Successful resolution of hyperammonemia following hematopoietic cell transplantation with directed treatment of Ureaplasma parvum infection.
Hyperammonemia following hematopoietic cell transplantation (HCT) has been characterized as idiopathic and is associated with a very high mortality. A causal relationship between Ureaplasma infection and hyperammonemia in immunocompromised lung transplant recipients has recently been described. We document the first case of hyperammonemia following HCT associated with Ureaplasma parvum. The initiation of appropriate antibiotics resulted in rapid resolution of hyperammonemic encephalopathy and eradication of the implicating organism.


Hormonal therapy in a patient with ovarian agenesis and possible SLE: a choice to be made.
Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives.


Comparison of Esophagectomy outcomes between a National Center, a National Audit Collaborative, and an International database using the Esophageal Complications Consensus Group (ECCG) standardized definitions.
The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data from the Irish National Center (INC) with both published benchmark studies. All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied, with data recorded prospectively and entered onto a secure online database (Esodata.org). 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%,nrespectively. Anastomotic leak rate was 5.4%, pneumonia 18.2%, respiratory failure 10%, ARDS 2.7%, atrial dysrhythmia 22.8%, recurrent nerve injury 3%, and delirium in 5% of patients. Compared with both ECCG and DUCA, where MIE constituted 47 and 86% of surgical approaches, respectively, overall complications were similar, as were severity of complications; however, anastomotic leak rate was several-fold less, and mortality was significantly lower (P < 0.001). In this consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publications, a low mortality and anastomotic leak rate were the key differential findings. Although not risk stratified, the severity of complications from this 'open' series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.


MR imaging in aneurysmal bone cyst of the orbit.
Aneurysmal bone cyst is a benign fibro-osseous lesion usually described in the long bones. Intraorbital aneurysmal bone cyst is a rare clinical entity with an entirely different outcome and prognosis as compared to the usual pediatric orbital tumors. The authors report magnetic resonance imaging (MRI) features of an orbital mass lesion in a 4-year-old child who presented with painless proptosis of right eye. Characteristic MRI findings led to a suspicion of an aneurysmal bone cyst that was totally excised via a right frontotemporal craniotomy. Appreciation of characteristic MRI features can be of extreme help for appropriate diagnosis and management of this rare entity.


[Views from Dordogne, and the moon, on suicide].
Death-rate by suicide in Dordogne, department of Aquitaine (France), remains above the national average: 25.4 for 100000 inhabitants in Dordogne per year between 1990 and 1993, against 20.4 in France between 1989 and 1991. They are mostly old peasants of the west and the north of the department, and rural people in their thirties, who kill themselves. But the frightful high rate of suicides registered from 1975 to 1985 (31.8 in Dordogne between 1980 and 1982, against 25.3 in France for the same period), and which hit mostly young adults and the population around the town of Nontron, appears reduced. These suicides express, under the pressure of contemporary upset of the occidental society, the old crisis of abandonment of the rural areas in crispation. The most fragile succumb- and not only in the Perigord. Moreover, the suicides are here more important in September and in January. The sociological explanation of G. Masterton (1991) is plausible. The rates of suicides are also studied according to the lunar months. In Dordogne, the maximum and minimum rates of suicides are situated every year in two consecutive lunar phases. Further, these values are scheduled from one year to another, alternatively in the ascending period of the moon and then, in the descending period. Lastly, mathematic analysis of the suicides registered in the whole of 4 similar french departments (stepped according their latitude), during 2 years (1991-1992) and at the time of the first 3 days of each lunar phase, reveals that their rate is significantly lower in Full Moon than in the First Quarter period; this is equally true in the department of Maine and Loire. Further, Ph. Brosseau had shown (1987) that the French dies less in Full Moon, and more in New Moon period. The Full Moon period seems to protect the fragile subjects against their own death.


Successful management of a cesarean scar defect with dehiscence of the uterine incision by using wound lavage.
Cesarean scar defects (CSDs) that can be visualized using transvaginal ultrasonography (TVUS) may cause prolonged menstruation, irregular genital bleeding, and secondary infertility; surgical repair is sometimes necessary. We present a case of CSD, with dehiscence of the uterine incision, which was managed using wound lavage. A 38-year-old woman (gravida 4, para 4) had delivered her third and fourth children by cesarean section. Upon the resumption of menstruation, 9 months after her second cesarean section, she demonstrated prolonged menstruation and the presence of a menstrual fistula due to dehiscence of the cesarean section incision from the myometrium to the serosa. We treated the defect by lavaging with a physiological saline solution. After lavaging the wound 3 times, spontaneous healing of the dehiscent muscle layer was successfully achieved. The treatment was complication-free and the healing of the muscle layer has been maintained for more than 8 months.


Depression but not seizure factors or quality of life predicts suicidality in epilepsy.
The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed.


Intravenous and oral cyclophosphamide pulse therapy in rheumatic diseases: side effects and complications.
Twenty five patients (12 with systemic lupus erythematosus, 6 with Wegener's granulomatosis, and 7 with miscellaneous rheumatic diseases) who had been on intravenous or oral cyclophosphamide pulse therapy for more than 3 months were evaluated for safety of treatment. Side effects were reported by 20 patients (80%), mainly nausea (17 patients, 68%). Complications were observed in 13 patients (52%), of whom 6 had severe infections (24%). Oral cyclophosphamide given in repeated low dose pulses (5 mg/kg for 3 consecutive days) is better tolerated with regard to nausea than intravenous administration. The use of cyclophosphamide therapy is recommended in patients with disease that does not respond to conventional regimens, although the attending physician should be aware that infections may appear at any time during treatment, and effective prophylaxis against nausea is required.


No evidence of mitochondrial abnormality in skeletal muscle of patients with iron-deficient anaemia.
Patients with iron deficiency anaemia complain of decreased exercise capacity. We asked whether this is due to defective oxidative ATP synthesis in skeletal muscle as a consequence of reduced blood oxygen content and/or intrinsic mitochondrial abnormalities. We used 31P magnetic resonance spectroscopy to examine skeletal muscle bioenergetics in iron-deficient patients and in age- and sex-matched controls. The patients were recruited from the primary care population. We studied seven symptomatic female iron-deficient patients (aged 32-70 years) with haemoglobin (Hb) concentration, [Hb], 8.0 g dl-1. Six had menorrhagia, the cause in the seventh patient remained undiagnosed. Results were compared with those of 8 healthy female controls (aged 25-48 years) with mean [Hb] 13.7 g dl-1. The right calf muscle was by studied 31P magnetic resonance spectroscopy in a 1.9 T super-conducting magnet. We measured the intracellular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), adenosine triphosphate (ATP) and the intracellular pH at rest, during plantar flexion exercise and during recovery from exercise. Exercise duration was reduced in the patients, yet end-exercise PCr/(PCr+Pi) was higher and adenosine diphosphate (ADP) lower than in controls. After exercise, initial PCr recovery was slowed but this was probably because of the lower cytosolic ADP concentration. Mitochondrial ATP synthesis was not limited by oxygen supply or an intrinsic mitochondrial defect. Therefore, the reduced exercise capacity seen in iron deficiency could be due to central causes and not to skeletal muscle metabolic abnormalities.


How to establish and sustain a joint venture in China.
Joint ventures with Chinese companies provide one of the most effective ways for international companies to establish a foothold in the booming Chinese economy. The benefits, opportunities and challenges of establishing a joint venture are explored here. Current partnering trends and successful Sino-foreign joint ventures in the fast-growing medical device industry in China are also highlighted.


Immunohistochemical detection of ras oncogene p21 product in liver cirrhosis and hepatocellular carcinoma.
Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody RAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen, whereas hepatocytes of cirrhotic nodules from 80 of 92 HCC patients (87.4%), and 10 of 32 patients without HCC (59.4%) were positive. This difference was statistically significant (p less than 0.05). The incidence of p21 expression by hepatocytes was significantly higher in macronodular cirrhotic patients than in those with micronodular cirrhosis (p less than 0.05) and tended to be higher in those positive for hepatic hepatitis B virus markers than in those that were negative (p less than 0.1). All 16 patients with liver cell dysplasia, and 17 of 18 with adenomatous hyperplasias showed increased expression of p21 antigen. In HCC it was detected on tumor cells of 63 of 101 patients (62.4%). Characteristically, its expression in well-differentiated HCC was mild and uniformly diffuse, and in moderately differentiated tumors was markedly heterogeneous in both intensity and distribution, whereas no expression was observed in cells of poorly differentiated HCC. These observations suggest that elevated ras p21 antigen expression is important in the development of both cirrhotic nodules and HCC, but that after tumor development, its sustained elevation is no longer necessary for cell proliferation and progression through the grades of anaplasia.


Assessment of fatigue in cancer patients.
Increased recognition of the problem of fatigue in cancer patients can be attributed, in part, to the development of measures that have provided researchers with the tools necessary for quantifying and characterizing fatigue and exploring its etiology and treatment. Although a consensus regarding the definition of fatigue is lacking, there is general agreement that it is a subjective and multidimensional phenomenon whose assessment requires the use of self-report methods. Consistent with this view, several multidimensional measures of fatigue have been developed and validated for use with cancer patients. These measures differ considerably in their format and content and, as with the definition of fatigue, there is no consensus at the present time regarding the dimensional structure of fatigue. In addition to measuring fatigue on a continuum along one or more dimensions, it may also be possible to assess a clinical syndrome of cancer-related fatigue. Criteria for assessing fatigue in this manner have been proposed and are currently undergoing evaluation. Despite the progress that has been made, there are several important unresolved issues in the assessment of fatigue in cancer patients. These include how to distinguish fatigue from depression, how to use self-reports of fatigue in clinical decision-making, how to capture temporal changes in fatigue, and how best to address the continuing lack of consensus regarding the conceptualization and measurement of fatigue.


Copper regulation and homeostasis of Daphnia magna and Pseudokirchneriella subcapitata: influence of acclimation.
This study aimed to evaluate (1) the capacity of the green alga Pseudokirchneriella subcapitata and the waterflea Daphnia magna to regulate copper when exposed to environmentally realistic copper concentrations and (2) the influence of multi-generation acclimation to these copper concentrations on copper bioaccumulation and homeostasis. Based on bioconcentration factors, active copper regulation was observed in algae up to 5 microg Cu L(-1) and in daphnids up to 35 mug Cu L(-1). Constant body copper concentrations (13+/-4 microg Cu g DW(-1)) were observed in algae exposed to 1 through 5 microg Cu L(-1) and in daphnids exposed to 1 through 12 microg Cu L(-1). At higher exposure concentrations, there was an increase in internal body copper concentration, while no increase was observed in bioconcentration factors, suggesting the presence of a storage mechanism. At copper concentrations of 100 microg Cu L(-1) (P. subcapitata) and 150 microg Cu L(-1) (D. magna), the significant increases observed in body copper concentrations and in bioconcentration factors may be related to a failure of this regulation mechanism. For both organisms, internal body copper concentrations lower than 13 microg Cu g DW(-1) may result in copper deficiency. For P. subcapitata acclimated to 0.5 and 100 microg Cu L(-1), body copper concentrations ranged (mean+/-standard deviation) between 5+/-2 microg Cu g DW(-1) and 1300+/-197 microg Cu g DW(-1), respectively. For D. magna, this value ranged between 9+/-2 microg Cu g DW(-1) and 175+/-17 microg Cu g DW(-1) for daphnids acclimated to 0.5 and 150 microg Cu L(-1). Multi-generation acclimation to copper concentrations >or =12 microg Cu L(-1) resulted in a decrease (up to 40%) in body copper concentrations for both organisms compared to the body copper concentration of the first generation. It can be concluded that there is an indication that P. subcapitata and D. magna can regulate their whole body copper concentration to maintain copper homeostasis within their optimal copper range and acclimation enhances these mechanisms.


In vitro and in vivo availability of commercial prednisone tablets.
A three-way crossover bioavailability study was performed using nine adult male volunteers with three different commercial prednisone tablets. Plasma samples were assayed for prednisolone, the active metabolite of prednisone, by a radioimmunoassay method. Statistical analysis showed significant differences in the rate of appearance of prednisolone in plasma but not in the amount converted to prednisolone. The results suggest that differences in in vivo rates of appearance of prednisolone in plasma correlate with in vitro rates of dissolution.


The complete mitochondrial genome of Eoscarta assimilis (Hemipera: Cercopidae) and phylogenetic analysis of Cercopidae.
The complete mitochondrial genome (mitogenome) of Eoscarta assimilis (Uhler, 1896) was sequenced in the current paper. The total length of the mitogenome is 17,231 bp and it consists of 37 genes including 22 transfer RNA (tRNAs), 13 protein-coding (PCGs) and 2 ribosomal RNA (rRNAs). The 13 PCGs initiated with the start codon ATN, but ND4 started with TTG. All of the PCGs ended with TAA, apart from COX3 which terminated by incomplete TAG. A ML tree based on sequences of 15 complete mitogenomes (13 Cercopidae and 2 outgroup) suggests that E. assimilis is more closely related to the genus Callitettix. The phylogenetic analysis supports the monophyly of the family Cercopidae and the genus Cosmoscarta, and the paraphyly of the subfamily Callitettixinae. This mitogenome information for E. assimilis could facilitate future evolutionary studies to related insects.


Immediate breastfeeding and skin-to-skin contact during cesarean section decreases maternal oxidative stress, a prospective randomized case-controlled study.
Immediate skin-to-skin contact (ISSC) and early breastfeeding are recommended for the wellbeing of the neonate. In this study, we aimed to evaluate the effect of ISSC and early breastfeeding on maternal oxidative stress and postoperative pain. A total of 90 patients were randomized into two groups based on the timing of skin-to-skin contact and breastfeeding. Group 1 (n = 45) was provided ISSC and breastfeeding in the operating room during the cesarean section (C/S). Group 2 (n = 45) breastfed their babies 1 h after the C/S. As markers of oxidative stress, maternal serum levels of total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress indices (OSI) were evaluated. Maternal oxytocin levels and the relation between these parameters and postoperative pain were also evaluated. The postoperative TAS levels were significantly higher, whereas TOS and OSI levels were lower in Group 1 than Group 2. Negative correlations between oxytocin level and postoperative TOS and OSI were observed, as was a positive correlation between oxytocin level and postoperative TAS. The effect of ISSC and early breastfeeding on mothers was documented for the first time in this study. Our results demonstrated ISSC and early breastfeeding during C/S reduce maternal oxidative stress.


Application of 3D Slicer Combined With Simple Coordinate Method in Operation of Cerebral Arteriovenous Malformations in Functional Areas.
The authors report a case of intracranial arteriovenous malformation in functional areas, initially presenting with symptomatic epilepsy was surgically excised by the Neurosurgery Department of our hospital. The patient's head computed tomography, magnetic resonance imaging, and digital subtraction angiography examination suggested intracranial arteriovenous malformations in the left frontal functional area. A preoperative 3D-reconstruction technique was used to reconstruct the malformed vascular mass, supplying arteries, draining veins, and precise surgical resection was performed. Postoperative pathology indicated vascular malformation. No seizures occurred after surgery. There was no further neurological impairment. Preoperative use of image postprocessing techniques can facilitate precise surgical resection of brain arteriovenous malformations. Three-dimensional Slicer in cerebral arteriovenous malformations in functional areas not only shortened the preoperative planning time but also improved the efficiency of the surgery. Reduce the incidence of postoperative complications. It is helpful for further popularization and application.


Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults.
The effect of daily supplementation of 800 mg dl alpha-tocopheryl acetate for 30 d on general health, nutrient status, hepatic and renal function, intermediary metabolism, hematological status, plasma nutrients and antioxidant status, thyroid hormones, and urinary creatinine concentrations was studied in 32 healthy elderly (> 60 y) people who participated in a double-blind, placebo-controlled, residential trial. The subjects reported no side effects due to the supplements. Supplementation had no effect on body weight, plasma total protein, albumin, glucose, total cholesterol and triglycerides, conjugated and unconjugated bilirubin, alkaline phosphatase, indicators of hepatic and renal function, hematologic status, thyroid hormones, or serum and urinary creatinine concentrations and creatinine clearance. Supplementation did cause a significant increase in serum vitamin E, and a small (5%) but significant (P < 0.05) increase in plasma zinc in the vitamin E-supplemented group. Thus, short-term supplementation with 800 mg vitamin E/d has no adverse effect on healthy older adults.


Apoptotic effect of rituximab on peripheral blood B cells in rheumatoid arthritis.
Rituximab (RTX) has proven efficacious in the treatment of rheumatoid arthritis (RA). Herein, we assessed the apoptosis-inducing capability of RTX in vitro on RA peripheral blood B-cell subsets and also compared the effects of RTX on B cells from rheumatoid factor-positive (RF+) and RF- patients. The likely relevance of B cells in disease was assessed by measuring B-cell-modulating serum cytokines. Peripheral blood B cells were isolated and cultured with the presence or absence of RTX. The levels of apoptosis within the naïve, memory and IgD+CD27+ B-cell subpopulations were determined by cytofluorometric analysis and caspase 3/7 assays. Levels of serum cytokines were measured with a multiplex cytokine array system. RTX induced significant apoptosis in all B-cell subsets in both RA and controls. In naïve and memory B cells from RA patients, RTX induced significantly higher levels of apoptosis than in controls. RTX induced apoptosis of B cells in RF+ and RF- patients. Serum levels of interleukin-1beta (IL-1beta), IL-4, IL-10 and IL-13 were profoundly increased in RF+ patients compared to RF- patients and controls. Although our cohort was small (10 RA patients), the data suggest that RTX induces apoptosis in all investigated subsets of B cells from RA patients. Interestingly, memory B cells from RA patients were more sensitive to RTX than memory cells from normal controls, suggesting that the delay in treatment response to RTX observed in clinical trials may be due in part to memory cell depletion. The apoptotic effects of RTX were similar in RF+ and RF- patients, but serum levels of B-cell-activating cytokine levels were only elevated in RF+ but not RF- patients. These data suggest that RTX is less effective in RF- RA because B cells play a less significant role in RA pathogenesis in RF- patients.


The untapped potential of targeting NRF2 in neurodegenerative disease.
Since its initial discovery almost three decades ago, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to regulate a host of downstream transcriptional responses and play a critical role in preventing or promoting disease progression depending on the context. Critically, while the importance of proper nuclear factor erythroid 2-related factor 2 function has been demonstrated across a variety of pathological settings, the ability to progress NRF2-targeted therapeutics to clinic has remained frustratingly elusive. This is particularly true in the case of age-related pathologies, where nuclear factor erythroid 2-related factor 2 is a well-established mitigator of many of the observed pathogenic effects, yet options to target this pathway remain limited. Along these lines, loss of nuclear factor erythroid 2-related factor 2 function has clearly been shown to enhance neuropathological outcomes, with enhancing nuclear factor erythroid 2-related factor 2 pathway activation to prevent neurodegenerative/neurological disease progression continuing to be an active area of interest. One critical obstacle in generating successful therapeutics for brain-related pathologies is the ability of the compound to cross the blood brain barrier (BBB), which has also hampered the implementation of several promising nuclear factor erythroid 2-related factor 2 inducers. Another limitation is that many nuclear factor erythroid 2-related factor 2 activators have undesirable off-target effects due to their electrophilic nature. Despite these constraints, the field has continued to evolve, and several viable means of targeting nuclear factor erythroid 2-related factor 2 in a neuropathological context have emerged. In this perspective, we will briefly discuss the key findings and promising therapeutic options that have been discovered to date, as well as highlight emerging areas of NRF2-neurodegeneration research that provide hope for successfully targeting this pathway in the future.


Rapid Model to Evaluate the Anti-Obesity Potential of a Combination of Syzygium aromaticum (Clove) and Cuminun cyminum (Cumin) on C57BL6/j Mice Fed High-Fat Diet.
Several studies have demonstrated that the phytochemical contents of plants are potential anti-obesity agents. In this study we examine the effect of using a combination of dry buttons from Syzygium aromaticum and seeds from Cuminum cyminum (CC) on C57BL6/J mice induced with obesity via high-fat-diet (HFD). The aim of this study is to demonstrate that the method proposed in the study reduced obesity significantly after several weeks of experimentation. The extract from both plants was extracted using ultrasound to enhance the extraction of phytochemicals. Optimum extraction conditions were obtained with ethanol as follows: 50:50 v/v water with an ultrasound power of 300 W, and ultrasonication time of 30 minutes. The simultaneous administration of the CC extract in HFD for 5 weeks led to the regulation of lipid profiles (cholesterol and triglycerides), reduction of food intake, weight gain, adipose tissue and liver weight. Findings obtained by this obese model indicate that CC extract can prevent obesity. Compared with the traditional 16 weeks method (8 weeks to get fat, and 8 weeks to lose weight), similar results were obtained in the present study obese model in less time of experimentation.


Shotgun bisulfite sequencing of the Betula platyphylla genome reveals the tree's DNA methylation patterning.
DNA methylation plays a critical role in the regulation of gene expression. Most studies of DNA methylation have been performed in herbaceous plants, and little is known about the methylation patterns in tree genomes. In the present study, we generated a map of methylated cytosines at single base pair resolution for Betula platyphylla (white birch) by bisulfite sequencing combined with transcriptomics to analyze DNA methylation and its effects on gene expression. We obtained a detailed view of the function of DNA methylation sequence composition and distribution in the genome of B. platyphylla. There are 34,460 genes in the whole genome of birch, and 31,297 genes are methylated. Conservatively, we estimated that 14.29% of genomic cytosines are methylcytosines in birch. Among the methylation sites, the CHH context accounts for 48.86%, and is the largest proportion. Combined transcriptome and methylation analysis showed that the genes with moderate methylation levels had higher expression levels than genes with high and low methylation. In addition, methylated genes are highly enriched for the GO subcategories of binding activities, catalytic activities, cellular processes, response to stimulus and cell death, suggesting that methylation mediates these pathways in birch trees.


[Psychotherapy combined with use of the vacuum constrictive device for erectile impotence].
Psychotherapy and the vacuum constriction device were used to treat 125 men with different types of erectile impotence. 58 came with their wives (Group 1), the wives of 49 did not agree to come (Group 2), and 18 men did not want to inform their wives of their condition (Group 3). Age ranges and means for the 3 groups were, respectively: 26-82 (56.2 +/- 2.8); 24-80 (53.1 +/- 2.2); and 25-76 (59.3 +/- 2.7). All groups received 6-10 combined treatments, and in all 3 groups there was improvement in the objective parameters of sexual function (nocturnal penile tumescence, penile brachial index, maximal penile rigidity). But only in Group I was there improvement in subjective parameters (spontaneous erection, adequate coitus without the vacuum device). After treatment, successful coitus, with or without use of the device, was achieved in 91.3% of Group I, 69.3% of Group II and 50.0% of Group III. These results indicate that regardless of type of erectile impotence, the greatest degree of success is achieved when the patient comes for treatment together with his wife.


Arthroscopic Bankart suture repair.
The purpose of this paper was to report our experience with an arthroscopic technique of repair for the Bankart lesion following shoulder instability. Twenty-seven patients (average age, 21.7 years) were followed for an average of 36 months after arthroscopic suture stabilization of anterior shoulder instability. Patients were excluded if instability was multidirectional or voluntary and if there was radiographic evidence of a significant loss of glenoid bone stock. Clinical evaluation using a functional grading system showed that 10 patients were rated as excellent, 5 good, and 12 poor. Fourteen patients returned to their previous level of activity. There were 12 patients rated as failed; all had recurrent instability of the shoulder. Success was associated with a period of immobilization of 3 weeks or longer and a history of acute injury, especially subluxation. Failures were associated with shorter immobilization periods after surgery and in patients who had recurrent dislocations. The younger patient, who may not have complied with the immobilization protocol, also seemed to be associated with failure. Contact sports seems to leave a patient at high risk for recurrence. We recommend caution in the use of arthroscopic procedures for the competitive athlete in whom a second surgery and rehabilitation might mean loss of more sports participation.


A clinical trial of cimetidine in acute pancreatitis.
A prospective randomized clinical trial was carried out to evaluate the efficacy of cimetidine in the treatment of acute pancreatitis. One hundred and sixteen patients with a clinical diagnosis of acute pancreatitis and an elevated serum amylase level were included in the study. All patients were treated with fluids, given intravenously, analgesia and nasogastric tube suction, if required. In addition, on a random basis, 52 received cimetidine given intravenously and 64 did not. There were no significant differences in the clinical courses of the two groups.


Treatment strategies for Behçet's disease.
Behçet's disease (BD) is a multisytemic vasculitis characterized by oral and genital ulceration, other skin lesions, uveitis and manifestations affecting the blood vessels, CNS and gastrointestinal system. It is rare in the Western world but is frequent in the Middle and Far East. The aim of this review is to discuss treatment strategies in BD. These might vary between simple reassurance and a combination of immunosuppressives. A systematic literature search was done using the Cochrane and Medline databases in June 2008. The EULAR recommendations for the management of BD were also taken into account. The last two decades have witnessed considerable improvement in eye disease and musculoskeletal involvement. However, the treatment of thrombophlebitis, CNS, and gastrointestinal manifestations remains problematic.


How to write a patient case report.
Guidelines for writing patient case reports, with a focus on medication-related reports, are provided. The format of a patient case report encompasses the following five sections: an abstract, an introduction and objective that contain a literature review, a description of the case report, a discussion that includes a detailed explanation of the literature review, a summary of the case, and a conclusion. The abstract of a patient case report should succinctly include the four sections of the main text of the report. The introduction section should provide the subject, purpose, and merit of the case report. It must explain why the case report is novel or merits review, and it should include a comprehensive literature review that corroborates the author's claims. The case presentation section should describe the case in chronological order and in enough detail for the reader to establish his or her own conclusions about the case's validity. The discussion section is the most important section of the case report. It ought to evaluate the patient case for accuracy, validity, and uniqueness; compare and contrast the case report with the published literature; derive new knowledge; summarize the essential features of the report; and draw recommendations. The conclusion section should be brief and provide a conclusion with evidence-based recommendations and applicability to practice. Patient case reports are valuable resources of new and unusual information that may lead to vital research.


Acoustofluidic scanning fluorescence nanoscopy with large field of view.
Nanoscale fluorescence imaging with a large-field view is invaluable for many applications such as imaging of subcellular structures, visualizing protein interaction, and high-resolution tissue imaging. Unfortunately, conventional fluorescence microscopy has to make a trade-off between resolution and field of view due to the nature of the optics used to form an image. To overcome this barrier, we have developed an acoustofluidic scanning fluorescence nanoscope that can simultaneously achieve superior resolution, a large field of view, and enhanced fluorescent signal. The acoustofluidic scanning fluorescence nanoscope utilizes the super-resolution capability of microspheres that are controlled by a programable acoustofluidic device for rapid fluorescent enhancement and imaging. The acoustofluidic scanning fluorescence nanoscope can resolve structures that cannot be achieved with a conventional fluorescent microscope with the same objective lens and enhances the fluorescent signal by a factor of ~5 without altering the field of view of the image. The improved resolution with enhanced fluorescent signal and large field of view via the acoustofluidic scanning fluorescence nanoscope provides a powerful tool for versatile nanoscale fluorescence imaging for researchers in the fields of medicine, biology, biophysics, and biomedical engineering.


Apoptosis is restricted to the thalamus in thiamine-deficient rats.
Thiamine deficiency (TD) produces lesions in the thalamus, mamillary and medial geniculate nuclei, and inferior colliculus. To clarify the pathogenesis of these lesions, we examined the occurrence of hallmarks of apoptosis following TD in rat brain. Histological assessment showed apoptotic cells in the thalamus and medial geniculate nucleus but not in the inferior colliculus. We used terminal deoxynucleotidyl transferase-mediated deoxyuridine (dUPT)-biotin nick-end labelling (TUNEL) and gel electrophoresis to demonstrate that TD is associated with apoptotic cell death. In the thalamus, DNA fragmentation appeared from day 14 of deficiency and preceded the appearance of ataxia. The inferior colliculus and mamillary nucleus were without electrophoretic DNA fragments, and only rare TUNEL-positive labelling was observed. This model shows a rare combination of both apoptosis and necrosis in the same lesioned brain.


Medical Management of Chronic Subdural Hematoma.
Chronic subdural hematoma (CSDH) is a commonly encountered disease in the field of neurosurgery, typically resulting from head trauma. Several medical treatments have been introduced to manage patients with CSDH though surgical drainage is the main strategy to manage symptomatic patients. This review is aimed to meticulously examine contemporary pharmacological approaches, based on a thorough understanding of CSDH pathophysiology. Finally, the review offers a glance into future perspectives to enhance the management of CSDH.


Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study.
Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with <or=3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. At the end of week 4, 54% of patients achieved serum phosphorus control at dosages <or=3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden.


Phosphorothioate DNA Stabilized Fluorescent Gold and Silver Nanoclusters.
Unmodified single-stranded DNA has recently gained popularity for the templated synthesis of fluorescent noble metal nanoclusters (NCs). Bright, stable, and biocompatible clusters have been developed primarily through optimization of DNA sequence. However, DNA backbone modifications have not yet been investigated. In this work, phosphorothioate (PS) DNAs are evaluated in the synthesis of Au and Ag nanoclusters, and are employed to successfully template a novel emitter using T15 DNA at neutral pH. Mechanistic studies indicate a distinct UV-dependent formation mechanism that does not occur through the previously reported thymine N3. The positions of PS substitution have been optimized. This is the first reported use of a T15 template at physiological pH for AgNCs.


Some immunological considerations in liver transplantation.
Immunological considerations of special interest in liver transplantation are examined. It is concluded that liver transplants between human beings generate typical rejection reactions although they may, overall, be somewhat more mild than those encountered in transplanted kidneys and hearts. This is the case in some animals for reasons which are not yet clear. There is evidence that the transplanted liver can suffer immune attack better than other organs. Whether graft-vs.-host activity is of clinical importance is uncertain. The advent of cyclosporin immunosuppression has improved the outlook for liver recipients but multiple complications of immunosuppression will still occur and demand skillful management.


Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.
A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity.


Immunohistochemical identification of infiltrating mononuclear cells in tubulointerstitial nephritis associated with Sjögren's syndrome.
Using monoclonal antibodies, immunoperoxidase analysis was performed on eight renal biopsy samples obtained from patients with Sjögren's syndrome-associated tubulointerstitial nephritis. In all cases the interstitial infiltrates were predominantly CD5-positive T-cells (mean 66%), whereas both B-cell (CD19-positive) and monocyte (CD15-positive) populations participated to a lesser degree. CD16-positive NK/K cells were rarely encountered. The CD4/CD8 ratio was consistently higher than 1.0 (mean 2.08). The lymphocytes which invaded the tubular epithelial cells to present a feature of tubulitis were CD8-positive, suggesting that they were cytotoxic T-cells. These results were in general accord with those obtained in the salivary glands of patients with Sjögren's syndrome. It was thus concluded that the same immunological process was probably operative in the renal tubulointerstitial tissue as in the salivary glands to induce the characteristic tissue changes of Sjögren's syndrome.


The effect of variation of residual ridge angle on partial denture abutment tooth movement.
Using a laboratory model simulating a free-end saddle partial denture situation, the effect of variation of the angulation of the crest of the residual alveolar ridge to the horizontal on movement of the abutment tooth and saddle was observed. It was found that the inclination of the residual ridge affected the direction and magnitude of abutment tooth movement. The direction of abutment tooth movement was not related to the position of the occlusal rest. However, the magnitude of saddle and abutment tooth movement is affected by the design of the clasp used.


Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, affecting almost 1% of world population. Although the exact cause of RA is not known but the complex interaction between inflammatory mediators like tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) is accountable for cartilage destruction in joints. Gold is used for arthritis treatment since long without knowing its mechanism of action. Hence, the present study was designed to assess antiarthritic activity of nanogold (AuNGs) in collagen-induced arthritic (CIA) rat model by virtue of decreasing inflammatory mediators and oxidative stress. After induction CIA rats were treated with AuNGs in phosphate buffer at a dose of 20 μg/kg body weight for 20 days and found a significant decrease in the level of inflammatory mediators like TNF-α, IL-1β, COX-2 and transcription factor NF-kB (Nuclear factor-kB), which was found to be elevated in CIA rats. Additionally imbalance in oxidant and antioxidant status were determined and perceived that AuNGs remarkably attenuates the imbalance in level of antioxidant and oxidant near to normal. In consistent to biochemical results, mRNA expression of NF-kB, TNF-α, COX-2, and iNOS were also up-regulated in CIA rats, which were considerably down regulated by AuNGs treatment. These findings were positively correlated with the histological results of joints, displayed reduced inflammation and bone erosion in treated group. This study demonstrates the ability of AuNGs to ameliorate production of inflammatory mediators and oxidative stress in CIA rats. Induction of arthritis in rats showed increased inflammation, which activate the transcription factor NF-kB through activation of of IkB kinases (IKK) and ubiquination/proteosome degradation of IKB and transportation of activated NF-kB from cytoplasm to nucleus. In nucleus activated NF-kB bind to the promoter region of target gene and up regulate the production of pro-inflammatory cytokines, COX-2 and other inflammatory mediators that leads to cartilage destruction. AuNGs inhibit the activation of NF-kB and other inflammatory mediators and attenuate inflammation and cartilage destruction. COX-2: cyclooxygenase-2; IKK: IkB kinases; IKB: I Kappa B; IL-1β: interleukin-6; IL-6: interleukin-6; iNOS: inducible nitric oxide synthase; NF-kB: nuclear transcription factor kappa B; ROS: reactive oxygen species; TNF-α: tumour necrosis factor-alpha.


Diet-induced arteriopathies in the rabbit aorta and oral vasculature.
Advanced atherosclerosis in the form of fibro-fatty intimal plaques has been produced in the rabbit aorta and oral vasculature (labial, lingual, gingival, palatal, periodontal and alveolar arteries) by dietary means. The animals were fed a hypercholesteremic diet and a normocholesteremic diet on alternate months for two years. In the aorta and in many of the oral vessels, the formation of the intimal atheromas was paralleled by a degeneration of the tunica media. The lingual arteries rivaled the aorta and coronary arteries in vulnerability to the diet-induced arteriopathies.


The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration.
MicroRNAs (miRNAs) are highly conserved molecules that regulate protein levels post-transcriptionally. Aberrant miRNA expression presents in various musculoskeletal disorders, such as osteoporosis, osteoarthritis and rheumatoid arthritis. The expression levels of miRNAs are characterized by endogenous properties and tissue specificity. This raises the possibility that miRNAs could serve as useful clinical biomarkers in the diagnosis of certain diseases. Intervertebral disc degeneration (IDD) is one of the major causes of back pain, and a process characterized by a cascade of molecular, cellular, biochemical and structural changes. The presence of dysregulated miRNA expression in patients with disc degeneration diseases indicates that miRNAs may play a vital role in the pathogenesis of IDD. Here, we provide an introduction of the roles of miRNAs in the process of IDD, and the prospective application of miRNAs as biomarkers for IDD. Copyright © 2017 John Wiley & Sons, Ltd.


Preventability of incident cases of tuberculosis in recently exposed contacts.
Contacts of tuberculosis (TB) cases are at risk for TB. If contact screening and intervention are effective, one would expect a reduced incidence of TB in contacts who have been screened. To measure the incidence of TB in contacts during a 2-year follow up, and to estimate the preventability of incident cases. A retrospective cohort study of 783 contacts screened in Victoria, Australia, in 1991. Contacts were matched with the TB registry for the following 2 years. Screening records were reviewed. The rate of TB in contacts was 511/100000 population/year for the first 2 years. In Poisson regression models the only significant variable predicting disease was skin test reaction size. Six of eight incident cases were potentially preventable, with a lowest achievable incidence rate of 128/100000/year. Contacts who underwent screening for TB through a state screening programme had a high incidence of TB during the 2 year follow up. Published rates of TB of 425-670/100000 in untreated contacts suggests that the Victorian screening programme had minimal impact on the natural history of disease progression. Intrinsic programme factors such as the appropriateness of the guidelines, adherence to guidelines and rates of preventive therapy need to be evaluated. The devolution of the TB programme in the 1980s also reduced its efficacy. Systematic assessment of screening programmes for efficacy and outcome is part of good public health practice.


An active-like structure in the unphosphorylated StyR response regulator suggests a phosphorylation- dependent allosteric activation mechanism.
StyR belongs to the FixJ subfamily of signal transduction response regulators; it controls transcription of the styABCD operon coding for styrene catabolism in Pseudomonas fluorescens ST. The crystal structure of unphosphorylated StyR is reported at 2.2 A resolution. StyR is composed of an N-terminal regulatory domain (StyR-N) and a C-terminal DNA binding domain (StyR-C). The two domains are separated by an elongated linker alpha helix (34 residues), a new feature in known response regulator structures. StyR-C is structured similarly to the DNA binding domain of the response regulator NarL. StyR-N shows structural reorganization of the phosphate receiving region involved in activation/homodimerization: specific residues adopt an "active-like" conformation, and the alpha4 helix, involved in dimerization of the homologous FixJ response regulator, is trimmed to just one helical turn. Overall, structural considerations suggest that phosphorylation may act as an allosteric switch, shifting a preexisting StyR equilibrium toward the active, dimeric, DNA binding form.


Effects of Supraphysiological Doses of Sex Steroids on Wheel Running Activity in Mice.
The regulatory mechanisms of physical activity are postulated to include environmental and biological/genetic factors. In particular, the sex steroids appear to have profound effects on wheel running in rodents. The purpose of this project was to investigate the effects of 17β-estradiol and testosterone on wheel running distance, duration, and speed in male and female C57BL/6J mice. The mice (N=46) were provided free access to running wheels interfaced with computers to track daily running distance, duration, and speed. Activity was assessed at baseline in intact mice, after surgical gonadectomy, and after replacement with either 17β-estradiol or testosterone. Upon removal of the gonads, physical activity levels were significantly reduced in both males and females. Distance (10-30% of baseline) and duration (20-47% of baseline) measures were most affected by the loss of endogenous steroids, while running speed (60-77% of baseline) though significantly reduced-decreased by a much lower magnitude. Testosterone replacement fully recovered running distance, duration, and speed to pre-surgical levels in both sexes (100% of baseline). Distance (30-42% of baseline) and duration (43-47% of baseline) were partially recovered by 17β-estradiol, but not to baseline levels. Speed (100% of baseline) was fully recovered by 17β-estradiol replacement in males and females. This study suggests that physical activity in mice is affected by endogenous steroids and can be altered by exogenous steroid replacement. The differences in the recovery abilities of 17β-estradiol and testosterone suggest that both estrogenic and androgenic pathways may be involved to variable degrees in activity regulation.


Calmodulin/calmodulin-dependent protein kinase II mediates SAAF-induced motility activation of ascidian sperm.
Ca2+-influx and membrane hyperpolarization by sperm-activating and -attracting factor (SAAF) released from the unfertilized egg of the ascidians Ciona cause a transient increase in cAMP, which triggers activation of sperm motility. We demonstrated here the presence of Ca2+-binding protein, calmodulin (CaM), and CaM-dependent kinase II (CaMKII) in the sperm. CaM antagonist, W-7, and CaMKII inhibitor, KN-93, suppressed SAAF-induced membrane hyperpolarization, increase in cAMP, and activation of sperm motility, but inactive analogues of W-7 and KN-93, namely W-5 and KN-92, respectively, did not. Subsequent addition of K+ ionophore, valinomycin, hyperpolarized the plasma membrane, increased cAMP, and conferred motility to the immotile sperm even in the presence of W-7 and KN-93. Addition of IBMX activated motility of sperm, which has been immobilized by W-7 and KN-93. These suggest that increased [Ca2+]i through influx of Ca2+ by SAAF binds to CaM to activate CaMKII. The activated CaMKII may cause membrane hyperpolarization to increase cAMP, which triggers the activation of sperm motility in Ciona.


Examining the FDA's oversight of direct-to-consumer advertising.
Our analysis examined the effects of the Food and Drug Administration's (FDA's) 1997 draft guidance regarding advertisements for prescription drugs broadcast directly to consumers. We found that although direct-to-consumer (DTC) advertising spending by pharmaceutical companies has increased, more than 80 percent of their promotional spending is directed to physicians. DTC advertising appears to increase the use of prescription drugs among consumers. The FDA's oversight has not prevented companies from making misleading claims in subsequent advertisements, and a recent policy change has lengthened the FDA's review process, raising the possibility that some misleading campaigns could run their course before review.


Long-term adaptation of pancreatic response by dogs to dietary fats of different degrees of saturation: olive and sunflower oil.
Mongrel dogs were fed, from weaning to 9 months of age, on one of two diets that differed only in the type of fat content (virgin olive oil or sunflower oil) to compare the composition of exocrine pancreatic secretion in the basal period and in response to food. In resting pancreatic flow, electrolytes and the specific activities of amylase, lipase and chymotrypsin were similar in both experimental groups. However, lipase and amylase outputs, and amylase and protein concentrations were significantly higher in the group fed on the diet rich in sunflower oil. Food intake was not followed by any change in flow-rate or electrolyte or protein content in the group given the diet rich in olive oil. Amylase activity and output were also lower in this group, as was lipase output, whereas activity and specific activity of chymotrypsin were lower in dogs fed on the diet containing sunflower oil. The differences traceable to the composition of the two types of dietary fat supplied may be related to the balance between factors that stimulate and inhibit pancreatic secretion.


Efficient compressed sensing reconstruction for 3D fluorescence microscopy using OptoMechanical Modulation Tomography (OMMT) with a 1+2D regularization.
OptoMechanical Modulation Tomography (OMMT) exploits compressed sensing to reconstruct high resolution microscopy volumes from fewer measurement images compared to exhaustive section sampling in conventional light sheet microscopy. Nevertheless, the volumetric reconstruction process is computationally expensive, making it impractically slow to use on large-size images, and prone to generating visual artefacts. Here, we propose a reconstruction approach that uses a 1+2D Total Variation (TV1+2) regularization that does not generate such artefacts and is amenable to efficient implementation using parallel computing. We evaluate our method for accuracy and scaleability on simulated and experimental data. Using a high quality, but computationally expensive, Plug-and-Play (PnP) method that uses the BM4D denoiser as a benchmark, we observe that our approach offers an advantageous trade-off between speed and accuracy.


Effect of an acidifying diet combined with zeolite and slight protein reduction on air emissions from laying hens of different ages.
The objectives of the study were to evaluate the effectiveness of a reduced-emission (RE) diet containing 6.9% of a CaSO(4)-zeolite mixture and slightly reduced CP to 21-, 38-, and 59-wk-old Hy-Line W-36 hens (trials 1, 2, and 3, respectively) on egg production and emissions of NH(3), H(2)S, NO, NO(2), CO(2), CH(4), and non-CH(4) total hydrocarbons as compared with feeding a commercial (CM) diet. At each age, 640 hens were allocated, randomly to 8 environmental chambers for a 3-wk period. On an analyzed basis, the CM diet contained 18.0, 17.0, and 16.2% CP and 0.25, 0.18, and 0.20% S in trials 1, 2, and 3, and the RE diet contained 17.0, 15.5, and 15.6% CP and 0.99, 1.20, and 1.10% S in trials 1, 2, and 3. Diets were formulated to contain similar Ca and P contents. Average daily egg weight (56.3 g), average daily egg production (81%), average daily feed intake (92.4 g), and BW change (23.5 g), across ages, were unaffected by diet (P > 0.05) over the study period. Age effects were observed for all performance variables and NH(3) emissions (P < 0.05). In trials 1, 2, and 3, daily NH(3) emissions from hens fed the RE diets (185.5, 312.2, and 333.5 mg/bird) were less than emissions from hens fed the CM diet (255.1, 560.6, and 616.3 mg/bird; P < 0.01). Daily emissions of H(2)S across trials from hens fed the RE diet were 4.08 mg/bird compared with 1.32 mg/bird from hens fed the CM diet (P < 0.01). Diet (P < 0.05) and age (P < 0.05) affected emissions of CO(2) and CH(4). A diet effect (P < 0.01) on NO emissions was observed. No diet or age effects (P > 0.05) were observed for NO(2) or non-CH(4) total hydrocarbons. Results demonstrated that diet and layer age influence air emissions from poultry operations.


Positive affect as implicit motivator: on the nonconscious operation of behavioral goals.
Recent research has revealed that nonconscious activation of desired behavioral states--or behavioral goals--promotes motivational activity to accomplish these states. Six studies demonstrate that this nonconscious operation of behavioral goals emerges if mental representations of specific behavioral states are associated with positive affect. In an evaluative-conditioning paradigm, unobtrusive linking of behavioral states to positive, as compared with neutral or negative, affect increased participants' wanting to accomplish these states. Furthermore, participants worked harder on tasks that were instrumental in attaining behavioral states when these states were implicitly linked to positive affect, thereby mimicking the effects on motivational behavior of preexisting individual wanting and explicit goal instructions to attain the states. Together, these results suggest that positive affect plays a key role in nonconscious goal pursuit. Implications for behavior-priming research are discussed.


[Pancreatitis and pregnancy - a contribution to the discussion on pathogenesis (author's transl)].
No unambiguous elucidation has yet been achieved regarding aetiology and pathogenesis of gestational pancreatitis. Impairment of blood circulation seems to play a major pathogenetic role. The problem is discussed, with reference being made to one case each of hyperlipidaemia and severe hypertensive late gestosis.


Comparative study of high flow nasal catheter device and noninvasive positive pressure ventilation for sequential treatment in sepsis patients after weaning from mechanical ventilation in intensive care unit.
The hypoxemia condition after mechanical ventilation (MV) weaning is not rare among sepsis patients, so we compared the efficacy in two different intervention groups: high-flow nasal cannula device group and non-invasive positive pressure ventilation (NPPV) group. This is a retrospective cohort study. Participants were patients with sepsis receiving high-flow nasal catheter (HFNC) device or NPPV within 24 hours after weaning from MV. The primary outcome was tracheal re-intubation within 72 hours after extubation. Secondary outcomes included: oxygenation index, complication rate, patient comfort evaluation, HFNC/NPPV treatment time, ICU length of stay (LOS), ICU mortality, and in-hospital 28-day mortality. A total of 283 patients were included in the study with 167 in the HFNC group and 116 in the NPPV group. The re-intubation rates after extubation in both groups were respectively 4.2% and 5.2% without significant difference. Patients in the HFNC group experienced lower incidence of delirium, reflux aspiration, facial pressure ulcer and other complications, and higher score of patients comfort than that in the NPPV group. There was no significant difference in ICU LOS, ICU mortality and in-hospital 28-day mortality between the two groups. HFNC and NPPV have similar efficacy in the sequential treatment of sepsis patients after weaning from MV. Compared with NPPV, those extubated to HFNC had lower rate of complications such as reflux aspiration and facial pressure ulcers. The patients extubation to HFNC is more comfortable (and associated with less delirium) than to NPPV.


Kinome analyses of inflammatory responses to swine barn dust extract in human bronchial epithelial and monocyte cell lines.
Exacerbated inflammation upon persistent barn organic dust exposure is a key contributor to the pathogenesis of lung inflammation and lung function decline. Barn dust constituents and the mechanisms contributing to the exacerbated inflammation are not clearly known. We set out to understand the inflammatory effects of Swine Barn Dust Extracts (SBDE) on human lung epithelial (BEAS2B) and macrophage (THP-1 monocyte derived) cell lines on a kinome array to determine phosphorylation events in the inflammatory signaling pathways. Upon identifying events unique to SBDE or those induced by innate immune ligands in each cell line, we validated the signaling pathway activation by transcriptional analyses of downstream inflammatory cytokines. Our findings indicate that SBDE-mediated pro-inflammatory effects are predominantly due to the induction of neutrophilic chemokine IL-8. Differentially phosphorylated peptides implicated in IL-8 induction in BEAS2B cell line include, TLR2, 4, 5, 7, 8, 9, PKC, MAP kinases (p38, JNK), inflammasomes (NLRP1, NLRP3), NF-κB and AP-1. In the THP-1 cell line, in addition to the aforementioned peptides, peptides corresponding to RIG-I-like receptors (RIG-I, MDA5) were found. This is the first report to demonstrate the application of a kinome array to delineate key inflammatory signaling pathways activated upon SBDE exposure in vitro.


Enhanced protection by melatonin and meloxicam combination in a middle cerebral artery occlusion model of acute ischemic stroke in rat.
Mixed efficacy of neuroprotective drugs in clinical trials has led to the emergence of the approach of combination therapy in stroke. The present study was carried out to investigate the effect of the combination of melatonin (potent antioxidant) and meloxicam (preferential inhibitor of cyclooxygenase-2 enzyme) against a middle cerebral artery occlusion model of stroke in rats. Male Wistar rats in the weight range of 250-300 g were used. Rats were anesthetized using chloral hydrate (400 mg/kg i.p) and subjected to 2 h of transient middle cerebral artery occlusion. Melatonin was administered at a dose of 20 mg/kg i.p. four times: at the time of middle cerebral artery occlusion, 1.5 h after middle cerebral artery occlusion, at the time of reperfusion, and 1 h after reperfusion. Meloxicam (2.5 mg/kg) was administered 4 h after middle cerebral artery occlusion. Motor performance tests (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress, and triphenyltetrazolium chloride staining were carried out 24 h after middle cerebral artery occlusion. A vehicle-treated group was run in parallel. It was observed that melatonin treatment improved the motor performance and significantly attenuated the levels of malondialdehyde (MDA) as compared with the middle cerebral artery occluded group. Meloxicam treatment at the dose used neither showed significant improvement on the motor performance nor decreased the levels of MDA significantly as compared with the middle cerebral artery occluded group. However, when the combination of the two drugs was used, better protection was observed as was evident by the significant decrease in the percent foot fault errors, the increase in the time spent on the rotarod, and the increase in the six-point neurological score and grip test score. There was also a significant decrease in the levels of MDA in the combination group. The results of the present study demonstrate that enhanced protection is observed with the use of a combination of melatonin plus meloxicam in the middle cerebral artery occlusion model of acute ischemic stroke in rats.


Some effects of acupuncture at Jen Chung (Go-26) on cardiovascular dynamics in dogs.
The cardiovascular effects of two types of acupuncture, needling with twirling and moxibustion by electrocautery, at Jen Chung (Go-26) were studied in dogs with chronically implanted electromagnetic flowmeter probes, during 0.75% halothane anesthesia with a succinylcholine drip to allow controlled ventilation. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, acid-base and blood gases were measured over a two hour period. During and following moxibustion by electrocautery at Jen Chung (Go-26) there was a generally significant increase (5% level) in cardiac output and stroke volume and an initially significant increase in heart rate, mean arterial pressure and pulse pressure. There was a significant decrease in total peripheral resistance following moxibustion by electrocautery and an initially significant decrease in total peripheral resistance following moxibustion by electrocautery and an initially significant decrease in total peripheral resistance following needling with twirling. It was observed in this investigation that moxibustion by electrocautery at Jen Chung (Go-26) produced more significant changes in cardiovascular dynamics in dogs than needling with twirling.


Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People.
This study assesses Autism-Spectrum Quotient (AQ) scores in a 'big data' sample collected through the UK Channel 4 television website, following the broadcasting of a medical education program. We examine correlations between the AQ and age, sex, occupation, and UK geographic region in 450,394 individuals. We predicted that age and geography would not be correlated with AQ, whilst sex and occupation would have a correlation. Mean AQ for the total sample score was m = 19.83 (SD = 8.71), slightly higher than a previous systematic review of 6,900 individuals in a non-clinical sample (mean of means = 16.94) This likely reflects that this big-data sample includes individuals with autism who in the systematic review score much higher (mean of means = 35.19). As predicted, sex and occupation differences were observed: on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52), and individuals working in a STEM career (m = 21.92, SD = 8.92) scored higher than individuals non-STEM careers (m = 18.92, SD = 8.48). Also as predicted, age and geographic region were not meaningfully correlated with AQ. These results support previous findings relating to sex and STEM careers in the largest set of individuals for which AQ scores have been reported and suggest the AQ is a useful self-report measure of autistic traits.


Effect of tibial drill angles on bone tunnel aperture during anterior cruciate ligament reconstruction.
Anatomic reconstruction of the anterior cruciate ligament has received greater attention as patient outcome assessment has become increasingly sophisticated. A goal during anatomic reconstruction should be the creation of a tibial tunnel aperture that is similar in size and orientation to the native anterior cruciate ligament insertion. Aperture morphology depends primarily on three factors: (1) drill-bit diameter, (2) the angle at which the tunnel intersects the tibial plateau (drill-guide angle), and (3) the tibial tunnel orientation in the transverse plane (transverse drill angle). We evaluated the influence of the aforementioned factors on tibial bone-tunnel aperture size and orientation. With use of various drill-bit diameters at different drill-guide angles, tunnel aperture areas were calculated on the basis of an elliptical shape. The change in tunnel aperture orientation within the transverse plane (along the tibial plateau surface) was quantified by calculating the change in anteroposterior and mediolateral lengths of the aperture. Use of a 9-mm drill-bit at a 45 degrees drill-guide angle created a 90-mm(2) bone-tunnel aperture area. Decreasing the drill-guide angle from 65 degrees to 30 degrees resulted in an increase in area of 81%. An aperture oriented 45 degrees relative to the orientation of the native insertion of the anterior cruciate ligament in the transverse plane fell short of the anatomic anteroposterior distance by 2.3 mm and exceeded the mediolateral distance by 1.4 mm on the basis of a 9-mm drill-bit at a drill-guide angle of 45 degrees. During anterior cruciate ligament reconstruction, the drill-bit diameter, sagittal drill angle, and transverse drill angle can all affect tibial tunnel aperture size and orientation. An improperly sized and oriented tunnel aperture may increase the risk of damaging surrounding structures. An optimal combination of these parameters should be chosen during anatomic reconstruction of the anterior cruciate ligament.


Biotransformation of 1,1,1,3,3-Pentafluoropropane (HFC-245fa).
1,1,1,3,3-Pentafluoropropane (HFC-245fa) is being developed as a CFC substitute. 1,1,1,3,3-Pentafluoropropane has a low potential for toxicity: the only remarkable toxic effect seen in rats after inhalation exposure to 1,1,1,3,3-pentafluoropropane in concentrations of up to 50,000 ppm for 90 days was an increased incidence of diffuse myocarditis. To elucidate the possible role of biotransformation in 1,1,1,3,3-pentafluoropropane-induced cardiotoxicity, the biotransformation of 1,1,1,3,3-pentafluoropropane was investigated in rats after inhalation exposure and in rat and human liver microsomes. Male and female rats were exposed by inhalation to 50 000, 10 000, and 2000 ppm 1,1,1,3,3-pentafluoropropane for 6 h, urine was collected for 72 h, and metabolites excreted were identified by 19F NMR spectroscopy and quantified by GC/MS. Trifluoroacetic acid and inorganic fluoride were identified as major urinary metabolites of 1,1,1,3,3-pentafluoropropane; 3,3,3-trifluoropropanoic acid and 1,1,1,3,3-pentafluoropropane-2-ol were minor metabolites. The extent of 1,1,1,3,3-pentafluoropropane biotransformation after inhalation was dependent on exposure concentrations. Neither 3,3,3-trifluoropropanoic acid nor 3,3,3-trifluoropyruvic acid were metabolized to trifluoroacetic acid in vitro or in rats. In rat and human liver microsomes, 1,1,1,3,3-pentafluoropropane was biotransformed by a cytochrome P450-dependent reaction to trifluoroacetic acid and 3,3,3-trifluoropropanoic acid. Rates of trifluoroacetic acid formation were 99.2 +/- 20.5 pmol (mg of protein)(-)(1) min(-)(1) and of 3,3,3-trifluoropropanoic acid formation were 17.5 +/- 4.0 pmol (mg of protein)(-)(1) min(-)(1) in liver microsomes from male rats. In human liver microsomes, rates of trifluoroacetic acid formation ranged from 0 to 11.6 pmol (mg of protein)(-)(1) min(-)(1), and rates of 3,3,3-trifluoropropanoic acid formation ranged from 0.7 to 7.6 pmol (mg of protein)(-)(1) min(-)(1). The results show that 1,1,1,3,3-pentafluoropropane is metabolized at low rates in vivo and in vitro. The toxic effects of 1,1,1,3,3-pentafluoropropane may be associated with the formation of the minor metabolite 3,3,3-trifluoropropanoic acid, which is highly toxic in rats.


Intermediate-dose cytarabine treatment delivered at moderate infusion rates for de novo acute myeloid leukemia-results of a phase I-II study.
Published randomized trials on different cytarabine doses for the treatment of acute myeloid leukemia (AML) provide evidence of a dose-response effect. However, high-dose cytarabine (HIDAC) regimens correlate with increased morbidity and toxicity related mortality. Typical HIDAC regimens deliver 6 g/m2/d in infusion rates of 500-3000 mg/m2/h. However, pharmacokinetic measurements indicate that intracellular Ara-CTP formation is saturated at lower infusion rates than used in HIDAC schedules, probably causing cytarabine accumulation in the plasma and increased toxicity. It was our objective to investigate in a prospective non-randomized phase I-II study feasibility and efficacy of intermediate doses of cytarabine delivered at the presumptive saturating moderate infusion rate (mir-IDAC), as induction therapy in order to optimize intensified treatment for acute myeloid leukemia. Forty previously untreated patients younger than 60 years of age with de novo AML received intermediate doses of cytarabine (2-4 g/m2/d) at moderate infusion rates (250-667 mg/m2/h) over 6 or 8 h. Cytarabine was applied on alternate days (day 1, 3, 5, 7) in combination with an anthracycline as induction and consolidation therapy. Thirty-two of the 40 patients (80%, 95%CI:64-91%) achieved CR after induction treatment. Treatment-related mortality during induction chemotherapy was 2.5%. No cerebellar toxicity was observed. After two to four mir-IDAC courses stem cell harvesting was successful in 71% of the patients eligible for high-dose chemotherapy. After three years 56% (95%CI:40-72%) of all patients are alive and 59% (95%CI:42-76%) of the patients who entered CR are free of leukemia. In conclusion, favorable long-term outcomes and moderate acute toxicities were observed in patients with de novo AML treated with IDAC schedules delivered at moderate infusion rates (mir-IDAC) starting as induction treatment. The data suggest that a randomized trial should now be undertaken to examine whether mir-IDAC has clinical advantages over HIDAC.


Nanohybrids of Pt-Functionalized Al2O3/ZnO Core-Shell Nanorods for High-Performance MEMS-Based Acetylene Gas Sensor.
Metal oxide nanostructures are the most promising materials for the fabrication of advanced gas sensors. However, the main challenge of these gas sensors is humidity interference and issues related to the selectivity and high operating temperature, which limits their response in real-time applications. In this study, we proposed nanohybrids of Pt-functionalized Al2O3/ZnOcore-shell nanorods (NRs) for a real-time humidity-independent acetylene gas sensor. The core ZnO NRs have been fabricated on microelectromechanical system (MEMS) microheater, followed by a coating of a thin nanoscale moisture-blocking conformal Al2O3 shell by atomic layer deposition (ALD) and decoration of Pt NPs using photochemical deposition and e-beam evaporation. Prior to the fabrication, a COMSOL simulation was performed to optimize the microheater design and moisture-blocking layer thickness. A comparative study of the decoration of Pt NPs on the ZnO surface by photochemical (s-Pt/ZnO) and e-beam evaporation (e-Pt/ZnO) and a Al2O3 thin moisture-blocking shell layer (Pt/Al2O3/ZnO) in sensor response has been conducted. The fabricated sensors (s-Pt/ZnO) and (e-Pt/ZnO) showed a high response ΔR/R (%) of 96.46% and 68.15% to 200 ppm acetylene at 120 °C and detect trace concentrations of acetylene down to 1 ppm, but the response is influenced by humidity. Moreover, the sensor (Pt/Al2O3/ZnO) exhibited nearly the same sensing characteristics and high acetylene selectivity despite the wide range of humidity variation from 20% RH to 70% RH. The Pt-functionalized Al2O3/ZnOcore-shell NR-based sensor showed better sensing and stable performance than other sensors (s-Pt/ZnO and e-Pt/ZnO) under humidity conditions.


Magnetic Solid Phase Extraction Based on Oleic Acid Coated Fe3O4 for the Determination of Benzo[α]pyrene in Cigarette Smoke Coupled with High-Performance Liquid Chromatography.
In this work, a simple and effective method based on magnetic solid-phase extraction combined with high-performance liquid chromatography was developed for the determination of benzo[α]pyrene (BaP) in cigarette smoke. Oleic acid coated Fe3O4 (Fe3O4-OA) was synthesized and directly used as an efficient sorbent for the first time in magnetic solid-phase extraction (MSPE) procedure for the clean-up of BaP in cigarette smoke extracts. The synthesized Fe3O4-OA was characterized by transmission electron microscopy, X-ray diffraction and Fourier transformed infrared spectroscopy. The extraction via Fe3O4-OA was dispersed in the extracts of cigarette smoke followed by the magnetic isolation, acetonitrile-tetrahydrofuran (ACN-THF; v/v = 9:1) was used for desorption of the analyte. The effects of important parameters such as the amount of adsorbent, solution pH, the content of acetonitrile, temperature and sorption time were investigated. The method showed good linearity for the determination of BaP in the concentration range of 0.5-50 ng mL-1 with a regression coefficient (R2) of 0.9987. The limit of detection and limit of quantification for BaP were obtained to be 0.12 and 0.41 ng mL-1, respectively. The mean recoveries were in the range from 81.0% to 97.6% at low, medium, high spiked levels, and the relative standard deviations were in the range of 2.7-6.8%. Combined with high-performance liquid chromatography and fluorescence detection, a simple and effective method was developed for the analysis of BaP in cigarette smoke.


Field-induced refractive index variation in the dark conglomerate phase for polarization-independent switchable liquid crystal lenses.
Liquid crystal lenses are an emerging technology that can provide variable focal power in response to applied voltage. Many designs for liquid-crystal-based lenses are polarization dependent, so that 50% of light is not focused as required, making polarization-independent technologies very attractive. Recently, the dark conglomerate (DC) phase, which is an optically isotropic liquid crystalline state, has been shown to exhibit a large change in refractive index in response to an applied electric field (Δn=0.04). This paper describes computational modeling of the electrostatic solutions for two different types of 100 μm diameter liquid crystal lenses, which include the DC phase, demonstrating that it shows great potential for efficient isotropic optical switching in lenses. A feature of the field dependence of the refractive index change in the DC phase is that it is approximately linear in a certain range, leading to the prediction of excellent optical quality for driving fields in this regime. Interestingly, a simulated microlens is shown to exhibit two modes of operation: a positive lens based upon a uniform bulk change in refractive index at high voltages, and a negative lens resulting from the induction of a gradient index effect at intermediate voltages.


LINC00461 Knockdown Enhances the Effect of Ixazomib in Multiple Myeloma Cells.
LINC00461 has been implicated to be involved in several types of cancer while its roles in multiple myeloma remain unclear. Our study aims to investigate the roles of LINC00461 in multiple myeloma and explore its effects on ixazomib therapy. LINC00461 and small nuclear ribonucleoprotein polypeptide (SNRP) B2 knockdown stable cell lines were constructed. Cell viability assays including MTT, cell number counting, and colony formation were performed. RNA-pull down and immunoblotting assays were conducted to determine the intramolecular interactions. qRT-PCR and western blotting were conducted to determine the levels of target genes. Kaplan-Meier analysis was used to evaluate overall survival rates. Knockdown of LINC00461 or SNRPB2 enhanced ixazomib's cytotoxicity, as well as affected its regulatory effects on cell apoptosis and cell cycle distribution. Further results showed that LINC00461 knockdown reduced the expression levels of SNRPB2 by their interactions. Additionally, a positive correlation between LINC00461 and SNRPB2 was found in patients with multiple myeloma. Low expression of SNRPB2 was associated with a high survival rate in patients with multiple myeloma. Knockdown of LINC00461 enhanced the therapeutic effects of ixazomib against multiple myeloma in part by the regulation of SNRPB2.


Insecticidal activity of some new synthetic compounds against different mosquito species.
Insecticidal activity of an organosilane (HOE 84498, OMS 3055), Organophosphorous (MAT 9460, OMS 3052) and a synthetic pyrethroid compound (Trebon, OMS 3002) was evaluated against adult and larval stages of eight species of mosquitoes. Insecticidal activity of these compounds was limited to larval stages only. Highest activity of HOE 84498 was found against both Cx. tritaeniorhynchus and Anopheles culicifacies (LC50-0.0065 mg/I), MAT 9460 against Armigeres subalbatus (LC50-0.00043 mg/I) and Trebon against Cx. quinuefasciatus (LC50-0.00579 mg/I). Adulticidal effect was observed at higher dosages of 25-100 ug/cm2 of MAT 9460 and HOE 84498 against all the species with LT50 ranging from 22.15-33.76 min. No appreciable residual effect was evident for the three compounds on the surfaces treated at the rate of 1-100 mg/m2 against any mosquito species.


Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins.
Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay. The expression levels of WW Domain Containing E3 Ubiquitin Protein Ligase 1 (Wwp1), SMAD Specific E3 Ubiquitin Protein Ligase 1 (Smurf1), SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and Itch were all significantly increased in the fracture callus of WT mice, which was associated with elevated expression of NF-κB members and total ubiquitinated proteins. Callus tissue isolated from Itch KO mice expressed higher levels of osteoblast-associated genes, including Runx2, a positive regulator of osteoblast differentiation, but osteoclast-associated genes were not increased. Both NF-κB RelA and RelB proteins were found to bind to the NF-κB binding site in the mouse Itch promoter. Our findings indicate that Itch depletion may have a strong positive effect on osteoblast differentiation in fracture callus. Thus, ubiquitin E3 ligase Itch could be a potential target for enhancing bone fracture healing.Cite this article: J. Liu, X. Li, H. Zhang, R. Gu, Z. Wang, Z. Gao, L. Xing. Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins. Bone Joint Res 2017;6:154-161. DOI: 10.1302/2046-3758.63.BJR-2016-0237.R1.


What do graduates think about a two-week rational pharmacotherapy course in the fifth year of medical education?
The present study aims to assess the short- and mid-term post-graduation impact of a pharmacotherapy course in the fifth year at Marmara University School of Medicine by an objective (OSCE) and a subjective (questionnaires) evaluation. Statistical comparison of pretest, posttest-exposed case and posttest-unexposed case scores indicated both a retention and a transfer effect of training. The post-course questionnaire revealed that 95%of the students found the course useful and necessary; 97% reported that they will apply a rational pharmacotherapy approach using this model and communicate better with their patients. The post-graduation questionnaire also showed that the majority of them have learned general principles of rational pharmacotherapy(90%), gained good prescribing (90%) and communication skills (87.5%), and understood the importance of non-pharmacological treatment alternatives (100%). In general, they stated that they would apply the principles during their medical practice and they believed their colleagues would do too. In conclusion, the present study demonstrates the benefit of a clinical pharmacology programme focused on rational pharmacotherapy during the clinical years of medical education.


Issues impacting genetic network reverse engineering algorithm validation using small networks.
Genetic network reverse engineering has been an area of intensive research within the systems biology community during the last decade. With many techniques currently available, the task of validating them and choosing the best one for a certain problem is a complex issue. Current practice has been to validate an approach on in-silico synthetic data sets, and, wherever possible, on real data sets with known ground-truth. In this study, we highlight a major issue that the validation of reverse engineering algorithms on small benchmark networks very often results in networks which are not statistically better than a randomly picked network. Another important issue highlighted is that with short time series, a small variation in the pre-processing procedure might yield large differences in the inferred networks. To demonstrate these issues, we have selected as our case study the IRMA in-vivo synthetic yeast network recently published in Cell. Using Fisher's exact test, we show that many results reported in the literature on reverse-engineering this network are not significantly better than random. The discussion is further extended to some other networks commonly used for validation purposes in the literature. The results presented in this study emphasize that studies carried out using small genetic networks are likely to be trivial, making it imperative that larger real networks be used for validating and benchmarking purposes. If smaller networks are considered, then the results should be interpreted carefully to avoid over confidence. This article is part of a Special Issue entitled: Computational Methods for Protein Interaction and Structural Prediction.


Hybrid thin films of graphene nanowhiskers and amorphous carbon as transparent conductors.
A new form of hybrid carbon-based thin film was prepared via a pyridine chemical vapour deposition method. The as-obtained films consist of agglomerated flowerlike graphene nanowhiskers embedded in a uniform matrix of amorphous carbon. Schottky solar cells made from the hybrid films and n-type silicon show conversion efficiencies of approximately 1% under AM 1.5 illumination.


First evidence of microplastic pollution in the El Quetzalito sand beach of the Guatemalan Caribbean.
In Guatemala, assessment of the impacts of microplastic pollution in marine and coastal protected areas has not yet been carried out. Therefore, the main goal of this paper was to evaluate the abundance, composition, physical forms, and the possible sources of plastic debris in the El Quetzalito Beach. The area was intended for biodiversity conservation but has been excessively contaminated by plastic materials from land-based activities. The results state that plastic debris negatively impact the Caribbean coast of Guatemala and are released by storm water and riverine transport from the Motagua River. With a high abundance of 279 items/m2 (30 items/kg d.w.), composed mainly of polystyrene foam beads (66.8%) and polypropylene fragments (25.8%), the microplastic sources are the deterioration of large plastics. As these plastics are commonly used in industrial, commercial, fishing, and household activities, these findings reinforce the need to improve effective sustainable management actions of solid waste treatment and disposal in the Guatemalan cities.


Quality Culture Survey Report.
The Parenteral Drug Association conducted an anonymous global survey of quality culture in the pharmaceutical industry to determine whether there is a relationship between certain quality behaviors and certain quality attributes, and whether these quality attributes could be used as surrogates (or proxy variables) to assess quality culture. Other studies have shown that an unhealthy quality culture is a root cause of many quality or compliance issues seen by sites and organizations. Statistical analysis of survey data suggests that certain attributes are driving good behaviors, and the demographic data suggests that this relationship holds irrespective of the geographic location of the site. Executive survey respondents had a more optimistic view of the current state of quality culture than survey respondents at large, with cross-functional vision showing the biggest gap (P-value = 0.07, F-Test). The top five quality attributes that can serve as surrogates for quality culture were (1) Management communication that quality is everyone's responsibility, (2) Site has formal quality improvement objectives and targets, (3) Clear performance criteria for feedback and coaching, (4) Quality topics included in at least half of all-hands meetings, and (5) Collecting error prevention metrics. These identified mature quality attributes are related to management responsibility, and continual improvement of the pharmaceutical quality system sections of ICH Q10, and therefore may be amenable to be incorporated in audit programs or in regulatory inspections. Additional research and discussion is required to build a coherent approach, which the pharmaceutical industry and regulators can adopt.


Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis.
Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. CircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294. CircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions. CircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC.


Effect of changes in dietary components on the serum bilirubin in Gilbert's syndrome.
Patients with Gilbert's syndrome were placed on low calorie diets and isocaloric diets sequentially severely reduced in carbohydrate, protein, or fat content. Significant increases in the serum bilirubin concentration occurred after the low calorie diet, but not after the isocaloric nutrient-depleted diets. Thus caloric deprivation per se and not changes in dietary components is responsible for diet-induced hyperbilirubinemia.


Connecting common genetic polymorphisms to protein function: A modular project sequence for lecture or lab.
Single nucleotide polymorphisms (SNPs) in DNA can result in phenotypes where the biochemical basis may not be clear due to the lack of protein structures. With the growing number of modeling and simulation software available on the internet, students can now participate in determining how small changes in genetic information impact cellular protein structure and function. We have developed a modular series of activities to engage lab or lecture students in examining the basis for common phenotypes. The activities range from basic phenotype testing/observation to DNA sequencing and simulation of protein structure and dynamics. We provide as an example study of the bitterness receptor TAS2R38 and PTC tasting, however these activities are applicable to other SNPs or genomic variants with a direct connection to an observable phenotype. These activities are modular and can be mixed to meet the student capabilities and infrastructure availability. The complete sequence of activities will demonstrate the direct connection between gene structure, protein structure and organism function. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):526-536, 2016.


Arterial stiffness - a cardiovascular risk factor to assess among primary care patients.
Arterial stiffness is a characteristic of the arterial wall strongly associated with ageing and hypertension. It has been confirmed as a significant cardio-vascular risk factor. Despite available non- invasive measurement methods of central artery stiffening, it has not become a prevalent diagnostic marker in primary care so far. This article provides an overview of pathophysiology of arterial stiffness, possible diagnostic techniques, association with cardiovascular conditions and potential perspective of primary care to implement an additional distinctive parameter to evaluate cardiac risk.


Production of tumor necrosis factor alpha and interleukin 1 beta by peripheral blood mononuclear cells from chronic hepatitis type C patients during interferon therapy.
To elucidate the role of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in chronic hepatitis type C (CH(C], TNF alpha and IL-1 beta released from peripheral blood mononuclear cells were measured in 6 CH(C) patients before and during interferon therapy. During the therapy, TNF-alpha levels were significantly high in two patients whose serum ALT levels turned normal, while IL-1 beta levels did not show significant change. These results suggest that TNF-alpha takes part in improvement of CH(C).


Clinical outcomes of immediate transepithelial photorefractive keratectomy after suction loss during small-incision lenticule extraction.
To investigate the surgical outcomes of immediate transepithelial photorefractive keratectomy (PRK) after suction loss during small-incision lenticule extraction (SMILE) and compare the outcomes with those of uneventful SMILE. Eyereum Eye Clinic, Seoul, South Korea. Retrospective case series. This study included 24 eyes of 12 patients who had uneventful SMILE in one eye and immediate transepithelial PRK after the development of suction loss during the lenticule cut in the contralateral eye. Visual acuity assessments, manifest refraction, and measurements of corneal wavefront aberrations were performed preoperatively and 6 months postoperatively. At 6 months, the mean uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were -0.04 ± 0.05, -0.09 ± 0.05, and -0.02 ± 0.24 diopter (D), respectively, in the transepithelial PRK group and -0.10 ± 0.07, -0.06 ± 0.07, and -0.04 ± 0.17 D, respectively (P = .036, P = .109, and P = .671, respectively), in the uneventful SMILE group. The 6-month Snellen UDVA was better than 20/20 for 11 (92%) and 12 (100%) of eyes in the transepithelial PRK and uneventful SMILE groups, respectively. All 24 eyes showed unchanged or improved CDVA and a significant increase in the total corneal higher-order aberrations postoperatively. Corneal spherical aberrations exhibited a significant postoperative increase only in the transepithelial PRK group. Immediate transepithelial PRK after early suction loss during SMILE might be safe and effective, with refractive outcomes that are comparable with those after uneventful SMILE.


Antibacterial effect of graphene oxide (GO) nano-particles against Pseudomonas putida biofilm of variable age.
Graphene oxide (GO) has been reported to possess antibacterial activity; therefore, its accumulation in the environment could affect microbial communities such as biofilms. The susceptibility of biofilms to antimicrobials is known to depend on the stage of biofilm maturity. The aim of this study was to investigate the effect of GO nano-particles on Pseudomonas putida KT2440 biofilm of variable age. FT-IR, UV-vis, and Raman spectroscopy confirmed the oxidation of graphene while XPS confirmed the high purity of the synthesised GO over 6 months. Biofilms varying in maturity (24, 48, and 72 h) were formed using a CDC reactor and were treated with GO (85 μg/mL or 8.5 μg/mL). The viability of P. putida was monitored by culture on media and the bacterial membrane integrity was assessed using flow cytometry. P. putida cells were observed using confocal microscopy and SEM. The results showed that GO significantly reduced the viability of 48-h biofilm and detached biofilm cells associated with membrane damage while the viability was not affected in 24- and 72-h biofilms and detached biofilm cells. The results showed that susceptibility of P. putida biofilm to GO varied according to age which may be due to changes in the physiological state of cells during maturation. Graphical abstract.