12-month longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder.
Although cognitive deficits are observed in the early stages of bipolar disorder, the longitudinal course of neuropsychological functioning during this period is unknown. Such knowledge could provide etiologic clues into the cognitive deficits associated with the illness, and could inform early treatment interventions. The purpose of the present study was to evaluate cognitive change in bipolar disorder in the first year after the initial manic episode. From an initial pool of 65 newly diagnosed patients with bipolar disorder (within three months of the end of the first manic or mixed episode) and 36 demographically similar healthy participants, 42 patients [mean age 22.9 years, standard deviation (SD) = 4.0] and 23 healthy participants [mean age 22.9 years (SD = 4.9)] completed baseline, six-month, and one-year neuropsychological assessments of multiple domains including processing speed, attention, verbal and nonverbal memory, working memory, and executive function. Patients also received clinical assessments, including mood ratings. Although patients showed consistently poorer cognitive performance than healthy individuals in most cognitive domains, patients showed a linear improvement over time in processing speed (p = 0.008) and executive function (p = 0.004) relative to the comparison group. Among patients, those without a history of alcohol/substance abuse or who were taken off an antipsychotic treatment during the study showed better improvement. The early course of cognitive functioning in bipolar disorder is likely influenced by multiple factors. Nevertheless, patients with bipolar disorder showed select cognitive improvements in the first year after resolution of their initial manic episode. Several clinical variables were associated with better recovery, including absence of substance abuse and discontinuation of antipsychotic treatment during the study. These and other factors require further investigation to better understand their contributions to longitudinal cognitive functioning in early bipolar disorder.


Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the formation of tracheal and nervous systems.
During gene activation, the effect of binding of transcription factors to cis-acting DNA sequences is transmitted to RNA polymerase by means of co-activators. Although co-activators contribute to the efficiency of transcription, their developmental roles are poorly understood. We used Drosophila to conduct molecular and genetic dissection of an evolutionarily conserved but unique co-activator, Multiprotein Bridging Factor 1 (MBF1), in a multicellular organism. Through immunoprecipitation, MBF1 was found to form a ternary complex including MBF1, TATA-binding protein (TBP) and the bZIP protein Tracheae Defective (TDF)/Apontic. We have isolated a Drosophila mutant that lacks the mbf1 gene in which no stable association between TBP and TDF is detectable, and transcription of a TDF-dependent reporter gene is reduced by 80%. Although the null mutants of mbf1 are viable, tdf becomes haploinsufficient in mbf1-deficient background, causing severe lesions in tracheae and the central nervous system, similar to those resulting from a complete loss of tdf function. These data demonstrate a crucial role of MBF1 in the development of tracheae and central nervous system.


[Neurophysiologic mechanisms of the disorders in recognition of emotions in endogenic depression].
In 46 male patients with endogenic depressions of different nosology (22 patients with affective disorder, 24 with juvenile slow-progredient schizophrenia) and 22 healthy individuals (a control group) visual evoked potentials (EPs) were registered during recognition of emotionally positive, negative or neutral facial expression. It was found that deficient recognition of emotions in depressions was determined by alteration of different stages of information analysis. In inferio-temporal and occipetal cortical areas the Eps revealed delayed primary analisis of visual information and reduction of components responsible for classification stage and decision making. In anteriocentral cortical areas only late stages of analysis were altered, and they were depending on nosology of depressive sindrom. Dynamics of topographic maps revealed disturbance of analysis in the right hemisphere in patients with affective disorders and in left hemisphere in schisophrenics. In both groups of patients deficit of interhemispheric transfere was found.


cis-platinum ototoxicity in children.
Cis-platinum is an ototoxic antineoplastic drug. Evaluation of auditory thresholds in 33 children receiving cis-platinum shows that a threshold shift at 6 and 8 kHz is first measurable after a cumulative dose of 201 to 300 mg/m2. A 35- to 40-dB high-frequency threshold shift is evident after a cumulative cis-platinum dose of 301 to 400 mg/m2. Increasing cumulative doses of cis-platinum are associated with a greater degree of hearing loss. Receiver-operator characteristic curves were used to find a criterion value that effectively identified threshold shifts that were due to cis-platinum ototoxicity. A 15-dB or greater shift in the 6- and 8-kHz threshold average identifies a high true-positive (50%) and low false-positive (0%) rate of cis-platinum-induced hearing loss. Using this criterion, cis-platinum ototoxicity affected 77% of children who received cis-platinum (median cumulative dose 360 mg/m2).


Collaboration between hospital and primary care nurses: a literature review.
Nurses play an important role in the treatment and care of adults in both hospital and primary health care working within complex and fragmented organizational systems. As the nature of health care changes and hospital and primary care sectors become more closely associated, nurses in both sectors have an obligation to increase their collaboration. This study aimed to increase the understanding of collaboration between nurses working with adults in hospital and primary health care, and to facilitate the future measurement of this collaboration. A literature review was undertaken in July and August 2013 using CINAHL and MEDLINE databases from the earliest to August 2013. The searches produced 4951 citations that were reduced to 22 articles for review using a four-step inclusion strategy. Inductive content analysis was used to analyse the data. It is suggested that collaboration is a process that contains (1) collaboration precursors: the opportunity to participate, knowledge and shared objectives; (2) elements of collaboration: competency, awareness and understanding of work roles and interaction; and (3) processes and outcomes: the events or behaviours that are the consequences of the collaboration between hospital and primary healthcare nurses. The results indicate that collaboration between hospital and primary healthcare nurses is an important and integral part of the work of nurses and a process consisting of several predictable issues leading to useful care outcomes. Current healthcare changes make it a requirement for hospital and primary healthcare nurses to collaborate when working with adults to continue to meet the needs of patients. The findings of this study can be used to improve collaboration in practice and to devise research to improve collaboration between hospital and primary healthcare nurses.


Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?
Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context. To perform a systematic review of studies investigating the role of bile acids in intestinal inflammation and present potentially relevant clinical implications. Pubmed search for English language articles published up to May 2015. Terms used were: 'bile', 'bile acid', 'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. Experimental studies support a variable role for bile acids in intestinal barrier homoeostasis. This may be attributed to different physicochemical properties, variable effects on epithelia and immune cells via bile acids-specific receptors, or through a cross-talk with the gut microbiome. A reduction in the bile acids pool, with lower concentrations of secondary forms, has been recognised for some time in Crohn's disease and associated to ileal dysfunction and bile acids malabsorption. Recent work suggests that these changes, including an increase in sulphated forms, are related to inflammatory activity in both Crohn's disease and UC. The detrimental effects of 'western diet' elements such as emulsifiers and fat, which have been implicated in the development of the current IBD and obesity epidemics, may also be bile acid-mediated. Although there are only a few observational clinical studies to support an interaction, in vivo human and animal studies support an association between bile acids metabolism, the gut microbiome and intestinal inflammation. This may well prove to have significant diagnostic and therapeutic implications.


Behavioral and biochemical effects of methylphenidate in schizophrenic and nonschizophrenic patients.
The authors examined the specific behavioral and biochemical effects of intravenous methylphenidate in a sample of schizophrenic and nonschizophrenic patients. Twenty drug-free patients participated in a double-blind, placebo randomized study of methylphenidate, with multiple samples of plasma homovanillic acid (HVA) and serum growth hormone (GH) obtained during the infusion procedure. Methylphenidate caused a significant increase in positive symptoms that was relatively specific to the schizophrenic patients and was evident even in those with otherwise dormant symptomatology. When behavioral response was correlated with the biochemical responses (i.e., changes in plasma HVA and GH), there was a significant positive relationship between the increase in the BPRS-positive symptoms as well as the hostility/suspiciousness factor, and the increase in GH. These results suggest that the expression of psychotic symptoms may be associated with increased dopaminergic postsynaptic sensitivity, although the nonspecific nature of methylphenidate's actions discourages a stronger interpretation of the results.


Quantitative and qualitative investigation of the stress experiences of intensive care unit patients mechanically ventilated for more than 12 hr.
The aim was to qualitatively and quantitatively clarify the stress experiences of patients who were mechanically ventilated in an intensive care unit (ICU) for more than 12 hr. The participants were adult patients without cognitive impairment who were mechanically ventilated in a general ICU for more than 12 hr. The Japanese version of the ICU Stressful Experiences Questionnaire (ICU-SEQJ) survey was performed before subjects were discharged from the ICU to collect narratives about how they felt and what they thought during their ICU stay. The results were analyzed in a collective and complementary way by dividing ICU-SEQJ scores into quartiles and comparing the first (low stress experience group) and third quartiles (high stress experience group). A total of 96 subjects were enrolled in the study, with 25 scoring in the high stress experience group and 24 in the low stress experience group. The high stress experience group had significantly longer duration of intubation, higher amounts of analgesics and sedative drugs, higher C-reactive protein, lower level of deepest sedation and greater absence of medical history than the low stress experience group. Analysis of the subjects' narratives revealed "Unbearable holistic discomfort", "Pain of being unable to control myself as before" in the high stress experience group and "Responding by giving meaning" in the low stress experience group. Nurses must recognize that long intubation hours and invasive procedures are subjective stress experiences that may cause patients to suffer holistic discomfort and lose their sense of control.


Suppression of electrical storm by biventricular pacing in a patient with idiopathic dilated cardiomyopathy and ventricular tachycardia.
This study presents a patient with idiopathic dilated cardiomyopathy who had suffered from multiple ICD shocks. Amiodarone and a beta-blocker failed to suppress ventricular tachycardia. His ECG showed a very wide QRS complex with an intraventricular conduction delay, so biventricular (BV) pacing was attempted. The BV pacing successfully prevented the multiple ICD shocks accompanied with an improvement in left ventricular systolic function and physical activity.


Idiosyncratic drug hepatotoxicity revisited: new insights from mechanistic toxicology.
Drug-induced hepatotoxicity is a serious problem and has repeatedly led to the withdrawal of a drug after successful launching. Although reactive metabolites (which are predictable) are often involved, genetic or acquired host factors (which are unpredictable) can increase the penetrance and expressivity of the potential hepatotoxicity in a small subset of patients. The molecular mechanisms underlying liver injury are largely unknown. Evidence suggests, however, that there are four major modes of action: covalent modification of target proteins and oxidoreductive stress; immune-mediated reactions; interference with hepatobiliary export; and mitochondrial injury. A better prediction will include new animal models, new biomarkers, and genomics/transcriptomics analysis.


Acute colonic pseudo-obstruction: a possible role for the colocolonic reflex.
In diverse clinical settings, injury or impairment of the peripheral autonomic nervous system may cause acute colonic pseudo-obstruction. The mechanism has remained elusive since Ogilvie's original description. In classic Ogilvie's syndrome, colonic pseudo-obstruction is associated with malignant invasion of the prevertebral ganglia, and may be mediated through the colocolonic reflex, described in a guinea pig model. We have treated three patients with acute colonic pseudo-obstruction due to: 1) malignant invasion of the prevertebral plexus (classic or true Ogilvie's syndrome), 2) clonidine, and 3) herniorrhaphy under epidural anesthesia. In this paper, we discuss the possible role of the colocolonic reflex in the pathophysiology of acute colonic pseudo-obstruction, and the delineation of true Ogilvie's syndrome from the other many causes of acute colonic pseudo-obstruction.


Education and audit can improve the identification of excessive drinkers among medical inpatients.
This study investigated the effect of education and audit on the identification and management of medical inpatients with excessive alcohol consumptions by use of a cross-sectional survey of medical and nursing notes, compared with historical controls. We report the proportion of medical and nursing notes containing qualitative and quantitative drinking histories, the use of the CAGE questionnaire, and notification of alcohol consumption in discharge summaries. A total of 1,979 out of 2,680 (74%) notes of eligible patients were examined. The number of medical notes containing quantitative alcohol histories rose from 175/792 (22%) among historical controls, to 242/690 (35%) after training of junior medical and nursing staff, and to 241/497 (48%) after feedback of results in a clinical audit meeting. The number of medical notes with no recorded alcohol history changed from 309/792 (39%) to 287/690 (42%) to 152/497 (31%), respectively (chi 2 for trend = 97.2, p < 0.0001). The number of nursing notes containing quantified alcohol histories rose from 31/792 (4%) among historical controls, to 123/690 (18%) after training, and to 237/497 (48%) after feedback of results in a clinical audit meeting. The number of nursing notes with no recorded alcohol history fell from 309/792 (90%), to 512/690 (74%), to 205/497 (41%) respectively (chi 2 for trend = 353.7, p < 0.0001). The proportion of patients found to be drinking excessively rose from 40/792 (5.1%) to 57/690 (8.3%) to 45/497 (9.1%) (chi 2 for trend = 8.25, p = 0.004). There was little worthwhile improvement in use of the CAGE questionnaire and in discharge summaries. Education and audit are effective ways of improving the identification of excessive drinkers by both junior doctors and nurses alike. Other aspects of management are less responsive.


Next-generation sequencing of microRNAs reveals a unique expression pattern in different types of pituitary adenomas.
Pituitary adenomas (PAs) are considered the most common intracranial tumor to cause serious morbidity because of dysregulated pituitary hormone secretions. Aberrant expression of microRNAs (miRNAs) is correlated with the development and function of the pituitary gland as well as the tumorigenesis of hypothalamic-pituitary axis-related pituitary tumors. In this study, we showed the differential expression patterns of miRNAs in NFPAs (nonfunctioning pituitary adenomas), GHPAs (growth hormone-secreting pituitary adenomas) and PRLPAs (prolactin-secreting pituitary adenomas) compared to those in three normal pituitary glands using the HiSeq 2000 sequencing system (Illumina). We validated miRNA expression using real-time quantitative polymerase chain reaction (RT-qPCR) analyses of samples from 73 patients (13 GHPAs, 42 NFPAs, and 18 PRLPAs) and 6 normal pituitary gland. We observed that miR-34c-3p was significantly downregulated in our PRLPA samples (p < 0.01), along with miR-34b-5p, miR-378 and miR-338-5p (all p < 0.05). In NFPAs, miR-493-5p was downregulated, and miR-181b-5p was significantly upregulated (p < 0.01). In GHPAs, miR-184 was significantly upregulated (p < 0.05). We observed that the tumor suppressive miR-124-3p was downregulated in both NFPAs and GHPAs. Taken together, we showed distinctive miRNA expression patterns in these three PAs, and these miRNA signatures in PA may have therapeutic potential as novel biomarkers for each type of PA.


Long-term survival in peritoneal mesothelioma. The role of radiotherapy and combined modality treatment.
Ten patients with peritoneal mesothelioma were treated at the Joint Center for Radiation Therapy between 1968 and 1985. Six of the ten patients remained free of disease at 19+ to 78+ months after diagnosis. The six patients received sequential surgical debulking, combination chemotherapy, and whole-abdomen irradiation. Four patients not treated with this multimodality approach died with disease. This approach may have an impact on the natural course of peritoneal mesothelioma, and warrants further study.


Synthesis and biological evaluation of irreversible EGFR tyrosine kinase inhibitors containing pyrido[3,4-d]pyrimidine scaffold.
In the present study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-TKIs to overcome acquired EGFR-T790M resistance. The most promising compound 25h inhibited HCC827 and H1975 cells growth with the IC50 values of 0.025 μM and 0.49 μM, respectively. Meanwhile, 25h displayed potent inhibitory activity against the EGFRL858R (IC50 = 1.7 nM) and EGFRL858R/T790M (IC50 = 23.3 nM). 25h could suppress EGFR phosphorylation in HCC827 and H1975 cell lines and significantly induce the apoptosis of HCC827 cells. Additionally, compound 25h could remarkably inhibit cancer growth in established HCC827 xenograft mouse model at 50 mg/kg in vivo. These results indicated that the 2,4-disubstituted 6-(5-substituted pyridin-2-amino)pyrido[3,4-d]pyrimidine derivatives can serve as effective EGFR inhibitors and potent anticancer agents.


Evaluation of spatial R maximum cardiac vector changes in exercise testing: pre-exercise versus post-exercise measurements.
R wave amplitude changes during exercise have been a controversial issue as both increase and decrease in amplitude have been reported in patients with coronary arterial disease. This variability in response is attributed to change in position and heart axis on exercise. In view of this limitation, this study evaluated the change in spatial R maximum amplitude on exercise, which should not be affected by the above factors. Twenty patients with ischaemic heart disease (male 20, age 38-61 years) and 9 control subjects (male 9, age 32-65 years) were studied. Orthogonal leads, X, Y, Z were recorded using corrected Frank lead system on a stereokinematic vectorcardiograph (Tonnies). The magnitude of spatial R maximum cardiac vector increased from 0.1 to 0.6 mV in 8/9 control subjects and decreased or showed no change in 18 of the 20 patients with coronary arterial disease. In the control group, the mean value at the end of exercise (0.98 +/- 0.34 mV) was significantly less (P less than 0.01) as compared to pre-exercise value (1.09 +/- 0.2 mV). Our preliminary observations thus indicate that, with exercise, the magnitude of spatial R maximum cardiac vector decreases or shows no alteration in height in patients with coronary arterial disease whereas it increases in normal subjects.


An advanced toothbrush with improved plaque removal efficacy.
To compare the plaque removal efficacy and safety of a new advanced manual toothbrush, the Oral-B CrossAction, with seven other toothbrushes. Seven independent, cross-over design clinical studies were conducted using the same examiner who was blind to the identity of the test products and treatment assignments. In each study, approximately 75 healthy adult subjects from a general population brushed with their randomly assigned toothbrush (CrossAction or comparison brush) at Visit 1 for 1 min without supervision or instruction in brushing technique. Subjects returned after a 1-week washout period and brushed with the alternate toothbrush (Visit 2). Plaque was evaluated before and after brushing using the Rustogi Modified Navy Plaque Index. Statistical analyses were conducted by an independent statistician who remained blind to the identity of all test products. Each of the toothbrushes tested provided significant (P < or = 0.0001) reductions in plaque scores after a single brushing. In each of the studies, the CrossAction toothbrush removed significantly (P < or = 0.0001) greater amounts of whole mouth, gingival margin, and approximal plaque than the compared toothbrush. All toothbrushes were found to be safe, with no changes in oral tissues or restorations observed over the course of each study. The results from these studies were consistent, demonstrating that the CrossAction toothbrush significantly enhances the ability of subjects to remove more plaque during normal brushing compared to seven other toothbrushes.


Electron microscopic observation of gastric mucosal capillaries in diabetics--relationship between diabetic microangiopathy and complications following gastrectomy.
An electron microscopic study was made of the gastric mucosal capillaries (GMC) of diabetic patients. Ultrastructural findings, including diabetic microangiopathy (DMA), and clinical features of these diabetic patients were investigated in relation to anastomotic leakage after gastrectomy. The gastric mucosa of resected stomachs from 12 diabetics and 10 nondiabetics were examined. Ultrastructurally, DMA was demonstrated in the stomachs of diabetics, in which the basement membrane of GMC was thicker. The degree of this DMA in the stomach significantly correlated with the duration of diabetes and the degree of DMA found in the skin, but not with age and fasting plasma glucose (FPG) level. Marked DMA was observed with significant frequency in diabetics with anastomotic leakage after gastrectomy. In our hospital, anastomotic leakage after gastrectomy occurred in 9 out of 53 diabetics. Diabetics with anastomotic leakage had severe FPG, a long duration of diabetes and diabetic retinopathy. It seems reasonable to presume that anastomotic leakage after gastrectomy occurs more frequently in diabetics with ultrastructurally severe DMA, clinically severe FPG and relatively long duration of diabetes.


Low blood glucose--an NCT investigation.
Babies are being tested for hypoglycaemia and treated unnecessarily. Inaccurate blood glucose testing strips are still being used. In many units research evidence is not being followed. Differences in care between hospitals means that some babies are not receiving the most appropriate care. Mothers receive conflicting advice. Some health professionals do not have confidence in breast feeding. Formula milk is being given to breast fed babies, interfering with the establishment of lactation.


Change detection for Lake Burullus, Egypt using remote sensing and GIS approaches.
Lake Burullus is the second largest natural coastal lake in Egypt. It has an economic importance for fish yield. However, several anthropogenic activities such as industrial, agriculture, and reclamation activities lead to a deterioration of its water quality and a decrease of the water body area of the lake. This study aims to detect the spatiotemporal changes of Lake Burullus in the period 1972-2015 using 12 Landsat {(1,3-MSS), (4,5-TM), and (7-ETM+)} imageries and water indices approach. To extract water feature from imageries, the Normalized Difference Water Index (NDWI) and the Water Ratio Index (WRI) were applied. The NDWI was applied to the MSS imageries. For other TM and ETM+ imageries, the WRI was applied. Obtained results show a significant decrease in the water area of the Lake Burullus, where it lost about (49%) of its surface area during the period from the year 1972 to the year 2015. A rapid decrease in the lake surface area was noticed through the period from 1972 to 1984. A prediction model was built depending on the calculated water area of the lake. Finally, the multi-temporal maps of the lake surface area are overlaid to produce a map for the changes of the lake surface area using Geographic Information System (GIS).


Modifications of the anti-oxidant metabolism during proliferation and differentiation of colon tumor cell lines.
The anti-oxidant metabolism was studied at different times after sub-culture in 2 colon cell lines previously characterized for their growth and differentiation properties. The HT29 cell line is mainly composed of proliferative and undifferentiative cells, while the derived 5-fluorouracil (FUra)-adapted cells undergo growth-dependent differentiation, which is complete at post-confluence. In the 2 cell lines, all the anti-oxidant parameters studied appeared to be related to proliferation, with increased activity of superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GSR), and glutathione transferase (GST), and decreased glucose-6-phosphate dehydrogenase (G6PD) activity and glutathione content, in parallel with slowing down of proliferation. At post-confluence, these metabolic parameters remained stable, except for GPX activity, which continued to increase, and CAT activity, which decreased. The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities. SOD1, CAT and GST activity and glutathione content, which remained at similar levels in the 2 cell lines for all times studied, appeared unrelated to the differentiation process. GSR and GPX activity, which was lower in FUra-adapted than in parental cells only at post-confluence, could be considered as markers of differentiated cells. The higher SOD2 and lower G6PD activity observed in FUra-resistant cell in comparison with parental cells at all times after sub-culture could be characteristic both of differentiative and of differentiated cells. Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra-adapted cells. These results demonstrate that modifications of the anti-oxidant metabolism occur in relation with proliferation and differentiation, and suggest a particular role for SOD2 in these cellular processes.


A new subjective refraction method--the meridional polarized vernier optometer.
The purpose of this study was to develop a more accurate and precise method for measuring subjective sphero-cylindrical refractive errors. It employed the principles of a vernier optometer and meridional refraction. A meridional polarized vernier optometer was used to measure the refraction of three subjects. Trial lenses were added to change the refractive error by known amounts and refractions were repeated to assess accuracy. Refractions were within the range expected. The instrument had a slight bias (+0.04D) and 95 percent confidence interval of +/- 0.45D for measuring change in refractive error. Mean standard deviation for repeated measurements was 0.08D. This new approach has the potential to measure subjective refractive errors more accurately than is possible with current methods.


Relationship between LH and oestradiol in IVF cycles before GnRH antagonist initiation.
The objective of this prospective study was to assess the relationship of LH and oestradiol on day 7 of the cycle in patients stimulated with recombinant FSH (rec-FSH) for IVF before initiation of gonadotrophin-releasing hormone (GnRH) antagonist. One hundred and forty-six women treated for IVF using GnRH antagonists for premature LH rise suppression were stimulated with 150 IU of rec-FSH from day 2 to day 6 of the cycle. On cycle day 7, LH concentrations (median 1.8, range 0.1-7.51) were positively associated with oestradiol concentrations on the same day by multiple regression analysis controlling for patient's age, concentrations of FSH and LH on cycle day 2, FSH concentrations on cycle day 7 and follicular index on cycle day 7. In conclusion, the higher the endogenous unsuppressed LH concentrations on day 7 of the cycle after 5 days of stimulation with rec-FSH for IVF, the higher the serum oestradiol concentrations on the same day.


Follow-up schedules after treatment for malignant melanoma.
Existing follow-up guidelines after treatment for melanoma are based largely on dated literature and historical precedent. This study aimed to calculate recurrence rates and establish prognostic factors for recurrence to help redesign a follow-up schedule. Data were retrieved from the Sydney Melanoma Unit database for all patients with a single primary melanoma and American Joint Committee on Cancer (AJCC) stage I-II disease, who had received their first treatment between 1959 and 2002. Recurrence rates, timing and survival were recorded by substage, and predictive factors were analysed. Recurrence occurred in 18.9 per cent (895 of 4748) of patients overall, 5.2 per cent (95 of 1822) of those with stage IA disease, 18.4 per cent (264 of 1436) with IB, 28.7 per cent (215 of 750) with IIA, 40.6 per cent (213 of 524) with IIB and 44.3 per cent (86 of 194) with IIC disease. Overall, the median disease-free survival time was 2.6 years, but there were marked differences between AJCC subgroups. Primary tumour thickness, ulceration and tumour mitotic rate were important predictors of recurrence. A new follow-up schedule was proposed: stage I annually, stage IIA 6-monthly for 2 years and then annually, stage IIB-IIC 4-monthly for 2 years, 6-monthly in the third year and annually thereafter.


Comparison of the gonadal development and plasma levels of sex steroid hormones in diploid and triploid sea bass, Dicentrarchus labrax L.
The goal of this study was to compare the reproductive physiology of triploid and diploid European sea bass (Dicentrarchus labrax L.). Gonads of diploid and triploid fish (males and females) were examined both microscopically and macroscopically, together with the plasma levels of the major sex steroids produced (testosterone and estradiol-17beta) when fish were adults. Prior to sexual maturation, the gonadosomatic index (GSI) of triploid males was similar to that of diploids. However, the GSI in 4-year-old adult triploid males was 1.8 times lower than that of diploids (P < 0.05). All diploid males exhibited normal gonadal development. In contrast, in triploid males spermatogenesis was impaired during late meiosis, affecting severely spermiogenesis. This was achieved by an increasing imbalance in the amount of DNA present in daughter cells of the same type as spermatogenesis progressed, as demonstrated by abnormal cell sizes, culminating in inviable spermatids. Thus, no spermiating triploid fish were observed during 4 years, which included three full consecutive maturation cycles. Furthermore, the germ cells from triploids were significantly larger than those from diploids (P < 0.001). Seasonal profiles of plasma levels of testosterone in 4-year-old males were essentially similar in both ploidies. On the other hand, triploid females had rudimentary ovaries containing oogonia and primary oocytes that were arrested during meiotic prophase I, while diploid females exhibited all stages of ovarian development. Diploid females showed levels of testosterone and estradiol-17beta significantly higher than those of triploids (P < 0.05), in which no endocrine signs of maturation were observed at all. Regarding sex ratios, triploids had 10% more females than diploids (P < 0.05) but in both ploidies males predominated, as is usually found in this species under culture conditions. These results show that triploidy blocked the initial phases of meiosis in females and the latter ones in males, resulting in the absence of or reduced gonadal development, respectively. In conclusion, we provide an explanation for the lack of gonadal development in triploid male fish, and, to the best of our knowledge, we report for the first time a case in which induced triploidy completely blocks meiosis in both sexes, thus conferring functional sterility in the sea bass.


The effect of diabetes on the molecular localization of maternal and fetal zinc and copper metalloprotein in the rat.
The molecular localization of maternal and fetal zinc and copper metalloproteins in diabetic and control rats was studied. Compared to controls, liver and kidneys of diabetic dams showed an increased concentration of zinc and copper that was associated with metallothionein. In contrast, fetuses of diabetic dams had lower zinc and metallothionein levels than fetuses from controls. The abnormal maternal trace element metabolism seen with diabetes resulted in alterations of zinc uptake and/or retention of their fetuses.


The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically.
Cdc37 associates with the heat-shock protein 90 (Hsp90) molecular chaperone as one of several auxiliary proteins that are collectively referred to as Hsp90 co-chaperones. Cdc37 has been proposed to be a specificity factor for Hsp90, directing it notably towards kinases. It is not known whether Cdc37 is essential for viability in the budding yeast Saccharomyces cerevisiae because of Hsp90-dependent or -independent functions or both. Sti1 and Cpr7 are non-essential Hsp90 co-chaperones that bind to a common surface on Hsp90 through tetratricopeptide repeats (TPR). We have found that Sti1 is specifically retained from yeast extracts by immobilized Cdc37. Similarly, the endogenous proteins are also found in a complex. Moreover, purified recombinant Sti1 and Cdc37 interact in the complete absence of Hsp90. Complexes between Cdc37 and Sti1 are not unique to this TPR protein since endogenous Cdc37 can be co-purified with exogenously expressed Cpr7 fused to glutathione-S-transferase. The heterogeneity of Cdc37 complexes, both with and without Hsp90, may expand the functional diversity of Cdc37. Here we show that the combination of cdc37 and sti1 mutations is synthetically lethal, suggesting that direct contacts between Cdc37 and Sti1 may at least contribute to vital functions in yeast.


Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration.
The purpose of this study was to study the effect of minocycline and several neurotrophic factors, alone or in combination, on photoreceptor survival and macro/microglial reactivity in two rat models of retinal degeneration. P23H-1 (rhodopsin mutation), Royal College of Surgeon (RCS, pigment epithelium malfunction), and age-matched control rats (Sprague-Dawley and Pievald Viro Glaxo, respectively) were divided into three groups that received at P10 for P23H-1 rats or P33 for RCS rats: (1) one intravitreal injection (IVI) of one of the following neurotrophic factors: ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), or basic fibroblast growth factor (FGF2); (2) daily intraperitoneal administration of minocycline; or (3) a combination of IVI of FGF2 and intraperitoneal minocycline. All animals were processed 12 days after treatment initiation. Retinal microglial cells and cone photoreceptors were immunodetected and analyzed qualitatively in cross sections. The numbers of microglial cells in the different retinal layers and number of nuclei rows in the outer nuclear layer (ONL) were quantified. IVI of CNTF, PEDF, or FGF2 improved the morphology of the photoreceptors outer segment, but only FGF2 rescued a significant number of photoreceptors. None of the trophic factors had qualitative or quantitative effects on microglial cells. Minocycline treatment reduced activation and migration of microglia and produced a significant rescue of photoreceptors. Combined treatment with minocycline and FGF2 had higher neuroprotective effects than each of the treatments alone. In two animal models of photoreceptor degeneration with different etiologies, minocycline reduces microglial activation and migration, and FGF2 and minocycline increase photoreceptor survival. The combination of FGF2 and minocycline show greater neuroprotective effects than their isolated effects.


Extra-anatomical veno-venous surgical bypass for central vein occlusion in patients with ipsilateral arterio-venous fistula (AVF) for haemodialysis - A single centre experience.
Central vein occlusion is a common complication related to central vein catheter insertion for haemodialysis which can be unmasked by an ipsilateral fistula creation, leading to a dysfunctional arteriovenous fistula (AVF). We describe an extra-anatomical venous bypass surgical procedure performed to maintain vascular access and reduce the symptoms of swelling of the ipsilateral upper limb, neck and face. We report 20 consecutive patients with end-stage renal failure (ESRF) who had central vein occlusion and were not amenable to endovascular intervention. They underwent extra-anatomical vein to vein surgical bypass. The axillary and iliac or femoral veins were approached via infraclavicular and extraperitoneal groin incisions respectively. In all the patients, an externally supported 6 or 8 mm polytetrafluoroethylene (PTFE) graft was used as a conduit and was tunnelled extra-anatomical. All patients had double antiplatelet (Aspirin and Clopidogrel) therapy post-operatively. Substantial improvement in the facial, neck and upper limb swelling was noticed following this diversion surgery. The vein to vein bypass was patent at 12 months in 10 out of 20 patients. Graft infection occurred in two (10%) cases. Re-thrombectomy or assisted patency procedure (stent/plasty) was done in four (20%) cases. The patients with preoperative fistula flow rate of more than 1500 ml/min and post-operative graft flow rate of more than a 1000 ml/min were patent at 12 months (P=0.025 and p=0.034 respectively). Axillary to iliac/femoral vein bypass can salvage functioning ipsilateral fistula threatened by occluded upper central vein.


Influence of plasmonic array geometry on energy transfer from a quantum well to a quantum dot layer.
A range of seven different Ag plasmonic arrays formed using nanostructures of varying shape, size and gap were fabricated using helium-ion lithography (HIL) on an InGaN/GaN quantum well (QW) substrate. The influence of the array geometry on plasmon-enhanced Förster resonance energy transfer (FRET) from a single InGaN QW to a ∼80 nm layer of CdSe/ZnS quantum dots (QDs) embedded in a poly(methyl methacrylate) (PMMA) matrix is investigated. It is shown that the energy transfer efficiency is strongly dependent on the array properties and an efficiency of ∼51% is observed for a nanoring array. There were no signatures of FRET in the absence of the arrays. The QD acceptor layer emission is highly sensitive to the array geometry. A model was developed to confirm that the increase in the QD emission on the QW substrate compared with a GaN substrate can be attributed solely to plasmon-enhanced FRET. The individual contributions of direct enhancement of the QD layer emission by the array and the plasmon-enhanced FRET are separated out, with the QD emission described by the product of an array emission factor and an energy transfer factor. It is shown that while the nanoring geometry results in an energy transfer factor of ∼1.7 the competing quenching by the array, with an array emission factor of ∼0.7, results in only an overall gain of ∼14% in the QD emission. The QD emission was enhanced by ∼71% for a nanobox array, resulting from the combination of a more modest energy transfer factor of 1.2 coupled with an array emission factor of ∼1.4.


Stimulation of osteoclastogenesis by enhanced levels of MIP-1alpha in BALB/c mice in vitro.
We compared osteoclast (OC) formation in bone marrow-derived macrophages (BMM) from C57BL/6 (B/6) and BALB/c (B/c) mice. After stimulation of receptor activator of nuclear factor-kappaB ligand (RANKL), enhanced OC formation and higher level of macrophage inflammatory protein-1alpha (MIP-1alpha) were observed in the BMM from B/c mice. In this study, we determined whether MIP-1alpha is responsible for stimulated OC formation in the BMM. OC formation was evaluated in BMM. Expression of MIP-1alpha during OC formation was analyzed at the mRNA and protein levels. Apoptosis of mature OCs was evaluated by observing the degradation of DNA. Activation of nuclear factor-kappaB (NF-kappaB) was measured by electrophoretic mobility shift assay. After stimulation by RANKL expression of MIP-1alpha at the mRNA and protein levels was much higher in BMM from B/c mice than in BMM from B/6 mice. Transcripts of the MIP-1alpha receptors, CCR1 and CCR5, were present at similar levels in unstimulated BMM of the two strains. Blockade of MIP-1alpha inhibited OC formation, and exogenously added MIP-1alpha stimulated it in RANKL-stimulated BMM. MIP-1alpha affected not only the early precursors but also mature OCs. It prevented apoptosis of mature OCs by activating NF-kappaB, and the effect of RANKL on survival was dependent on its ability to induce MIP-1alpha. MIP-1alpha, induced by RANKL during OC differentiation, increases OC formation by acting on OC progenitor cells, and prolongs survival of mature OC via signaling through NF-kappaB. The enhanced OC formation in BMM from B/c mice could be due to, at least in part, to their higher levels of MIP-1alpha.


The effect of bupivacaine paracervical block on the neurobehavioural responses of newborn infants.
The effects of maternal bupivacaine paracervical block on neonatal neurobehavioural responses were studied at the ages of 3 h, 1 day, 2 days and 4-5 days. Subjects were healthy, term neonates born vaginally to 10 mothers with paracervical block and to 12 mothers without analgesia. No statistically significant differences were found in the responses between the groups. It is concluded that paracervical block with a small dose of bupivacaine, applied by experienced obstetricians to non-risk parturients with healthy foetuses, has no detrimental effects on newborn behaviour or neurological recovery.


Evaluation of human chaperonin 10 and high-sensitivity C-reactive protein levels of infertile women who underwent ovulation induction and intra-uterine insemination.
The implantation of embryo is one of the crucial steps of a successful pregnancy. The foetus should be protected from maternal immune system, for the appropriate implantation and modification in maternal immunity is crucial. We investigated high-sensitivity C-reactive protein (hs CRP), which is an indicator of low-grade inflammation and Cp10 that has immunosuppressant and growth-promoting capabilities at embryo levels in ovulation induction and intra-uterine insemination (IUI)applied in infertile women. The ovulation induction was maintained by clomiphene citrate or gonadotropins for 42 infertile patients. After successful ovulation induction, IUI was carried out. The blood samples were taken 2 and 8 days after IUI to evaluate Cp10 and hs CRP levels. The pregnant and non-pregnant groups' results were analyzed. The Cp10 levels 8 days after IUI were higher in pregnant group, whereas there was no difference for the 2 days after levels between pregnant and non-pregnant group. The hs CRP levels were similar for both 2nd and 8th days when we compared pregnant and non-pregnant groups. The Cp10 levels increased from day 2 to day 8 in pregnant group. In contrast, the Cp10 levels decreased in non-pregnant group. The change in hs CRP levels from day 2 to day 8 was not significant in pregnant and non-pregnant groups. The Cp10 levels were higher in early phases of fertilisation and elevated through the preceding days of conception in pregnant patients, while it decreased in non-pregnant patients with failed cycles.


Comparison of Different Generalizations of Clustering Coefficient and Local Efficiency for Weighted Undirected Graphs.
Binary undirected graphs are well established, but when these graphs are constructed, often a threshold is applied to a parameter describing the connection between two nodes. Therefore, the use of weighted graphs is more appropriate. In this work, we focus on weighted undirected graphs. This implies that we have to incorporate edge weights in the graph measures, which require generalizations of common graph metrics. After reviewing existing generalizations of the clustering coefficient and the local efficiency, we proposed new generalizations for these graph measures. To be able to compare different generalizations, a number of essential and useful properties were defined that ideally should be satisfied. We applied the generalizations to two real-world networks of different sizes. As a result, we found that not all existing generalizations satisfy all essential properties. Furthermore, we determined the best generalization for the clustering coefficient and local efficiency based on their properties and the performance when applied to two networks. We found that the best generalization of the clustering coefficient is [Formula: see text], defined in Miyajima and Sakuragawa ( 2014 ), while the best generalization of the local efficiency is [Formula: see text], proposed in this letter. Depending on the application and the relative importance of sensitivity and robustness to noise, other generalizations may be selected on the basis of the properties investigated in this letter.


Management of Major Depression in Adults With Diabetes: Implications of Recent Clinical Trials.
Major depressive disorder is present in 15%-20% of patients with diabetes and impairs functioning and quality of life. It has unique importance in diabetes because of its association with poor compliance with diabetes treatment, poor glycemic control, and an increased risk for micro- and macrovascular disease complications. These observations have inspired several recent clinical trials to determine whether these associations may be favorably influenced by depression treatment. The outcome data are scant but promising and suggest that psychotherapy and pharmacotherapy can have important positive effects on both mood and glycemic control. Unfortunately, even after successful treatment, recurrence of depression is the norm. Afflicted subjects are seldom asymptomatic for an entire year at a time. Factors related to the medical illness (eg, presence of diabetes complications, hyperglycemia) are associated with a poorer prognosis for recovery from depression, a finding that suggests that optimal relief of depression in diabetes may require vigorous, simultaneous management of the medical and psychiatric conditions. Whether maintenance antidepressant treatment is useful in preventing depression recurrence and promoting better glycemic control in diabetes is unknown, but this question is the focus of an ongoing clinical trial.


Introducing the Rhamphoriaceae, fam. nov. (Sordariomycetes), two new genera, and new life histories for taxa with Phaeoisaria- and Idriella-like anamorphs.
Two new genera, Rhamphoriopsis and Xylolentia, are described for lignicolous perithecial ascomycetes occurring in terrestrial habitats. Fresh material, living cultures, morphology, and DNA sequence data (nuc rDNA internal transcribed spacers [ITS1-5.8S-ITS2 = ITS], 18S and 28S genes, and second largest subunit of RNA polymerase II = RPB2) of these taxa and morphologically similar fungi were studied to determine their relationships. A monophyletic clade including Rhamphoria, Rhodoveronaea, a dematiaceous hyphomycete Linkosia multiseptum, and the two new genera was recovered in the Sordariomycetes based on the 18S-28S-RPB2 data set. It is introduced as the family Rhamphoriaceae and strongly supported by Bayesian and maximum likelihood methods. Its members are characterized by perithecial ascomata with a cylindrical or rostrate neck, the absence of stromatic tissue or clypeus, similar anatomy of two-layered ascomatal walls, cylindrical paraphyses, unitunicate asci with a distinct, nonamyloid apical annulus, and dictyoseptate or transversely septate, hyaline or brown ascospores. The mode of conidiogenesis is holoblastic, predominantly on polyblastic-denticulate conidiogenous cells. The Phaeoisaria-like anamorph has been linked to Rhamphoria and Rhamphoriopsis, whereas conidia and conidiophores of Idriella-like synanamorph were formed in vitro in two species of Rhamphoria. The Veronaea-like anamorph is associated with Rhodoveronaea. The anamorph of Xylolentia is a dematiaceous hyphomycete with conidiogenous cells with sympodially extending rachis. A key to members of the family is provided. The classification and nature of species boundaries in Rhamphoria are discussed, and diagnostic characters such as ascospore shape, number of transverse and longitudinal septa, a degree of constriction at the septa, and ability to produce ascoconidia are evaluated.


Tuberculosis of the orbit.
Two cases of orbital tuberculosis in white Canadians are reported. The two patients did not suffer from pulmonary tuberculosis, the orbital disease was associated with tuberculosis sinusitis in the first case and blood-borne from constrictive tuberculous pericarditis in the second case. Acid-fast bacilli are difficult to detect in the pathological specimens and the diagnosis is usually based on the following: (1) the positive tuberculin skin test; (2) the caseating granulomatous inflammatory lesion on histopathology, which is highly suggestive of active tuberculosis; (3) the positive culture for Mycobacterium tuberculosis if the specimens are obtained early in the course of the disease; and (4) the complete resolution of the disease with the specific antituberculous medications.


Isolation and characterization of novel rhesus monkey embryonic stem cell lines.
ESCs are important as research subjects since the mechanisms underlying cellular differentiation, expansion, and self-renewal can be studied along with differentiated tissue development and regeneration in vitro. Furthermore, human ESCs hold promise for cell and tissue replacement approaches to treating human diseases. The rhesus monkey is a clinically relevant primate model that will likely be required to bring these clinical applications to fruition. Monkey ESCs share a number of properties with human ESCs, and their derivation and use are not affected by bioethical concerns. Here, we summarize our experience in the establishment of 18 ESC lines from rhesus monkey preimplantation embryos generated by the application of the assisted reproductive technologies. The newly derived monkey ESC lines were maintained in vitro without losing their chromosomal integrity, and they expressed markers previously reported present in human and monkey ESCs. We also describe initial efforts to compare the pluripotency of ESC lines by expression profiling, chimeric embryo formation, and in vitro-directed differentiation into endodermal, mesodermal, and ectodermal lineages.


Tailoring CT Dose to Patient Size: Implementation of the Updated 2017 ACR Size-specific Diagnostic Reference Levels.
To use an automatic computed tomography (CT) dose monitoring system to analyze the institutional chest and abdominopelvic CT dose data as regards the updated 2017 American College of Radiology (ACR) diagnostic reference levels (DRLs) based on water-equivalent diameter (Dw) and size-specific dose estimates (SSDE) to detect patient-size subgroups in which CT dose can be optimized. All chest CT examinations performed between July 2016 and April 2017 with and without contrast material, CT of the pulmonary arteries, and abdominopelvic CT with and without contrast material were included in this retrospective study. Dw and SSDE were automatically calculated for all scans using a previously validated in-house developed Matlab software and stored into our CT dose monitoring system. CT dose data were analyzed as regards the updated ACR DRLs (size groups: 21-25 cm, 25-29 cm, 29-33 cm, 33-37 cm, 37-41 cm). SSDE and volumetric computed tomography dose index (CTDIvol) were used as CT dose parameter. Overall, 30,002 CT examinations were performed in the study period, 3860 of which were included in the analysis (mean age 62.1 ± 16.4 years, Dw 29.0 ± 3.3 cm; n = 577 chest CT without contrast material, n = 628 chest CT with contrast material, n = 346 CT of chest pulmonary, n = 563 abdominopelvic CT without contrast material, n = 1746 abdominopelvic CT with contrast material). Mean SSDE and CTDIvol relative to the updated DRLs were 43.3 ± 26.4 and 45.1 ± 27.9% for noncontrast chest CT, 52.3 ± 23.1 and 52.0 ± 23.1% for contrast-enhanced chest CT, 68.8 ± 29.5 and 70.0 ± 31.0% for CT of pulmonary arteries, 41.9 ± 29.2 and 43.3 ± 31.3% for noncontrast abdominopelvic CT, and 56.8 ± 22.2 and 58.8 ± 24.4% for contrast-enhanced abdominopelvic CT. Lowest dose compared to the DRLs was found for the Dw group of 21-25 cm in noncontrast abdominopelvic CT (SSDE 30.4 ± 21.8%, CTDIvol 30.8 ± 21.4%). Solely the group of patients with a Dw of 37-41 cm undergoing noncontrast abdominopelvic CT exceeded the ACR DRL (SSDE 100.3 ± 59.0%, CTDIvol 107.1 ± 63.5%). On average, mean SSDE and CTDIvol of our institutional chest and abdominopelvic CT protocols were lower than the updated 2017 ACR DRLs. Size-specific subgroup analysis revealed a wide variability of SSDE and CTDIvol across CT protocols and patient size groups with a transgression of DRLs in noncontrast abdominopelvic CT of large patients (Dw 37-41 cm).


[Meeting Report of the Uropathology Working Group of the German Society of Pathology, 2018].


Urgent treatment of acute hypertension.
Acute severe elevation of the blood pressure is a life-threatening event which requires prompt and effective action. Comparative studies of the agents discussed are lacking. Also, hypertensive crises occur in diverse clinical settings and afflict a heterogeneous group of patients. No single drug is ideal in all situations and treatment must be chosen to suit the individual patient.


Preventing stone retropulsion during intracorporeal lithotripsy.
Several studies of ureteroscopic treatment for ureteral stones have reported that most stone clearance failures can be attributed to stone fragment retropulsion. Stone retropulsion can result in increased operative time and cost-resulting from the need to change from the semi-rigid ureteroscope to a flexible instrument to chase migrated calculi-and additional procedures to treat residual migrated fragments are often required. The degree of migration depends mainly on the energy source used for lithotripsy; pneumatic and electrohydraulic lithotripters are associated with a greater degree of retropulsion than lasers. Different stone-trapping strategies and devices have been developed to minimize stone migration. Novel devices include the Lithovac(®) suction device, the Passport(™) balloon, the Stone Cone(™), the PercSys Accordion(®), the NTrap(®), and stone baskets such as the LithoCatch(™), the Parachute(™), and the Escape(®). Some authors have also reported on the use of lubricating jelly and BackStop(®) gel (a reverse thermosensitive polymeric plug); these devices are instilled proximal to the stone prior to the application of kinetic energy in order to prevent retrograde stone migration.


Employee testing raises workplace privacy issues.
With increasing frequency, employers are considering mandatory screening for substance abuse and AIDS. These tests are focusing attention on an area of growing concern for hospitals--employees' right to privacy in the workplace--and prompting trustees to define an institutional philosophy for their hospital.


Clinical evaluation of laparoscopic repair of large hiatal hernias with TiMesh.
The use of mesh for laparoscopic repair of large hiatal hernias may decrease recurrence rates in comparison with primary suture repair. The type of mesh material, as well as its size and shape, is still a matter of debate. The aim of this study was to evaluate a lightweight polypropylene mesh (TiMesh) repair of hiatal hernias, with particular reference to symptomatic relief, patient satisfaction and quality of life (QOL). From a prospectively maintained clinical database, 40 consecutive patients were identified who underwent elective laparoscopic hiatal hernia repair with TiMesh between November 2004 and December 2006. QOL and symptom analysis was carried out using Quality of Life in Reflux and Dyspepsia (QOLRAD) and dysphagia questionnaires preoperatively, and postoperatively after 6 weeks, 6 months, and 1 year. The mean age of the patient was 65.2 years (range: 40-93 years). Total complication rate was 7.5%; all complications were treated without residual disability. There was no 30-day mortality. Median hospital stay was 2.7 days (range 2-13 days). Completed questionnaires were obtained from 37 (92.5%) of 40 patients. After 1 year, more than 90% of patients were satisfied with their symptomatic outcome and regarded their surgery as successful. There was a significant improvement in QOL, measured with QOLRAD at all postoperative time-points (P < 0.001). There was no difference between pre- and postoperative dysphagia scores. Laparoscopic repair of large hiatal hernias with TiMesh yields good symptomatic and clinical outcome. Further studies are needed to show whether the use of this lightweight polypropylene mesh is associated with a reduction in recurrence rates after hiatal hernia repair in the longer term.


Cryogenic gallium phosphide acousto-optic deflectors.
We present measurements of the acoustic intensity in a gallium phosphide acousto-optic deflector for the 0.6-1.3-GHz frequency range and the 8-295-K temperature range. The data show a significant increase in the available time aperture of this deflector as a result of cryogenic cooling.


Sequential agonist activation and site-specific mediation of acute cyclosporine constriction in rat renal arterioles.
Evidence suggests that acute and chronic cyclosporine (CsA) nephropathy may be related to its renal vasoconstrictor effects. While the mechanism of CsA-induced renal vasoconstriction is uncertain, several studies indicate that endogenous constrictor agonists including endothelins (ET), platelet activating factor (PAF), and thromboxane A2 (TXA2) play a mediating role. In this study, two possible mechanisms explaining the participation of multiple constrictor agonists in CsA vasoconstriction were investigated: sequential activation of agonists initiated by CsA and site-specific mediation of CsA constriction by different agonists. The acute constrictor effects of CsA were examined in isolated rat renal afferent (AA) and efferent arterioles (EA) without and with specific receptor antagonists of ETA (BQ123, 10(-7) M), PAF (L-659,989, 10(-7) M), and TXA2/PGH2 (SQ29,548, 10(-7) M) in the bathing media. Both BQ123 and L-659,989 completely inhibited CsA, constriction in AA, but had no significant inhibiting effect in EA. Constriction to ET-1 was also blocked by the PAF antagonist L-659,989 in AA, but not EA. There was no effect of SQ29,548 on CsA constriction in AA--however, there was partial attenuation of CsA constriction in EA. Based on these results in isolated rat renal arterioles, it is suggested that CsA-induced constriction in AA is likely mediated by sequential activation of ET and PAF. However, CsA constriction of EA involves a different mechanism or mediator that, in part, may involve TXA2/PGH2 stimulation.


Changes in the Pancreas in Experimental Diabetes and the Effect of Lycopene on These Changes: Proliferating, Apoptotic, and Estrogen Receptor α Positive Cells.
This study aimed to investigate the changes occurring in estrogen receptor (ER) α-positive cells, proliferating cells, apoptotic cells and malondialdehyde (MDA) expression in the pancreas of experimentally induced adult diabetic rats and to determine the effect of orally administered lycopene on these changes. Experimental diabetes was induced using a single dose of 50 mg/kg streptozotocin (STZ). Following the administration of STZ, four groups of animals were established: Control + corn oil, control + lycopene, diabetic + corn oil and diabetic + lycopene. The expressions of ER α, Ki-67, and MDA were determined through immunohistochemistry in sections taken from pancreas tissue samples at the end of the experiment. Apoptotic cells were determined through the TUNEL method. In the diabetic groups, the densities of ER α expression in islets and ER α-positive cells in exocrine parts increased. Whereas the number of proliferating Ki-67 positive cells was higher in the diabetic groups, no significant difference was observed in terms of apoptotic cell number between the control and diabetic groups. Lycopene in general did not have any effect on any of the parameters analyzed in the study. The presence of ER α-positive cells around the islets was demonstrated for the first time in diabetic groups. Based on these observations, demonstrating the antioxidant effects of lycopene in the pancreas of diabetic rats may be possible by increasing the dose and/or the duration of lycopene. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2000-2007, 2017. © 2017 Wiley Periodicals, Inc.


Kinetics of interstitially administered monoclonal antibodies for purposes of lymphoscintigraphy.
The clearance rates of radiolabeled murine monoclonal intact IgG, F(ab')2 Fab and of an IgM following subcutaneous administration were evaluated in normal mice and rats using nuclear imaging and counting techniques. These studies suggest no significant difference in clearance rate exists between intact IgG and its F(ab')2 fragment, and little difference between these moieties and intact IgM. Fab is cleared considerably faster than the others, however. While significant differences in clearance rates exist, the magnitude of the differences are not as large as those following intravenous injection particularly when ambulation by the animal is allowed. When ambulation is allowed, clearance rates of all classes and fragments are accelerated and quite similar. Injection into the subcutaneous tissues of the footpad results in consistently faster clearance than an injection into the subcutaneous tissues of the abdomen. Ambulation considerably increased the clearance of antibodies, presumably by increasing lymph flow. These studies imply that the choice of intact antibody versus fragments for kinetic reasons may be less critical (particularly if ambulation is allowed) by the subcutaneous as compared with the intravenous delivery route. This kinetic information should be useful in designing imaging protocols with radiolabeled antibodies administered subcutaneously for purposes of imaging disease processes involving the lymphatics.


[Therapy for Ocular Graft-vs-Host Disease].
Therapy for ocular graft-vs-host disease (ocular GvHD) is challenging for ophthalmologists as progress of the disease often occurs rapidly and is unforeseeable. Primary goal is the preservation or restoration of visual acuity, however, studies on ocular GvHD that have investigated therapeutic concepts are limited. In contrast, most therapeutic recommendations from consensus conferences derive from studies on dry eye diseases other than ocular GvHD. This review demonstrates the available therapies in the following categories: local, systemic, surgical and prophylactic. Primary targets are anti-inflammation, anti-fibrosis and lubrification of the ocular surface. In conclusion, studies strictly on ocular GvHD are needed to enable better evidence-based therapeutic decision-making in the future.


Preparation and properties of nanometer titanium dioxide/silk fibroin blend membrane.
A novel nanometer titanium dioxide (nanoTD)/silk fibroin (SF) blend membrane was prepared and characterized by AFM, FTIR, DSC, and XRD. The strength, solubility and thermal properties and the antibacterial activity of the blend membrane were then investigated. The results show that at a nanoTD/SF weight ratio of 0.1%, nanoTD particles were evenly dispersed in the blend membrane. The blend membrane exhibited a crystalline 2theta XRD peak at 21.1 degrees and the decomposition temperature was 28.72 degrees C higher than for a pure SF membrane. The results show that the blend membrane had higher crystallinity and better antibacterial activity and strength than a pure SF membrane, whereas its solubility was lower.


Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2007. A report of the Australian Mycobacterium Reference Laboratory Network.
The Australian Mycobacterium Reference Laboratory Network collects and analyses laboratory data on new cases of disease caused by the Mycobacterium tuberculosis complex. In 2007, a total of 872 cases were identified by bacteriology; an annual reporting rate of 4.1 cases per 100,000 population. Isolates were identified as M. tuberculosis (n=867), M. africanum (n=4) and M. bovis (n=1). Fifteen children aged under 10 years had bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility testing were available for 871 of 872 isolates for isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of 98 (11.3%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least H and R (defined as multi-drug resistance, MDR) was detected in 24 (2.8%) isolates, all from overseas-born patients; 17 were from the respiratory tract (sputum n=16, endotracheal aspirate n=1). Thirteen patients with MDR-TB were from the Papua New Guinea-Torres Strait Islands zone. Of the 98 M. tuberculosis isolates resistant to at least one of the standard drugs, 54 (55.1%) were from new cases, 9 (9.2%) from previously treated cases, and no information was available on the remaining 35 cases. Seven were Australian-born, 90 were overseas- born, and the country of birth of 1 was unknown. Of the 90 overseas-born persons with drug resistant disease, 66 (73.3%) were from 5 countries: India (n=16); Papua New Guinea (n=15); the Philippines (n=12); Vietnam (n=12); and China (n=11). No XDR-TB was detected in 2007.


T2 prep three-dimensional spiral imaging with efficient whole brain coverage for myelin water quantification at 1.5 tesla.
Quantitative assessment of myelination is important for characterizing tissue damage and evaluating response to therapy in white matter diseases such as multiple sclerosis. Conventional multicomponent T(2) relaxometry based on the two-dimensional (2D) multiecho spin echo sequence is a promising method to measure myelin water fraction, but its clinical utility is impeded by the prohibitively long data acquisition and limited brain coverage. The objective of this study was to develop a signal-to-noise ratio efficient 3D T(2) prep spiral gradient echo (3D SPIRAL) sequence for full brain T(2) relaxometry and to validate this sequence using 3D multiecho spin echo as reference standard in healthy brains at 1.5 T. 3D SPIRAL was found to provide similar myelin water fraction in six selected white and gray matter areas using region-of-interest signal averaging analysis (N = 7, P > 0.05). While 3D multiecho spin echo only provided partial brain coverage, 3D SPIRAL enabled whole brain coverage with a fivefold higher acquisition speed per imaging slice and similar signal-to-noise ratio efficiency. Both 3D sequences provided superior signal-to-noise ratio efficiency when compared to the conventional 2D multiecho spin echo approach.


Physiologic benefits of pulsatile perfusion during mechanical circulatory support for the treatment of acute and chronic heart failure in adults.
A growing population experiencing heart failure (100,000 patients/year), combined with a shortage of donor organs (less than 2200 hearts/year), has led to increased and expanded use of mechanical circulatory support (MCS) devices. MCS devices have successfully improved clinical outcomes, which are comparable with heart transplantation and result in better 1-year survival than optimal medical management therapies. The quality of perfusion provided during MCS therapy may play an important role in patient outcomes. Despite demonstrated physiologic benefits of pulsatile perfusion, continued use or development of pulsatile MCS devices has been widely abandoned in favor of continuous flow pumps owing to the large size and adverse risks events in the former class, which pose issues of thrombogenic surfaces, percutaneous lead infection, and durability. Next-generation MCS device development should ideally implement designs that offer the benefits of rotary pump technology while providing the physiologic benefits of pulsatile end-organ perfusion.


Cognitive Benefits of Online Social Networking for Healthy Older Adults.
Research suggests that older adults who remain socially active and cognitively engaged have better cognitive function than those who are isolated and disengaged. This study examined the efficacy of learning and using an online social networking website, Facebook.com, as an intervention to maintain or enhance cognitive function in older adults. Forty-one older adults were assigned to learn and use Facebook (n = 14) or an online diary website (active control, n = 13) for 8 weeks or placed on a waitlist (n = 14). Outcome measures included neuropsychological tests of executive functions, memory, and processing speed and self-report questionnaires about social engagement. The Facebook group showed a significant increase in a composite measure of updating, an executive function factor associated with complex working memory tasks, compared to no significant change in the control groups. Other measures of cognitive function and social support showed no differential improvement in the Facebook group. Learning and using an online social networking site may provide specific benefits for complex working memory in a group of healthy older adults. This may reflect the particular cognitive demands associated with online social networking and/or the benefits of social engagement more generally.


Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.
The basis of species-specific morphogenesis has been a topic of fascination and speculation for centuries. In 1828, Karl Ernst von Baer noted that at the pharyngula stage of development all vertebrate embryos are morphologically very similar. Most subsequent hypotheses have proposed that the vertebrate body plan develops by a conserved mechanism, and that divergent forms develop by differential elaboration on this basic plan. Gene cloning and expression studies have largely confirmed that the genetic pathways of embryonic patterning are highly conserved. The finding that the proteins encoded by paralogous and orthologous genes within and between species can functionally replace each another is no longer novel; in most cases this is the expected result. How, then, does divergent morphology arise between species? One hypothesis that fits well with comparative data is that divergent morphogenesis arises from genetic differences in the timing, level and pattern of orthologous gene expression during development. This idea is being tested using a functional genetic approach comparing limb morphogenesis between the mouse and bat.


[Utilization of a method of growing microorganisms on millipore filters in order to study their structure with a scanning electron microscope].
A comparative study of bacteria and their L-forms Actinomyces and blue-green algae, taken from centrifugates and grown on Millipore filters, was made with the use of scanning electron microscopy. The study revealed that only in the second case the location of the cells inside the colony was preserved and the architectonics of the colony remained unchanged. The anastomoses between the cells and slime on the cell surface, destroyed when other methods of making the preparations were used, could be easily detected.


Phase-shift cavity ring-down spectroscopy using mid-IR light from a difference frequency generation PPLN waveguide.
Approximately 200 microW of mid-infrared (mid-IR) light around 3081 cm(-1), produced by difference frequency generation (DFG) in a periodically poled lithium niobate crystal waveguide, has been used for phase-shift cavity ring-down spectroscopy measurements. The overlapping (12)C(2)H(4) (R)P(0)(14) and (P)R(6)(10) and (12)CH(2) (13)CH(2) (P)Q(3)(10) rotational lines of the nu(9) fundamental ethene vibrational band at 3081.0016 cm(-1) were probed in proof-of-principle experiments, and ethene detection was demonstrated with a minimum absorption coefficient of 1.4 x 10(-7) cm(-1) (approximately 4 min acquisition time). The compact DFG system, with a >35 cm(-1) tuning range, has a considerable potential for use in trace gas detection and in molecular spectroscopy.


Hypercoagulation in colorectal cancer: what can platelet indices tell us?
Colorectal cancer, as all solid malignancies, is accompanied by changes in the haemostatic mechanism favoring the establishment of a thrombotic potential, with platelets playing a key-role in this framework; they further link colorectal cancer progression and hypercoagulation with the immune-response against the neoplastic spread. Under this rationale, various studies have assessed the use of platelet indices as prognostic markers of the biological behavior of colorectal cancer, demonstrating significant results. We herein attempt to summarize in a narrative and critical approach the relevant available data and the underlying pathophysiology, stressing the necessity of a more thorough understanding and future implementation of platelet indices in all stages of care we deliver to colorectal cancer patients.


Structure refinement of Cu8GeS6 using X-ray diffraction data from a multiple-twinned crystal.
The structure of the orthorhombic room-temperature phase of Cu(8)GeS(6) (copper germanium sulfide), M(r) = 773.27, has been refined on the basis of X-ray diffraction data from a 12-fold twinned crystal applying a six-dimensional twin refinement technique. For 1804 unique reflections measured using Mo Kalpha radiation, R(F) was 0.083 with 77 structure parameters and 12 scale factors. The symmetry operations, the unit cell and other crystal data are (0, 0, 0; (1/2), (1/2), 0) + x, y, z; y, x, z; (1/4) - x, (3/4) - y, (1/2) + z; (3/4) - y, (1/4) - x, (1/2) + z; a = b = 9.9073 (3) Å, c = 9.8703 (4) Å, alpha = beta = 90 degrees, gamma = 90.642 (4) degrees; V = 968.7 (1) Å(3), Z = 4, D(x) = 5.358 Mg m(-3), µ = 21.70 mm(-1). The standard setting of the space group and the reduced unit cell are Pmn2(1); a = 7.0445 (3), b = 6.9661 (3), c = 9.8699 (5) Å; Z = 2.


Ribosomal protein S20 purified under mild conditions almost completely inhibits its own translation.
The efficiency of ribosomal protein S20 to act as repressor of its own synthesis in an in vitro system was found to depend greatly on the procedures employed to purify this protein. Whilst conventionally purified r-protein S20 inhibited its own synthesis by some 30%, up to 90% inhibition was observed if "milder" purification conditions were used. Evidence is presented that the latter preparation shows also a higher binding affinity to 16S rRNA.


A brief and critical review on hydrofluorosis in diverse species of domestic animals in India.
India is one of the fluoride-endemic countries where the maximum numbers of ground or drinking water sources are naturally fluoridated. In India, a total of 23, out of 36 states and union territories have drinking water contaminated with fluoride in varying concentration. In the present scenario, especially in rural India, besides the surface waters (perennial ponds, dams, rivers, etc.), bore wells and hand pumps are the principal drinking water sources for domestic animals such as cattle (Bos taurus), water buffaloes (Bubalus bubalis), sheep (Ovis aries), goats (Capra hircus), horses (Equus caballus), donkeys (Equus asinus) and dromedary camels (Camelus dromedarius). Out of 23 states, 17 states, namely Andhra Pradesh, Assam, Bihar, Chhattisgarh, Gujarat, Haryana, Jharkhand, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Odisha (Orissa), Punjab, Rajasthan, Telangana, Uttar Pradesh and West Bengal, have fluoride beyond the maximum permissible limit of 1.0 or 1.5 ppm in drinking water. This situation is a great concern for the animal health because fluoride is a slow toxicant and causes chronic diverse serious health hazards or toxic effects. Despite the fact that domestic animals are the basic income sources in rural areas and possess a significant contributory role not only in the agriculture sector but also in the strengthening of economy as well as in sustainable development of the country, research work on chronic fluoride intoxication (hydrofluorosis) due to drinking of fluoridated water in domestic animals rearing in various fluoride-endemic states is not enough as compared to work done in humans. However, some interesting and excellent research works conducted on different aspects of hydrofluorosis in domesticated animals rearing in different states are briefly and critically reviewed in the present communication. Author believes that this review paper not only will be more useful for researchers to do some more advance research work on fluoride-induced toxicosis in different species of animals but will also be helpful in the making of health policy for domestic animals at state and national level for the mitigation of hydrofluorosis in India.


The left anterior extrapleural approach for innominate artery transection in a patient with tracheostomy and a neurological disorder.
Although innominate artery transection for innominate artery compression of the trachea is recently used for prevention of life-threatening complications (e.g. massive bleeding and obstructive apnoea) in patients with neurological disorders, pre-existing tracheostomy poses a risk of mediastinal infection with sternotomy. We successfully performed innominate artery transection on such a patient via the left anterior extrapleural approach without sternotomy after confirming the anatomical configuration on three-dimensional multidetector row computed tomography angiography.


Treatment of hypertensive cerebellar hemorrhage--surgical or conservative management?
One hundred and one consecutive patients with hypertensive cerebellar hemorrhage were analyzed to determine the criteria for surgery. New criteria based on the patient's Glasgow Coma Scale score at admission and the maximum diameter of the hematoma, as disclosed by computed tomography, are proposed from a retrospective analysis of 52 earlier cases. The criteria are as follows: 1) patients with Glasgow Coma Scale scores of 14 or 15 and with a hematoma of less than 40 mm in maximum diameter are treated conservatively; 2) for the patients with Glasgow Coma Scale scores of 13 or less at admission or with a hematoma measuring 40 mm or more, hematoma evacuation with decompressive suboccipital craniectomy should be a treatment of choice; and 3) for the patient whose brain stem reflexes are entirely lost with flaccid tetraplegia or whose general condition is poor, intensive therapy is not indicated. The validity of these criteria was tested and confirmed in 49 recent cases.


[Around the Semipalatinsk proving grounds: the radioecological situation and the population radiation doses in Semipalatinsk Province (based on data from the report of the Interdepartmental Commission)].
The paper represents some results of a joint commission, organized by the USSR Ministry of Health by order of the USSR Council of Ministers at public requests. The commission worked in the area neighbouring the proving ground at Semipalatinsk in the period of May-July 1988. A radiological situation there was investigated after underground nuclear testing on July 8, 1989. The results of measurements and archive data were used to estimate doses of radiation exposure of the population in the period of 1949 (nuclear testing on the ground and in the atmosphere) and in the period of underground testing, It was shown that in the period of 1949-1963 approximately 10,000 people received increased doses of external and internal irradiation. A high level of radiation-induced chromosome aberrations was noted among them. The highest effective equivalent doses of external and internal irradiation were received by the residents in the villages of Folon' (1.6 Gy during the first testing in 1949), Karaul (0.37 Gy), Sarzhal (0.20 Gy), Semenovka (0.02 Gy). The annual effective equivalent doses at that period did not exceed 0.0056 Gy (the highest value) for the Semipalatinsk residents. Proceeding from the values of collective doses probable long-term effects (malignant tumors) were assessed. Recommendations and conclusions of the commission are presented.


The gut microbiota and its potential role in obesity.
The human GI tract harbors a diverse and dynamic microbial community comprising bacteria, archaea, viruses and eukaryotic microbes, which varies in composition from individual to individual. A healthy microbiota metabolizes various indigestible dietary components of the host, maintains host immune homeostasis and nutrient intake, but, an imbalanced microbiota has been reported to be associated with many diseases, including obesity. Rodent studies have produced evidence in support of the causal role of the gut microbiota in the development of obesity, however, such causal relationship is lacking in humans. The objective of this review is to critically analyze the vast information available on the composition, function and alterations of the gut microbiota in obesity and explore the future prospects of this research area.


Age-related cognitive recovery after general anesthesia.
This study was designed to quantify the rate of mental recovery in elderly and young patients after general anesthesia for intraabdominal surgery (cholecystectomy). Forty patients (25-83 yr) were given four tests assessing neuropsychological function once preoperatively and on five occasions postoperatively. Two of the four neuropsychological tests showed impairment in scores in the elderly patients on the first postoperative day (Symbol Digit Modalities Test, P less than 0.004; The Trail Making Test, P less than 0.03). In addition, one of the tests (Symbol Digit Modalities Test) showed a deterioration in the younger patients (P less than 0.05). The changes that did occur in these tests on the first postoperative day reverted to baseline levels thereafter. There were no significant changes in the remaining two tests, the Mini Mental State Test or the Digit Span Test, at any time in either group. We conclude that postoperative mental deterioration is no greater in elderly than in young patients.


Oro-facial impairment in stroke patients.
Stroke is considered one of the leading causes of death and acquired disability with a peak prevalence over the age of 80 years. Stroke may cause debilitating neurological deficiencies that frequently result in sensory deficits, motor impairment, muscular atrophy, cognitive deficits and psychosocial impairment. Oro-facial impairment may occur due to the frequent involvement of the cranial nerves' cortical representation areas, central nervous system pathways or motoneuron pools. The aim of this narrative, non-systematic review was to discuss the implications of stroke on oro-facial functions and oral health-related quality of life (OHRQoL). Stroke patients demonstrate an impaired masticatory performance, possibly due to reduced tongue forces and disturbed oral sensitivity. Furthermore, facial asymmetry is common, but mostly discrete and lip restraining forces are reduced. Bite force is not different between the ipsi- and contra-lesional side. In contrast, the contra-lesional handgrip strength and tongue-palate contact during swallowing are significantly impaired. OHRQoL is significantly reduced mainly because of the functional impairment. It can be concluded that impaired chewing efficiency, dysphagia, facial asymmetry, reduced lip force and OHRQoL are quantifiable symptoms of oro-facial impairment following a stroke. In the absence of functional rehabilitation, these symptoms seem not to improve. Furthermore, stroke affects the upper limb and the masseter muscle differently, both, at a functional and a morphological level. The rehabilitation of stroke survivors should, therefore, also seek to improve the strength and co-ordination of the oro-facial musculature. This would in turn help improve OHRQoL and the masticatory function, subsequently preventing weight loss and malnutrition.


Advances in dietary enrichment with n-3 fatty acids.
Evidence for the effectiveness of the enrichment of food products with n-3 fatty acids by inclusion of either plant- or fish-derived materials in the diets of chickens, turkeys, ostriches, cows, pigs, and goats has been reviewed. Both linseed oil/meal and fish products can increase the levels of total n-3 fatty acids in animal products, including milk, eggs, meat, and deli products. The extent of this increase in n-3 fatty acid contents seems to be dependent on the nature of diet supplementation. Encapsulation of linseed oil may result in higher milk cow ALA contents, as compared to unprotected linseed oil. Available literature indicates that the levels of EPA and DHA in food products may be increased more, if the animals' diet was supplemented with fish products rather than linseed products. However, organoleptic properties of food products may be compromised. This pitfall may be reduced by the addition of antioxidants and/or application of micro-encapsulation. Generation of transgenic animals and plants has shown very promising results. Thus far, transgenic pigs and mice have been successfully generated. These animals have a low ratio of n-6:n-3 fatty acids in their tissues and milk. The advantages and disadvantages of the above-mentioned methods have been discussed. The evidence for health-promoting effects of such enriched food products has been included.


Cramér-Rao bound for Intravoxel Incoherent Motion Diffusion Weighted Imaging fitting.
The precision of parameter estimation for Intravoxel Incoherent Motion Diffusion Weighted Imaging (IVIM-DWI) was investigated by examining their Cramér-Rao bounds (CRBs) under the presence of Rician noise. Monte Carlo (MC) simulation was also conducted to validate the CRB results. The estimation uncertainties of true diffusion coefficient (D) and perfusion fraction (f0) could reach 3.89% and 11.65% respectively with typical parameter values at a moderate signal-to-noise ratio (SNR) of 40. However, to estimate pseudo diffusion coefficient (D*) within 10% uncertainty requires SNR>122. The results also showed that the estimation precision of each parameter is not only dependent on SNR but also their true values, while this mutual dependency is complicated. Under some particular cases, estimation uncertainty for certain parameters might be smaller than 5% at a moderate SNR of 40. However, the simultaneous precise estimation for all three parameters is theoretically difficult and highly SNR demanding.


Effects of rest, exercise and warming on serum creatine kinase levels in primary hypothyroidism.
1. Serum creatine kinase and oral temperature were measured in 20 patients with primary hypothyroidism before and after 48 h bed rest. Fifteen of these patients were heated during the 48 h period. The remaining five acted as control subjects. In addition, creatine kinase and oral temperature were measured in five control subjects after a 30 min period of exercise and again after a 30 min period of resting. 2. The oral temperature rose and the serum creatine kinase levels fell only in those patients who were actively warmed. In the control subjects the period of exercise followed by resting caused no significant change in creatine kinase levels. 3. A subnormal body temperature appears to be an important determinant of the raised serum creatine kinase levels seen in patients with primary hypothyroidism.


[Let's study exponential function related to anesthesiology by using computer graphics--Part I: Wash-out exponential function].
A computer simulation is used to analyze physical or biophysical changes related to anesthesiology mostly by computer oriented experts. Recent development in a personal computer and its program, however, has made it possible for more anesthesiologists to have an experience of computer analysis. For example, graphic expression of exponential functions can easily be obtained by using a computer program, such as "Graphnote" by Fukutake Pub. Co. In this literature, the author first explained the wash-out exponential function. Then estimation of changes in the hematocrit and serum protein concentration associated with blood loss during surgery was given as an example of biophysical phenomena related to anesthesiology, to which the wash-out exponential function is applicable for mathematical simulation. Besides, the author demonstrated the way to draw exponential function curves by using "Graphnote", so that the readers can express the curves by themselves.


The emerging genetics of cancer.
The rapid progress in molecular biology has allowed investigators to define some of the basic mechanisms of carcinogenesis. At the molecular level, cellular transformation results from the occurrence of two or three distinct genetic events that uncouple the cell from its normal regulatory mechanisms. One family of genes, the oncogenes, may be particularly important in the process. The aberrant expression of oncogenes, either by mutation or simply by increased transcription, may result in cellular transformation. The genes usually code for growth factors, growth factor receptors or for proteins involved in the transduction of growth signals into the nucleus. Genetic activation causes the cell to continuously sense a message to undergo mitosis, and the cell no longer responds to its normal regulatory signals. The concepts are rapidly moving into the clinical realm as the genetic mechanisms of particular neoplasms have been investigated. The neuroblastoma is the first tumor system in which the biologic characteristics of the tumor were found to be related to a known oncogene; the amplification of the myc gene is an independent marker of the aggressiveness of the tumor. In addition, much progress has been made in defining the specific genetic lesions responsible for retinoblastomas, Wilms' tumors and carcinomas of the colon that arise in patients with familial polyposis coli. As more knowledge accumulates regarding the exact mechanisms through which the proteins encoded by oncogenes affect these carcinomas and others, it may become possible to design pharmacologic agents rationally to hinder their growth selectively.


Ubiquitin signals protein trafficking via interaction with a novel ubiquitin binding domain in the membrane fusion regulator, Vps9p.
The conserved vacuolar protein-sorting (Vps) pathway controls the trafficking of proteins to the vacuole/lysosome. Both the internalization of ubiquitylated cargo from the plasma membrane and its sorting at the late endosome via the Vps pathway depend on ubiquitin (Ub) binding motifs present in trafficking regulators. Here we report that Ub controls yet a third step in the Vps pathway. Vps9p, which promotes endosomal and Golgi-derived vesicle fusion, binds directly to Ub via a Cue1p-homologous (CUE) domain. The CUE domain is structurally related to the Ub-associated (UBA) domain. In an assay for vacuolar delivery of a transmembrane receptor fused to Ub, a Ub mutation impairing interaction with Vps9p led to a cytoplasmic block in receptor trafficking. This block resembled that of a receptor fused to wild-type Ub but expressed in a vps9-null background. Strikingly, this trafficking defect caused by a mutant Ub was rescued by deletion of the Vps9p CUE domain, indicating that lack of the CUE domain renders Vps9p independent of Ub for activation in vivo. We thus provide evidence for biochemical and genetic interactions between Ub and a novel Ub binding domain in Vps9p. Ub plays a positive role, whereas the CUE domain plays both positive and negative roles in Vps9p function in trafficking.


Electrodiagnostic evidence of subclinical disease states in drug abusers.
One hundred drug abusers, free of clinical signs or symptoms of disease, were examined by electrodiagnostic techniques. Sensory conduction of median, ulnar and sural nerves was evaluated in terms of latency, velocity and amplitude of evoked potential. Motor nerve latencies and conduction velocities of median, ulnar and personeal nerves were determined. Definite changes in the evoked sensory potentials of median and sural nerves of subjects using heroin or LSD were demonstrated. The sensory amplitude changes were suggestive of axonal degreneration because of normal duration. Maximum motor conduction velocity was abnormal in one patient who admitted using a variety of drugs; five heroin and two barbiturate users showed dispersed motor responses suggesting small fiber involvement. No abnormality could be shown in marjuana smokers. Signifcance of these findings is explained, emphasizing important potential for recognition of subclinical abnormalities and the opportunity for disease prevention.


A simple technique to harvest two kidneys from one donor rat for transplantation.
Kidney transplantation in rats is a widely used and well established model in transplantation immunology and preservation research. With the conventional method, only one kidney is harvested from the donor rat. We developed a technique to harvest two kidneys separately from one donor, subsequently both kidneys were successfully implanted into two recipient rats. This technique which leads to a reduction of the number of experimental animals used is discussed in detail.


Biocatalytic Synthesis of Nitriles through Dehydration of Aldoximes: The Substrate Scope of Aldoxime Dehydratases.
Nitriles, which are mostly needed and produced by the chemical industry, play a major role in various industry segments, ranging from high-volume, low-price sectors, such as polymers, to low-volume, high-price sectors, such as chiral pharma drugs. A common industrial technology for nitrile production is ammoxidation as a gas-phase reaction at high temperature. Further popular approaches are substitution or addition reactions with hydrogen cyanide or derivatives thereof. A major drawback, however, is the very high toxicity of cyanide. Recently, as a synthetic alternative, a novel enzymatic approach towards nitriles has been developed with aldoxime dehydratases, which are capable of converting an aldoxime in one step through dehydration into nitriles. Because the aldoxime substrates are easily accessible, this route is of high interest for synthetic purposes. However, whenever a novel method is developed for organic synthesis, it raises the question of substrate scope as one of the key criteria for application as a "synthetic platform technology". Thus, the scope of this review is to give an overview of the current state of the substrate scope of this enzymatic method for synthesizing nitriles with aldoxime dehydratases. As a recently emerging enzyme class, a range of substrates has already been studied so far, comprising nonchiral and chiral aldoximes. This enzyme class of aldoxime dehydratases shows a broad substrate tolerance and accepts aliphatic and aromatic aldoximes, as well as arylaliphatic aldoximes. Furthermore, aldoximes with a stereogenic center are also recognized and high enantioselectivities are found for 2-arylpropylaldoximes, in particular. It is further noteworthy that the enantiopreference depends on the E and Z isomers. Thus, opposite enantiomers are accessible from the same racemic aldehyde and the same enzyme.


Major mental disorders in Butajira, southern Ethiopia.
Previous studies conducted in Ethiopia lack information on the prevalence of specific mental disorders in rural communities. The lifetime and one-month prevalence of specific ICD-10 mental disorders and their associated socio-demographic factors were determined using the translated Amharic version of the Composite International Diagnostic Interview (CIDI) in a rural population. A total of 501 community subjects selected from a predominantly rural district by stratified random sampling were interviewed by non-clinician interviewers. The weighted aggregate lifetime prevalence of psychiatric morbidity was 31.8% (26.7% when substance dependence was not included). The most frequent specific diagnoses were: dissociative disorders (6.3%), mood disorders (6.2%), somatoform disorders (5.9%), and anxiety disorders (5.7%). After adjustment in a multivariate logistic model, female sex was shown to have a statistically significant association with mood disorders (Odds Ratio, OR = 3.84, 95% CI: 1.90, 7.73) and somatoform disorders (OR = 2.30, 95% CI: 1.13, 4.60). Severe cognitive and mood disorders were significantly associated with being elderly, i.e. 60 or more years of age (OR = 7.71, 95% CI: 1.58, 7.53; and OR = 3.68, 95% CI = 1.36, 9.95, respectively). Khat dependence was associated with being Muslim and with earning a low income. (OR = 3.5, 95% CI: 1.02, 11.98; and OR = 0.32, 95% CI: 0.10, 0.96, respectively). It is concluded that psychiatric morbidity is a major public health problem in the rural community.