Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an extract of Cupressus arizonica. A double blind study.
non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy. We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy (SLIT) in patient with Cupressaceae pollen respiratory allergy. twenty patients with Cupressaceae pollen (C. sempervirens) rhinoconjunctivitis, mild asthma or both were randomly chosen for sublingual immunotherapy (10 patients) or placebo treatment (10 patients) using a double blind placebo controlled technique. We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens. The patients underwent treatment for 12 months (from april 1999 to april 2000). Symptoms and drug scores as well as nasal provocation tests were recorded. The pollen counts were carried out, during all the same period. we found significantly lower symptom scores (p < 0.05) and drug consumption scores (p < 0.05) in the immunotherapy group than in the placebo group, during the pollen season, after the first year of therapy. Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group (p < 0.01). No untoward reactions have been observed. SLIT with Cupressus arizonica (pollen extracts) produced, after one year treatment, a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity. SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy.


The epidemiology and etiology of pediatric ocular trauma.
Eighteen million people worldwide have uniocular blindness from traumatic injury. Injuries occur disproportionally commonly in childhood. Every year a quarter of a million children present with serious ocular trauma. For the vast majority the injury is preventable. We review the international literature that identifies high-risk circumstances.


Restoring After Central Nervous System Injuries: Neural Mechanisms and Translational Applications of Motor Recovery.
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.


Postsynaptic scaffold protein Homer 1a protects against traumatic brain injury via regulating group I metabotropic glutamate receptors.
Traumatic brain injury (TBI) produces excessive glutamate, leading to excitotoxicity via the activation of glutamate receptors. Postsynaptic density scaffold proteins have crucial roles in mediating signal transduction from glutamate receptors to their downstream mediators. Therefore, studies on the mechanisms underlying regulation of excitotoxicity by scaffold proteins can uncover new treatments for TBI. Here, we demonstrated that the postsynaptic scaffold protein Homer 1a was neuroprotective against TBI in vitro and in vivo, and this neuroprotection was associated with its effects on group I metabotropic glutamate receptors (mGluRs). Upon further study, we found that Homer 1a mainly affected neuronal injury induced by mGluR1 activation after TBI and also influenced mGluR5 function when its activity was restored. The ability of Homer 1a to disrupt mGluR-ERK signaling contributed to its ability to regulate the functions of mGluR1 and mGluR5 after traumatic injury. Intracellular Ca(2+) and PKC were two important factors involved in the mediation of mGluR-ERK signaling by Homer 1a. These results define Homer 1a as a novel endogenous neuroprotective agent against TBI.


Toward the Exact Exchange-Correlation Potential: A Three-Dimensional Convolutional Neural Network Construct.
A deep neural network is constructed to yield in principle exact exchange-correlation potential. It requires merely the electron densities of small molecules and ions and yet can determine the exchange-correlation potentials of large molecules. We train and validate the neural network based on the data for H2 and HeH+ and subsequently determine the ground-state electron density of stretched HeH+, linear H3+, and H-He-He-H2+. Moreover, the deep neural network is proven to model the van der Waals interaction by being trained and validated on a data set containing He2. Comparisons to B3LYP are given to illustrate the accuracy and transferability of the neural network.


What does potential for hostility measure? Gender differences in the expression of hostility.
We examined the construct validity of Potential for Hostility (PH) for healthy undergraduate males and females. In Study 1, 45 males and 76 females were rated for PH. Subjects then completed the Cook Medley Hostility Scale (Ho) and a trait negative affectivity (NA) scale. For males, PH correlated with Cynicism, a subscale of the Ho, but was unrelated to NA. However, for females, PH was unrelated to self-reported hostility and minimally related to NA. In Study 2, 52 males and 91 females again were rated for PH in addition to state NA; subjects also provided self-reported state NA and PH measures. For males, convergence was found between observed and self-reported PH scores, but no such relation was found for females; only self-reported and observed state NA predicted females' PH rating. Thus, the Structured Interview method of hostility assessment may not be measuring the same hostility construct in females as it is in males.


Psychiatric symptoms in patients with asthma causality, comorbidity, or shared genetic etiology.
Despite the range of diverse studies that attempt to understand the comorbidity of asthma and psychiatric diagnoses, it is still not possible to provide a reliable quantitative estimate of the increased risk for anxiety and mood disorders in children with asthma. A new hypothesis for this comorbidity has evolved, however. It is likely that the stress of having a chronic illness increases the likelihood of the development of anxiety and depressive symptoms. If this were a sufficient etiologic explanation, however, increased comorbidities of psychiatric illnesses would be found in all chronic pediatric illnesses. More precise prevalence estimates of these comorbidities require the completion of large studies that use a longitudinal design and reliable and well-validated assessment instruments. The most promising direction for future research is the definition of underlying genetic vulnerabilities that reflect autonomic regulation, may contribute to the onset of some forms of asthma, and are associated with increased risk for anxiety and mood disorders.


Supplementation of exogenous bile acids improve antitrichomonal activity and enhance intestinal health in pigeon (Columba livia).
The study investigated the effects of supplementation of bile acids in drinking water on antitrichomonal activity, growth performance, immunity and microbial composition of pigeon. A total of 180 pairs of White King parent pigeons were randomly assigned to 5 treatments of 6 replications with 6 pairs of parent pigeons and 12 squabs in each replicate. The control (CON) group drank water without any additions. The metronidazole (MTZ) group drank water with 500 μg/mL metronidazole for 7 d and without any additions in other days. The else groups drank water with 500, 750, and 1,250 μg/mL bile acid (BAL, BAM, BAH) for 28 d. The results showed that Trichomonas gallinae (T. gallinae) in MTZ, BAL, BAM, and BAH groups were lower than that in CON group at 14, 21, and 28 d of parent pigeons (P < 0.05) and at 21 and 28 d of squabs (P < 0.05). Albumin and alanine transaminase in CON group were higher than those in MTZ, BAL, and BAH groups (P < 0.05). The levels of soluble CD8 were higher in MTZ and BAH groups compared with CON group (P < 0.05). The lesions in oral mucosa, thymus, liver, and spleen tissues of CON group could be observed. Abundance-based coverage estimator (ACE) index in BAH group was higher than that in CON and MTZ groups. Simpson index in CON and BAH groups was higher than MTZ group (P < 0.05). Lactobacillus was the highest colonized colonic bacteria in genera that were 77.21, 91.20, and 73.19% in CON, MTZ, and BAH, respectively. In conclusion, drinking water supplemented with 500, 750, and 1,250 μg/mL bile acid could inhibit growth of T. gallinae in both parent pigeons and squabs. Squabs infected with T. gallinae in control group had higher mortality rate and more serious tissue lesions. Squabs in bile acids treated group had more sCD8 in serum and abundant intestinal morphology. Bile acids could be an efficient drinking supplements to inhibit T. gallinae and improve pigeon adaptive immunity and intestinal health.


[Exclusive use of blue dye to detect sentinel lymph nodes in breast cancer].
The use of a dye and radiocolloid to detect sentinel lymph nodes in breast cancer increases the detection rates. However the use of either method alone does not modify the false negative rate. Therefore there is no formal contraindication for the exclusive use of dye to detect nodes. To report a prospective analysis of the exclusive blue dye technique for sentinel node biopsy in patients with early breast cancer. We analyzed the first 100 women with pathologically proven breast cancer who met the inclusion criteria. Patent blue dye was used as colorant. In the first 25 cases sentinel node was identified using radiocolloid and blue dye an then an axillary dissection performed. In the next 25 women, blue dye was used exclusively for detection and an axillary dissection was performed. In the next 50 cases, blue dye was used and only isolated sentinel node biopsy was performed. In 92 of the 100 women a sentinel node was successfully detected. In the first 50 women, the false negative rate of sentinel lymph node detection was 6.9%. No complications occurred. During follow-up, lasting three to 29 months, no axillary relapse was observed. Sentinel node biopsy in patients with early breast cancer using exclusively blue dye is feasible and safe.


Surprise and change: variations in the strength of present and absent cues in causal learning.
It is said that "absence makes the heart grow fonder." But, when and why does an absent event become salient to the heart or to the brain? An absent event may become salient when its nonoccurrence is surprising. Van Hamme and Wasserman (1994) found that a nonpresented but expected stimulus can actually change its associative status-and in the opposite direction from a presented stimulus. Associative models like that of Rescorla and Wagner (1972) focus only on presented cues; so, they cannot explain this result. However, absent cues can be permitted to change their value by assigning different learning parameters to present and absent cues. Van Hamme and Wasserman revised the Rescorla-Wagner model so that the a parameter is positive for present cues, but negative for absent cues; now, changes in the associative strength of absent cues move in the opposite direction as presented ones. This revised Rescorla-Wagner model can thus explain such otherwise vexing empirical findings as backward blocking, recovery from overshadowing, and backward conditioned inhibition. Moreover, the revised model predicts new effects. For example, explicit information about the absence of nonpresented cues should increase their salience (that is, their negative a value should be larger), leading to stronger associative changes than when no explicit mention is made of cue absence. Support for this prediction is detailed in a new causal judgment experiment in which participants rated the effectiveness of different foods' triggering a patient's allergic reaction. Overall, these and other findings encourage us to view human causal learning from an associative perspective.


Membrane curvature regulates the spatial distribution of bulky glycoproteins.
The glycocalyx is a shell of heavily glycosylated proteins and lipids distributed on the cell surface of nearly all cell types. Recently, it has been found that bulky transmembrane glycoproteins such as MUC1 can modulate membrane shape by inducing membrane protrusions. In this work, we examine the reciprocal relationship of how membrane shape affects MUC1's spatial distribution on the cell membrane and its biological significance. By employing nanopatterned surfaces and membrane-sculpting proteins to manipulate membrane curvature, we show that MUC1 avoids positively-curved membranes (membrane invaginations) and accumulates on negatively-curved membranes (membrane protrusions). MUC1's curvature sensitivity is dependent on the length and the extent of glycosylation of its ectodomain, with large and highly glycosylated forms preferentially staying out of positive curvature. Interestingly, MUC1's avoidance of positive membrane curvature enables it to escape from endocytosis and being removed from the cell membrane. These findings also suggest that the truncation of MUC1's ectodomain, often observed in breast and ovarian cancers, may enhance its endocytosis and potentiate its intracellular accumulation and signaling.


Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review.
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.


Response kinetics of host and experimental solid tumour after adriamycin.
The effects of adriamycin (Adr) on the solid-tumour model, hepatoma 3924A, and on critical organs of the host, were determined at intervals after single injections of 60 mg/m2 of the agent. A reduced rate of tumour growth was evident 4 days after treatment, continued to Day 11, and then returned to rates comparable to control values. On Day 11 tumour volumes of treated animals were 38% of control. During the period of reduced growth, 3H-TdR incorporation into tumour DNA and percentage labelled tumour cells were less than control values. DNA concentration in tumour was not affected by drug treatment, which differs from observations made in other studies employing 5-fluorouracil (FU). No evidence of significantly increased necrosis or fibrosis of the tumour was found after Adr. The Adr treatment caused loss of 60% of the tibial marrow by Day 4, as measured by total DNA content. Marrow DNA recovered to control levels between Days 7 and 11. Incorporation of 3H-TdR into heart DNA was reduced more than 40% during the first week after Adr treatment; enhanced incorporation was observed on Day 11, and control levels were attained by Day 17. No significant pathological evidence of cardiac toxicity was found 2-21 days after Adr but degeneration of myocardial cells and oedema was prominent at 14 weeks.


Improvement in Extensive Moderate Plaque Psoriasis With a Novel Emollient Spray Formulation of Betamethasone Dipropionate 0.05.
A novel formulation of 0.05% betamethasone dipropionate in an emollient spray vehicle (DFD-01) was developed to deliver steroid to the skin layers most affected by psoriasis. To compare the efficacy and safety of DFD-01 to its vehicle for the treatment of moderate plaque psoriasis over 4 weeks. Two Phase 3 trials enrolled adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10-20% body surface area [BSA]) and randomized them 2:1 to DFD-01 or Vehicle. Products were applied twice daily to affected areas for 28 days. Treatment success was defined as an IGA=0 or 1 and ≥ 2-grade improvement from baseline. Primary endpoint was the proportion of subjects achieving treatment success at day 15. Moderate psoriasis subjects were enrolled in Study 1 (174 DFD-01; 87 Vehicle) and Study 2 (182 DFD-01; 95 Vehicle). Mean BSA was 13-14%. Treatment success was achieved in significantly more subjects using DFD-01 than Vehicle at day 15 in both Study 1 (P<0.001) and Study 2 (P=0.002), and at day 29 (both studies P<0.001). Treatment success with DFD-01 was significant at day 8 in Study 1 (P=0.003) but not in Study 2 (P=0.156). Erythema, scaling, and plaque elevation scores of target lesions were significantly reduced as early as day 4 with DFD-01. Adverse events were similar between groups, with no increase between 2 and 4 weeks. These studies demonstrate DFD-01's excellent efficacy and safety for the treatment of extensive psoriasis (10-20% BSA). DFD-01 achieved treatment success in significantly more subjects than Vehicle after 2 and 4 weeks of treatment, and showed early onset of action with improved signs of erythema, scaling and elevation of target lesions after 4 days of treatment. This medium potency formulation provides a safe and effective choice for topical steroid treatment of psoriasis.


Post-partum isolated ovarian abscess in an asplenic host.
A 23-yr-old splenectomized female developed an isolated ovarian abscess, a very rare complication, following a normal delivery. Apart from the palpated 'cyst', findings on pelvic examination were unremarkable, as is often the case with ovarian abscess. The patient recovered after conservative 'cystectomy'. We suggest that the asplenic state plays a role in the development of this very rare complication.


Colony structure in a plant-ant: behavioural, chemical and genetic study of polydomy in Cataulacus mckeyi (Myrmicinae).
Social organisation of colonies of obligate plant-ants can affect their interaction with myrmecophyte hosts and with other ants competing for the resources they offer. An important parameter of social organisation is whether nest sites of a colony include one or several host individuals. We determined colony boundaries in a plant-ant associated with the rainforest understorey tree Leonardoxa africana subsp. africana, found in coastal forests of Cameroon (Central Africa). This myrmecophyte is strictly associated with two ants, Petalomyrmex phylax and Cataulacus mckeyi. Plants provide food and nesting sites for P. phylax, which protects young leaves against insect herbivores. This mutualism is often parasitised by C. mckeyi, which uses but does not protect the host. The presence of C. mckeyi on a tree excludes the mutualistic ant. Because Petalomyrmex-occupied trees are better protected, their growth and survival are superior to those of Cataulacus-occupied trees, giving P. phylax an advantage in occupation of nest sites. C. mckeyi often colonises trees that have lost their initial associate P. phylax, as a result of injury to the tree caused by disturbance. Polydomy may allow C. mckeyi to occupy small clumps of trees, without the necessity of claustral colony foundation in each tree. Investigating both the proximate (behavioural repertoire, colony odour) and the ultimate factors (genetic structure) that may influence colony closure, we precisely defined colony boundaries. We show that colonies of C. mckeyi are monogynous and facultatively polydomous, i.e. a colony occupies one to several Leonardoxa trees. Workers do not produce males. Thus, the hypothesis that polydomy allows workers in queenless nests to evade queen control for their reproduction is not supported in this instance. This particular colony structure may confer on C. mckeyi an advantage in short-distance dispersal, and this could help explain its persistence within the dynamic Leonardoxa system.


Nicotinamide adenine dinucleotide and the sirtuins caution: Pro-cancer functions.
This scoping review aims to perform a brief but comprehensive assessment of existing peer-reviewed literature and determine whether raising nicotinamide adenine dinucleotide can prevent or promote tumorigenesis. The examination of extensive peer-reviewed data regarding the synthesis of nicotinamide adenine dinucleotide has been performed with a focus on nuclear dynamics and the deoxyribose nucleic acid repair pathway. Various enzymatic protective functions have been identified from nicotinamide adenine dinucleotide levels, as well as the threat role that is also explored. Nicotinamide adenine dinucleotide precursors and sirtuin-activating compounds are becoming ubiquitous in the commercial market. Further research into whether elevating levels of nicotinamide adenine dinucleotide or overexpression of sirtuins can increase the potential for neoplasm or other age-related pathophysiology is warranted due to the high energy requirements of certain diseases such as cancer.


Exploring professionals' practices and perspectives on supporting parents with intellectual disabilities: a qualitative study.
Evidence suggests that parents with intellectual disabilities require appropriate parenting support. However, professional practices vary widely, and several barriers and challenges persist in supporting parents with intellectual disabilities. To identify effective and collaborative practices, this study investigated practices reported by professionals and their roles in providing services to parents with intellectual disabilities. Semi-structured interviews were conducted with 22 professionals from three sectors (disability, early childhood, and healthcare), and the content was analysed using inductive thematic analysis. Thematic analyses yielded four main themes: (1) Perceived professional practices, (2) professional stances, (3) the frame of reference and the ethics of support, (4) the experience of providing support. They are described in terms of content and distribution across sectors to provide an overview of practices as well as potential discrepancies. This study concludes by developing recommendations on good practices for support professionals to respond as adequately as possible to meet the needs of parents and future parents with intellectual disabilities, which include structural support and guidelines for professionals to provide sensitive, family-centred, and enabling support.


Experimental and clinical study of a new permanent myocardial atrial sutureless pacing lead.
A new permanent lead has been developed for atrial epicardial use. Early clinical evaluation (26 human implants) following thorough canine studies indicates that the new lead is safe, effective, and reliable. Canine thresholds and P-wave amplitudes as a function of implant time are similar to those of transvenous atrial "J" leads. Human thresholds at implant are higher than canine, but change less with time. Implant and acute repositioning were found to be easy. There have been no lead-related operations.


Response of pineal serotonin N-acetyltransferase activity in male guinea pigs exposed to light pulses at night.
Serotonin N-acetyltransferase (NAT), which is crucial for the formation of melatonin, undergoes a typical day/night rhythm in the pineal gland with low levels during daytime and high levels at night. Short pulses of light given at night have been shown to rapidly depress NAT activity in some species, but not in others, the reasons for this difference being unclear. As diurnality and nocturnality of the experimental animals may play a role and since diurnally active animals have been little investigated in this respect, in the present study the diurnally active guinea pig was investigated. Male guinea pigs kept under a lighting regimen of LD 12:12 (lights off at 1700 hrs) were killed between 1200 or 1300 hrs and between 0000 and 0200 hrs, at night in the dark or after exposure to 10 or 45 min of light. The results obtained show that the day/night difference of NAT activity is about 2-fold. 10 min or 45 min of light given at night significantly depress pineal NAT activity. Re-exposure to darkness for 1 hr of animals previously given light for 10 min leads to restoration of NAT activity. These findings together with data from the literature suggest that it does not appear to be the activity pattern (diurnality versus nocturnality) of an animal nor the amplitude of the day/night difference of pineal NAT activity that account for the suppressibility or non-suppressibility of pineal NAT activity by light at night.


Distinct regions of the striatum underlying effort, movement initiation and effort discounting.
The ventral striatum is believed to encode the subjective value of cost-benefit options; however, this effect has notably been absent during choices that involve physical effort. Previous work in freely moving animals has revealed opposing striatal signals, with greater response to increasing effort demands and reduced responses to rewards requiring effort. Yet, the relationship between these conflicting signals remains unknown. Using functional magnetic resonance imaging with a naturalistic maze-navigation paradigm, we identified functionally segregated regions within the ventral striatum that separately encoded effort activation, movement initiation and effort discounting of rewards. In addition, activity in regions associated with effort activation and discounting oppositely predicted striatal encoding of effort during effort-based decision-making. Our results suggest that the dorsomedial region hitherto associated with action may instead represent the cost of effort and raise fundamental questions regarding the interpretation of striatal 'reward' signals in the context of effort demands. This has implications for uncovering the neural architecture underlying motivated behaviour.


Assessing activity in joint replacement patients.
Outcome evaluations of lower extremity joint reconstructions should include an assessment of patient activity. In vivo wear assessments of total joint prostheses should be based on a measure of use, not time in situ or a proxy such as age or gender; however, clinicians lack a simple method to reliably assess the activity of patients with joint replacement. The modern pedometer can be a satisfactory means of quantifying the use of lower extremity joints. The pedometer, however, requires special effort on the part of the physician or evaluator and the patient. Therefore, we compared the quantitative assessment of walking activity of 100 total joint replacement patients, as measured with a pedometer, to the UCLA activity score and a simple visual analog scale that can easily be employed during a routine office evaluation. Both the UCLA activity rating (P = .002) and the visual analog scale rating of the investigator (P = .00001) had a strong correlation with the average steps per day as recorded by the pedometer. There was, however, up to a 15-fold difference in the average steps per day for individual patients with the same UCLA score. The visual analog scale as rated by the patients of their own activity did not have as strong a correlation with the pedometer data (P = .08) as did patient age (P = .049). For practical reasons, the pedometer is probably best reserved for the evaluation of extreme cases of activity (or inactivity). This study indicates that both the UCLA activity rating and the investigator visual analog scale are valid for routine activity assessment in a clinical setting. Adjustments of the UCLA activity score for the frequency and intensity of activity, as can be done with the investigator visual analog scale, increase the accuracy of the activity rating.


Functional heterogeneity of gonadotrophs in the ovine fetus: analysis by reverse hemolytic plaque assay.
Stimulation of sheep fetal gonadotrophs with 10(-7) M luteinizing hormone releasing hormone (LHRH) for 3 h in culture wells increased luteinizing hormone (LH) release over basal values. Using the reverse hemolytic plaque assay (RHPA), we demonstrated that this increase was due to a recruitment of LH-secreting cells. During gestation, the percentage of LH-containing cells able to release and the mean size of plaques were the highest at around 100-130 days and were usually lower in females than in males. In an attempt to delineate the involvement of protein kinase C (PKC) in LH release, cells were treated with an activator of PKC, phorbol 12-myristate 13-acetate (PMA). Stimulation of cells with 10(-6) M PMA for 3 h enhanced LH release in culture wells 2- to 3-fold more than did 10(-7) M LHRH. This increase was a consequence of an enhanced number of LH-secreting cells and, in males only, of an enhancement of the mean plaque size. The percentage of LH-secreting cells among LH-containing cells and the plaque areas were maximal between 110 and 120 days of gestation in both sexes. They were usually lower in females than in males. Stimulation of cells with LHRH plus PMA enhanced LH release in culture wells in an additive manner when compared to either factor alone in both sexes and at all fetal ages. This additive effect reflected an increase in the number of secreting cells. Under these conditions, plaque sizes were larger than the plaque sizes obtained with PMA alone in males and in females in late gestation. In conclusion, our results show that LHRH stimulated LH secretion from sheep fetal cells by recruiting secreting cells when compared to controls. Both 100-120 days of gestation and were higher in males than in females. Results following treatment of cells with PMA, either alone or in combination with LHRH, suggest that these two secretagogues act on two different subpopulations of gonadotrophs and probably through different pathways.


Sadness and happiness are amplified in solitary listening to music.
Previous studies have shown that music is a powerful means to convey affective states, but it remains unclear whether and how social context shape the intensity and quality of emotions perceived in music. Using a within-subject design, we studied this question in two experimental settings, i.e. when subjects were alone versus in company of others without direct social interaction or feedback. Non-vocal musical excerpts of the emotional qualities happiness or sadness were rated on arousal and valence dimensions. We found evidence for an amplification of perceived emotion in the solitary listening condition, i.e. happy music was rated as happier and more arousing when nobody else was around and, in an analogous manner, sad music was perceived as sadder. This difference might be explained by a shift of attention in the presence of others. The observed interaction of perceived emotion and social context did not differ for stimuli of different cultural origin.


Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis.
To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease.


Significantly increased antibody response to heterogeneous nuclear ribonucleoproteins in cerebrospinal fluid of multiple sclerosis patients but not in patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.
It has been reported that antibodies (Abs) against heterogeneous nuclear ribonucleoproteins (hnRNPs) are associated with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). However, these studies were done under nonmasked conditions. In order to determine whether Abs against hnRNPs associate with HAM/TSP and MS, the authors assayed Abs against two major hnRNPs, hnRNP A1 and A2/B1, in 105 cerebrospinal fluid (CSF) samples under fully masked conditions. Samples included 40 cases of HAM/TSP, 28 of MS, and 37 of other neurological diseases. Anti-hnRNP A1 Abs, and especially anti-hnRNP A2/B1 Abs, were found significantly more often in the CSF of MS patients than in other groups. However, there was no difference in the incidence of anti-hnRNP A1 Abs between HAM/TSP and other disease groups.


CRAVAT: cancer-related analysis of variants toolkit.
Advances in sequencing technology have greatly reduced the costs incurred in collecting raw sequencing data. Academic laboratories and researchers therefore now have access to very large datasets of genomic alterations but limited time and computational resources to analyse their potential biological importance. Here, we provide a web-based application, Cancer-Related Analysis of Variants Toolkit, designed with an easy-to-use interface to facilitate the high-throughput assessment and prioritization of genes and missense alterations important for cancer tumorigenesis. Cancer-Related Analysis of Variants Toolkit provides predictive scores for germline variants, somatic mutations and relative gene importance, as well as annotations from published literature and databases. Results are emailed to users as MS Excel spreadsheets and/or tab-separated text files. http://www.cravat.us/


Influence of intraperitoneal Escherichia coli with septicemia on the healing of colonic anastomoses and skin wounds. An experimental study in the rat.
In rats a standardized left colonic resection was performed and colonic continuity restored by an end-to-end anastomosis in one layer. The rats were subjected to an LD50 septic challenge by intraperitoneal injection of live Escherichia coli pre- or postoperatively. Controls received saline in a corresponding manner. Groups of animals were sacrificed on the 3rd or 7th postoperative day. The breaking strengths of the anastomosis and of the skin wound were measured. The collagen content of the anastomotic segments was analyzed. There were no differences in anastomotic or skin wound strength between septic animals and controls. Collagen content was unaffected. Wound healing was not influenced by sepsis in this model.


Analytical-physical profile of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent.
The structure elucidation, physical and chemical parameters and hydrolysis kinetics of 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (WHR-1142 A, lidamidine hydrochloride), a novel antidiarrheal agent, were determined. The stability of the substance in aqueous solution (pH 1-13) was studied at 50 degrees, 65 degrees and 80 degrees C.


EIF1AX Mutation in a Patient with Hürthle Cell Carcinoma.
The EIF1AX gene is a novel cancer gene that has been reported in the tumorigenesis of papillary thyroid carcinoma, follicular variant papillary thyroid carcinoma, and anaplastic thyroid carcinoma. A 71-year-old woman presented with a right thyroid mass, which was follicular neoplasm on cytology. The fine needle aspirate of the nodule was examined by next-generation sequencing and found to harbor EIF1AX and TP53 mutations. Right thyroid lobectomy was performed with final pathology showing Hürthle cell carcinoma with capsular and vascular invasion. We report an EIF1AX mutation in a patient found to have Hürthle cell carcinoma.


PHLDB2 Mediates Cetuximab Resistance via Interacting With EGFR in Latent Metastasis of Colorectal Cancer.
Latent metastasis of colorectal cancer (CRC) frequently develops months or years after primary surgery, followed by adjuvant therapies, and may progress rapidly even with targeted therapy administered, but the underlying mechanism remains unclear. Here, we aim to explore the molecular basis for the aggressive behavior of latent metastasis in CRC. Transcriptional profiling and pathway enrichment analysis of paired primary and metastatic tumor samples were performed. The underlying mechanisms of pleckstrin homology-like domain, family B, member 2 (PHLDB2) in CRC were investigated by RNA immunoprecipitation assay, immunohistochemistry, mass spectrometry analysis, and Duolink in situ proximity ligation assay (Sigma-Aldrich, Shanghai, China). The efficacy of targeting PHLDB2 in cetuximab treatment was elucidated in CRC cell lines and mouse models. Based on the transcriptional profile of paired primary and metastatic tumor samples, we identified PHLDB2 as a potential regulator in latent liver metastasis. A detailed mechanistic study showed that chemotherapeutic agent-induced oxidative stress promotes methyltransferase-like 14 (METTL14)-mediated N6-methyladenosine modification of PHLDB2 messenger RNA, facilitating its protein expression. Up-regulated PHLDB2 stabilizes epidermal growth factor receptor (EGFR) and promotes its nuclear translocation, which in turn results in EGFR signaling activation and consequent cetuximab resistance. Moreover, Arg1163 (R1163) of PHLDB2 is crucial for interaction with EGFR, and the R1163A mutation abrogates its regulatory function in EGFR signaling. PHLDB2 plays a crucial role in cetuximab resistance and is proposed to be a potential target for the treatment of CRC.


Changes in vascularization of human breast cancer xenografts responding to antiestrogen therapy.
To elucidate the previously suggested vascular effect(s) of antiestrogen therapy, we studied the effect of estrogen withdrawal and tamoxifen on 1) vascular resistance, 2) glucose and oxygen consumption, and 3) vascular density in a perfused breast cancer line (ZR75-1). Furthermore, we examined ZR75-1 tumors by functional CT-scanning (fCT) to determine changes in parameters related to tumor capillary transfer constants and vascular volume fraction in response to antiestrogenic manipulations. The vascular resistance decreased significantly from 42.7 to 20.8 mmHg x min x g x ml(-1) (P< .03) on day 9 after estrogen withdrawal, but not after 9 days of tamoxifen treatment. The estrogen-depleted tumors were significantly smaller than controls on day 9. There was no difference in nutrient consumption or vascular density in any of the experimental groups compared to controls. fCT showed an increase (P < .03) in vascular volume fraction during tumor growth, and this parameter was significantly lower after estrogen withdrawal when compared to controls (P < .05). Vascular resistance correlated with tumor size (R = 0.7, P < .0001), indicating that vascular resistance increases during tumor growth. The changes in vascular parameters after estrogen withdrawal indicate a vascular remodeling effect. This inhibition of vascular development by hormone deprivation may have important implications for future planning of multimodal treatment regimens.


[Effect of gamma-glutamyl kinase gene knock-out on metabolism in L-arginine-producing strain Corynebacterium crenatum 8-193].
In order to optimize precursor supply for L-arginine biosynthesis, we constructed a Corynebacterium crenatum 8-193 mutant with gamma-glutamyl kinase gene (proB) in-frame deletion. The effects of proB knock-out on physiological characteristics of the mutant were investigated. The upstream and downstream fragments of proB were cloned from C. crenatum 8-193 chromosome and ligated to integration vector. The mutant C. crenatum 8-193-deltaproB was obtained by homologous recombination. The mutant phenotype can be reversed by complementation with proB gene from the expression vector. The physiological characteristics of the mutant were investigated by measurement of the activities of phosphoenolpyruvate carboxylase (PEPCx) and pyruvate carboxylase (PYC). The proB gene in-frame deletion was screened and confirmed by PCR, gamma-glutamyl kinase determination and complementation. The mutant lost the ability of growth on minimal medium without proline addition. The proB knock-out mutant resulted a decrease of cell mass by 9.6% and an increase of L-arginine accumulation by 13.6% compared with that of the parent strain. The analysis of by-products of fermentation broth showed that the concentrations of glutamate-related and aspartate-related amino acids increased, and the concentrations of alpha-ketoglutaric acid, PEP and succinic acid decreased. The specific activities of PEPCx and PYC increased in 8-193-deltaproB. The proB gene knock-out of the strain 8-193 blocked branch catabolism of L-glutamate and improved efficiency of the glucose utilization and L-arginine accumulation.


A case-control study of perfluoroalkyl substances and the risk of breast cancer in Taiwanese women.
Breast cancer (BC) is a common cancer in women worldwide; however, the incidence of BC is increasing in younger women, possibly associated with the environment. Perfluoroalkyl substances (PFAS) are one of endocrine disruptors that accumulate in environment and impact human health. This study aimed to investigate whether the PFAS and BC are associated. We enrolled 120 BCE patients and 119 controls at National Taiwan University Hospital (NTUH) and also collected bio-specimen and questionnaire from 2013 to 2015. All subjects' plasma PFAS levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionization (UHPLC-ESI-MS/MS). A logistic regression model was used to estimate the association between PFAS and BC. In the ≤50 years age group, the adjusted odds ratio (OR) was 2.34 (95% CI = 1.02, 5.38) for perfluorooctane sulfonate (PFOS) exposure per natural log unit increase. After stratifying the estrogen receptor (ER) status and age group, we obtained a positive association for PFHxS and PFOS concentrations with respect to the risk of ER positive tumors for ≤50 years age group. In conclusion, we found that PFAS were associated with the BC risk of ER positive tumors in young Taiwanese women. Further studies are needed to follow and explore whether these associations are causal.


Food intake patterns are altered during long-term zinc deficiency in rats.
Rats experience anorexia and reduction or cessation in growth after being provided a zinc-deficient diet. While zinc deficient, intake levels may be reduced 50% or more compared to control rats. In the present report, diurnal food intake patterns of male Sprague-Dawley rats were measured during zinc deficiency. In Study 1, rats consuming a modified AIN-93 diet were tested during the dark phase using an automated food weighing system. In zinc-deficient animals (Zn-), the onset of the first meal of the dark phase was delayed compared to zinc-adequate rats (Zn+; 106+/-47 vs. 23+/-5 min; p<0.05) and the number of meals consumed during the dark phase was reduced in Zn- vs. Zn+ rats (3.9+/-0.5 vs 7.1+/-0.4; p<0.05). In Study 2, diurnal food intake patterns were tested using a three-choice macronutrient self-selection paradigm of carbohydrate-, protein-, and fat-containing diets made deficient or adequate in zinc (1 or 30 mg Zn/kg diet). Food intake was recorded in the early-, mid-, late-dark period (4 h each) and light period (12 h). Carbohydrate intake was 70% of total intake of both Zn+ and Zn- rats during the first 5 days, but decreased significantly to 50% in the Zn- group during the last 5 days. Fat intake increased significantly in the Zn- group during the last 5 days. This increase was the result of 4 of 15 Zn- rats increasing their intake of fat significantly. Results of this study indicate that zinc status alters dark phase and macronutrient selection patterns by delaying consumption of the initial meal of the dark phase, reducing the average meal number and by changing the dominant macronutrient preference of some Zn- rats.


Ecotin modulates thrombin activity through exosite-2 interactions.
Ecotin is a Escherichia coli-derived protein that has been characterized as a potent inhibitor of serine-proteases. This protein is highly effective against several mammalian enzymes, which includes pancreatic and neutrophil-derived elastases, chymotrypsin, trypsin, factor Xa, and kallikrein. In this work we showed that ecotin binds to human alpha-thrombin via its secondary binding site, and modulates thrombin catalytic activity. Formation of wild type ecotin-alpha-thrombin complex was observed by native PAGE and remarkably, gel filtration chromatography showed an unusual 2:1 ecotin:enzyme stoichiometry. Analysis of the protease inhibitor effects on thrombin biological activities showed that (i) it decreases the inhibition of thrombin by heparin/antithrombin complex (IC50=3.2 microM); (ii) it produces a two-fold increase in the thrombin-induced fibrinogen clotting; and (iii) it inhibits thrombin-induced platelet aggregation (IC50=4.5 microM). Allosteric changes on thrombin structure were then evaluated. Complex formation with ecotin caused a three-fold increase in the rate of thrombin inhibition by BPTI, suggesting a displacement of the enzyme's 60-loop. In addition, ecotin modulated the enzyme's catalytic site, as demonstrated by changes in the fluorescence emission of fluorescein-FPRCK-alpha-thrombin (EC50=3.5 microM). Finally, solid phase competition assays demonstrated that heparin and prothrombin fragment 2 prevents thrombin interaction with ecotin. Altogether, these observations strongly support an ecotin interaction with thrombin anion-binding exosite-2, resulting in modulation of its biological activities. At this point, ecotin might be useful as a new tool for studying thrombin allosteric modulation.


Bacterial communities in full-scale wastewater treatment systems.
Bacterial metabolism determines the effectiveness of biological treatment of wastewater. Therefore, it is important to define the relations between the species structure and the performance of full-scale installations. Although there is much laboratory data on microbial consortia, our understanding of dependencies between the microbial structure and operational parameters of full-scale wastewater treatment plants (WWTP) is limited. This mini-review presents the types of microbial consortia in WWTP. Information is given on extracellular polymeric substances production as factor that is key for formation of spatial structures of microorganisms. Additionally, we discuss data on microbial groups including nitrifiers, denitrifiers, Anammox bacteria, and phosphate- and glycogen-accumulating bacteria in full-scale aerobic systems that was obtained with the use of molecular techniques, including high-throughput sequencing, to shed light on dependencies between the microbial ecology of biomass and the overall efficiency and functional stability of wastewater treatment systems. Sludge bulking in WWTPs is addressed, as well as the microbial composition of consortia involved in antibiotic and micropollutant removal.


Cultivation of Hair Matrix Cells from Cashmere Goat Skins and Exemplified Applications.
A functional interpretation of filtered candidates and predicted regulatory pathways related to cashmere growth from sequencing trials needs available cell models, especially for hair matrix cells (HMCs), whose continual proliferation and differentiation result in rapid hair growth. To fulfill such goals, we herein obtained primary goat HMCs via a microdissection-based method; optimized the selection of the culture medium and coating substances for better cell maintenance; and exemplified their usefulness through examining the effects of calcium and all-trans retinoic acid (ATRA) on cells using immunoblotting, flow cytometry, and other techniques. As a result, we successfully acquired primary and passaged goat HMCs with typical keratinocyte morphology. Calcium-free RPMI (Roswell Park Memorial Institute) 1640 and MEM (minimum Eagle's medium) outperformed normal DMEM/F12 (Dulbecco's modified Eagle's medium/Nutrient Mixture F-12) on long-term cell maintenance, whereas serum-free media K-SFM and EpiLife failed to support cell growth. HMCs differed molecularly and morphologically from their neighbor dermal papilla cells on expressions of feature genes, such as HOXC13, and on characteristic keratinocyte-like appearances versus fibroblast shapes, respectively. Higher calcium concentrations significantly stimulated the expression of the genes (e.g., KRT1 and IVL) involved in keratinocyte differentiation and, promoted cell proliferation. Moreover, 10-5 M ATRA obviously boosted goat HMC expansions and changed their cell cycle distributions compared to the controls. Our study shines a light on researches exploring the mechanisms underlying the growth of cashmere.


Improved system for construction and analysis of single-copy beta-galactosidase operon fusions in Yersinia enterocolitica.
We report a significantly improved system for studying single-copy lacZ operon fusions in Yersinia enterocolitica: a simple procedure for the stable integration of lacZ operon fusions into the ara locus and a strain with a deletion mutation that abolishes the low level of endogenous beta-galactosidase activity.


Incidence and predictors of acute limb ischemia in acute myocardial infarction complicated by cardiogenic shock.
To describe the incidence and predictors of acute limb ischemia (ALI) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Patients with index hospitalizations for AMI complicated by cardiogenic shock from 2016 to 2019 in the US National Readmission Database were identified. We evaluated the incidence of ALI and its associated mortality, length of stay, and cost of hospitalization. We used multivariable logistic regression to determine independent predictors of ALI in this population. A total of 84,615 patients had AMI complicated by cardiogenic shock and 1302 (1.54%) developed ALI. The rates of ALI increased from 1.29% in 2016 to 1.66% in 2019 (P ≤ .002). The use of microaxial mechanical circulatory support increased from 2.25% in 2016 to 13.36% in 2019 (P = .0001). The major predictors of ALI included peripheral arterial disease (odds ratio [OR], 7.34; 95% confidence interval [CI], 6.12-8.81), venoarterial extracorporeal membrane oxygenation (OR, 4.40; 95% CI, 3.19-6.07), and microaxial mechanical circulatory support (OR, 3.12; 95% CI, 2.74-3.55). ALI in patients with cardiogenic shock was associated higher mortality (39.20% vs 33.53%; P ≤ .0001). This nationwide observational study shows that ALI is an important complication of AMI with cardiogenic shock. This complication is associated with higher mortality. In addition to peripheral artery disease, the use of mechanical circulatory devices was associated with significantly higher rates of ALI.


Localization of an epitope of a calcium-dependent monoclonal antibody to the N-terminal region of the Gla domain of human factor VII.
The epitope of a calcium-dependent murine monoclonal antibody specific for human factor VII (Thim et.al., Biochemistry (1988) 27, 7785-7793) has been determined. Site-directed mutagenesis of residues 3 through 10 of factor VII eliminates the binding of this antibody but does not disturb the binding of a second antibody which binds nearby.


Sarcoidosis: psychotherapy and long-term outcome-a case report.
Sarcoidosis is a systemic, inflammatory disease of unknown aetiology, influenced by stressful life events and associated with a high incidence of alexithymic personality traits, and of depressive symptoms. The medical literature on sarcoidosis has called for a psychotherapeutic intervention to modify the perceived state of disease, the influence of stressful events and the depressive condition. Few studies have described cases treated with psychotherapy, and no information is available on its long-term outcome. We present the case of a patient with chronic sarcoidosis and periodical reacutizations with constantly pathological ESR. Twenty-four years after the diagnosis, a dynamic supportive-expressive psychotherapy for psychosomatic alexithymic patients was added to the medical therapy. At the beginning and at the end of the psychotherapy, and for the long-term outcome evaluations, Kellner's symptom questionnaire (SQ) was used to investigate psychological distress. The SQ scores, initially pathological, were normal at the end of the psychotherapy and for the following three years. Psychotherapy, without antidepressive drugs, resolved the depression. The depressive symptoms disappeared, along with the normalization and stabilization of the ESR. After three years, the outcome was positive. This is the first study describing a successful psychotherapy and its long-term outcome on a patient with sarcoidosis.


Pigment-targeted light wavelength and intensity promotes efficient photoautotrophic growth of Cyanobacteria.
A consensus is lacking whether monochromatic rather than broad-spectrum illumination is more efficient for photosynthetic microbe production platforms. Light wavelength and intensity were tuned to pigment composition for growth of the Cyanobacterium Synechocystis PCC 6803. Phycocyanin (PC)-targeting LEDs (620nm) provided more than 6times the peak efficiency of white LEDs, with peak efficiency growth rates of 0.063h(-1) at 81μEm(-2)s(-1) and 0.039h(-1) at 126μEm(-2)s(-1) for red and white LEDs, respectively. Chlorophyll a (Chl a)-targeting LEDs (680- and 440-nm) performed poorly. Indeed, 10 times greater mass abundance was observed for PC than Chl a. PC levels did not change while Chl a levels decreased when Synechocystis transitioned from white light at 50μEm(-2)s(-1) to 250μEm(-2)s(-1) with 620nm, 680nm, or white LEDs. This work demonstrates that light wavelengths and intensity need to be optimized for each strain.


The recombinant kringle domain of urokinase plasminogen activator inhibits VEGF165-induced angiogenesis of HUVECs by suppressing VEGFR2 dimerization and subsequent signal transduction.
The recombinant kringle domain (UK1) of urokinase plasminogen activator was previously reported to exert antiangiogenic activity against Vascular Endothelial Growth Factor (VEGF)-induced angiogenesis in both in vitro and in vivo models. In this study, we explored the molecular signaling mechanisms involved in the antiangiogenic activity of UK1 by examining VEGF signaling proteins. VEGF165 stimulates the phosphorylation of VEGF signaling molecules, and pretreatment with UK1 blocked VEGF-induced signal transduction associated with proliferation, survival, and migration. UK1 also suppressed VEGF165-induced activation of MMP-2. Moreover, UK1 suppressed the phosphorylation and activation of VEGFR2 in VEGF-stimulated human umbilical cord vein endothelial cells (HUVECs) by blocking the dimerization of VEGFR2. Overall, our findings suggest that UK1 inhibits VEGF-induced proliferation, migration, and matrix metalloproteinase activity of HUVECs by suppressing VEGFR2 dimerization and subsequent angiogenic signals.


A high-resolution multi-shell 3T diffusion magnetic resonance imaging dataset as part of the Amsterdam Ultra-high field adult lifespan database (AHEAD).
In order to further our understanding of brain function and the underlying networks, more advanced diffusion weighted magnetic resonance imaging (DWI MRI) data are essential. Here we present freely available high-resolution multi-shell multi-directional 3 Tesla (T) DWI MRI data as part of the 'Amsterdam Ultra-high field adult lifespan database' (AHEAD). The 3T DWI AHEAD dataset include 1.28mm isotropic whole brain DWI data of 49 healthy adult participants between 18 and 90 years old. The acquired data include DWIs at three non-zero b-values (48 directions, b-value 700 s/mm2; 56 directions, b-value 1000 s/mm2; 64 directions, b-value 1600 s/mm2) including a total of twelve volumes with a b-value of 0 s/mm2 (b0 volumes). In addition, eight b0 volumes with a reversed phase encoding direction were acquired to correct for distortions. To facilitate future use, the DWI data have been denoised, corrected for eddy currents, susceptibility-induced off-resonance field distortions, bias fields, and are skull stripped.


Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.
Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p < 0.001). Nuclear YAP expression did not associate with other variables such as lymph node involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types of invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p < 0.001) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.


Recognition and treatment of endotoxemia.
Endotoxemia occurs secondary to several diseases that disrupt the mucosal barrier to bacteria or their toxins. The effects of endotoxemia are varied and are mediated by a wide variety of proinflammatory substances. Although evidence certainly exists to incriminate the cyclooxygenase-derived products of arachidonic acid in the early responses to endotoxemia, various other mediators must also be considered. Treatment presently involves fluid replacement, correction of acid-base abnormalities, augmentation of cardiovascular function, and inhibition of cyclooxygenase activity.


Agonist-induced cyclic ADP ribose production in airway smooth muscle.
Cyclic ADP-ribose (cADPR) triggers sarcoplasmic reticulum (SR) Ca(2+) release in airway smooth muscle (ASM). SR Ca(2+) release is an important component of the intracellular Ca(2+) ([Ca(2+)](i)) response of ASM to agonists. Whether cADPR is endogenously produced in ASM during agonist stimulation has not been established. In this study, cADPR production was examined in acutely dissociated porcine ASM cells. ACh stimulation (> or = 1 microM) significantly increased cADPR levels, peaking between 30s and 1 min. This effect was inhibited by M(2) and M(3) muscarinic receptor antagonists. Histamine ((> or = 5 microM) increased cADPR levels to a greater extent than ACh, while diphenhydramine blocked histamine-induced cADPR elevation. Both bradykinin (100 nM) and endothelin-1 (100 nM) also increased cADPR levels to a greater extent than ACh or histamine. These results indicate that in porcine ASM, certain agonists acting via receptors increase cADPR levels. Furthermore, the extent of cADPR responses to agonist varies, possibly reflecting differences in G-protein coupling.


Seroconversion rates and measles antibody titers induced by measles vaccination in Latin American children six to 12 months of age.
A collaborative study was conducted to determine how 2,042 infants responded serologically to measles vaccination in six study areas and to help define the optimal age for measles vaccination in children of Latin America. The results suggest that local factors affect the seroconversion rate and that a success rate of 90% can be attained if initial vaccination is given at nine to 11 months of age, depending on the area. Post-vaccination titers also varied, and higher titers were generally observed in groups with higher seroconversion rates.


Comparative Analysis of Gut Microbiota in Centenarians and Young People: Impact of Eating Habits and Childhood Living Environment.
The composition of centenarians' gut microbiota has consistently been used as a model for healthy aging studies. However, there is an incomplete understanding of how childhood living conditions and eating habits affect the development and composition of gastrointestinal microbiota in centenarians with good cognitive functions. We compared the gut microbiota as well as the living and eating habits of the oldest-old group and the young people group. The richness and diversity of microbiota and the abundance of hereditary and environmental microbes were higher in people with longevity than young people. People with longevity ate more potatoes and cereal products. In their childhood, they had more exposure to farm animals and did not have sewers compared with young people. Young people's gut microbiota contained more butyrate-producing bacteria and bacteria that characterized an animal-based Western diet. These results expand our understanding of the effects of childhood environment and diet on the development and stability of the microbiota in people with longevity.


Enhanced osteogenic differentiation of stem cells via microfluidics synthesized nanoparticles.
Advancement of bone tissue engineering as an alternative for bone regeneration has attracted significant interest due to its potential in reducing the costs and surgical trauma affiliated with the effective treatment of bone defects. We have improved the conventional approach of producing polymeric nanoparticles, as one of the most promising choices for drug delivery systems, using a microfluidics platform, thus further improving our control over osteogenic differentiation of mesenchymal stem cells. Molecular dynamics simulations were carried out for theoretical understanding of our experiments in order to get a more detailed molecular-scale insight into the drug-carrier interactions. In this work, with the sustained intracellular delivery of dexamethasone from microfluidics-synthesized nanoparticles, we explored the effects of particle design on controlling stem cell fates. We believe that the insights learned from this work will lead to the discovery of new strategies to tune differentiation for in situ differentiation or stem cell therapeutics. The use of mesenchymal stem cells has been described by many researchers as a novel therapy for bone regeneration. One major hurdle in this approach is the control of osteogenic differentiation. In this article, the authors described elegantly their microfluidic system in which dexamethasone loaded nanoparticles were produced. This system would allow precise fabrication of nanoparticles and consequently higher efficiency in cellular differentiation.


The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis.
More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 The canonical function of the RB1 gene product, pRB, is to repress the E2F transcription factor family, but pRB also functions to regulate cellular differentiation in part through its binding to the histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that KDM5A promotes SCLC proliferation and SCLC's neuroendocrine differentiation phenotype in part by sustaining expression of the neuroendocrine transcription factor ASCL1. Mechanistically, we found that KDM5A sustains ASCL1 levels and neuroendocrine differentiation by repressing NOTCH2 and NOTCH target genes. To test the role of KDM5A in SCLC tumorigenesis in vivo, we developed a CRISPR/Cas9-based mouse model of SCLC by delivering an adenovirus (or an adeno-associated virus [AAV]) that expresses Cre recombinase and sgRNAs targeting Rb1, Tp53, and Rbl2 into the lungs of Lox-Stop-Lox Cas9 mice. Coinclusion of a KDM5A sgRNA decreased SCLC tumorigenesis and metastasis, and the SCLCs that formed despite the absence of KDM5A had higher NOTCH activity compared to KDM5A+/+ SCLCs. This work establishes a role for KDM5A in SCLC tumorigenesis and suggests that KDM5 inhibitors should be explored as treatments for SCLC.


Higher BMI is associated with worse asthma control and quality of life but not asthma severity.
Asthma and obesity tend to co-occur, but relatively few studies have linked obesity, measured using body mass index (BMI), to clinically relevant measures of asthma morbidity. This study assessed BMI in a Canadian sample of asthma outpatients, and evaluated associations between BMI and levels of asthma severity, asthma control, and asthma-related quality of life. A total of 382 adult asthma patients underwent demographic and medical history interviews on the day of their clinic visit. Patients' self-reported height and weight were used to calculate BMI (kg/m(2)). Asthma severity was classified according the GINA (2002) guidelines. Patients completed the Asthma Control (ACQ) and Asthma Quality of Life (AQLQ) Questionnaires and underwent standard pulmonary testing (spirometry). A total of 139 (36%) patients had a normal BMI; 149 (39%) patients were overweight; and 94 (25%) patients were obese. There was no relationship between BMI and asthma severity when controlling for age and sex. Patients with higher BMI scores had higher ACQ and lower AQLQ scores, independent of age, sex and asthma severity. Results identify higher BMI and obesity as potential behavioral factors related to worse asthma control and quality of life, but not asthma severity, and suggest important avenues for asthma management and control initiatives.


A note on the distribution of glial cells in the molecular layer of the dentate gyrus.
The distribution of the perikarya of astrocytes and other glial cells in the molecular layer of the dentate gyrus has been studied in gold chloride-sublimate preparations of rats and of normal and reeler mice, and in plastic embedded material from young adult rats. Contrary to previous reports (Rose et al. [7]), we have found no evidence for a distinct "line" or "band" of astrocyte cell bodies along the interface between the zones of termination of the entorhinal and hippocampal afferents to the dentate gyrus. Indeed, apart from a conspicuous accumulation of astrocytes immediately beneath the pial surface and hippocampal fissure, the distribution of glial cells across the extent of the molecular layer appears to be more or less random. In view of this it is difficult to ascribe a critical role to the astrocytes in either determining the normal distribution of afferent fibers to the dentate gyrus or in promoting their re-organization following its partial deafferentation.


Medial gastrocnemius muscle fascicle function during heel-rise after non-operative repair of Achilles tendon rupture.
To better understand muscle remodelling in dynamic conditions after an Achilles tendon rupture, this study examined the length of medial gastrocnemius muscle fascicles during a heel-rise at 6- and 12-months after non-operative ATR treatment. Participants (15 M, 3F) were diagnosed with acute Achilles tendon rupture. Medial gastrocnemius subtendon length, fascicle length and pennation angle were assessed in resting conditions, and fascicle shortening during bi- and unilateral heel-rises. Fascicle shortening was smaller on the injured side (mean difference [95% CI]: -9.7 mm [-14.7 to -4.7 mm]; -11.1 mm [-16.5 to -5.8 mm]) and increased from 6- to 12 months (4.5 mm [2.8-6.3 mm]; 3.2 mm [1.4-4.9 mm]) in bi- and unilateral heel-rise, respectively. The injured tendon was longer compared to contralateral limb (2.16 cm [0.54-3.79 cm]) and the length decreased over time (-0.78 cm [-1.28 to -0.29 cm]). Tendon length correlated with fascicle shortening in bilateral (r = -0.671, p = 0.002; r = -0.666, p = 0.003) and unilateral (r = -0.773, p ≤ 0.001; r = -0.616, p = 0.006) heel-rise, at 6- and 12-months, respectively. In the injured limb, the change over time in fascicle shortening correlated with change in subtendon length in unilateral heel-rise (r = 0.544, p = 0.02). This study showed that the lengths of the injured tendon and associated muscle can adapt throughout the first year after rupture when patients continue physiotherapy and physical exercises. For muscle, measures of resting length may not be very informative about adaptations, which manifest themselves during functional tasks such as unilateral heel-rise.


Novel SARS-CoV-2/COVID-19: Origin, pathogenesis, genes and genetic variations, immune responses and phylogenetic analysis.
In this review, we focused on the origins of the novel coronavirus (SARS-CoV-2), origin, pathogenesis, immune responses, genes and genetic variations, phylogenetic analyses, and potential therapeutic strategies to summarize approaches for developing broadly effective preventions and vaccines to cope COVID-19. Towards the end of 2019, SARS-CoV-2 has emerged in association with the SARS, later was named COVID-19 caused an environment of chaos worldwide and infected a massive number of lives. Since these epidemics or pandemics had spread to 210 countries and territories around the world and 2 international conveyances with 6,467,229 confirmed cases, including, 382,766 deaths, as of June 03, 2020 (https://www.worldometers.info/coronavirus/), hence the World Health Organization declared it as a global Public Health Emergency. There are no clinically approved vaccines or antiviral drugs available for either of new or old corona infections; thus, the development of effective therapeutic and preventive strategies that can be readily available to cope with these strains.


Distribution of Ig classes and IgG subclasses among human B cells activated by Nocardia opaca-delipidated cell mitogen or by pokeweed mitogen.
The relative proportions of cells synthesizing the three major Ig classes or one of the four IgG subclasses in cultures stimulated with pokeweed mitogen (PWM) or Nocardia-delipidated cell mitogen (NDCM) were investigated. In cultures of human peripheral blood mononuclear cells (PB MNC) stimulated with PWM, the number of IgG-containing cells (CC) was higher than the number of IgM-CC, and a substantial number of IgA-CC was found. Conversely, in NDCM-stimulated PB MNC cultures IgM-CC outnumbered IgG-CC and only few IgA-CC were detected. In those cultures, the removal of T cells resulted in an increase in the number of IgM-CC concomitant with a decrease in the number of IgG-CC. A substantial number of cells containing simultaneously IgG or IgA in addition to IgM could be found in PWM-stimulated cultures. These cells were virtually absent in NDCM-stimulated cultures. The relative proportions of IgG subclass-CC were IgG1-CC greater than IgG2-CC greater than IgG3-CC greater than or equal to IgG4-CC in PWM-stimulated and IgG2-CC greater than IgG1-CC greater than IgG3-CC greater than or equal to IgG4-CC in NDCM-stimulated cultures. The removal of T cells from NDCM-stimulated cultures did not result in major alteration of this distribution. The role of T cells and of the genomic order of the Igh-C genes in their phenotypic expression triggered in vitro by PBA is discussed.


Interdisciplinary team interactions: a qualitative study of perceptions of team function in simulated anaesthesia crises.
We placed anaesthesia teams into a stressful environment in order to explore interactions between members of different professional groups and to investigate their perspectives on the impact of these interactions on team performance. Ten anaesthetists, 5 nurses and 5 trained anaesthetic assistants each participated in 2 full-immersion simulations of critical events using a high-fidelity computerised patient simulator. Their perceptions of team interactions were explored through questionnaires and semi-structured interviews. Written questionnaire data and interview transcriptions were entered into N6 qualitative software. Data were analysed by 2 investigators for emerging themes and coded to produce reports on each theme. We found evidence of limited understanding of the roles and capabilities of team members across professional boundaries, different perceptions of appropriate roles and responsibilities for different members of the team, limited sharing of information between team members and limited team input into decision making. There was a perceived impact on task distribution and the optimal utilisation of resources within the team. Effective management of medical emergencies depends on optimal team function. We have identified important factors affecting interactions between different health professionals in the anaesthesia team, and their perceived influences on team function. This provides evidence on which to build appropriate and specific strategies for interdisciplinary team training in operating theatre staff.


Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab.
Patients with metastatic colorectal cancer (mCRC) with activating mutations at codon 12 or 13 of the KRAS gene are currently excluded from treatment with monoclonal antibodies against the epidermal growth factor receptor (EGFR), for example, cetuximab. Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. We conducted an analysis to study the influence of the KRAS p.G13D mutation in patients with mCRC who were treated with cetuximab. We analyzed the KRAS mutation status of 110 patients who were treated with cetuximab between September 2003 and October 2008 at Hospital Clínico, San Carlos. We compared progression-free survival, overall survival, and response rate according to KRAS mutation status. Patients with mutations at codon 13 compared with those with other KRAS mutations showed no statistically significant differences in progression-free survival (4.96 months [95% CI, 3.04-6.89 months] vs. 3.10 months [95% CI, 1.58-4.61 months]; hazard ratio [HR] 0.88 [95% CI, 44-1.75]; P = .72) and overall survival (8.2 months [95% CI, 4.2-12.1 months] vs. 14.6 months [95% CI, 8.0-21.2 months]; HR 0.50 [95% CI, 0.23-1.09]; P = .084). Patients with KRAS wild-type tumors have a longer progression-free survival (7.30 months [95% CI, 4.48-10.12 months]; HR 0.46 [95% CI, 0.23-0.91]; P = .025) and overall survival (19.0 months [95% CI, 10.2-27.8 months]; HR 0.32 [95% CI, 0.15-0.69]; P = .004) than patients with p.G13D-mutated tumors. Differences in the response rate were not observed between groups. Patients with mCRC and mutation at codon 13 of the KRAS gene do not appear to benefit from treatment with cetuximab. These results support the current clinical practice.


High-resolution manometric guidance during laparoscopic Heller myotomy: Impact on quality of life and symptom severity for children with achalasia.
High-resolution esophageal manometry (HREM) during laparoscopic Heller myotomy (LHM) with fundoplication for achalasia allows tailoring of myotomy length and wrap tightness. The purpose of this study is to quantify long-term postoperative symptom severity and quality of life using validated questionnaires. Children ≤18 years with achalasia who previously underwent LHM with intraoperative HREM from 2010 to 2017 were prospectively surveyed. Eckardt Symptom Score (ESS), Achalasia Severity Questionnaire (ASQ), Pediatric Quality of Life Inventory (PedsQL), and Pediatric GERD Symptom and Quality of Life (PGSQ) questionnaires were administered. Scores for historical controls were obtained from prior survey instrument validation studies as comparison. Of 30 eligible patients, 12 (40%) completed the surveys. Mean age at time of surgery was 13 ± 3 years. Assessment was performed at least 10 months after surgery with mean time elapsed of 3.6 ± 2 years. Average premyotomy lower esophageal sphincter (LES) pressure, postmyotomy LES pressure, and postfundoplication LES pressure were 30 ± 10 mmHg, 14 ± 6 mmHg, and 18 ± 9, respectively. ESS (2.3/12), ASQ (39/100 ± 16), PGSQ (symptom: 0.6/4 ± 0.4, school: 0.4/4 ± 0.4), and overall PedsQL (82/100 ± 15) were similar to those of healthy historical controls. Children with achalasia undergoing LHM with intraoperative HREM had sustained long-term symptom improvement and quality of life scores comparable to healthy patients. Retrospective, II.


High-speed chromosome sorting.
Structural and genetic characterization of chromosomes is necessary to understand both normal and pathologic physiology in any species. Flow cytometry and cell sorting technologies provide a means for precise measurement of chromosomal makeup as well as for the isolation of specific chromosomes for further study. Advancements in molecular biology protocols and pressures from large-scale sequencing endeavors placed increased demand on the developers of these instruments for enhanced throughput and quality of results. The ensuing improvements in sorting performance led to the development of a new generation of cytometers known as high-speed cell sorters. These machines provide superior results in less time and are cheaper and simpler to operate than their predecessors. Robust chromosome sorting can now be performed in the laboratories of individual investigators for a variety of gene- and sequence-specific studies. Resolution of the flow karyotype with increased refinement, and the development of new applications for this technology will assure that cell sorting continues to play an important role in cytogenetics, our understanding of molecular processes such as evolution and disease etiology, and ultimately serve as a launching point for predictive medicine.


Safety improvements through Intelligent Transport Systems: a South African case study based on microscopic simulation modelling.
Intelligent Transport Systems (ITS) can facilitate the delivery of a wide range of policy objectives. There are six main objectives/benefits identified in the international literature: Safety (reduction of (potential) crashes), mobility (reduction of delays and travel times), efficiency (optimise the use of existing infrastructure), productivity (cost saving), energy/environment and customer satisfaction [Mitretek Systems, 2001. Intelligent Transport System Benefits: 2001 update, Under Contract to the Federal Highway Administration, US Department of Transportation, Washington, DC, US]. In the South African context, there is an interest for measures that can reduce (potential) crashes. In South Africa the number of year on year traffic related fatalities is still increasing. In 2005 the number of fatalities was 15393 (from 14135 in 2004) while the estimated costs for the same period increased from R8.89-billion to R9.99-billion [RTMC, 2007. Interim Road Traffic and Fatal Crash Report 2006, Road Traffic Management Corporation, Pretoria, SA]. Given the extent of the road safety problem and the potential benefits of ITS, the need for further research is apparent. A study with regards to the potential of different types of models (macroscopic, mesoscopic and miscroscopic simulation models) led to the use of Paramics. Two corridors and three types of ITS measures were investigated and safety benefits were estimated.


A renal transplant patient with intractable hiccups and review of the literature.
Intractable hiccups in transplanted patients may be caused by various medical conditions including infections. We report a case of a 44-year-old man who suffered from intractable hiccups after cadaveric kidney transplantation. We identified 3 different hiccup periods with different causes: 1) steroid and anesthetics use, 2) severe ulcerose herpetic and mycotic esophagitis, and 3) pleuropneumonia caused by nosocomial methicillin-resistant Staphylococcus epidermidis and pulmonary abscess requiring thoracic surgery.


Screen-printed transcutaneous oxygen sensor employing polymer electrolytes.
A disposable, transcutaneous oxygen sensor has been designed and implemented using screen-printing technology for all fabrication stages. The sensor incorporates an integral heating element to promote transcutaneous diffusion of blood gases so that a reliable estimation of arterial blood gas concentration can be obtained. The oxygen sensing part of the device consists of a screen-printed Clark cell implemented as electrodes, electrolyte and membrane. A three-electrode configuration is employed with gold working and counter electrodes and a silver/silver chloride reference electrode. Several different polymer electrolyte and membrane materials were evaluated in the construction of the device, and their performances were compared. A fully automated gas testing rig was constructed to enable oxygen levels to be varied under computer control. Cyclic voltammetry and static analysis of the sensors were carried out at different oxygen concentration levels and in various test environments. Linear relationships were established with an averaged sensitivity level of 0.02 microA(mmHg)(-1) and high regression coefficients of 0.99. The prototype covered with a polytetrafluoroethylene membrane gave the experimental result of I (microA) = -0.025PO2 (mmHg) - 0.085. Several factors influenced the performance of the sensors. The investigations have greatly contributed towards an understanding of the suitability of the materials in achieving a viable, low-cost sensor.


A novel colorimetric and "turn-off" fluorescent probe based on catalyzed hydrolysis reaction for detection of Cu2+ in real water and in living cells.
A novel and highly selective fluorescent 1,8-naphthalimide-based probe, 3, was designed and synthesized for rapid Cu2+ detection in a CH3CN-H2O (3:1, v/v, pH = 7.4) solution by means of a distinct hydrolysis mechanism via its Cu2+-promoting feature. Upon treatment with Cu2+, the fluorescence response of probe 3 at 550 nm abruptly decreased, which was visible to the naked eye, and this response was accompanied by a clear change of the color of the solution; the color changed from the original yellow color to colorless. This color change occurred due to the Cu2+-promoted hydrolysis of 3, which yielded a fluorescence-quenched product. It is inspiring that probe 3 exhibited excellent sensitivity, a short response time and strong anti-interference recognition. Compared with the allowable amount of Cu2+ (∼20 μM) in drinking water, the detection limit of 3 for Cu2+ is calculated to be 9.15 nM, which is much lower than the amount defined by standards. The probe can be successfully applied for the determination of Cu2+ in real aqueous samples. Furthermore, probe 3 can be used as a fluorescent sensor to detect Cu2+ in biological environments, demonstrating its low toxicity to organisms and good cell permeability in live cell imaging.


Comparison of the efficacy and safety of thoracic endovascular aortic repair with open surgical repair and optimal medical therapy for acute type B aortic dissection: A systematic review and meta-analysis.
Current treatment approaches for acute type B aortic dissection (TBAD) are diversified. Thoracic endovascular aortic repair (TEVAR) as an effective and convenient intervention has been adopted extensively. However, the superior efficacy and safety of TEVAR have not yet been well evaluated. This meta-analysis was designed to comprehensively compare the efficacy and safety of TEVAR with open surgical repair and optimal medical therapy for acute type B aortic dissection. A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2020 was conducted for relevant studies that compared the efficacy of TEVAR and other conventional interventions in the treatment of TBAD. The primary outcomes were early mortality and midterm or long term survival. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. A total of 18 studies including 12,789 patients were identified. 30-day/in-hospital mortality was significantly lower in TBAD patients with TEVAR than open surgical repair (OSR), with a pooled OR of 0.54 (95% CI 0.43-0.68; P < 0.00001). Compared with optimal medical therapy (OMT), TEVAR experienced lower incidence of long-term death (≥5-yr mortality), with a pooled OR of 0.46 (95% CI 0.24-0.86; P = 0.02). However, no significant difference between TEVAR and OSR or OMT in long-term survival was found. Compared with OSR, lower incidence of cardiac and pulmonary complications as well as shorter length of stay were observed in TEVAR. Compared with OMT, TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay. Our analysis shows that TEVAR may be favorable in reducing 30-day/in-hospital mortality (than OSR) and long-term mortality (than OMT). TEVAR experienced equal efficacy with OSR and OMT in long-term survival. TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay than OMT; and lower incidence of cardiac and pulmonary complications as well as shorter length of stay than OSR. However, TEVAR indicated similar incidence of other complications and outcomes with OSR and OMT. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy TEVAR.


Outcomes after radiotherapy for squamous cell carcinoma of the eyelid.
Squamous cell carcinoma (SCC) of the eyelid is a rare malignancy with metastatic potential. In the current study, the outcomes of patients with SCC of the eyelid were evaluated after definitive and postoperative radiation therapy. The medical records of all patients treated with radiotherapy for SCC of the eyelid at 1 institution between 1950 and 2005 were reviewed. Patient records were analyzed for clinical characteristics, pathologic features, radiation techniques, and outcomes. Survival rates were calculated using the Kaplan-Meier method; factors affecting survival were assessed using the log-rank test. During the study period, 39 patients with 42 eyelid SCCs were treated with radiotherapy. Thirty-two tumors were treated with primary radiotherapy and 10 were treated with postoperative radiotherapy after wide local excision. Surviving patients were followed for a median of 76 months. The 5-year disease-specific and overall survival rates for all patients were 86% and 71%, respectively. At 5 years, local, regional, and distant disease control rates for all tumors were 88%, 95%, and 97%, respectively. There were no significant differences in the 5-year local, regional, and distant control rates between tumors treated with definitive and those treated with postoperative radiotherapy. There were no grade 3 or 4 complications. Primary radiotherapy for SCC of the eyelid provides excellent locoregional control with reasonable complication rates and should be considered an alternative to surgery in selected patients.


[The correction of postvagotomy disorders of the motor function in the small intestine by using antihypoxants and antioxidants].
Study of the electric activity of small intestine smooth muscle in vagotomized rats demonstrated diminution and disturbance of intestinal motility. These changes were most expressed within 30 days after vagotomy. Injection of antihypoxant sodium gamma-oxybutyrate and antioxidant dibunol to the vagotomized rats resulted in normalization of intestinal motility.


Electronegativity-Induced Charge Balancing to Boost Stability and Activity of Amorphous Electrocatalysts.
Amorphization is an efficient strategy to activate intrinsically inert catalysts. However, the low crystallinity of amorphous catalysts often causes high solubility and poor electrochemical stability in aqueous solution. Here, a different mechanism is developed to simultaneously stabilize and activate the water-soluble amorphous MoSx Oy via a charge-balancing strategy, which is induced by different electronegativity between the co-dopants Rh (2.28) and Sn (1.96). The electron-rich Sn prefers to stabilize the unstable apical O sites in MoSx Oy through charge transfer, which can prevent the H from attacking. Meanwhile, the Rh, as the charge regulator, shifts the main active sites on the basal plane from inert Sn to active apical Rh sites. As a result, the amorphous RhSn-MoSx Oy exhibits drastic enhancement in electrochemical stability (η10 increases only by 12 mV) after 1000 cycles and a distinct activity (η10 : 26 mV and Tafel: 30.8 mV dec-1 ) for the hydrogen evolution reaction in acidic solution. This work paves a route for turning impracticably water-soluble catalysts into treasure and inspires new ideas to design high-performance amorphous electrocatalysts.


[Unusual clinical presentations of vestibular schwannomas].
The aim of this study is evaluate the unusual ways of initial presentation of the vestibular schwannomas. We performed a retrospective study of the patients who underwent resection of acoustic neuromas on our service, including for analysis only the cases which initial symptom was not the hearing loss. Tumor size, localization, clinical presentation, and age of the patients were considered. Nine patients present with atypical symptoms. The most common complain in this group were facial paresthesias (22,2 %). None of them complained about other otological symptoms. A significant group of patients did not present with the otological symptoms classically associated with vestibular schwannoma. Clinical knowledge of these kinds of symptoms may lead to earlier detection of these lesions.


The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon-alpha and ribavirin combination therapy.
To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-alpha) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN-alpha2b, 6 million units thrice weekly, plus RBV 1,000-1,200 mg daily for 24 weeks. Thyroid function, anti-thyroglobulin and antiperoxidase autoantibodies were tested at enrollment (M0), at the end-of-treatment (M6) and 6 months after end-of-treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN-alpha plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.


Morbidities of lung cancer surgery in obese patients.
Obesity is a risk factor for increased perioperative morbidity and mortality in surgical patients. There have been limited studies to correlate the morbidity of lung cancer resection with obesity. We performed a retrospective study of patients who underwent surgical resection for lung cancer at the Medical College of Wisconsin, Milwaukee, from 2006 to 2010. Data on patient demographics, weight, pathological findings, and hospital course were abstracted after appropriate institutional review board approval. Perioperative morbidity was defined as atrial fibrillation, heart failure, respiratory failure, pulmonary embolism, or any medical complications arising within 30 days after surgery. The Fisher exact test was used to test the association between body mass index (BMI) and perioperative morbidities. Between 2006 and 2010, 320 lung resections were performed for lung cancer. The median age was 67 (interquartile range, 59-75) years, and 185 (57.8%) were females. A total of 121 (37.8%) of patients had a BMI lower than 25, and 199 (62.18%) patients had a BMI of 25 or higher. The 30-day mortality rate was 1.8% (n = 6) in the whole group; only 2 of these patients had a BMI of 25 or higher. Perioperative morbidity occurred in 28 (23.14%) of patients with a normal BMI and in 47 (23.61%) of patients with a BMI of 25 or higher (P = .54). Specific morbidities encountered by patients with normal versus BMI of 25 or higher were as follows: atrial fibrillation, 11 (9.09%) versus 24 (12.06%) (P = .46); pulmonary embolism, 1 (0.83%) versus 3 (1.51%) (P = 1.0); congestive heart failure, 2 (1.65%) versus 2 (1.01%) (P = .63); renal failure, 4 (3.3%) versus 2 (1.0%) (P = .29); respiratory failure, 12 (9.92%) versus 17 (8.54%) (P = .69); and acute respiratory distress syndrome, 2 (1.65%) versus 1 (0.50%) (P = .55). The median hospital stay was 5 days in the lower BMI group and 4 days in the BMI of 25 or higher group (P = .52). Overweight and normal weight patients do not differ significantly in rates of perioperative morbidities, 30-day mortality, and length of stay. Our study indicates that potential curative surgical resections can be offered to even significantly overweight patients.


Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material: first results of a modified PAIR method.
Surgery is the treatment of choice in echinococcal cysts with cystobiliary fistulas. PAIR (puncture, aspiration, injection, and reaspiration of scolecidals) is contraindicated in these cases. To evaluate a modified PAIR method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material. Twelve patients were treated: 10 patients with multivesicular cysts which contained non-drainable material and were complicated by spontaneous intrabiliary rupture, secondary cystobiliary fistulas, cyst infection, or obstructed portal or hepatic veins; and two patients with large univesicular cysts and a ruptured laminated membrane, one obstructing the portal and hepatic veins and one a suspected cystobiliary fistula. The methods used, termed PEVAC (percutaneous evacuation of cyst content), involved the following steps: ultrasound guided cyst puncture and aspiration of cyst fluid to release intracystic pressure and thereby to avoid leakage; insertion of a large bore catheter; aspiration and evacuation of daughter cysts and endocyst by injection and reaspiration of isotonic saline; cystography; injection of scolecidals only if no cystobiliary fistula was present; external drainage of cystobiliary fistulas combined with endoprosthesis or sphincterotomy; catheter removal after complete cyst collapse and closure of the cystobiliary fistula. In all 12 patients initial cyst size was 13.1 (6-20) cm (mean (range)). At follow up 17.9 (4-30) months after PEVAC, seven cysts had disappeared and five cysts had decreased to 2.4 (1-4) cm (p=0.002). In eight patients with multivesicular cysts, a cystobiliary fistula, and infection, cyst size was 12.5 (6-20) cm, catheter time 72.3 (28-128) days, and hospital stay 38.1 (20-55) days. At 17.3 (4-28) months of follow up, six cysts had disappeared and in two cysts residual size was 1 and 2.9 cm, respectively (p=0.012). In four patients without a cystobiliary fistula, cyst size was 14.4 (12.7-16) cm, catheter time 8.8 (3-13) days, and hospital stay 11.5 (8-14) days. At 19.3 (9-30) months of follow up, one cyst had disappeared and three cysts were 85 (69-94)% smaller (2.2 (1-4) cm) (p=0.068). PEVAC is a safe and effective method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material.


Artificial liver: review and Cedars-Sinai experience.
During the past decade, whole organ transplantation has become the only clinically effective method of treating fulminant hepatic failure and chronic liver failure due to specific genetic, hepatocellular, and anatomic defects of liver function. However, wider application of liver transplantation is restricted by shortage of organ donors, high cost, relatively high morbidity, and need for life-long immunosuppression. As a result, investigators have attempted to develop alternative methods to treat liver insufficiency. These ranged from use of plasma exchange to utilization of detoxification columns and extracorporeal devices loaded with various liver tissue preparations. Recently, advances in hepatocyte isolation and culture techniques, improved understanding of hepatocyte-matrix interactions, availability of new biomaterials, improved hollow-fiber technology, and better understanding of flow and mass transport across semipermeable membranes have resulted in the development of a new generation of liver assist devices. Some of these devices, including the one developed by the authors, are currently being tested in the clinical setting. In this paper, the past experience with liver support systems is reviewed, the present status of the field is critically examined, and the results of a phase I clinical trial with the bioartificial liver, utilizing primary porcine hepatocytes, are summarized.