Carbohydrates--the renewable raw materials of high biotechnological value.
Carbohydrates are the potential biomolecules derived from nature. Their molecular diversity has led to a bewildering variety of species, structures and characteristics all performing a large array of functions of great significance. Biologically they are vital as message (immunological) carriers, physiologically they are useful as energy (nutritional) reserves, and technologically they are needed for altering the texture and consistency (functional) of foods. Recent advances in glycobiology have opened up a new understanding of the role of sugars in biology and medicine. Noncellulosic beta-(1-3)-linked D-glucans, a group of polysaccharides found as constituents of fungi, algae, and higher plants, exhibit many interesting properties, depending on their molecular conformation. They are excellent 'biological response modifiers' and show significant immunomodulatory activities. They elicit a variety of host defense biological responses, for example, potent antitumor activity. On the other hand, the mixed-linkage ((1-3/1-4)-beta-linked) glucans are important constituents of cereal cell walls, where they perform properties of physiological importance, such as water holding capacity, porosity, and plasticity, which are useful at different stages of growth/development of plants. Of late, carbohydrate-based therapeutics are becoming the promise against many chronic diseases of today and tomorrow. Some of the characteristic features, structural attributes, functional significance, and applications of a selected few carbohydrate species are the subject matter of this review.


The importance of cross-reactions between species: mouse allo-anti-Ia monoclonal antibodies as a powerful tool to define human Ia subsets.
Three mouse allo-anti-Ia monoclonal antibodies recognizing epitopes specific for either I-E gene products (H81.98.21 and H40.315.7 Mabs) or shared between I-E and I-A gene products (H82.246.3 Mab) were used to analyze the human Ia molecules against which they cross-react. The results indicated that in the Ia pool of the human B cell line Raji the three Mabs were able to recognize at least three distinct subsets differing each other both in their alpha as well as in their beta subunits. The comparison with the previously defined human Ia subsets NG1, NGe, and DC1 suggested the following similarities: H81.98.21 specific Ia molecules similar to NG1; H82.246.3 specific Ia molecules similar to NG2, and including probably NG1; H40.315.7 specific molecules similar to DC1 in their alpha subunits and probably heterogeneous in their beta subunits with characteristics of the DC1, NG1, and NG2 subunits altogether. The heterogeneity of the human Ia molecules and the possible similarities with the mouse Ia system were discussed.


Influence of meteorological parameters in the seasonality of influenza viruses circulating in Northern Cameroon.
Several studies have demonstrated the role of meteorological parameters in the seasonality of influenza viruses in tropical and subtropical regions, most importantly temperature, humidity, and rainfall. This study aimed to describe the influence of meteorological parameters in the seasonality of influenza viruses in Northern Cameroon, a region characterized by high temperatures. This was a retrospective study performed in Garoua Cameroon from January 2014 to December 2016. Monthly proportions of confirmed influenza cases from six sentinel sites were considered as dependent variables, whereas monthly values of mean temperature, average relative humidity, and accumulated rainfall were considered as independent variables. A vector error correction model was used to determine the relationship between influenza activity and the meteorological variables. Analysis showed that there was a statistically significant association between overall influenza activity and influenza A activity with respect to average relative humidity. A unit increase in humidity within a given month leads to more than 85% rise in the overall influenza and influenza A activity 2 months later. Meanwhile, none of the three meteorological variables could explain influenza B activity. This observation is essential in filling the gap of knowledge and could help in the prevention and control strategies to strengthen influenza surveillance program in Cameroon.


Influence of adrenalectomy on the development of the neonatal thymus in the rat.
Adrenalectomy of 1-, 6-, 11- and 16-day-old male and female rats did not cause any changes in the weight of thymus 5 days later. Adrenalectomy on days 21, 26, 31 and 81 of age induced a significant hypertrophy of the thymus 5 days later. These results indicate that after about the time of weaning, the thymus is under some inhibitory regulation by the adrenal gland.


[Spontaneous uterine rupture associated with placenta increta in a primipara].
An infrequent clinical case with spontaneous uterine rupture in a 14 weeks primigesta with symptoms and signs of hemoperitoneum with hypovolemic shock. The emergency laparotomy revealed 2,000 ml of hemoperitoneum and a rupture of depth of 5 cm the diameter with fetus alive in the inner. Ovular emptying and histerorraphya were carried out. Biopsy in the edge of the uterine rupture revealed placenta increta.


A new method to determine discoloration kinetics of uncoated white tablets occurring during stability testing-an application of instrumental color measurement in the development pharmaceutics.
The tristimulus color coordinates CIELAB and associated parameter Color Intensity (CI) have been shown to be a quantifiable variable for whiteness of uncoated tablets. Whereas any of L*, a* or b* indicates the discoloration of white tablets to a certain degree, it alone cannot reflect the full extent of discoloration. The CI has been defined which is able to describe the discoloration kinetics with acceptable regression coefficients. The evaluation of the CIELAB values from the stability data has shown that the discoloration of the white tablets means an intensification of yellowish or brownish color which is manifested by more or less constant hue angle (hab) values and increasing chroma (Cab*) values. In the view of these data the discoloration kinetics can physically be expressed by the CI. With the CI values the discoloration kinetics can be calculated by linear or polynomial regression with acceptable confidence intervals. The discoloration rates determined under several storage temperatures follow the Arrhenius equation and the activation energy can be estimated for the products. The CI values are unambiguously connected to the visual perception of the corresponding tablets. By means of the discoloration kinetics based on the CI values, it has become possible to statistically determine, the period of time uncoated tablets remain white.


In vitro and in vivo evaluation of leukoreduced platelets stored for 7 days in CLX containers.
Extension of platelet (PLT) storage and concomitant use of a bacterial detection system would provide logistical advantages by reducing outdating and improving patient care through promotion of the use of sensitive detection systems. This study evaluated the in vitro characteristics and in vivo viability of leukoreduced PLT units derived from PLT-rich plasma stored for 5 days (control) versus 7 days (test) in CLX plastic containers. Two whole-blood units were collected from each subject into a leuko-reduction filtration system (Leukotrap RC-PL system, Pall Medical) in a paired design, the second 2 days after the first. These were leukoreduced (Leukotrap PL) and stored for 7 and 5 days. Poststorage samples from test and control units were randomly labeled with (51)Cr or (111)In and simultaneously infused autologously to determine recovery and survival. Small but significant (p < 0.05, paired t test) differences between 5 and 7 days of storage were seen in in vitro variables such as extent of shape change, hypotonic shock response, morphology, and P-selectin expression. In vivo recovery declined on average 11 percent with the two additional days of storage from 54.4 +/- 13.6 to 48.7 +/- 15.0 percent (p < 0.002); survival decreased on average 19 percent from 6.7 +/- 1.0 to 5.4 +/- 1.7 days (p < 0.002). Storage for 7 days was associated with reduced recovery and survival and in vitro variables, suggestive of extension of the storage lesion. These differences, however, were small in magnitude and unlikely to have significant clinical effects. Current collection and storage systems provide PLTs that are as functional at 7 days as those licensed for 7-day storage two decades ago.


In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites.
We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5' splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189,249 U2-dependent 5' splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5' splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (R(i)) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity = 97.1%) and normal splicings in 36 of 38 sites (specificity = 94.7%). Simulation of all possible exonic mutations at positions -3, -2 and -1 of the 189 249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5' splice site.


N-terminal truncation of Stat5a/b circumvents PIAS3-mediated transcriptional inhibition of Stat5 in prostate cancer cells.
Transcription factor Stat5a/b is critical for prostate cancer cell survival and for prostate xenograft tumor growth. In addition, the Stat5a/b signaling pathway may contribute to progression of organ-confined prostate cancer to castration-resistant and/or metastatic disease. Expression of nuclear Stat5a/b is clustered to high grade human prostate cancers, and nuclear Stat5a/b in primary prostate cancer predicts early disease recurrence after initial treatment. Here, we show by Western blotting and electromobility shift assay that Stat5a/b protein in human prostate cancer is N-terminally truncated. This short form of Stat5a/b is generated post-translationally in vivo in prostate cancer cells and is the predominant form of Stat5a/b that binds to DNA. We further demonstrate by mutagenesis and co-immunoprecipitations that the N-domain of Stat5a/b is required for binding to PIAS3, and that PIAS3 inhibits transcriptional activity of Stat5a/b in breast cancer cells but not in prostate cancer cells. Thus, the proteolytic cleavage of the N-terminus of Stat5a/b may be a mechanism by which Stat5 evades the transcriptional repression by PIAS3 in prostate cancer cells, and results in increased Stat5-driven gene expression and prostate cancer progression.


Enhanced myocardial protection with adenosine.
This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated perfused rabbit hearts were subjected to 120 minutes of hypothermic (32 degrees C) multidose cardioplegia-induced ischemia. Control hearts (n = 23) received modified St. Thomas's cardioplegia, and the remaining hearts received cardioplegia with either 100 microM (n = 11), 200 microM (n = 11), or 400 microM (n = 11) adenosine. After ischemia and 45 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Postischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosinetreated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection and improved recovery of both systolic and diastolic function after global ischemia, presumably metabolically by reducing depletion of adenosine triphosphate or enhancing repletion of adenosine triphosphate and enabling improved postischemic recovery.


Blended learning is an effective strategy for acquiring competence in public health biostatistics.
We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. The trial was conducted with 69 Masters' students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p < 0.001) and knowledge test score (35.89 ± 3.66 vs. 22.56 ± 7.12; p < 0.001), with estimated large effect size (d > 0.8). A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students.


[Immunotherapy in head and neck cancer].
The physiological immune response to malignant cells is based on the interaction of antigen-presenting cells, such as dendritic cells and macrophages, with T and B lymphocytes. CD8(+) effector and natural killer cells are primarily responsible for tumor cell lysis. Tumor cells exploit several mechanisms to influence the body's immune system and promote development and progress of solid head and neck malignancies. Via regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and cancer-associated fibroblasts, tumor cells promote development of suppressive signaling pathways that enable tumor progression. Novel immune therapeutics aim to influence these signaling pathways. Current studies are investigating agents which influence immune-stimulating or immune-suppressive cytokines, as well as drug-based Toll-like receptor activation and vaccination in head and neck cancer. Development of monoclonal antibodies allows for direct and highly specific binding of therapeutics to cell receptors - recently discovered immune checkpoint receptors are particularly intriguing targets. Monoclonal antibodies directed specifically toward T cell-stimulating receptors such as CD28 and CD134, or immunosuppressive receptors CTLA-4 and PD-1, are currently under investigation and have shown promising results.


Trace amine-associated receptor 1 regulation of Kv1.4 channels in trigeminal ganglion neurons contributes to nociceptive behaviors.
Trace amines, such as tyramine, are endogenous amino acid metabolites that have been hypothesized to promote headache. However, the underlying cellular and molecular mechanisms remain unknown. Using patch-clamp recording, immunostaining, molecular biological approaches and behaviour tests, we elucidated a critically functional role of tyramine in regulating membrane excitability and pain sensitivity by manipulating Kv1.4 channels in trigeminal ganglion (TG) neurons. Application of tyramine to TG neurons decreased the A-type K+ current (IA) in a manner dependent on trace amine-associated receptor 1 (TAAR1). Either siRNA knockdown of Gαo or chemical inhibition of βγ subunit (Gβγ) signaling abrogated the response to tyramine. Antagonism of protein kinase C (PKC) prevented the tyramine-induced IA response, while inhibition of conventional PKC isoforms or protein kinase A elicited no such effect. Tyramine increased the membrane abundance of PKCθ in TG neurons, and either pharmacological or genetic inhibition of PKCθ blocked the TAAR1-mediated IA decrease. Furthermore, PKCθ-dependent IA suppression was mediated by Kv1.4 channels. Knockdown of Kv1.4 abrogated the TAAR1-induced IA decrease, neuronal hyperexcitability, and pain hypersensitivity. In a mouse model of migraine induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus, blockade of TAAR1 signaling attenuated mechanical allodynia; this effect was occluded by lentiviral overexpression of Kv1.4 in TG neurons. These results suggest that tyramine induces Kv1.4-mediated IA suppression through stimulation of TAAR1 coupled to the Gβγ-dependent PKCθ signaling cascade, thereby enhancing TG neuronal excitability and mechanical pain sensitivity. Insight into TAAR1 signaling in sensory neurons provides attractive targets for the treatment of headache disorders such as migraine.


Developmental regulation of neuronal genes by DNA methylation: environmental influences.
Steroid hormones have wide-ranging organizational, activational and protective actions in the brain. In particular, the organizational effects of early exposure to 17β-estradiol (E2) and glucocorticoids are essential for long-lasting behavioral and cognitive functions. Both steroid hormones mediate many of their actions through intracellular receptors that act as transcription factors. In the rodent cerebral cortex, estrogen receptor mRNA and protein expression are high early in postnatal life and declines dramatically as the animal approaches puberty. An understanding of the molecular mechanisms driving this developmental regulation of gene expression is critical for understanding the complex events that determine lasting brain physiology and prime the plasticity of neurons. Gene expression can be suppressed by the epigenetic modification of the promoter regions by DNA methylation that results in gene silencing. Indeed, the decrease in ERα mRNA expression in the cortex during development is accompanied by an increase in promoter methylation. Numerous environmental stimuli can alter the DNA methylation that occurs for ERα, glucocorticoid receptors, as well as many other critical genes involved in neuronal development. For example, maternal behavior toward pups can alter epigenetic regulation of ERα mRNA expression. Additionally perinatal stress and exposure to environmental estrogens can also have lasting effects on gene expression by modifying DNA methylation of these important genes. Taken together, there appears to be a critical window during development where, outside factors that alter epigenetic programming can have lasting effects on neuronal gene expression.


Traction-induced foveal damage predisposes eyes with pre-existing posterior vitreous detachment to idiopathic macular hole formation.
To propose a new mechanism for the development of idiopathic macular hole in the setting of pre-existing posterior vitreous detachment (PVD). Patients were examined clinically with fundus contact lens biomicroscopy and high-definition optical coherence tomography (OCT) was used to characterize the structural changes in the fovea following PVD. Two patients presented with vitreofoveal separation and were found by high-definition OCT to have subtle foveal disruption and irregularity of the foveal contour with no evidence of a full thickness macular hole. Sequential examination of these patients demonstrated delayed formation of idiopathic macular hole. Traction-induced inner foveal damage occurring before or coincident with spontaneous vitreofoveal separation destabilizes the fovea and predisposes some eyes to delayed macular hole formation.


Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study.
HER2-targeted therapies have substantially improved outcomes for patients with HER2-positive breast and gastric or gastro-oesophageal junction cancers. Several other cancers exhibit HER2 expression or amplification, suggesting that HER2-targeted agents can have broader therapeutic impact. Zanidatamab is a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. The aim of this study was to evaluate the safety and anti-tumour activity of zanidatamab across a range of solid tumours with HER2 expression or amplification. This first-in-human, multicentre, phase 1, dose-escalation and expansion trial included patients aged 18 years and older, with a life expectancy of at least 3 months, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and locally advanced or metastatic, HER2-expressing or HER2-amplified solid tumours of any kind who had received all available approved therapies. The primary objectives of part 1 were to identify the maximum tolerated dose, optimal biological dose, or recommended dose of zanidatamab; all patients were included in the primary analyses. Part 1 followed a 3 + 3 dose-escalation design, including different intravenous doses (from 5 mg/kg to 30 mg/kg) and intervals (every 1, 2, or 3 weeks). The primary objective of part 2 was to evaluate the safety and tolerability of zanidatamab monotherapy in solid tumours. This trial is registered with ClinicalTrials.gov (NCT02892123), and parts 1 and 2 of the trial are complete. Part 3 of the study evaluates the use of zanidatamab in combination with chemotherapy and is ongoing. Recruitment took place between Sept 1, 2016, and March 13, 2021. In Part 1 (n=46), no dose-limiting toxicities were detected and the maximum tolerated dose was not reached. The recommended dose for part 2 (n=22 for biliary tract cancer; n=28 for colorectal cancer; and n=36 for other HER2-expressing or HER2-amplified cancers excluding breast or gastro-oesophageal cancers; total n=86) was 20 mg/kg every 2 weeks. The most frequent treatment-related adverse events in part 1 of the study were diarrhoea (24 [52%] of 46 patients; all grade 1-2) and infusion reactions (20 [43%] of 46 patients; all grade 1-2). The most frequent treatment-related adverse events in part 2 of the study were diarrhoea (37 [43%] of 86 patients; all grade 1-2 except for one patient) and infusion reactions (29 [34%] of 86 patients; all grade 1-2). A total of six grade 3 treatment-related adverse events were reported in four (3%) of 132 patients. In part 2, 31 (37%; 95% CI 27·0-48·7) of 83 evaluable patients had a confirmed objective response. There were no treatment-related deaths. These results support that HER2 is an actionable target in various cancer histologies, including biliary tract cancer and colorectal cancer. Evaluation of zanidatamab continues in ongoing studies. Zymeworks.


Programmed gene expression change in mouse skin after ultraviolet radiation damage.
Ultraviolet (UV) radiation is a major cause of skin damage and carcinogenesis. Here, we systematically analyse the acute gene expression change in skin in vivo after UV exposure, aiming to establish the common C57BL/6 mouse strain as a convenient model for future pathological research and drug discovery. The back fur of C57BL/6 mice was depilated, and a mixed UV light source was used to irradiate the skin. Full-thickness skin samples were collected at 0, 0.5, 2, 6, 12 and 24 h. Total RNAs were extracted and subjected to RNA sequencing analysis. We found that the gene expression change in mouse skin is highly similar to previous reports in human skin. These include down-regulation of differentiation-related genes and extracellular matrix genes, and up-regulation of cytokine/chemokine genes. An early wave of activator protein 1 (AP-1) expression is induced, whereas activation of the p53 pathway is not significant. The impact of the AP-1 transcription factors and the antioxidant tea polyphenols is discussed. The analysis of acute gene expression change in skin after UV irradiation provides a starting point to investigate how the skin responds to genotoxic stress.


SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase.
Sirtuin 3 (SIRT3) modulates mitochondria-localized processes and is implicated in the metabolic reprogramming of cancer cells, especially fatty acid (FA) synthesis. However, the relationship between SIRT3 and aberrant lipid synthesis in cervical cancer remains unclear. Here, we investigated the clinical relevance of SIRT3 expression in cervical squamous cell carcinoma (CSCC), cervical intraepithelial neoplasia (CIN), and normal tissues. To analyze the role of SIRT3 in CCSC in vitro, endogenous SIRT3 levels were up- and down-regulated in SiHa and C33a cells, respectively, via lentiviral-based transfection. Levels were quantified using qRT-PCR. Acetylation levels for acetyl-coA carboxylase (ACC1) were measured with the anti-acetyllysine antibody. Knockdown of SIRT3 reduced levels of cellular lipid content in cells. To investigate the role of SIRT3 in cell proliferation, nude mice were xenografted with SIRT3-overexpressing or SIRT3-knockdown CCSC cells. Overall, the results demonstrate that SIRT3 significantly contributed to the reprogramming of FA synthesis in CCSC by up-regulating ACC1 to promote de novo lipogenesis by SIRT3 deacetylation. Moreover, the findings show that the SIRT3-mediated regulation of FA synthesis played a critical role in the proliferation and metastasis of CCSC cells, suggesting that SIRT3 has therapeutic potential in CCSC treatment.


HCA and HML isolated from the red marine algae Hypnea cervicornis and Hypnea musciformis define a novel lectin family.
HCA and HML represent lectins isolated from the red marine algae Hypnea cervicornis and Hypnea musciformis, respectively. Hemagglutination inhibition assays suggest that HML binds GalNAc/Gal substituted with a neutral sugar through 1-3, 1-4, or 1-2 linkages in O-linked mucin-type glycans, and Fuc(alpha1-6)GlcNAc of N-linked glycoproteins. The specificity of HCA includes the epitopes recognized by HML, although the glycoproteins inhibited distinctly HML and HCA. The agglutinating activity of HCA was inhibited by GalNAc, highlighting the different fine sugar epitope-recognizing specificity of each algal lectin. The primary structures of HCA (9193+/-3 Da) and HML (9357+/-1 Da) were determined by Edman degradation and tandem mass spectrometry of the N-terminally blocked fragments. Both lectins consist of a mixture of a 90-residue polypeptide containing seven intrachain disulfide bonds and two disulfide-bonded subunits generated by cleavage at the bond T50-E51 (HCA) and R50-E51 (HML). The amino acid sequences of HCA and HML display 55% sequence identity (80% similarity) between themselves, but do not show discernible sequence and cysteine spacing pattern similarities with any other known protein structure, indicating that HCA and HML belong to a novel lectin family. Alignment of the amino acid sequence of the two lectins revealed the existence of internal domain duplication, with residues 1-47 and 48-90 corresponding to the N- and C-terminal domains, respectively. The six conserved cysteines in each domain may form three intrachain cysteine linkages, and the unique cysteine residues of the N-terminal (Cys46) and the C-terminal (Cys71) domains may form an intersubunit disulfide bond.


Transient atrial mechanical dysfunction assessed in acute phase of embolic stroke of undetermined source.
Paroxysmal atrial fibrillation (PAF) has been suggested as a major cause of embolic stroke of undetermined source (ESUS). Transient atrial mechanical dysfunction (stunning) frequently occurs after conversion of atrial fibrillation to sinus rhythm. The study aim was to determine if reversible atrial mechanical dysfunction in ESUS could help elucidate the mechanism of stroke. Eighty-five consecutive patients with acute ischemic stroke were enrolled according to the following inclusion criteria: [1] ≥55 years old; [2] normal sinus rhythm upon admission; [3] no apparent embolic source; and [4] transthoracic echocardiographic evaluation had been performed in both the early phase (<72 h) and late phase (>7 days) after stroke onset. There were 27 patients in the lacunar or atherothrombotic infarction group (controls), 22 in the PAF group, and 36 in the ESUS group. To determine atrial stunning, transmitral flow velocity profiles (Doppler peak E- [early diastolic] and A- [atrial systolic] waves) were obtained. In the early phase, an E/A velocity ratio ≥ 1.0 was less common in the control group (1 patient, 3.7%) than in the PAF group (19 patients, 86.4%; p < 0.001) and ESUS group (10 patients, 27.8%; p < 0.05). In the late phase, the E/A ratio decreased to less than 1.0 in six patients (31.6%) who had PAF and in eight patients (80.0%) who had ESUS. Transient atrial mechanical dysfunction could be a helpful finding for elucidating the stroke mechanism in patients with ESUS, and early echocardiographic assessment could improve its detection.


Effects of a Passive Back-Support Exosuit on Erector Spinae and Abdominal Muscle Activity During Short-Duration, Asymmetric Trunk Posture Maintenance Tasks.
To examine the effects of asymmetry and lower extremity mobility restrictions on the effectiveness of a passive back-support exosuit in short-duration, static trunk flexion postures. The effectiveness of trunk exoskeletons/suits for sagittally symmetric trunk posture maintenance has been investigated, but there has been limited study of the effects of asymmetric trunk postures or lower extremity motion restriction. Sixteen participants held trunk flexion postures involving trunk flexion (20°, 40°, 60°), asymmetry (0°, 30°), and lower extremity mobility (Free, Restricted) for 3 s. Participants held these postures with and without an exosuit while erector spinae and abdominal muscle activities were collected. There were no significant interactions between exosuit and asymmetry or exosuit and lower extremity motion restrictions, indicating no significant effects of these factors on the effectiveness of the exosuit at reducing trunk muscle activity. The exosuit was found to be effective at reducing erector spinae muscle activity regardless of asymmetry of posture or lower extremity restrictions (average 21%, from 11.2% MVC to 8.8% MVC). The magnitude of the erector spinae activity at 60° of trunk flexion with the exosuit was similar to that seen at 20° without the exosuit. The exosuit consistently provided biomechanical benefit through reduced activation of the erector spinae muscles and neither asymmetry of trunk posture nor lower extremity restriction influenced this effectiveness. Trunk exoskeletons/suits can reduce trunk muscle activation and understanding how characteristics of the trunk postures assumed impact these responses may help target tasks wherein these devices may be effective.


Detoxification of ochratoxin A, a food contaminant: Prevention of growth of Aspergillus ochraceus and its production of ochratoxin A.
The toxicity of ochratoxin A (OTA), a mycotoxin produced by fungi ofAspergillus orPenicillium genera is now well documented. Its nephrotoxicity, immunosuppression, teratogenicity, and carcinogenicity have been widely studied. Physical and biochemical methods have been studied to prevent these toxinogenicAspergillus andPenicillium from producing OTA, and/or to destroy the mycotoxin when already produced in a liquid or a solid medium. Repeated freezing at - 20†C and thawing at + 26†C aleatory reduce OTA production in a liquid medium. Exposure to UV B for different periods of time is efficient in preventing OTA production in a liquid medium. Gamma-irradiation from 2 to 5 kGy gives good results in preventing the production of OTA or destroying it when already produced. Carboxypeptidase is very efficient at 5 units/50 ml in a liquid medium for cleaving the OTA already produced.


Functional tests in women with patellofemoral pain: Which tests make a difference in physical therapy evaluation.
Patellofemoral pain (PFP) is characterized by anterior knee, which intensifies during functional activities that require the eccentric action of the quadriceps muscle, specially. In ths way, quantitatively measurable functional tests that simulate these activities should be included in the physical therapy evaluation. To identify which functional tests are most indicated for the evaluation of women with PFD. This study evaluated 100 young women (50 with PFP), during the execution of the following functional performance tests: Triple hop, Vertical Jump, Single leg squat, Step Down, YBalance tests, Lunge test and running. Dynamic valgus was also assessed in the tests. The isometric muscle strength of the following muscle groups: hip abductors, extensors and lateral rotators, knee extensors, evertors, and plantar flexors were evaluated. Functional Perception were evaluated by Anterior Knee Pain Scale and Activities of Daily Living Scale. PFP group showed lower performance during the Y-Balance, triple hop, vertical jump tests and running. Was observed an increase in dynamic valgus during Triple Hop, Vertical Jump tests and running in PFP group, besides a poorer perception of function. For all lower limb muscle groups, the PFP group showed a reduction in peak isometric force. The YBalance, triple hop, vertical jump tests, and running should be included in the physical therapy evaluation, in addition to aspects of lower limb muscle strength.


Effect of transmural versus nontransmural myocardial infarction on inducibility of ventricular arrhythmias during sympathetic stimulation in dogs.
Transmural myocardial infarction interrupts sympathetic nerves and denervates viable muscle distal to myocardial infarction. The effect of sympathetic stimulation on responses to programmed ventricular stimulation was studied in dogs without myocardial infarction (Group I: n = 5), with transmural anterior wall myocardial infarction (Group II: n = 6) and with nontransmural anterior wall myocardial infarction (Group III: n = 9). Ventricular effective refractory period during sympathetic stimulation decreased by 16 +/- 18, 1 +/- 2 and 12 +/- 8 ms (mean +/- SD) in viable muscle of the inferoapical left ventricle in Groups I, II and III, respectively, suggesting efferent sympathetic denervation by transmural myocardial infarction only. Sustained ventricular tachycardia or fibrillation was induced more easily during sympathetic stimulation in six of the six dogs with transmural infarction, but in only two of the nine dogs with nontransmural infarction (p less than 0.01). It is concluded that the partial sympathetic denervation produced by transmural myocardial infarction enhances the ease of induction of ventricular tachycardia and fibrillation during sympathetic stimulation. A similar mechanism may lead to increased risk for lethal arrhythmias during periods of high sympathetic tone in patients with transmural myocardial infarction.


Decreased response to IL-12 and IL-18 of peripheral blood cells in rheumatoid arthritis.
Inflamed synovium of rheumatoid arthritis (RA) has been associated with a T helper (Th)1 cytokine profile but the blood situation remains to be clarified. We studied the differential IFN-gamma producing activity of peripheral blood mononuclear cells (PBMCs) from RA patients (RA-PBMCs) and from healthy controls (H-PBMCs) in response to IL-12 and IL-18. RA-PBMCs had a decreased IFN-gamma production in response to IL-12 and IL-18 when compared with H-PBMCs. RA-PBMCs activated with phytohemagglutinin and phorbol 12-myristate 13-acetate showed an increased sensitivity to IL-12 and IL-18, but still the RA-PBMC response was lower. IL-18 increased IL-12-stimulated IFN-gamma production from RA synovium cells obtained after collagenase digestion more effectively than that of RA- or H-PBMCs. A specific inhibitor of IL-18 bioactivity, IL-18-binding protein (IL-18BP), down-regulated IL-12-induced IFN-gamma production by RA- or H-PBMCs and had a remarkable effect on RA synovium cells. In conclusion, RA disease combines a polarized immune response with an active Th1 in inflamed joints and a reduced Th1 pattern in peripheral circulation.


Water, environment, and socioeconomic justice in California: A multi-benefit cropland repurposing framework.
Low-income, rural frontline communities of California's Central Valley experience environmental and socioeconomic injustice, water insecurity, extremely poor air quality, and lack of fundamental infrastructure (sewage, green areas, health services), which makes them less resilient. Many communities depend financially on agriculture, while water scarcity and associated policy may trigger farmland retirement further hindering socioeconomic opportunities. Here we propose a multi-benefit framework to repurpose cropland in buffers inside and around (400-m and 1600-m buffers) 154 rural disadvantaged communities of the Central Valley to promote socioeconomic opportunities, environmental benefits, and business diversification. We estimate the potential for (1) reductions in water and pesticide use, nitrogen leaching, and nitrogen gas emissions, (2) managed aquifer recharge, and (3) economic and employment impacts associated with clean industries and solar energy. Retiring cropland within 1600-m buffers can result in reductions in water use of 2.18 km3/year, nitrate leaching into local aquifers of 105,500 t/year, greenhouse gas emissions of 2,232,000 t CO2-equivalent/year, and 5388 t pesticides/year, with accompanying losses in agricultural revenue of US$4213 million/year and employment of 25,682 positions. Buffer repurposing investments of US$27 million/year per community for ten years show potential to generate US$101 million/year per community (total US$15,578 million/year) for 30 years and 407 new jobs/year (total 62,697 jobs/year) paying 67 % more than prior farmworker jobs. In the San Joaquin Valley (southern Central Valley), where groundwater overdraft averages 2.3 km3/year, potential water use reduction is 1.8 km3/year. We have identified 99 communities with surficial soils adequate for aquifer recharge and canals/rivers within 1600 m. This demonstrates the potential of managed aquifer recharge in buffered zones to substantially reduce overdraft. The buffers framework shows that well-planned land repurposing near disadvantaged communities can create multiple benefits for farmers and industry stakeholders, while improving quality of life in disadvantaged communities and producing positive externalities for society.


ThPOK inhibits the immune escape of gastric cancer cells by inducing STPG1 to inactivate the ERK pathway.
Gastric cancer is the second most frequently diagnosed cancer worldwide. Weak immunogenicity helps cancer cells escape from immune elimination and grow into predominant subpopulations. This study aimed to investigate the effect of Zinc finger and BTB domain containing 7B (Zbtb7b, Alias ThPOK) on T cell activation after coculture with gastric cancer cells. Cell Counting Kit-8 assay (CCK-8) was performed to explore the viability of gastric cancer cells. Flow cytometry analysis was used to measure CD3+ T cell proliferation and the ratio of activated IFN-γ+ T cells which were co-incubated with gastric cancer cells (HGC-27, SNU-1). The binding between ThPOK and the promoter of its target sperm tail PG-rich repeat containing 1 (STPG1) was explored using ChIP and luciferase reporter assays. Relative gene expression was quantified using RT-qPCR. ThPOK was expressed at a low level in gastric cancer tissues and cells at mRNA and protein levels. Gastric cancer patients with lower ThPOK expression had poorer prognosis. ThPOK overexpression suppressed gastric cancer cell viability and increased T cell activation. ThPOK served as a transcription factor for STPG1. STPG1 expression was also at a low level in the tissues and cells of gastric cancer. ThPOK positively regulated the mRNA and protein levels of STPG1 in gastric cancer cells. Moreover, ThPOK was demonstrated to bind with STPG1 promoter. STPG1 upregulation also exerted inhibitory effects on gastric cancer cell viability and T cell activation. Additionally, ThPOK and STPG1 were revealed to inactivate the ERK pathway in gastric cancer cells. ThPOK inhibits gastric cancer cell viability and increases T cell activation by inducing STPG1 to inactivate the ERK pathway.


Changes to the end-stage renal disease quality incentive program.
Monitoring the quality of dialysis care has long been a component of the Medicare ESRD program. As part of the 2008 Medicare Improvements for Patients and Providers Act (MIPPA), Congress mandated the Quality Incentive Program (QIP), which linked measures of care quality to payments. The legislation embraced the idea that this linkage of federal money to performance would encourage the purchase of greater 'value.' The first 2 program years for the QIP use a simple scoring methodology and a limited scope of quality metrics. For payment year 2014 (performance period calendar year 2012), the program changes substantially, with an expanded number of quality measures and a more complex scoring methodology. In this article, we describe the program structure, quality measures, scoring system, and financial impact.


Soda Consumption is Associated with Risk-Taking Behaviors in Adolescents.
Soda consumption is on the rise among children and adolescents. The purpose of this study was to test the hypothesis that increased soda consumption predicts risk-taking behavior among high school students. To test this hypothesis, we used data from the 2011 Youth Risk Behavior Surveillance System to compare the odds of engaging in a series of risk-taking behaviors among students who reported no soda consumption, occasional soda consumption (1 - 6 times per week), and daily soda consumption (≥ 7 times per week). Daily soda consumption was associated with increased odds of engaging in 90% of the risk behaviors analyzed. In addition, there were sex differences in the magnitude of the relationships for many of these behaviors. These data suggest that in addition to increased risk of obesity, dental caries, and reduced sleep quality, soda consumption is associated with increased risk-taking behavior.


Phenotypic and HLA-DRB1 allele characterization of Swedish cardiac sarcoidosis patients.
Early detection and initiation of treatment in cardiac sarcoidosis (CS) is believed to be crucial to reduce morbidity and mortality. The diagnosis of CS is challenging, especially in isolated CS (ICS). Certain human leukocyte antigen (HLA-DRB1) alleles associate with different phenotypes of sarcoidosis. Phenotypic and genotypic characterization of patients with CS may improve our ability to identify patients being at risk for developing CS. 87 patients with CS, identified at two Swedish university hospitals were included. Phenotypic characteristics were extracted from the medical records and the patients were HLA-DRB1 typed. Median age at diagnosis was 55 years, 37% were women. HLA-DRB1 distribution was similar to a general sarcoidosis population. A majority of patients (51/87) had CS as the first sarcoidosis presentation. They were younger (p = 0.04), more often presenting with ventricular tachycardia (VT) or atrioventricular block (AVB) grade II or III (p < 0.001), had lower left ventricular ejection fraction (LVEF) (p = 0.002), lower serum angiotensin converting enzyme (s-ACE) (p = 0.025), and fewer extra cardiac manifestations (ECM) (p = 0.02) than those presenting with CS later. Of Swedish CS patients, 59% presented with cardiac involvement as first manifestation. They had more severe cardiac symptoms than patients presenting with CS later. This phenotype disclosed less ECM and lower s-ACE thus diagnosis can be missed or delayed. We did not observe significant differences in HLA-DRB1 allele frequency between patients with CS compared to sarcoidosis in general. Awareness of CS as a primary manifestation can enable early detection and adequate intervention.


Functional plasticity in ventral temporal cortex following cognitive rehabilitation of a congenital prosopagnosic.
We used functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to measure neural changes associated with training configural processing in congenital prosopagnosia, a condition in which face identification abilities are not properly developed in the absence of brain injury or visual problems. We designed a task that required discriminating faces by their spatial configuration and, after extensive training, prosopagnosic MZ significantly improved at face identification. Event-related potential results revealed that although the N170 was not selective for faces before training, its selectivity after training was normal. fMRI demonstrated increased functional connectivity between ventral occipital temporal face-selective regions (right occipital face area and right fusiform face area) that accompanied improvement in face recognition. Several other regions showed fMRI activity changes with training; the majority of these regions increased connectivity with face-selective regions. Together, the neural mechanisms associated with face recognition improvements involved strengthening early face-selective mechanisms and increased coordination between face-selective and nonselective regions, particularly in the right hemisphere.


Dietary alpha-linolenic acid suppresses the formation of lysophosphatidic acid, a lipid mediator, in rat platelets compared with linoleic acid.
Rats fed a high linoleic acid (LA, 18:2n-6) diet or a high alpha-linolenic acid (ALA, 18:3n-3) diet for 4 months after weaning. Platelets from the high-LA group contained more arachidonic acid (AA, 20:4n-6) and less eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) compared with those from the high-ALA group. Incorporation of [32P]orthophosphate into platelet phospholipids was increased by thrombin-treatment, and was greater by ca. 30% in the high-LA group than in the high-ALA group both in the presence and absence of thrombin. The formation of [32P]lysophosphatidic acid (LPA), a lipid messenger, in [32P]orthophosphate-labeled platelets was increased 6.6-fold in the high-LA group and 4.1-fold in the high-ALA-group by thrombin-treatment. The formation of [32P] LPA in activated platelets was reduced by 35% in the high-ALA group.


The N-AcetylCysteine and RAMipril in Takotsubo Syndrome Trial (NACRAM): Rationale and design of a randomised controlled trial of sequential N-Acetylcysteine and ramipril for the management of Takotsubo Syndrome.
Takotsubo Syndrome(TTS), contrary to historical reports, is now increasingly recognised to be associated with substantial mortality and morbidity, both in the short- and long-term. Although TTS is often precipitated by a catecholamine "pulse", in-hospital hypotension is a common occurrence, increasing the risk of mortality. Furthermore, despite the transient catecholamine stimulus, there is increasing evidence that there are significant long term sequelae, including persistently impaired left ventricular(LV) systolic dysfunction, myocardial oedema with fibrosis, as well as persistent impairment of quality of life. A definitive therapeutic option to limit the extent of initial myocardial injury, and to accelerate recovery in TTS is therefore justified. However to date, there has been a lack of prospective studies in this area. NACRAM is a multi-centre, randomised, placebo-controlled trial, sequentially testing early use of intravenous N-acetylcysteine(NAC), followed by/or oral ramipril for 12 weeks. The rationale for utilising these agents is related to their effects on limiting nitrosative stress and expression of the inflammasome activator thioredoxin interacting protein(TXNIP); both processes fundamental to the pathogenesis of TTS. NACRAM is assessing resolution of myocardial oedema on cardiac magnetic resonance imaging(CMR), improvements in LV systolic function as measured by global longitudinal strain(GLS) on echocardiography, quality of life, and inflammatory markers. To the best of our knowledge, NACRAM will be the first prospective study to help definitively evaluate a therapeutic option in acute attacks of TTS.


Community factors influencing psychiatric hospital utilization in rural and urban Ireland.
The role of community factors in psychiatric hospital utilization in rural and urban Ireland was evaluated using Hollingshead & Redlich's conceptual model. Rural and urban differences in identification of psychiatric disorders, attitude to psychiatric facilities and social isolation were assessed using a community survey (N = 200). No difference was found in the recognition of schizophrenic behavior. Rural residents tended to normalize neurotic behavior and significantly fewer recognized it as deviant. The two communities did not differ in the identification of alcoholism or neuroses as mental illness. Rural individuals had a more negative attitude to psychiatric facilities, and sought help more frequently from relatives who were less accessible than their urban counterparts.


Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.
Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients.


Comparison of predicted native structures of Met-enkephalin based on various accessible-surface-area solvent models.
We examine the variation and similarity of the native structures predicted from various accessible-surface-area solvent models for peptide Met-enkephalin. Both ECEPP/2 and ECEPP/3 force fields have been used in conjunction with ten different sets of accessible-surface-area parameterization. The native structures were determined by an implementation of the basin hopping Monte Carlo technique. The results suggest that the implicit solvent models examined in this study should be employed in computer simulations with extreme caution. In addition, the effect of fixing or not fixing the peptide angles omega has been examined. We conclude that fixing omega generally gives rise to a poor prediction.


An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development of secretory diarrhea and cystic fibrosis. The oldest CFTR ortholog identified is from dogfish shark, which retains similar structural and functional characteristics to the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transport in vertebrates. However, the identification of an early CFTR ortholog with altered structure or function would provide critical insight into the evolution of epithelial anion transport. Here, we describe the earliest known CFTR, expressed in sea lamprey (Petromyzon marinus), with unique structural features, altered kinetics of activation and sensitivity to inhibition, and altered single-channel conductance compared to human CFTR. Our data provide the earliest evolutionary evidence of CFTR, offering insight regarding changes in gene and protein structure that underpin evolution from transporter to anion channel. Importantly, these data provide a unique platform to enhance our understanding of vertebrate phylogeny over a critical period of evolutionary expansion.


Thalamic rhythms in cat during quiet wakefulness and immobility.
In this study we tried to get some more information on the cortical 'mu' rhythms in normal cat and their thalamic pacemaker. Mu (14 c/sec) activity develops when the animal is motionless, in a state of 'quiet waking.' It is distinct from other sensorimotor rhythms, with distinct cortical distributions, distinct frequencies and appearing under different behavioural and environmental conditions. The cortical mu focus was shown to be centred within a restricted part of area SI, in the forepaw and wrist projection field. The related thalamic focus was localized in a small zone of the VP nucleus that also corresponded to the hand and wrist projection area. A coherence study confirmed the close relationship between the two foci, thalamic and cortical. After unilateral electrolytic destruction of the thalamic area, a small mu activity persisted, on the ipsilateral cortex, originating from the opposite side. After bilateral lesion of the VP foci, no mu activity could ever be recorded on either side, while the other sensorimotor rhythms were left intact.


Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats.
Methamphetamine (METH) is one of the most powerful psychostimulant that leads to long lasting cognitive impairment. Earlier researches demonstrated that ovarian hormones including estrogen and progesterone ameliorate cognitive function against various central nervous system disorders. Moreover, recent studies demonstrate a neuroprotective role against methamphetamine toxicity. In current study the effects of estrogen and progesterone alone or in combination, on spatial learning and memory in METH-exposed ovariectomized (OVX) rats are investigated. Three weeks after ovariectomy, the animals were treated by estrogen (1mg/kg, i.p.) and progesterone (8mg/kg, i.p.) alone and in combination or vehicle during 14 consecutive days. On the 28th day, rats were exposed to a single-day METH regimens (four injections of 6mg/kg, s.c, at 2h intervals) 30min after the hormones treatment. Finally, spatial learning and memory were examined using the Morris water maze 2days after the last treatment. The findings showed that estrogen and progesterone did not have significant effect on spatial learning and memory in non METH-exposed OVX rats. The treatment with estrogen and progesterone alone in METH-exposed rats, significantly improved spatial learning and memory impairment. On the other hand, the cognitive performance of animals that received combination of estrogen plus progesterone in METH-exposed rats did not significantly differ from that of METH-exposed animals that received vehicle injections. Taken together, the present findings suggest that treatment with ovarian hormones can partially improve spatial learning and memory deficits induced by methamphetamine in OVX rats.


A qualitative study utilizing Interpretative phenomenological analysis to explore disclosure in adolescents with turner syndrome.
To explore the experiences of diagnostic disclosure and disclosure to others in adolescents with Turner syndrome (TS) and their parents/guardians. In addition, we sought to examine the impact of TS on girls with TS and their family's lives. A qualitative method utilizing interpretative phenomenological analysis (IPA) was employed. Five girls with TS and one parent/guardian of each girl completed dyadic and individual semi-structured interviews. Interviews were audio recorded and analysed verbatim. Data were analysed in accordance with IPA guidelines, with a focus on the dynamic interactions within dyads. Analyses identified three superordinate themes across the 10 participant accounts: communication and support, stigmatization of TS, and psychological consequences. Ten related subthemes are described alongside relevant quotations, highlighting a gradual process of diagnostic disclosure within families and wider health care systems. Both girls and their parents appeared to express a general desire to conceal TS from others, indicating possible TS-related stigma. The results also demonstrate the varying impact TS can have within families. The findings provide insight into the lived experience of receiving a diagnosis of TS and the possible difficulties around disclosure to others. Potential recommendations for clinicians and parents include ensuring direct conversations about infertility occur within treatment and facilitating open, honest communication.


B lymphocytic lymphoma (large cell) of possible splenic marginal zone origin presenting with prominent splenomegaly and unusual cordal red pulp distribution.
Two cases of large cell lymphoma, B-cell type, primarily involving the red pulp of the spleen rather than the white pulp are described. A number of unusual features suggest that this may be a lymphoma originating from a distinct splenic B-cell lymphocyte whose origin may be the marginal zone of the spleen or the splenic cords. The patients presented with splenomegaly, cytopenias, and no peripheral lymphadenopathy. The gross appearance of the spleens was beefy red without tumor nodules. The tumor cells were primarily in the splenic cords and surrounding residual normal white pulp. There was a minimal hemic phase. The tumor cells had abundant cytoplasm, surface IgM, IgD, kappa, and FC receptors, tartrate-resistant acid phosphatase, but no alkaline phosphatase or interleukin-2 receptors. They had a similar DNA aneuploidy. The most unusual feature was that tumor cells in both cases had phagocytic properties. These lymphomas may be clinically more indolent than their follicular center counterparts.


Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease--a cohort study.
Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD. At a tertiary care center we followed a historical cohort of amiodarone-treated CHD patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with last thyroid assessment on amiodarone. Cumulative incidence of AIT was calculated. AIT association with nutritional status was hypothesized a priori. AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO initiation compared with the rest of the cohort (mean ± standard deviation: 21.9 ± 2.9 vs. 25.1 ± 5.0; p<0.001). Patients with BMI<21 were more likely to develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%, p=0.059). On multivariate analysis body mass index and goiter remained independent predictors of outcome. BMI<21 at initiation of amiodarone therapy and presence of goiter are strong predictors of AIT in this population. Its incidence is time dependent. These predictors can be used clinically in assessing overall impact of amiodarone therapy in congenital heart disease patients.


Physicochemical compatibility between ketoprofen lysine salt injections (Artrosilene) and pharmaceutical products frequently used for combined therapy by intravenous administration.
Ketoprofen lysine salt (Artrosilene) Fiale) is a non-steroidal anti-inflammatory agent frequently administered by intravenous infusion in association regimen with other drugs, such as steroidal anti-inflammatory, anti-hemorrhagic, anti-spastic, anti-ulcer, and antibacterial drugs. The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt (Artrosilene) Fiale) and other injectable drugs frequently used in association. Physicochemical properties of ketoprofen lysine salt mixtures with different drugs, including colour, clarity, pH and drug content were observed or measured before and after (up to 5 h) mixing at room temperature and under light protection. Results show that the association of Artrosilene Fiale with different drugs does not cause, up to 5 h from mixing, any significant variation in the physicochemical parameters mentioned above. In conclusion, the results obtained demonstrated the physicochemical compatibility of ketoprofen lysine salt (Artrosilene) Fiale) with several drugs.


Impact of acetaminophen on the efficacy of immunotherapy in cancer patients.
Acetaminophen (APAP) use has been associated with blunted vaccine immune responses. This study aimed to assess APAP impact on immunotherapy efficacy in patients with cancer. Exposure to APAP was assessed by plasma analysis and was correlated with clinical outcome in three independent cohorts of patients with advanced cancer who were treated with immune checkpoint blockers (ICBs). The immunomodulatory effects of APAP were evaluated on a preclinical tumor model and on human peripheral blood mononuclear cells (PBMCs) from healthy donors. Detectable plasma APAP levels at treatment onset were associated with a significantly worse clinical outcome in ICB-treated cancer patients, independently of other prognostic factors. APAP significantly reduced ICB efficacy in the preclinical MC38 model, as well as the production of PD-1 blockade-related interferon-γ secretion by human PBMCs. Moreover, reduction of ICB efficacy in vivo was associated with significantly increased tumor infiltration by regulatory T cells (Tregs). Administration of APAP over 24 h induced a significant expansion of peripheral Tregs in healthy individuals. In addition, interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly up-regulated upon treatment with ICB in cancer patients taking APAP. This study provides strong preclinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB.


Prandial hyperglycemia: is it important to track and treat?
Prandial hyperglycemia comprises 16 to 18 hours in type 2 diabetes. Depending on quality of diabetes control, 30% to 70% of the variance of hemoglobin A(1c) is determined by postprandial glucose excursions. A large amount of evidence now shows that postprandial/postchallenge glucose value is an independent cardiovascular risk factor, especially for coronary heart disease. Excessive postprandial hyperglycemia initiates a cascade of proatherogenic disturbances, which leads to endothelial dysfunction and plaque instability. Measurement of 2-hour postprandial glucose after big meals should be performed once or twice a week in subjects with type 2 diabetes. Measurement of 2-hour glucose after a 75-g oral glucose tolerance test is the only way to detect subjects with impaired glucose tolerance and isolated postchallenge hyperglycemia in the diagnosis for diabetes. a-Glucosidase inhibitors, glinides, and short-acting analogue insulin allow a well-tailored control of type 2 diabetes with excessive postprandial hyperglycemia. Prospective trials have demonstrated that strict control of postprandial hyperglycemia reduces the incidence of cardiovascular events.


Body mass, estrogen levels, and hot flashes in midlife women.
This study was undertaken to determine whether body mass index (BMI) is associated with hot flashes and whether the mechanism by which BMI increases the risk of hot flashes is by lowering estrogen levels. A case-control study was conducted among midlife women to examine risk factors for hot flashes. Cases were women who reported experiencing hot flashes (n = 353). Controls were women who reported never experiencing hot flashes (n = 258). Each participant completed a questionnaire and provided a blood sample for estrogen measurement. Compared with normal weight women, very obese women had significantly higher odds of hot flashes. The odds ratios remained elevated although attenuated when the hormone variables were added to the model. These results indicate that very obese women are at increased risk for hot flashes compared with normal weight women. Estrogen levels may partly explain this relationship; however, other mechanisms appear to be involved as well.


Intron delays and transcriptional timing during development.
The time taken to transcribe most metazoan genes is significant because of the substantial length of introns. Developmentally regulated gene networks, where timing and dynamic patterns of expression are critical, may be particularly sensitive to intron delays. We revisit and comment on a perspective last presented by Thummel 16 years ago: transcriptional delays may contribute to timing mechanisms during development. We discuss the presence of intron delays in genetic networks. We consider how delays can impact particular moments during development, which mechanistic attributes of transcription can influence them, how they can be modeled, and how they can be studied using recent technological advances as well as classical genetics.


Biorefining of by-product streams from sunflower-based biodiesel production plants for integrated synthesis of microbial oil and value-added co-products.
This study focuses on the valorisation of crude glycerol and sunflower meal (SFM) from conventional biodiesel production plants for the separation of value-added co-products (antioxidant-rich extracts and protein isolate) and for enhancing biodiesel production through microbial oil synthesis. Microbial oil production was evaluated using three oleaginous yeast strains (Rhodosporidium toruloides, Lipomyces starkeyi and Cryptococcus curvatus) cultivated on crude glycerol and nutrient-rich hydrolysates derived from either whole SFM or SFM fractions that remained after separation of value-added co-products. Fed-batch bioreactor cultures with R. toruloides led to the production of 37.4gL(-1) of total dry weight with a microbial oil content of 51.3% (ww(-1)) when a biorefinery concept based on SFM fractionation was employed. The estimated biodiesel properties conformed with the limits set by the EN 14214 and ASTM D 6751 standards. The estimated cold filter plugging point (7.3-8.6°C) of the lipids produced by R. toruloides is closer to that of biodiesel derived from palm oil.


Thyroid nodule recognition based on feature selection and pixel classification methods.
Statistical approach is a valuable way to describe texture primitives. The aim of this study is to design and implement a classifier framework to automatically identify the thyroid nodules from ultrasound images. Using rigorous mathematical foundations, this article focuses on developing a discriminative texture analysis method based on texture variations corresponding to four biological areas (normal thyroid, thyroid nodule, subcutaneous tissues, and trachea). Our research follows three steps: automatic extraction of the most discriminative first-order statistical texture features, building a classifier that automatically optimizes and selects the valuable features, and correlating significant texture parameters with the four biological areas of interest based on pixel classification and location characteristics. Twenty ultrasound images of normal thyroid and 20 that present thyroid nodules were used. The analysis involves both the whole thyroid ultrasound images and the region of interests (ROIs). The proposed system and the classification results are validated using the receiver operating characteristics which give a better overall view of the classification performance of methods. It is found that the proposed approach is capable of identifying thyroid nodules with a correct classification rate of 83 % when whole image is analyzed and with a percent of 91 % when the ROIs are analyzed.


Effect of 60-minute head-down tilt on arterial baroreflex function in anesthetized dogs.
Arterial baroreflex control of heart rate was assessed in 6 anesthetized dogs with a bolus infusion of phenylephrine before and during cardiopulmonary receptor stimulation by 6 degrees head-down tilt (HDT) for 60 min. No difference in arterial baroreflex function was observed between the control and HDT conditions. It appears that the attenuation of baroreflex function that occurs during acute stimulation of cardiopulmonary baroreceptors disappears when cardiopulmonary baroreceptors reset after prolonged stimulation.


The effects of central catecholamine depletions on spatial learning in rats.
The role of forebrain catecholamine systems in spatial learning was assessed using a recently described place navigation task. Rats were required to learn the spatial location of a platform hidden 1 cm below the surface in order to escape from a large pool filled with opaque water. Circumscribed destruction of dopamine or noradrenaline neurones was achieved with bilateral stereotaxic injections of 6-hydroxydopamine. Rats with neostriatal dopamine depletions showed regulatory impairments, mild akinesia and increased latencies to escape during training on both the spatial task and on a non-spatial control task. However their normal transfer test performance indicated that their deficit was not due to impaired spatial learning. Similarly, spatial learning and transfer test performance were unimpaired by mesocorticolimbic dopamine depletions or by extensive noradrenaline loss in cortex and hippocampus following dorsal noradrenergic bundle lesions. These findings suggest that considerable spatial learning can occur in the absence of each of the major telencephalic catecholamine systems.


Oxidation of benzidine and its derivatives by thyroid peroxidase.
Human thyroid peroxidase (hTPO) catalyzes a one-electron oxidation of benzidine derivatives by hydrogen peroxide through classical Chance mechanism. The complete reduction of peroxidase oxidation products by ascorbic acid with the regeneration of primary aminobiphenyls was observed only in the case of 3,3',5,5'-tetramethylbenzidine (TMB). The kinetic characteristics (k(cat) and K(m)) of benzidine (BD), 3,3'-dimethylbenzidine (o-tolidine), 3,3'-dimethoxybenzidine (o-dianisidine), and TMB oxidation at 25 degrees C in 0.05 M phosphate-citrate buffer, pH 5.5, catalyzed by hTPO and horseradish peroxidase (HPR) were determined. The effective K(m) values for aminobiphenyls oxidation by both peroxidases raise with the increase of number of methyl and methoxy substituents in the benzidine molecule. Efficiency of aminobiphenyls oxidation catalyzed by either hTPO or HRP increases with the number of substituents in 3, 3', 5, and 5' positions of the benzidine molecule, which is in accordance with redox potential values for the substrates studied. The efficiency of HRP in the oxidation of benzidine derivatives expressed as k(cat)/K(m) was about two orders of magnitude higher as compared with hTPO. Straight correlation between the carcinogenicity of aminobiphenyls and genotoxicity of their peroxidation products was shown by the electrophoresis detecting the formation of covalent DNA cross-linking.


Keratin 18 Depletion as a Possible Mechanism for the Induction of Apoptosis and Ferroptosis in the Rat Hippocampus After Hypobaric Hypoxia.
Memory impairment is one of the neuropsychological effects of hypobaric hypoxia (HH), which can be associated with programmed cell death, such as apoptosis and ferroptosis. Emerging evidence indicates crosstalk between apoptosis and ferroptosis, while the crosstalk between HH-induced apoptosis and ferroptosis in the hippocampus has not been clarified. Here, microarray profiles were extracted to analyze the differentially expressed genes with and without HH exposure, and keratin 18 (Krt18) was found to be a potential gene related to both apoptosis and ferroptosis. Then, we conducted morphological observations that showed that apoptosis and ferroptosis coexisted in the rat hippocampus after HH exposure. Combined with the real-time q-PCR analysis, the mRNA expression of Krt18 decreased significantly after HH exposure for 1 day and 3 days, and Mapk10 (JNK3) was upregulated at the corresponding time points. After exposure for 7 days, Krt18 and JNK3 showed no significant change. In conclusion, Krt18 may regulate apoptosis and ferroptosis simultaneously, possibly via the JNK signaling pathway, which might provide a potential central target for apoptosis and ferroptosis in hippocampal injury after HH exposure.


Mandibular first premolar with five root canals: a case report.
Understanding the anatomical morphology of the root canal is key for successful root canal treatment. The aims of this case presentation are to report a unique case of root canal treatment involving five root canals in the mandibular first premolar and to highlight the importance of variation in root canals of mandibular first premolars in clinical practice. A 25-year-old male with intermittent pain in relation to the lower right posterior teeth over 3 weeks was diagnosed with symptomatic pulpitis in tooth #44. Four root canals were found, including mesiobuccal, distobuccal-1, distobuccal-2, and distolingual roots, and the Mtwo rotary system was used for root canal preparation. The four root canals were filled after 2 weeks, when a fifth canal was found, located in the buccal cavity. The fifth canal was confirmed to be the mesiolingual root canal by cone beam computed tomography (CBCT) and was found to be curved. After completion of the root canal filling, CBCT was performed, and a three-dimensional root canal image was reconstructed. After 1 week of observation, the tooth was repaired using composite resin filling. This is the first case presentation of a fifth canal of the mandibular first premolar and advances our understanding of variations in the anatomy of the mandibular first premolar. This case report provides a reference for the treatment of mandibular first premolars.


The effects of red blood cell extracts on the proliferation of erythrocyte precursor cells, in vivo.
Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 microgram per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cells proliferation completely but simply lengthens the cell cycle, mainly by increasing the GI phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.


Multiple early gastric cancer with duodenal invasion.
Early gastric cancers with duodenal invasion are rare, and no previous case of multiple early gastric cancer, one invading the duodenal bulb, has been reported. A 79-year-old woman was investigated for upper abdominal discomfort. Endoscopic examination revealed an irregular nodulated lesion in the antrum area, and a reddish aggregated-type semi-circumferential nodulated lesion extending from the prepyloric area to the duodenal bulb through the normal mucosa with the antrum lesion. Biopsy revealed a tubular adenoma for the antrum lesion and a well-differentiated tubular adenocarcinoma for the prepyloric lesion. Distal gastrectomy with sufficient duodenal resection was performed. Microscopically, the antrum lesion appeared as a papillary adenocarcinoma, and the prepyloric lesion as a mainly papillary adenocarcinoma which partially invaded the submucosa without any sequential elongation for endoscopic findings. The lesion extended into the duodenal bulb, and was 12 mm in length from the oral end of Brunner's gland's area and limited within the duodenal mucosa. Here, we present an unusual case of multiple early gastric cancer, one of which invaded the duodenum with relative wide mucosal spreading. This case illustrates that even early stage cancers located in the gastric antrum, particularly in the prepyloric area can invade the duodenum directly.


Improvement of mesophilic anaerobic co-digestion of agri-food waste by addition of glycerol.
Anaerobic co-digestion is a promising alternative to manage agri-food waste rather than landfilling, composting or incineration. But improvement of methane yield and biodegradability is often required to optimize its economic viability. Biomethanization of agri-food solid waste presents the disadvantage of a slow hydrolytic phase, which might be enhanced by adding a readily digestible substrate such as glycerol. In this study, strawberry extrudate, fish waste and crude glycerol derived from biodiesel manufacturing are mixed at a proportion of 54:5:41, in VS (VS, total volatile solids), respectively. The mesophilic anaerobic co-digestion at lab-scale of the mixture was stable at loads lower than 1.85 g VS/L, reaching a methane yield coefficient of 308 L CH4/kg VS (0 °C, 1 atm) and a biodegradability of 96.7%, in VS. Moreover, the treatment capacity of strawberry and fish waste was increased 16% at adding the crude glycerol. An economic assessment was also carried out in order to evaluate the applicability of the proposed process. Even in a pessimistic scenario, the net balance was found to be positive. The glycerol adding implied a net saving in a range from 25.5 to 42.1 €/t if compared to landfill disposal.


Comparison of chlordecone and estradiol effects on splenic T-cells in (NZBxNZW)F(1) mice.
Previous studies have shown that treatment of ovariectomized females with 17-beta estradiol (E2) accelerates the development of autoimmunity in the (NZBxNZW)F(1) murine lupus model. Treatment with estrogenic organochlorine pesticides (OCPs) such as chlordecone produces a similar effect. Although it is reasonable to postulate that the effects of chlordecone and related OCPs on autoimmunity are due to their estrogenic effects, this has not been clearly demonstrated. The objective of this study was to compare effects of chlordecone and E2 on splenic T lymphocyte parameters plausibly related to autoimmunity; specifically, on T-cell phenotype and functions. Ovariectomized (NZBxNZW)F(1) mice were treated for 6 weeks with implanted sustained-release pellets containing chlordecone or E2 at dosing rates shown previously to significantly shorten time to onset of disease. E2, but not chlordecone, increased the percentage of activated and memory CD4 T-cells, and reduced naive CD4 T-cells. E2 also elevated CD25 and glucocorticoid-induced TNF receptor (GITR) levels in CD4 T-cells, an effect not shared by chlordecone. On the other hand, both chlordecone and E2 increased Bcl-2 expression in CD4 T-cells and reduced CD4 T-cell apoptosis without affecting their proliferation. Although both treatments increased TNF-alpha and IL-2 secretion by CD4 T-cells, only chlordecone increased secretion of IFN-gamma and GM-CSF. E2, but not chlordecone, increased IL-10 secretion. These observations indicate that although it is considered an estrogenic OCP, chlordecone exerts effects on splenic T-cells that are different in a number of ways from E2.


Comparison of the efficacy and transmissibility of conventional NDV vaccines and vaccines prepared after back-passage through chickens.
In laboratory trials B1 and Lasota stains of Newcastle disease virus (NDV) back-passaged in chickens were found to have a greater spreading potential than presently available B1 and Lasota vaccines. Although the regular B1 and Lasota strains of NDV gave a routine serologic response when administered to 4-week-old chickens via the water, both vaccines had a low spreading potential since the geometric mean titer of the birds in contact with the B1 vaccinated birds did exceed 3.4 and the HI response of the nonvaccinated birds placed with the Lasota vaccinated birds did not exceed 4.1. The results from this study also indicate that these back-passaged vaccines elicit higher HI titers and are possibly more invasive than the regular B1 and Lasota vaccines. The data also suggest that the Lasota strain possesses a slightly greater spreading potential than the B1 strain of NDV.


Paradoxical growth-hormone responses to thyrotropin-releasing hormone in panic disorder.
Thyrotropin-releasing hormone (TRH) has been reported to stimulate growth hormone (GH) release in a variety of pathological conditions, including some studies of major depression. Because of the considerable phenomenological and neuroendocrine overlap between major depression and panic disorder, we investigated the rate of positive GH responses to TRH in 38 patients with panic disorder and 23 normal controls. There were no between-group differences in mean GH response to TRH or in the proportion of subjects with positive responses. These findings are discussed in the context of neuroendocrine regulation of GH secretion and the relationship between anxiety and affective disorders.


Submento-submandibular intubation: is the subperiosteal passage essential? Experience in 107 consecutive cases.
Adequate treatment of panfacial injuries often requires tracheostomy or alternating intubation through the nose and the mouth to keep the field free during the operation. Altemir's submental technique is an attractive option in these patients. We used the method with a slight modification in 107 operations in our unit to treat panfacial injuries. We had a low rate of complications and no increased operative time.


Effect of two dopamine agonists, TL-99 and 3-PPP, on prolactin secretion in the rat.
TL-99 and 3-PPP, two putative dopamine autoreceptor agonists, effectively suppressed serum prolactin (PRL) concentrations in rats treated with alpha-methyltyrosine. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by TL-99 and 3-PPP. These findings are supportive of the view that TL-99 and 3-PPP exert a dopamine agonist action at dopamine receptors in the anterior pituitary gland.


Young patients with focal seizures may have the primary motor area for the hand in the postcentral gyrus.
We determined whether the primary motor hand area was most frequently located in the precentral gyrus in young patients with intractable focal seizures. Sixty-five patients with focal seizures aged between 5 months and 20 years who underwent a two-stage epilepsy surgery using chronic subdural-EEG monitoring were studied. Pairs of subdural electrodes were electrically stimulated, and the brain region with contralateral hand movement induced by the lowest-intense stimulus was defined as the primary motor hand area. Contralateral hand movement was induced without afterdischarges in 50 children but not in the remaining 15 children. The unpaired t-test revealed that failure to induce contralateral hand motor movement was associated with younger age of subjects. Among the 50 patients with a positive motor response, the primary motor hand area was confined to the precentral gyrus in 9 patients, confined to the postcentral gyrus in 24, and located in both the pre- and post-central gyri in the remaining 17. The McNemar's test revealed that the observed frequency of 24 patients showing the primary motor hand area confined to the postcentral gyrus was larger than chance frequency. Logistic regression analysis failed to demonstrate that the observation of the primary motor hand area confined to the postcentral gyrus was associated with the age, the presence of dysplastic lesion or the seizure onset involving the frontal lobe. Our study failed to support the traditionally-accepted notion that the primary motor hand area is most frequently located in the precentral gyrus but rather demonstrated that a substantial proportion of young patients had the primary motor hand area in the postcentral gyrus.


Sense of purpose in life and allostatic load in two longitudinal cohorts.
Sense of purpose in life has been linked with better physical health, longevity, and reduced risk for disability and dementia, but the mechanisms linking sense of purpose with diverse health outcomes are unclear. Sense of purpose may promote better physiological regulation in response to stressors and health challenges, leading to lower allostatic load and disease risk over time. The current study examined the association between sense of purpose in life and allostatic load over time in adults over age 50. Data from the nationally representative US Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA) were used to examine associations between sense of purpose and allostatic load across 8 and 12 years of follow-up, respectively. Blood-based and anthropometric biomarkers were collected at four-year intervals and used to compute allostatic load scores based on clinical cut-off values representing low, moderate, and high risk. Population-weighted multilevel models revealed that sense of purpose in life was associated with lower overall levels of allostatic load in HRS, but not in ELSA after adjusting for relevant covariates. Sense of purpose in life did not predict rate of change in allostatic load in either sample. The present investigation supports sense of purpose predicting preserved differentiation of allostatic regulation, with more purposeful individuals demonstrating consistently lower allostatic load over time. Persistent differences in allostatic burden may account for divergent health trajectories between individuals low and high in sense of purpose.


The Molecular Control of Regulatory T Cell Induction.
Regulatory T cells (Tregs) are characterized by the expression of the master transcription factor forkhead box P3 (Foxp3). Although Foxp3 expression is widely used as a marker of the Treg lineage, recent data show that the Treg fate is determined by a multifactorial signaling pathway, involving cytokines, nuclear factors, and epigenetic modifications. Foxp3 expression and the Treg phenotype can be acquired by T cells in the periphery, illustrating that the Treg fate is not necessarily conferred during thymic development. The two main Treg populations in vivo, thymic Tregs and peripheral Tregs, differ in the pathways followed for their maturation. This chapter discusses the molecular control of Treg induction, in the thymus as well as the periphery.


Primary osteosarcoma of the lung: a case report and review of the literature.
Primary osteosarcoma of the lung is exceedingly rare. A 72-year-old man was admitted to our hospital; a primary osteosarcoma of the lung was diagnosed following computed tomography-guided needle biopsy. He died of rapidly progressing respiratory insufficiency without effective treatment seven months after the onset of symptoms. Macroscopic findings at autopsy showed typical histologic features of osteosarcoma without any bony lesion. Here we present a rare case and review the clinicopathological features of 20 previously reported cases.


Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission.
Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice. Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D1 and D2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups. Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2mg/kg, ip) and sulpride (50mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1mg/kg, ip), fluoxetine (1mg/kg, ip) and imipramine (0.1mg/kg, ip) and reduced immobility time in TST. Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D2 receptors) system.


OsCYT-INV1 for alkaline/neutral invertase is involved in root cell development and reproductivity in rice (Oryza sativa L.).
A short root mutant was isolated from an EMS-generated rice mutant library. Under normal growth conditions, the mutant exhibited short root, delayed flowering, and partial sterility. Some sections of the roots revealed that the cell length along the longitudinal axis was reduced and the cell shape in the root elongation zone shrank. Genetic analysis indicated that the short root phenotype was controlled by a recessive gene. Map-based cloning revealed that a nucleotide substitution causing an amino acid change from Gly to Arg occurred in the predicted rice gene (Os02g0550600). It coded an alkaline/neutral invertase and was homologous to Arabidopsis gene AtCyt-inv1. This gene was designated as OsCyt-inv1. The results of carbohydrate analysis showed an accumulation of sucrose and reduction of hexose in the Oscyt-inv1 mutant. Exogenously supplying glucose could rescue the root growth defects of the Oscyt-inv1 mutant. These results indicated that OsCyt-inv1 played important roles in root cell development and reproductivity in rice.


Using thallium-201 SPECT to detect recurrent or residual nasopharyngeal carcinoma after radiotherapy in patients with indeterminate CT findings.
The aim of this study is to evaluate the usefulness of thallium-201 (Tl-201) single-photon emission CT (SPECT) to detect recurrent or residual nasopharyngeal carcinomas (NPC) when CT findings are indeterminate. After radiotherapy, 30 NPC patients with indeterminate CT findings were included. CT, Tl-201, and biopsy were performed at least 4 months after radiotherapy and within 1 week of each other. The final results were based on histopathologic findings and clinical follow-up after at least 6 months. The rates for sensitivity, specificity, and accuracy of Tl-201 SPECT in detecting recurrent or residual NPC when there were indeterminate CT findings, were 86.7%, 93.3%, and 90.0%, respectively. These results suggest that Tl-201 SPECT is effective in detecting recurrent or residual NPC when CT findings are indeterminate.


Posttransplant Diabetes Mellitus (PTDM) Following Solid Organ Transplantation - Systematic Analysis of Prevalence and Total Mortality and Meta-Analysis of Randomized Interventional Studies Aimed at Lowering Blood Glucose.
A systematic review of the prevalence and prognosis of posttransplant diabetes mellitus (PTDM) following the transplantation of heart, lung, liver and kidney and a metaanalysis of randomised studies of glucose-lowering treatment is reported. We searched for publications on solid organ transplants and PTDM in relation to the risk and total mortality of PTDM and randomized controlled trials aiming at reducing glucose levels. PTDM prevalence one year after transplantation was reported to be 9-40%. Ten years after transplantation, 60-85% of people without PTDM and 30-76% of people with PTDM were alive. Following kidney transplantation, we identified six randomized controlled trials on the treatment of PTDM. Intervention ranged from 3 to 12 months. Four studies used intervention with oral glucose-lowering drugs, one used dietician appointments and exercise, and one used insulin treatment. Among the intermediate results reported, a reduction in HbA1c of 2.7 mmol/mol, and an increase in the odds ratio of serious adverse events of 3.0 was significant. In conclusion, information on the prevalence and effect on survival of PTDM is heterogeneous, and the randomized studies on the effect of treatment available are short and lack information on clinically important endpoints, such as mortality or morbidity.


Infant directed speech and the development of speech perception: enhancing development or an unintended consequence?
Infant directed speech (IDS) is a speech register characterized by simpler sentences, a slower rate, and more variable prosody. Recent work has implicated it in more subtle aspects of language development. Kuhl et al. (1997) demonstrated that segmental cues for vowels are affected by IDS in a way that may enhance development: the average locations of the extreme "point" vowels (/a/, /i/ and /u/) are further apart in acoustic space. If infants learn speech categories, in part, from the statistical distributions of such cues, these changes may specifically enhance speech category learning. We revisited this by asking (1) if these findings extend to a new cue (Voice Onset Time, a cue for voicing); (2) whether they extend to the interior vowels which are much harder to learn and/or discriminate; and (3) whether these changes may be an unintended phonetic consequence of factors like speaking rate or prosodic changes associated with IDS. Eighteen caregivers were recorded reading a picture book including minimal pairs for voicing (e.g., beach/peach) and a variety of vowels to either an adult or their infant. Acoustic measurements suggested that VOT was different in IDS, but not in a way that necessarily supports better development, and that these changes are almost entirely due to slower rate of speech of IDS. Measurements of the vowel suggested that in addition to changes in the mean, there was also an increase in variance, and statistical modeling suggests that this may counteract the benefit of any expansion of the vowel space. As a whole this suggests that changes in segmental cues associated with IDS may be an unintended by-product of the slower rate of speech and different prosodic structure, and do not necessarily derive from a motivation to enhance development.


Insights into the Structure-Performance Relationship and Viscosity Reduction Performance of Recyclable Magnetic Fe/Zeolite for Crude Oil Aquathermolysis.
Elucidating the structure-performance relationship of zeolites and their synergy with metals for the catalytic aquathermolysis of crude oil is crucial for designing efficient catalysts. Herein, the structure-performance relationship between the magnetic Fe-loaded zeolite's physicochemical properties and aquathermolysis performance is mainly explored. First, the catalytic aquathermolysis performance of various porous materials (Y, β, MCM-41, and ZSM-5 zeolites) was probed to investigate the effect of different topological structures on the viscosity reduction of heavy oil. Results showed that ZSM-5 has a favorable pore structure and acidity, and its viscosity reduction performance is 1.7-4.1 times those of other zeolites; therefore, it is more suitable as a carrier for aquathermolysis to reduce viscosity. Then, Fe substance (such as Fe2O3 and Fe3O4) was loaded onto the ZSM-5 support. It was found that Fe3O4/ZSM-5 had better performance compared with pure ZSM-5 and Fe2O3/ZSM-5, which could reduce the viscosity of heavy oil by 20.3%. Importantly, the Fe3O4/ZSM-5 catalyst is easily separated from crude oil due to its magnetism, hence it has the potential to be recycled and reused. In addition, the potential structure-performance relationship was systematically studied by X-ray diffraction (XRD), elemental analysis (EL), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). As a result, it was considered that Fe3O4/ZSM-5 broke C-S bonds and reduced the heavy components (resin and asphaltene) of crude oil. This study has a certain guiding significance for developing heterogeneous magnetic hydrothermal viscosity reduction catalysts.


The classification of HLA supertypes by GRID/CPCA and hierarchical clustering methods.
Biological experiments often produce enormous amount of data, which are usually analyzed by data clustering. Cluster analysis refers to statistical methods that are used to assign data with similar properties into several smaller, more meaningful groups. Two commonly used clustering techniques are introduced in the following section: principal component analysis (PCA) and hierarchical clustering. PCA calculates the variance between variables and groups them into a few uncorrelated groups or principal components (PCs) that are orthogonal to each other. Hierarchical clustering is carried out by separating data into many clusters and merging similar clusters together. Here, we use an example of human leukocyte antigen (HLA) supertype classification to demonstrate the usage of the two methods. Two programs, Generating Optimal Linear Partial Least Square Estimations (GOLPE) and Sybyl, are used for PCA and hierarchical clustering, respectively. However, the reader should bear in mind that the methods have been incorporated into other software as well, such as SIMCA, statistiXL, and R.