, and presented with the uncommon complication of myocardial infarction. Our high-risk patient was managed with the combination of simultaneous coronary artery bypass grafting and adrenalectomy.


Joint analysis of repeatedly observed continuous and ordinal measures of disease severity.
In biomedical studies often multiple measures of disease severity are recorded over time. Although correlated, such measures are frequently analysed separately of one another. Joint analysis of the outcomes variables has several potential advantages over separate analyses. However, models for response variables of different types (discrete and continuous) are challenging to define and to fit. Herein we propose correlated probit models for joint analysis of repeated measurements on ordinal and continuous variables measuring the same underlying disease severity over time. We demonstrate how to rewrite the models so that maximum-likelihood estimation and inference can be performed with standard software. Simulation studies are performed to assess efficiency gains in fitting the responses together rather than separately and to guide response variable selection for future studies. Data from a depression clinical trial are used for illustration.


Clinical evaluation of a new custom offset shoulder prosthesis for treatment of complex fractures of the proximal humerus.
Primary hemiarthroplasty of the shoulder is an accepted procedure to treat complex proximal humeral fractures. The goal of this study was to assess the functional outcome in patients treated with hemiarthroplasty using a custom offset shoulder prosthesis, either for an acute four-part fracture of the proximal humerus or following failed primary treatment of a complex humeral fracture. Thirty seven patients were followed up for a mean of 17 months after shoulder replacement (Group A: four-part-fractures; n = 26, Group B: posttraumatic necrosis/non-union after failed primary treatment; n = 11). The Constant-Murley-Score and radiological score according to Neer's classification were used for postoperative functional and radiological assessment. Following hemiarthroplasty, Group A achieved an average Constant Score of 52 and Group B of 46. The pain relief after hemiarthroplasty was about 53% in Group A and only 33% in Group B. The least satisfying partial function was shoulder mobility in both groups. Radiographic evaluation did not correlate with the Constant Score. Patients secondarily treated with arthroplasty seem to have less chance to achieve a satisfying functional outcome compared to those with immediate hemiarthroplasty. These results emphasise the importance of a careful initial decision to select the most appropriate treatment modality in complex fractures of the proximal humerus.


Effect of saliva contamination on bond strength with a hydrophilic composite resin.
To evaluate the influence of saliva contamination on the bond strength of metallic brackets bonded to enamel with hydrophilic resin composite. Eighty premolars were randomly divided into 4 groups (n = 20) according to bonding material and contamination: G1) bonded with Transbond XT with no saliva contamination, G2) bonded with Transbond XT with saliva contamination, G3) bonded with Transbond Plus Color Change with no saliva contamination and G4) bonded with Transbond Plus Color Change with saliva contamination. The results were statistically analyzed (ANOVA/Tukey). The means and standard deviations (MPa) were: G1) 10.15 ± 3.75; G2) 6.8 ± 2.54; G3) 9.3 ± 3.36; G4) 8.3 ± 2.95. The adhesive remnant index (ARI) ranged between 0 and 1 in G1 and G4. In G2 there was a prevalence of score 0 and similar ARI distribution in G3. Saliva contamination reduced bond strength when Transbond XT hydrophobic resin composite was used. However, the hydrophilic resin Transbond Plus Color Change was not affected by the contamination.


Gaze response to dyadic bids at 2 years related to outcomes at 3 years in autism spectrum disorders: a subtyping analysis.
Variability in attention towards direct gaze and child-directed speech may contribute to heterogeneity of clinical presentation in toddlers with autism spectrum disorders (ASD). To evaluate this hypothesis, we clustered sixty-five 20-month-old toddlers with ASD based on their visual responses to dyadic cues for engagement, identifying three subgroups. Subsequently, we compared social, language, and adaptive functioning of these subgroups at 3 years of age. The cluster displaying limited attention to social scenes in general exhibited poor outcome at 3 years; the cluster displaying good attention to the scene and to the speaker's mouth was verbal and high functioning at 3 years. Analysis of visual responses to dyadic cues may provide a clinically meaningful approach to identifying early predictors of outcome.


Access to highly functionalized imidazolones bearing α-amino acid esters via KOH-promoted annulation of amidines, nitrosoarenes and malonic esters.
An efficient approach to obtain highly functionalized imidazolones bearing α-amino acid esters through KOH-mediated one-pot three-component annulation of amidines, nitrosoarenes and malonic esters is reported. This reaction features broad substrate scope, a cheap and readily available promoter, good to high yields for most substrates and mild reaction conditions. The mechanism study shows that the KOH-mediated formation of the imine intermediate via the reaction of nitrosoarenes with malonic esters is a key step.


Multimodal approaches for inequality in kidney care: turning social determinants of health into opportunities.
Kidney disease is associated with major health and economic burdens worldwide, disproportionately carried by people in low and middle socio-demographic index quintile countries and in underprivileged communities. Social determinants such as education, income and living and working conditions strongly influence kidney health outcomes. This review synthesised recent research into multimodal interventions to promote kidney health equity that focus on the social determinants of health. Inequity in kidney healthcare commonly arises from nationality, race, sex, food insecurity, healthcare access and environmental conditions, and affects kidney health outcomes such as chronic kidney disease progression, dialysis and transplant access, morbidity and mortality. Multimodal approaches to addressing this inequity were identified, targeted to: patients, families and caregivers (nutrition, peer support, financial status, patient education and employment); healthcare teams (workforce, healthcare clinician education); health systems (data coding, technology); communities (community engagement); and health policy (clinical guidelines, policy, environment and research). The engagement of diverse patients, families, caregivers and communities in healthcare research and implementation, as well as clinical care delivery, is vital to counteracting the deleterious effects of social determinants of kidney health.


SERS-based detection of 5-S-cysteinyl-dopamine as a novel biomarker of Parkinson's disease in artificial biofluids.
The early detection of Parkinson's disease (PD) can significantly improve treatment and quality of life in patients. 5-S-Cysteinyl-dopamine (CDA) is a key metabolite of high relevance for the early detection of PD. Therefore, its sensitive detection with fast and robust methods can improve its use as a biomarker. In this work we show the potentialities of label-free SERS spectroscopy in detecting CDA in aqueous solutions and artificial biofluids, with a simple, fast and sensitive approach. We present a detailed experimental SERS band assignment of CDA employing silver nanoparticle (AgNP) substrates in aqueous media, which was supported by theoretical calculations and simulated Raman and SERS spectra. The tentative orientation of CDA over the AgNP was also studied, indicating that catechol and carboxylic acid play a key role in the metallic surface adsorption. Moreover, we showed that SERS can allow us to identify CDA in aqueous media at low concentration, leading to the identification of some of its characteristic bands in pure water and in synthetic cerebrospinal fluid (SCSF) below 1 × 10-8 M, while its band identification in simulated urine (SUR) can be reached at 1 × 10-7 M. In conclusion, we show that CDA can be suitably detected by means of label-free SERS spectroscopy, which can significantly improve its sensitive detection for further analytical studies as a novel biomarker and further clinical diagnosis in PD patients.


Efficient transfer of reporter gene-loaded nanoparticles to bone marrow stromal cells (D1) by reverse transfection.
Nucleic acids can be complexed with cationic polymer to form DNA nanoparticles (polyplex) which are then immobilized on the surface coated extracellular matrix protein (ECM), the process termed as reverse transfection. ECM-containing proteins provide a surface for cell attachment and sustain the release of polyplexes from their surface, thereby inducing transgene expression for prolonged period of time. Consequently, long-term expression of the desired protein can be achieved with the smaller amount of required DNA, as compared to bolus delivery. First of all, we investigated the different ECM components as a coating material and the range of optimal coating density in different ECM was examined for enhanced transfection to neighboring cells. Reporter genes such as luciferase (luc) and enhanced green fluorescent protein (eGFP) were initially used to quantitate transfection efficiencies from polyplex from the coated ECMs of Collagen type I (Col I), fetal bovine serum protein (FBS), bovine serum albumin (BSA). DNA was complexed with positively charged polyethyleneimine (PEI) at N/P ratio 9. Our initial work exhibited that, in the case of both NIH/3T3 cell line and bone marrow stromal (D1) cell line, Col I facilitated the greatest cell adhesion compared to the other coating proteins and 0.5 microg/cm2 of Col I coating density resulted in highest transfection efficiency. On the other hand, comparison of reverse delivery system with atelocollagen-I have shown that reverse delivery system to yield ten times higher transfection efficiency than atelocollagen-PEI/DNA delivery system and one hundred times higher than atelocollagen-naked plasmid delivery system. Moreover, the amount of DNA used for reverse delivery system was much lower than the other systems. This methodology would be applied to induce cellular differentiation in 3-dimensional scaffold after coating scaffolds with genes inducing the differentiation in the nanoparticle formulation. Our final goal is to search for the optimal conditions for the differentiation of stem cells to specific cell types.


[Punctate transcutaneous electrical nerve stimulation in functional vertebragenic disorders and in migraine].
Chronic and frequently relapsing headaches as well as myalgic-vertebragenic pain syndromes belong to the most frequent pain diseases. Among the non-medicamentous methods the techniques of the aimed reflex and stimulation therapy such as acupuncture, neural therapy and manual medicine particularly stood the test. As a non-invasive alternative we try to replace the needle acupuncture by punctuate transcutaneous electric nerve stimulation. With the help of self-constructed pocket stimulating current devices we treated 740 patients suffering from pain (420 with myo-vertebragenic and 320 with primary headaches) and achieved 90% of immediate successes and 70-80% improvement after 6 months. The treatments could be objectifie thermometrically. Own prospective randomized studies of placebo-treatment and medicamentously controlled studies of treatment and changes of the pain threshold by means of the PuTENS were briefly represented and the mechanism of action was discussed. The application of this effective, free of side effects, undangerous, economic method easily to be learned which is suitable for the autotherapy and sanatory therapy is recommended for the alleviation of pain.


Quantification of radiation induced DNA double-strand breaks in human fibroblasts by PFGE: testing the applicability of random breakage models.
To assess the applicability of methods of quantification of double-strand breaks (DSB) based on the random breakage paradigm, measuring yield and distribution of DSB induced by varying radiation quality. 240 kVp X-rays and (238)Pu alpha-particles were used to induce DSB in AG01522B primary human fibroblasts. DNA molecular weight distributions were resolved by means of three pulsed-field gel-electrophoresis (PFGE) protocols, which, when combined together, allowed separation and quantification of double-stranded fragments between 5.7 Mbp and 12 kbp. Several analytical methods quantified the DSB yields. Data showed significant differences in the fragmentation patterns according to radiation quality. For both X-rays and alpha-particles, it was observed that the shape of the fragmentation profiles deviates from the prediction of a random breakage mechanism. This is in contrast to other studies where sparsely ionizing radiations appeared to distribute breaks uniformly throughout the genome. Deviations from random breakage were more evident after high linear energy transfer (LET) radiation, which showed an excess of breaks <1 Mbp and a deficit in the production of fragments >1 Mbp, a value that could be dose-dependent. Current methods of DNA fragmentation analysis after induction of DSB may lead to contradictory conclusions on both DSB yields and distributions. This study showed that the application of different DSB quantification methods, derived from random breakage or supported by its concepts, resulted in different radiation biological effectivenesses (RBE) for the induction of DSB, depending on how these methods were employed. To compare experimental results from different laboratories, care should be taken to provide as many details as possible about the application of methods of quantification of DNA damage. For all the methods used, total DSB yields resulted in RBE less than those for mutation induction or reproductive cell death, suggesting that total DSB yields only gave a limited indication of the severity of the inflicted damage. Production of correlated breaks on the chromatin loop structures by single particle-track traversals may explain the deviations observed between experimental data and the predictions of the random breakage paradigm.


Can intra-radicular cleaning protocols increase the retention of fiberglass posts? A systematic review.
The presence of residues within the root canal after post-space preparation can influence the bond strength between resin cement and root dentin when using fiberglass posts (FGPs). Currently, there is no consensus in the literature regarding what is the best solution for the removal of debris after post-space preparation. This systematic review involved "in vitro" studies to investigate if cleaning methods of the root canal after post-space preparation can increase the retention of FGPs evaluated by the push-out test. Searches were carried out in PubMed (MEDLINE) and Scopus databases up to July2017. English language studies published from 2007 to July 2017 were selected. 475 studies were found, and 9 were included in this review. Information from the 9 studies were collected regarding the number of samples, storage method after extraction, root canal preparation, method of post-space preparation, endodontic sealer, resin cement, cleaning methods after post-space and presence of irrigant activation. Five studies presented the best results for the association of sodium hypochlorite (NaOCl) and ethylenediamine tetra-acetic acid (EDTA), while in the other 4 studies, the solutions that showed improved retention of FGPs were photon-induced photoacoustic streaming (PIPS), Qmix, Sikko and EDTA. The results showed heterogeneity in all comparisons due to a high variety of information about cleaning methods, different concentrations, application time, type of adhesive system and resin cements used. In conclusion, this review suggests that the use of NaOCl/EDTA results in the retention of FGPs and may thus be recommended as a post-space cleaning method influencing the luting procedure.


The current clinical management of Huntington's disease.
Huntington's disease is a neurodegenerative condition, characterized by movement disorders, cognitive decline, and psychiatric disturbance. We review the pharmacological management of the various movement disorders associated with the disease, the cognitive decline and the commonly encountered behavioral disturbances. We discuss the nonclassical features of the disease, important in the management of these patients. Nonpharmacological support including genetic counseling and therapy and the importance of palliative care are also addressed. Finally, experimental approaches that may soon impact upon clinical practice are discussed.


Effects of the administration of a-methyl-p-tyrosine on the striatal dopamine increase and the behavioral motor disturbances in rats exposed to high pressure.
When human divers and experimental animals are exposed to increased environmental pressure, they develop the high pressure neurological syndrome (HPNS). Moreover, it has been recently demonstrated that pressure exposure induced an increase in striatal dopamine (DA) release. In this study, the effects of intracerebroventricular administration of a-methyl-p-tyrosine on the pressure-induced striatal DA increase, and the behavioral motor disturbances of HPNS, including hyperlocomotor activity (HLA), tremor, and myoclonia were monitored in free-moving rats. Striatal DA release was monitored by in vivo voltammetry, and behavioral symptoms using piezoelectrical sensors. Results suggested that the pressure-induced striatal DA increase could be the consequence of a release in both newly synthesized and vesicular DA. Elsewhere, data also confirmed that the pressure-induced DA disturbances would be involved in the development of HLA.


The influence of an electric field on growth and trace metal content in aquatic plants.
It is known that both natural and artificial electric fields (EF) affect plants physiological parameters as well as germination, growth and yield. The present article describes results of a preliminary experiment on the impact of electric field on aquatic plants biogeochemistry. The objective of the present study was the assessment of the influence exerted by the electric field on growth and trace metals content of Elodea canadensis. In a laboratory experiment plants were exposed to the field intensity of 54 kV m-1 for 7 days. The plants length was measured and the content of Fe, Mn, Ni, Pb, and Zn was determined using atomic absorption spectrometry (AAS). Results showed that the application of electric field slightly enhanced the growth of E. canadensis shoots. The content of Mn and Ni was significantly lower, and Pb and Zn significantly higher in plants exposed to the electric filed, while Fe content did not differ between control and EF treatment. This provides a rationale for further studies on biological effects of electric field in trace metal contaminated waters and application of an electrically enhanced phytoremediation.


Piloting the use of indigenous methods to prevent Nipah virus infection by interrupting bats' access to date palm sap in Bangladesh.
People in Bangladesh frequently drink fresh date palm sap. Fruit bats (Pteropus giganteus) also drink raw sap and may contaminate the sap by shedding Nipah virus through saliva and urine. In a previous study we identified two indigenous methods to prevent bats accessing the sap, bamboo skirts and lime (calcium carbonate). We conducted a pilot study to assess the acceptability of these two methods among sap harvesters. We used interactive community meetings and group discussions to encourage all the sap harvesters (n = 12) from a village to use either bamboo skirts or lime smear that some of them (n = 4) prepared and applied. We measured the preparation and application time and calculated the cost of bamboo skirts. We conducted interviews after the use of each method. The sap harvesters found skirts effective in preventing bats from accessing sap. They were sceptical that lime would be effective as the lime was washed away by the sap flow. Preparation of the skirt took ∼105 min. The application of each method took ∼1 min. The cost of the bamboo skirt is minimal because bamboo is widely available and they made the skirts with pieces of used bamboo. The bamboo skirt method appeared practical and affordable to the sap harvesters. Further studies should explore its ability to prevent bats from accessing date palm sap and assess if its use produces more or better quality sap, which would provide further incentives to make it more acceptable for its regular use.


Survival rate of gastric and esophageal cancers in Ardabil province, North-West of Iran.
Upper gastrointestinal cancer is the most common cancer in Ardabil Province, North-West of Iran, accounting for more than 50% of all cancer deaths in this area. We conducted this study to determine the present survival rate of patients with esophageal and gastric cancers before launching interventional studies. A prospective follow-up study of 420 biopsy-proven patients (127 females, mean age: 64) with upper gastrointestinal cancer (141 esophageal and 279 stomach cancers) who were initially diagnosed in Aras Clinic, the main gastrointestinal referral center of Ardabil Province, from 2000 through 2004, was performed with collection of data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, etc. Data were gathered through direct interview with patients or their families in 303 cases and evaluation of death certificates in 55 patients. Follow-up was from cancer diagnosis until death, or immigration. Survival according to stage of disease, Lauren tumor type, tumor location, surgery, and adjuvant chemotherapy was analyzed, and results were compared with those of western series. Sixty-two cases were lost to follow-up. The one- and five-year survival rates in the patients with upper gastrointestinal cancer in Ardabil Province were 40.5%, and 0.8%, respectively. In the univariate analysis, men had a slightly lower survival rate than women (P = 0.21) and patients with esophageal cancer had a longer survival rate compared to stomach cancer patients (P = 0.15). Patients who had undergone surgery (P < 0.001) and/or chemotherapy (P < 0.001) survived longer than those without such treatments. Tumor morphology, age at diagnosis, radiotherapy, alcohol, and opium consumption did not show any significant effects on the survival rate of patients. In multivariate analysis, only smoking was remained as an independent factor for stomach cancer (P = 0.04) while in esophageal cancer, surgery and grade of differentiation were significant predictors of survival. Survival rate of stomach and esophagus cancer cases in Ardabil is relatively low. Intervention for early detection and therapy is necessary to increase survival.


Update on the role of endoplasmic reticulum stress in asthma.
Asthma has long attracted extensive attention because of its recurring symptoms of reversible airflow obstruction, airway hyperresponsiveness (AHR) and airway inflammation. Although accumulating evidence has enabled gradual increases in understanding of the pathogenesis of asthma, many questions regarding the mechanisms underlying asthma onset and progression remain unanswered. Recent advances delineating the potential functions of endoplasmic reticulum (ER) stress in meeting the need for an airway hypersensitivity response have revealed critical roles of unfolded protein response (UPR) pathways in asthma. In this review, we highlight the roles of ER stress and UPR activation in the etiology, pathogenesis and treatment of asthma and discuss whether the related mechanisms could be targets for therapeutic strategies.


A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis.
EAAT2 (excitatory amino acid transporter 2) is a high affinity, Na+-dependent glutamate transporter of glial origin that is essential for the clearance of synaptically released glutamate and prevention of excitotoxicity. During the course of human amyotrophic lateral sclerosis (ALS) and in a transgenic mutant SOD1 mouse model of the disease, expression and activity of EAAT2 is remarkably reduced. We previously showed that some of the mutant SOD1 proteins exposed to oxidative stress inhibit EAAT2 by triggering caspase-3 cleavage of EAAT2 at a single defined locus. This gives rise to two fragments that we termed truncated EAAT2 and COOH terminus of EAAT2 (CTE). In this study, we report that analysis of spinal cord homogenates prepared from mutant G93A-SOD1 mice reveals CTE to be of a higher molecular weight than expected because it is conjugated with SUMO-1. The sumoylated CTE fragment (CTE-SUMO-1) accumulates in the spinal cord of these mice as early as presymptomatic stage (70 days of age) and not in other central nervous system areas unaffected by the disease. The presence and accumulation of CTE-SUMO-1 is specific to ALS mice, since it does not occur in the R6/2 mouse model for Huntington disease. Furthermore, using an astroglial cell line, primary culture of astrocytes, and tissue samples from G93A-SOD1 mice, we show that CTE-SUMO-1 is targeted to promyelocytic leukemia nuclear bodies. Since one of the proposed functions of promyelocytic leukemia nuclear bodies is regulation of gene transcription, we suggest a possible novel mechanism by which the glial glutamate transporter EAAT2 could contribute to the pathology of ALS.


Male contraception.
Currently approved male-directed contraceptive methods include condoms and vas occlusion. Vas occlusion is very effective but is intended to be non-reversible. Condoms have a relatively high failure rate, at least partially due to compliance problems and are not accepted by many couples. The only other male-oriented methods in clinical trials utilize the administration of testosterone alone or its combination with another gonadotropin-suppressing agent such as a progestin or a gonadotropin-releasing hormone antagonist. Studies published in the 1990s demonstrated that a testosterone-containing hormonal contraceptive method suppressed spermatogenesis to azoospermia in most men and severe oligozoospermia in the remaining. The contraceptive efficacy after treatment with testosterone alone was comparable to that of female hormonal methods. Having proven that reversible male contraception is a reality, present trials are attempting to identify the best androgen delivery system and the most effective androgen plus progestin preparation. It is likely that the first marketed male hormonal contraceptive method will be a long-acting (injectable or implant) combination of an androgen plus a progestin. Research is continuing to identify other target areas for male contraceptive development, including agents with post-testicular and epididymal sites of action.


Pulmonary Hypertension in a Large Cohort with Hereditary Hemorrhagic Telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by arteriovenous malformations in the brain, liver, and lungs. Pulmonary hypertension (PH) is increasingly recognized as a severe complication of HHT. However, there are no studies describing the prevalence of PH in HHT compared to HHT-negative controls. To assess the estimated prevalence of PH in patients with HHT compared to HHT-negative controls. All consecutive subjects screened for HHT with available genetic testing and echocardiography-based peak tricuspid regurgitation velocity (TRV) measurement were included. Increased-probability PH was defined as a TRV >2.8 m/s. In 578 subjects, both echocardiography and genetic testing were available. A reliable TRV was measured in 383 (66.3%), of whom 127 had HHT type 1 (HHT1), 150 had HHT type 2 (HHT2), and 106 were HHT-negative controls, with a mean TRV of 2.3 ± 0.4, 2.4 ± 0.5, and 2.2 ± 0.3 m/s, respectively (p = 0.008 and p < 0.001 vs. controls). Increased-probability PH was found in 42 subjects (8.7% in HHT1, 18.0% in HHT2, and 3.8% in HHT-negative controls). HHT2 and hepatic arteriovenous malformations (HAVMs) were the most important predictors for increased-probability PH (odds ratio 5.6, p = 0.002, and odds ratio 11.3, p < 0.001, respectively). Heritable pulmonary arterial hypertension (HPAH) was diagnosed in 2 patients (0.7%) and only found in HHT2 (1.3%). The estimated prevalence of PH is higher in HHT patients compared to HHT-negative controls. This increase is especially present in HHT2 and mainly associated with the presence of HAVMs. HPAH appears to be rare in HHT patients and was only diagnosed in HHT2.


Guided-motion hinged knee replacement prosthesis: early survival rate and postoperative patient function and satisfaction.
Literature on the survival rates and function of hinged total knee replacement (HTKR) prostheses is scarce, and to our knowledge there is not yet any published literature on the Legion HK Hinge Knee Replacement prosthesis (Smith & Nephew) with guided-motion articulation. The objective of this study was to establish the early survival rate of this modern HTKR at a single institution and to investigate postoperative patient function and satisfaction. This retrospective study included patients who received the Legion HTKR prosthesis with guided-motion inserts as a primary or revision implant between October 11 and March 2016 at a tertiary care centre in Manitoba, Canada. Preoperative and postoperative functional scores on the 12-item Oxford Knee Score and postoperative patient satisfaction were assessed. Thirty-nine HTKR implantations (38 patients) were included in this study: 12 primary cases and 27 revision cases. Three revision surgeries and 4 perioperative complications were noted at a mean follow-up of 29.1 months. The 2-year survivorship of the HTKR system was 90.7%. Postoperative functional scores improved significantly and the majority of patients were satisfied or very satisfied at all follow-up time points. The early survival rate of a modern guided-motion HTKR prosthesis is similar to the survival rates of other hinged knee prostheses published in the literature. The prosthesis demonstrated substantial postoperative functional improvement when used in the setting of complex primary or revision total knee replacement.


The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma.
Resistance to immune checkpoint inhibitor therapies in melanoma is common and remains an intractable clinical challenge. In this study, we comprehensively profile immune checkpoint inhibitor resistance mechanisms in short-term tumor cell lines and matched tumor samples from melanoma patients progressing on immune checkpoint inhibitors. Combining genome, transcriptome, and high dimensional flow cytometric profiling with functional analysis, we identify three distinct programs of immunotherapy resistance. Here we show that resistance programs include (1) the loss of wild-type antigen expression, resulting from tumor-intrinsic IFNγ signaling and melanoma de-differentiation, (2) the disruption of antigen presentation via multiple independent mechanisms affecting MHC expression, and (3) immune cell exclusion associated with PTEN loss. The dominant role of compromised antigen production and presentation in melanoma resistance to immune checkpoint inhibition highlights the importance of treatment salvage strategies aimed at the restoration of MHC expression, stimulation of innate immunity, and re-expression of wild-type differentiation antigens.


Arabidopsis thaliana avoids freezing by supercooling.
Arabidopsis thaliana (L.) Heynh. has been described as a freezing-tolerant species based on freezing-resistance assays. Nonetheless, this type of experiment does not discriminate between freezing-tolerance and freezing-avoidance mechanisms. The purpose of this paper was to determine which of these two freezing-resistance mechanisms is responsible for freezing resistance in A. thaliana. This was achieved by comparing the thermal properties (ice-nucleation temperature and the freezing temperature) of leaves and the lethal temperature to 10, 50 and 90% of the plants (LT10, LT50, and LT90, respectively). Two wild-type genotypes were used (Columbia and Ler) and their mutants (esk-1 and frs-1, respectively), which differ in their freezing resistance. This study's results indicated that the mutant esk-1, described as a freezing-tolerant species showed freezing tolerance only after a cold-acclimation period. The mutant frs-1, described as freezing sensitive, presented freezing avoidance. Both wild genotypes presented LT50 similar to or higher than the ice-nucleation temperature. Thus, the main freezing-resistance mechanism for A. thaliana is avoidance of freezing by supercooling. No injury of the photosynthetic apparatus was shown by measuring the maximal photochemical efficiency (Fv/Fm) and pigments (chlorophyll and carotenoid) during cold acclimation in all genotypes. During cold acclimation, Columbia and esk-1 increased total soluble carbohydrates in leaves. esk-1 was the only genotype that presented freezing tolerance after cold acclimation. This feature could be related to an increase in sugar accumulation in the apoplast.


Simultaneous determination of sulfonamides in milk: In-situ magnetic ionic liquid dispersive liquid-liquid microextraction coupled with HPLC.
Four novel organic magnetic ionic liquids were synthesized and characterized. A new method of in-situ magnetic ionic liquid dispersive liquid-liquid microextraction coupled with HPLC was established to simultaneously separate, preconcentrate and determine trace amount of sulfonamides in milk samples for the first time. In this work, extraction procedure was free of volatile organic solvent. Extraction equilibrium was immediately achieved without further operation such as vortex shaking. Magnetic separation of two phases was effectively achieved by applying external magnetic field without need of centrifugation. Furthermore, only a very small amount of inorganic salts were generated. This is the first time to realize all these advantages in an analytical method. Under the optimal conditions, satisfactory enrichment factors, precisions, linear range and low limit of detection and quantitation were acquired. The validated method was successfully applied in the simultaneous analysis of 5 sulfonamides in real milk samples.


Intercellular adhesion molecule-1, intercellular adhesion molecule-3, and leukocyte integrins in leukocyte accumulation in membranoproliferative glomerulonephritis type I.
Marked intraglomerular infiltration of leukocytes is observed in membranoproliferative glomerulonephritis (MPGN). We recently demonstrated that this leukocyte infiltration develops partly through macrophage-1 (Mac-1)-positive cells and glomerular C3c deposits (Clin Exp Immunol 100:269-276, 1995). To further investigate the mediation of adhesion molecules in the leukocyte accumulation, we immunohistochemically examined the expression of intraglomerular leukocyte integrins and their ligands as well as surface markers for granulocytes/monocytes (CD15) and macrophages (CD68) in 26 patients with MPGN type I who had undergone repeated biopsies. These patients were divided into two groups. Group A included the patients who showed both normo-complementemia and urinary protein excretion less than 1 g/d at the follow-up biopsy (recovery group: n = 14). Group B (persistent group: n = 12) included the patients other than those in group A. At the initial biopsy, there was no difference in the degree of glomerular C3c deposition, glomerular intercellular adhesion molecule (ICAM)-1 expression, or the numbers of cells bearing leukocyte function-associated antigen-1 (LFA-1), Mac-1, and ICAM-3 between the two groups. At the follow-up biopsy, the degree of glomerular C3c deposition, and the numbers of cells bearing LFA-1, Mac-1, and ICAM-3, were significantly decreased only in group A (P < 0.01, P < 0.001, P < 0.001, and P < 0.01, respectively). No chronological change in ICAM-1 expression was observed in either group. Group B showed a chronological increase in the severity of glomerular injury and serum creatinine level, associated with persistent heavy proteinuria. Neither LFA-1- nor Mac-1-positive cells were positively correlated with ICAM-1 expression. Most of Mac-1-positive cells were CD15-positive cells (granulocytes/monocytes), and a considerable number of Mac-1-positive cells concurrently expressed ICAM-3. In contrast, most LFA-1-positive cells were considered to be CD68-positive cells (macrophages). The number of cells bearing LFA-1 was positively correlated with that of cells bearing ICAM-3 (P < 0.00001). These results suggest that the glomerular leukocytes, infiltrating through Mac-1/complement interaction, express ICAM-3 by themselves, and that LFA-1/ICAM-3 interaction might participate in the glomerular aggregation of leukocytes in MPGN type I. In this study, we could not conclude that LFA-1/ICAM-1 or Mac-1/ICAM-1 interaction was involved in the leukocyte accumulation in this disease.


The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the Finnish Diabetes Prevention Study.
Physical activity exerts anti-inflammatory effects, but genetic variation may modify its influence. In particular, the rs1800629 single-nucleotide polymorphism (SNP) in the tumor necrosis factor ( TNF) gene and the rs1800795 SNP in the interleukin-6 ( IL6) gene have been found to modify the effect of exercise training on circulating levels of C-reactive protein (CRP) and IL-6, respectively. We assessed whether rs1800629 and rs1800795 modified the effect of moderate-to-vigorous physical activity on changes in serum levels of high-sensitivity CRP and IL-6 in the Finnish Diabetes Prevention Study (DPS). Genotype and 1-year data on changes in physical activity, serum CRP and IL-6 were available for 390 overweight subjects with impaired glucose tolerance. The rs1800629 SNP in TNF interacted with the 1-year change in moderate-to-vigorous physical activity on changes in CRP among those who had high (≥3 mg/L) baseline CRP levels ( P = 0.034 for interaction). Carriers of the GG genotype showed a greater decrease in CRP with increasing physical activity than the individuals with the A allele. No interaction between the rs1800795 SNP in IL6 and changes in moderate-to-vigorous physical activity on the 1-year change in serum IL-6 was found. In conclusion, the rs1800629 SNP in the TNF gene may modify the effect of moderate-to-vigorous physical activity on serum levels of CRP.


Optical fingerprint of non-covalently functionalized transition metal dichalcogenides.
Atomically thin transition metal dichalcogenides (TMDs) hold promising potential for applications in optoelectronics. Due to their direct band gap and the extraordinarily strong Coulomb interaction, TMDs exhibit efficient light-matter coupling and tightly bound excitons. Moreover, large spin orbit coupling in combination with circular dichroism allows for spin and valley selective optical excitation. As atomically thin materials, they are very sensitive to changes in the surrounding environment. This motivates a functionalization approach, where external molecules are adsorbed to the materials surface to tailor its optical properties. Here, we apply the density matrix theory to investigate the potential of non-covalently functionalized monolayer TMDs. Considering exemplary molecules with a strong dipole moment, we predict spectral redshifts and the appearance of an additional side peak in the absorption spectrum of functionalized TMDs. We show that the molecular characteristics, e.g. coverage, orientation and dipole moment, crucially influence the optical properties of TMDs, leaving a unique optical fingerprint in the absorption spectrum. Furthermore, we find that the molecular dipole moments open a channel for coherent intervalley coupling between the high-symmetry K and [Formula: see text] points which may create new possibilities for spin-valleytronics application.


Sleep duration and breast cancer: a prospective cohort study.
Breast cancer incidence has increased during recent decades for reasons that are only partly understood. Prevalence of sleeping difficulties and sleepiness has increased, whereas sleeping duration per night has decreased. We hypothesized that there is an inverse association between sleep duration and breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. This population-based study includes information from women born in Finland before 1958. Sleep duration, other sleep variables, and breast cancer risk factors were assessed by self-administered questionnaires given in 1975 and in 1981. Breast cancer incidence data for 1976 to 1996 was obtained from the Finnish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox proportional hazards models adjusting for potential confounders. Altogether, 242 cases of breast cancer occurred over the study period among the 12,222 women with sleep duration data in 1975. For these women, the HRs for breast cancer in the short (< or =6 hours), average (7-8 hours), and long sleep (> or =9 hours) duration groups were 0.85 (CI, 0.54-1.34), 1.0 (referent), and 0.69 (CI, 0.45-1.06), respectively. Analysis restricted to the 7,396 women (146 cases) whose sleep duration in 1975 and 1981 were in the same duration group (stable sleepers) yielded HRs of 1.10 (CI, 0.59-2.05), 1.0, and 0.28 (CI, 0.09-0.88), with a decreasing trend (P = 0.03). This study provides some support for a decreased risk of breast cancer in long sleepers.


[Population-based survey of refractive error in school-aged children in Liwan District, Guangzhou].
To estimate the prevalence of refractive error in school-aged children in urban setting of Southern China. In this population-based cross-sectional study, children aged 5 to 15 years old were randomly selected by clustering sampling and door-to-door survey, and were examined in 71 schools and 19 community stations from October 2002 to January 2003. The examination included visual acuity measurement, ocular motility evaluation, retinoscopy, autorefraction under cycloplegia and examination of the external eye, anterior segment, media, and fundus. Of 5053 children living in 4814 households enumerated, 4364 (86.4%) were examined. The prevalence of myopia (spherical equivalent, SE < -0.50 D) was 35.1% (95% CI: 33.2%-36.9%) with retinoscopy, this rate increased from 3. 3% in 5-year-old to 73.1% in 15-year-old. Females had a significantly higher risk of myopia (adjusted odds ratio: 1.29, 95% CI: 1.11-1.51). The prevalence of hyperopia (SE > or = + 2.00 D) was 5.8% (95% CI: 5.3%-6.3%) and decreased from 16.7% in 5-year-old to less than 1% in 15-year-old. Astigmatism (cylinder > or = 0.75 D) was presented in 33.6% of children examined with retinoscopy and in 42.7% with autorefraction. The prevalence of myopia is high in Chinese school-age children living in urban Guangzhou, representing an important public health problem. The coverage and quality of refractive correction in the children need to be improved.


PC-1/PrLZ contributes to malignant progression in prostate cancer.
PC-1/PrLZ gene overexpression has been identified to be associated with prostate cancer progression. Previous studies have revealed that PC-1 possesses transforming activity and confers malignant phenotypes to mouse NIH3T3 cells. However, the functional relevance of PC-1 expression changes during prostate cancer development and progression remains to be evaluated. In this study, gain-of-function and loss-of-function analyses in LNCaP and C4-2 cells, respectively, were implemented. Experimental data showed that PC-1 expression was in positive correlation with prostate cancer cell growth and anchor-independent colony formation in vitro, as well as tumorigenicity in athymic BALB/c mice. Moreover, PC-1 expression was also found to promote androgen-independent progression and androgen antagonist Casodex resistance in prostate cancer cells. These results indicate that PC-1 contributes to androgen-independent progression and malignant phenotypes in prostate cancer cells. Furthermore, molecular evidence revealed that PC-1 expression stimulated Akt/protein kinase B signaling pathway, which has been implicated to play important roles in promoting androgen refractory progression in prostate cancer. Increased PC-1 levels in C4-2 cells may represent an adaptive response in prostate cancer, mediating androgen-independent growth and malignant progression. Inhibiting PC-1 expression may represent a novel therapeutic strategy to delay prostate cancer progression.


How to talk about cancer.
While 50% of people born after 1960 in the UK will develop cancer at some point, many find talking about it difficult. Cancer Research UK has therefore developed a free, online cancer awareness course, Talking About Cancer, as part of its Talk Cancer programme.


The Animal Kingdom Is Also a Bioengineering Field: Exploring the Art and Science of Vetinary Medicine [Retrospectroscope].
Medical science developed in tandem with the evolution of biological species and their associated diseases. Because of the close interaction between humans and other animals, even those in the wild, taking care of the former also means caring for the latter. Several scientific forerunners delved into animals' anatomical and physiological secrets in their quest to better understand animal biology and functions, thereby laying the foundation for animal medicine. Here, I briefly explore the long and complex road that led to the current state of veterinary science and provide a few examples of its present standing. (Contributions from the ancient world and eastern countries are not considered, as they represent a different area of interest.).


[Toxoplasmosis in French Guiana. Atypical (neo-)tropical features of a cosmopolitan parasitosis].
Toxoplasmosis, a typical cosmopolitan parasitosis, is a major health problem in French Guiana. Three factors account for this situation, i.e., (1) severity of toxoplasmosis in patients with HIV infection that is particularly prevalent in the area, (2) high risk of congenital transmission as shown by the steadily increasing prevalence of seropositivity in function of age in most of the Guianese population and (3) recent identification of severe primary toxoplasmosis infection in immunocompetent patients. In AIDS patients, the epidemiologic aspects of toxoplasmosis are correlated to the special features of the HIV-positive population in French Guiana and its clinical expression, mainly in the form of cerebral toxoplasmosis, does not suggest involvement of a particularly virulent strain of Toxoplasma. Similarly congenital toxoplasmosis does not present special tropical features other than problems associated with prevention, diagnosis and follow-up in poor and/or remote settings. These features are fully compatible with the classic domestic cat cycle of Toxoplasma gondii. However severe forms of primary infection, particularly in immunocompetent adults, appear to be associated with atypical features. These forms appear to be correlated with a forest-based cycle involving wild cats, which are still numerous in French Guiana, and their prey. Ingestion of undercooked wildcat prey, which is also a delicacy for man, can also be a source of contamination as can be consumption of untreated river water infected with oocysts excreted by felines. Observation of higher toxoplasmosis seroprevalence in wild noncarnivorous mammals that live by foraging on the ground in uninhabited forest zones suggests that infection can also be due to ingestion of oocysts eliminated into the soil. Since there are no domestic cats in the area, it must be assumed that these oocysts are shed by wild felines. More convincing proof can be seen in the fact that T. gondi strains presenting polymorphism, similarities and atypical genetic features can be found both in this animal reservoir, particularly in jaguars, and in patients presenting the more severe form of toxoplasmosis. In addition to the purely scientific interest of confirming the existence of the forest-based cycle, knowledge of this atypical form of toxoplasmosis that is probably not confined to French Guiana or to the Amazon region has obvious practical medical implications not only for diagnosis but also for therapy and prevention.


Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells.
Thymic epithelial cells (TECs) are essential for T cell development in the thymus, yet the mechanisms governing their differentiation are not well understood. Lin28, known for its roles in embryonic development, stem cell pluripotency, and regulating cell proliferation and differentiation, is expressed in endodermal epithelial cells during embryogenesis and persists in adult epithelia, implying postnatal functions. However, the detailed expression and function of Lin28 in TECs remain unknown. In this study, we examined the expression patterns of Lin28 and its target Let-7g in fetal and postnatal TECs and discovered opposing expression patterns during postnatal thymic growth, which correlated with FOXN1 and MHCII expression. Specifically, Lin28b showed high expression in MHCIIhi TECs, whereas Let-7g was expressed in MHCIIlo TECs. Deletion of Lin28a and Lin28b specifically in TECs resulted in reduced MHCII expression and overall TEC numbers. Conversely, overexpression of Lin28a increased total TEC and thymocyte numbers by promoting the proliferation of MHCIIlo TECs. Additionally, our data strongly suggest that Lin28 and Let-7g expression is reliant on FOXN1 to some extent. These findings suggest a critical role for Lin28 in regulating the development and differentiation of TECs by modulating MHCII expression and TEC proliferation throughout thymic ontogeny and involution. Our study provides insights into the mechanisms underlying TEC differentiation and highlights the significance of Lin28 in orchestrating these processes.


Common electrocardiographic artifacts mimicking arrhythmias in ambulatory monitoring.
Ambulatory electrocardiographic monitoring is used in clinical practice as a means of detecting cardiac arrhythmias during daily activities. Current equipment provides analysis for the detection of arrhythmias, ST-segment deviation, and more sophisticated analyses (late potentials, Q-T behavior, and heart-rate variability). However, despite the system used, a number of artifacts could mislead diagnosis. We prospectively searched for artifacts during ambulatory electrocardiography in patients referred for monitoring to our institution, a tertiary referral center. Patients were ambulatory at home, work, school, or within the hospital. We divided artifacts according to Krasnow and Bloomfield's classification (pseudoarrhythmia, nonarrhythmia), and we added a new category, artifacts in patients with pacemakers. Artifacts encountered mimicked sinus arrest, supraventricular arrhythmias, ventricular arrhythmias, and aberrancy. Examples of each one and diagnostic clues are provided to recognize these artifacts properly. A substantial amount of invalid data (false-positive findings because of electrocardiographic artifacts) were identified during ambulatory electrocardiographic monitoring that can lead to inappropriate interpretation and may result in severe diagnostic errors.


Advances in the Use of Regulatory T-Cells for the Prevention and Therapy of Graft-vs.-Host Disease.
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product. Despite these challenges, investigators have been able to successfully expand these cells both in vivo and in vitro and have demonstrated that they can be safely infused in humans for the prevention and treatment of GvHD with no increase in relapse risk or infections risk.


Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis.
The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.


An outbreak of avian urolithiasis on a large commercial egg farm.
A significant outbreak of avian urolithiasis was observed on a large commercial egg farm. From the initial outbreak site (a single laying house), the incidence of urolithiasis slowly spread in the ensuing months to numerous other laying houses. Increasing mortality associated with urolithiasis commenced during late growout to early lay and then leveled off when egg production peaked. At the height of the outbreak, mortality was typically 0.5% per week; 75% of this mortality was due to urolithiasis. The clinical and pathologic features of this condition are described. Both infectious bronchitis virus (IBV) and fowl adenoviruses were isolated from organ homogenates of sampled birds. A clone of the IBV strain was found to induce nephritis in specific-pathogen-free white leghorns.


Contribution of SAR11 bacteria to dissolved dimethylsulfoniopropionate and amino acid uptake in the North Atlantic ocean.
SAR11 bacteria are abundant in marine environments, often accounting for 35% of total prokaryotes in the surface ocean, but little is known about their involvement in marine biogeochemical cycles. Previous studies reported that SAR11 bacteria are very small and potentially have few ribosomes, indicating that SAR11 bacteria could have low metabolic activities and could play a smaller role in the flux of dissolved organic matter than suggested by their abundance. To determine the ecological activity of SAR11 bacteria, we used a combination of microautoradiography and fluorescence in situ hybridization (Micro-FISH) to measure assimilation of (3)H-amino acids and [(35)S]dimethylsulfoniopropionate (DMSP) by SAR11 bacteria in the coastal North Atlantic Ocean and the Sargasso Sea. We found that SAR11 bacteria were often abundant in surface waters, accounting for 25% of all prokaryotes on average. SAR11 bacteria were typically as large as, if not larger than, other prokaryotes. Additionally, more than half of SAR11 bacteria assimilated dissolved amino acids and DMSP, whereas about 40% of other prokaryotes assimilated these compounds. Due to their high abundance and activity, SAR11 bacteria were responsible for about 50% of amino acid assimilation and 30% of DMSP assimilation in surface waters. The contribution of SAR11 bacteria to amino acid assimilation was greater than would be expected based on their overall abundance, implying that SAR11 bacteria outcompete other prokaryotes for these labile compounds. These data suggest that SAR11 bacteria are highly active and play a significant role in C, N, and S cycling in the ocean.


Concurrent Control of Two Aphid-Borne Potyviruses in Cucurbits by Two-in-One Vaccine.
The application of attenuated viruses has been widely practiced for protecting crops from infection by related severe strains of the same species. Papaya ringspot virus W-type (PRSV W) and zucchini yellow mosaic virus (ZYMV) devastate cucurbits worldwide. However, the prevailing of these two viruses in cucurbits cannot be prevented by a single protective virus. In this study, we disclosed that co-infection of horn melon plants by two mild strains, PRSV P-type (PRSV P) HA5-1 and ZYMV-ZAC (a previously developed mild mutant of ZYMV) confers concurrent protection against PRSV P and ZYMV. Consequently, mild mutants of PRSV W were created by site-directed mutagenesis through modifications of the pathogenicity motifs FRNK and PD in helper component-protease (HC-Pro). A stable PRSV W mutant WAC (PRSV-WAC) with R181I and D397N mutations in HC-Pro was generated, inducing mild mottling, followed by symptomless recovery in cucurbits. Horn melon plants pre-infected by PRSV-WAC and ZYMV-ZAC showed no apparent interference on viral accumulation with no synergistic effects on symptoms. An agroinfiltration assay of mixed HC-Pros of WACHC-Pro + ZACHC-Pro revealed no additive effect of RNA silencing suppression. PRSV-WAC or ZYMV-ZAC alone only antagonized a severe strain of homologous virus, while co-infection with these two mild strains provided complete protection against both PRSV W and ZYMV. Similar results were reproduced in muskmelon and watermelon plants, indicating the feasibility of a two-in-one vaccine for concurrent control of PRSV W and ZYMV in cucurbits.


Phase transitions in periodically driven macroscopic systems.
We study the large-time behavior of a class of periodically driven macroscopic systems. We find, for a certain range of the parameters of either the system or the driving fields, the time-averaged asymptotic behavior effectively is that of certain other equilibrium systems. We then illustrate with a few examples how the conventional knowledge of the equilibrium systems can be made use of in choosing the driving fields to engineer new phases and to induce new phase transitions.