Outcomes Associated With Multiple Organ Dysfunction Syndrome in Critically Ill Children With Hyperglycemia.
Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. Thirty-five PICUs. Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. Randomization to a lower versus higher glucose target group. Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.


Lack of a clinically meaningful pharmacokinetic effect of rifabutin on raltegravir: in vitro/in vivo correlation.
Raltegravir is an HIV-1 integrase strand transfer inhibitor with potent activity against HIV-1. A prior investigation of raltegravir coadministered with rifampin demonstrated a decrease in plasma concentrations of raltegravir likely secondary to induction of UGT1A1, the enzyme primarily responsible for the metabolism of raltegravir. Little is known regarding the induction of UGT1A1 by rifabutin, an alternate rifamycin. In vitro characterization of the induction potency of rifampin and rifabutin on UGT1A1 was performed. In vitro studies indicate that rifabutin is a less potent inducer of UGT1A1 messenger RNA expression than is rifampin. A fixed-sequence, 2-period, clinical crossover study was conducted to assess the effect of rifabutin on plasma levels of raltegravir: period 1, 400 mg of raltegravir every 12 hours for 4 days; period 2, 400 mg of raltegravir every 12 hours and 300 mg of rifabutin once daily for 14 days. Geometric mean ratio (GMR) (coadministration of rifabutin and raltegravir vs raltegravir alone) of raltegravir area under the concentration-time curve from 0 to 12 hours post dose (AUC(0-12h)) and the 90% confidence interval (CI) was 1.19 (0.86-1.63); GMR of concentration at 12 hours (C(12h)) and 90% CI was 0.80 (0.68-0.94); and GMR of time to maximal concentration (C(max)) and 90% CI was 1.39 (0.87-2.21). Overall, coadministration of rifabutin did not alter raltegravir pharmacokinetics to a clinically meaningful degree.


GABAB receptor-mediated inhibition of serotonin release in the rat brain.
Rat brain frontal cortex or striatal slices preincubated with 3H-serotonin were superfused with physiological salt solution and tritium overflow was evoked by electrical field stimulation at a frequency of 3 Hz. 1. GABA 1 mmol/1 inhibited the evoked overflow from frontal cortex slices by about 30%. The inhibitory effect was abolished when the frequency of electrical stimulation was 10 instead of 3 Hz. Progabide and R(-)-baclofen were more potent, whereas muscimol was less potent than GABA itself in inhibiting the evoked overflow; the IC15 values of progabide, R(-)-baclofen, GABA and muscimol were 8.3, 15, 170 and greater than 320 mumol/1, respectively. S(+)-baclofen behaved as a partial agonist with a maximum inhibitory effect by about 15%. Nipecotic acid and aminooxyacetic acid were ineffective. The same held true for bicuculline, picrotoxin and diazepam. 2. Bicuculline, picrotoxin, diazepam, phentolamine and the serotonin receptor antagonist metitepin did not influence the inhibitory effect of GABA. By contrast, S(+)-baclofen attenuated the effects of GABA and R(-)-baclofen. 3. The evoked overflow from striatal slices was inhibited by GABA and progabide (IC15 values: 480 and 13 mumol/1, respectively). Nipecotic acid was ineffective. The results suggest that exogenous GABA inhibits serotonin release in the rat brain via GABAB receptors which may be assumed to be located presynaptically.


Preoperative chemotherapy does not increase complications after nonsmall cell lung cancer resection.
Neoadjuvant chemotherapy before resection of nonsmall cell lung cancer seems to increase survival, mainly in the early stage. Risks of postoperative complications after chemotherapy and surgery remain controversial. Here we review our experience with patients treated in one thoracic surgery center. Patients undergoing resection for nonsmall cell lung cancer after induction chemotherapy between January 1993 and March 2002 were reviewed. Data collected included age, sex, preoperative forced expiratory volume in 1 second (FEV1), hemoglobin, and arterial oxygen pressure tension (PaO2), postoperative complications, and global survival. The main objectives were postoperative mortality and morbidity. Postoperative mortality and morbidity were defined as complications or deaths occurring within 30 days after surgery. Predictive morbidity factors were identified by univariate and multivariate analysis and overall survival by the Kaplan-Meier method. In all, 114 patients were reviewed. Different induction chemotherapies were used, mainly cisplatin with vinorelbine or gemicitabine. Postoperative mortality was 2 of 114, 1 of 27 after pneumonectomy, and there were no deaths after lobectomy. Complications occurred in 29% of patients (33 of 114), usually infectious pneumonia and anemia requiring transfusion. Preoperative FEV1, hemoglobin, and PaO2 are not associated with morbidity in univariate or multivariate analysis. Preoperative chemotherapy does not increase postoperative mortality and morbidity after nonsmall cell lung cancer surgery, performed exclusively by thoracic surgeons.


Age and experience with dental operating microscope: Do these factors influence on the post space preparation and adhesion of glass fiber posts?
This study evaluated the influence of operator's age and experience with dental operating microscope (DOM) on the cleaning of post space walls and on bond strength of glass fiber posts associated with self-adhesive resin cement. Sixty bovine roots were selected. Root canal preparation was performed and roots were filled using gutta-percha/AH Plus. For post space preparation, specimens were divided into four groups (n = 15), according to operator's age and the use of DOM: (1) ≥40 years; (2) ≥40 years with magnification; (3) <40 years; (4) <40 years with magnification. Next, a high-speed bur of the post system and torque-controlled round burs were used for cleaning of post space. Five roots in each group were evaluated for the degree of cleanliness under a stereo microscope using a scoring system. In the remaining 10 specimens from each group, glass fiber posts were cemented with RelyX U200. Two slices (1 ± 0.1 mm) prepared on each root third of all specimens were evaluated by push-out analysis. The scoring system was analyzed using Kruskal-Wallis and push-out data using ANOVA. Significance level was set at 5%. No significant difference was observed in cleaning scores among groups (p > .05). There was no significant difference when comparing the groups and the root thirds (p > .05). The adhesive failure between dentin, cement, and post predominated in all groups. Operator's age and experience with DOM did not influence the cleanliness of root canal walls or the bond strength of glass fiber posts associated with self-adhesive resin cement for post space preparation. RESEARCH HIGHLIGHTS: Although magnification is considered part of Endodontics, little is known about the variables associated. Operator's age and experience with microscope on cleaning of canals and on push-out of posts with self-adhesive resin cement were evaluated.


Involvement of Na+ and HCO-3 in receptor-mediated endocytosis of alpha 2-macroglobulin, epidermal growth factor, and vesicular stomatitis virus.
alpha 2-Macroglobulin (alpha 2M), epidermal growth factor (EGF), and vesicular stomatitis virus (VSV) each enter cultured fibroblasts by receptor-mediated endocytosis. The present study defines some basic ionic requirements in the cell culture medium which are necessary for the maximal rate of endocytosis of these three ligands. Na+ and HCO-3 were both necessary for maximal endocytosis of 125I-alpha 2M, 125I-EGF, and 35S-VSV at 37 degrees C. The ion specificities for both the anion and cation requirements were established. The binding of 125I-alpha 2M to its cellular receptors at 4 degrees C was unaffected by the absence of Na+ and HCO-3 in the culture medium. In addition, the absence of Na+ and HCO-3 in the culture medium did not reduce cellular uptake of horseradish peroxidase by fluid phase endocytosis. Na+ and HCO-3 may be general requirements in receptor-mediated endocytosis.


In vivo measurements of T1 relaxation times of 31P-metabolites in human skeletal muscle.
The T1 relaxation times were estimated for 31P-metabolites in human skeletal muscle. Five healthy volunteers were examined in a 1.5 Tesla wholebody imaging system using an inversion recovery pulse sequence. The calculated T1 relaxation times ranged from 5.517 sec for phosphocreatine to 3.603 sec for -ATP.


Involvement of intrathalamic GABAB neurotransmission in the control of absence seizures in the rat.
The role of intrathalamic GABAB neurotransmission in the control of absence seizures was investigated. In rats with genetic absence epilepsy, bilateral injections of R-baclofen (50, 100 and 200 ng/side), a selective GABAB receptor agonist, into the specific relay nuclei and the reticular nuclei of the thalamus increased spontaneous spike and wave discharges in a dose-dependent fashion, whereas injections of a GABAB antagonist CGP 35,348 (1, 2.5 and 5 micrograms/side) into the same sites decreased these seizures dose-dependently. The effect of R-baclofen (200 ng/side) on spike and wave discharges could be blocked by a subsequent injection of CGP 35,348 (1 microgram/side) at the same site. Injections of R-baclofen (200 ng) or CGP 35,348 (5 micrograms) into the midline thalamus had no effect on these seizures. In non-epileptic rats, bilateral injections of R-baclofen (1 microgram/side) into the specific relay nuclei induced synchronized rhythmic oscillations on the cortical electroencephalogram. The results suggest that GABAB receptors in the ventrolateral thalamus and in the reticular nuclei are involved in an oscillatory activity which underlies the rhythmic spike and wave discharges recorded during spontaneous generalized non-convulsive seizures.


Copper-Catalyzed Enantioselective 1,4-Protosilylation of Alkynyl-substituted Enones to Synthesize the Highly Diastereomeric Chiral Homoallenylsilanes.
A copper-catalyzed 1,4-protosilylation of α-alkynyl-enones to form the functionalized chiral homoallenylsilanes was developed. In the presence of a chiral monopyridine oxazoline ligand, a variety of trisubstituted allene derivatives bearing a contiguous stereogenic center and axis were prepared in good yields with excellent enantioselectivities and diastereoselectivities.


Echocardiographic assessment of systolic and diastolic left ventricular function using an automatic boundary detection system. Correlation with established invasive and non invasive parameters.
Systolic and diastolic left ventricular function was assessed using an echocardiographic automatic boundary detection system (ABD) in 50 unselected patients undergoing left cardiac catheterisation. Automatic boundary detection system derived parameters (fractional area change [FAC], peak positive rate of area change [+dA/dt] and peak negative rate of area change [-dA/dt]) were compared with invasively (left ventricular angiography and pressures) and non invasively (Doppler mitral filling velocities and isovolumic relaxation time) acquired conventional indices of ventricular function. Adequate detection of endocardial boundaries and subsequent measurements using the ABD system were achieved in 40/50 (80%) patients in the short axis parasternal view, in 41/50 (82%) in the apical four chamber view and in 34/50 (68%) in both views. For the whole group of patients the FAC (maximal left ventricular diastolic area--minimal left ventricular systolic area/maximal left ventricular diastolic area) estimated in the short axis view correlated with the angiographic ejection fraction (EF) measured in the right oblique projection (r = 0.51, p < 0.001). There was only a weak correlation of the FAC estimated in the apical four chamber view with the EF (r = 0.36, p < 0.01). The mean FAC (mean value of the FAC in the short axis and apical four chamber views) correlated reasonably with the EF (r = 0.62, p < 0.0001). There was no correlation between ABD derived parameters and left ventricular end diastolic pressure (LVEDP) in these patients. In a subgroup of patients with normal coronary arteries and left ventricular function (n = 17), although there was no correlation between EF and FAC, there was a strong positive correlation between FAC (apical four chamber and mean) and LVEDP (r = 0.77, p < 0.01 and r = 0.87, p < 0.01 respectively). No correlation was found in these patients between EF and LVEDP. In a further subgroup of patients with angiographically abnormal left ventricular function (EF < 45%), there was a positive correlation between FAC (short axis, apical four chamber and mean) and EF (r = 0.52, p < 0.05, r = 0.83, p < 0.0001 and r = 0.80, p < 0.001 respectively) and a negative correlation between FAC (short axis and mean) and LVEDP (r = -0.52, p < 0.05 and r = -0.60, p < 0.01 respectively). There was also a negative correlation between LVEDP and EF in the same subgroup of patients (r = -0.65, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)


Breast cancer risks following antipsychotic use in women with bipolar disorder versus schizophrenia: A territory-wide nested case-control study spanning two decades.
Accrued epidemiologic data largely support an association of antipsychotic use with breast cancer in women with schizophrenia. No studies have specifically investigated such risks in women with bipolar disorder. This study aims to examine the association between antipsychotics and breast cancer in women with bipolar disorder and compare it against schizophrenia. We conducted a nested case-control study using a territory-wide public healthcare database in Hong Kong examining women aged ≥18 years with bipolar disorder or schizophrenia. Using incidence density sampling, women with a breast cancer diagnosis were matched by up to 10 control participants. In total, 672 case participants (109 with bipolar disorder) and 6,450 control participants (931 with bipolar disorder) were included. Results show a significant association of first-generation antipsychotics with breast cancer in both women with schizophrenia [adjusted odds ratio (aOR) 1.49, 95% confidence interval (CI) 1.17-1.90] or bipolar disorder (aOR 1.80, 95% CI 1.11-2.93). Second-generation antipsychotics was associated with breast cancer only in women with bipolar disorder (aOR 2.49, 95% CI 1.29-4.79), with no significant association found in women with schizophrenia (aOR 1.10, 95% CI 0.88-1.36). In conclusion, further research on breast cancer risks is warranted for women with bipolar disorder on antipsychotics.


Heart failure and tachycardia-induced cardiomyopathy.
Congestive heart failure is a major health care concern affecting almost six million Americans and an estimated 23 million people worldwide, and its prevalence is increasing with time. Long-standing tachycardia is a well-recognized cause of heart failure and left ventricular dysfunction and has led to the nomenclature, tachycardia-induced cardiomyopathy. Tachycardia-induced cardiomyopathy is generally a reversible cardiomyopathy with effective treatment of the causative arrhythmia, either with medications, surgery, or catheter ablation. Tachycardia-induced cardiomyopathy remains poorly understood and is likely under-diagnosed. A better understanding of tachycardia-induced cardiomyopathy and improved recognition of its presence in clinical practice is vital to the health of patients with this disorder. The goal of this review is to discuss the pathogenesis and clinical manifestations of tachycardia-induced cardiomyopathy, as well as approaches to its diagnosis and treatment.


Molecular Evolution of IDH Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study.
Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design. We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined. The molecular profile of our cohort was identical to that of other GBM cohorts (IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter-methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments. This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.


Aging, calcium channel signaling and vascular tone.
Calcium signaling in vascular smooth muscle is crucial for arterial tone regulation and vascular function. Several proteins, including Ca2+ channels, function in an orchestrated fashion so that blood vessels can sense and respond to physiological stimuli such as changes in intravascular pressure. Activation of the voltage-dependent Ca2+ channel, Cav1.2, leads to Ca2+ influx and consequently arterial tone development and vasoconstriction. Unique among Ca2+ channels, the vascular Cav3.2 T-type channel mediates feedback inhibition of arterial tone-and therefore causes vasodilation-of resistance arteries by virtue of functional association with hyperpolarizing ion channels. During aging, several signaling modalities are altered along with vascular remodeling. There is a growing appreciation of how calcium channel signaling alters with aging and how this may affect vascular function. Here, we discuss key determinants of arterial tone development and the crucial involvement of Ca2+ channels. We next provide an updated view of key changes in Ca2+ channel expression and function during aging and how these affect vascular function. Further, this article synthesizes new questions in light of recent developments. We hope that these questions will outline a roadmap for new research, which, undoubtedly, will unravel a more comprehensive picture of arterial tone dysfunction during aging.


Cadmium in Seminal Plasma of Fertile and Infertile Male Dromedary Camels.
The objective of this study was to investigate the cadmium (Cd) profile in seminal plasma of male dromedary camel with impotentia generandi (post-coital infertility, IG group, n = 14) in comparison with known fertile males (FERT group, n = 5). Andrological examination was carried out for all animals. Semen was collected with electroejaculation and examined for volume, concentration, motility, viability, and abnormality. Seminal fluid was harvested after centrifugation and analyzed for Cd using atomic absorption spectrophotometer. Results showed that sperm concentration, motility, and viability were higher, while sperm abnormality was lower in IG group than in FERT group (P < 0.05). Cd was higher in seminal plasma of IG group than in FERT group (P = 0.04). Negative correlation was found between Cd concentration and sperm concentration (r = - 0.511, P = 0.04). There was also a tendency for negative correlation between Cd concentration and the testicular size (r = - 0.455, P = 0.05). In conclusion, Cd may be one of factors causing infertility in male dromedary camels.


Restriction-refeeding of calories and protein induces changes to slow wave and paradoxical sleep that parallel changes in body lipid and protein levels in rats.
Recent data have suggested that the activity of various brain nuclei is modulated during sleep. In this context, we developed the idea that sleep may participate in adapting brain responsiveness to feeding, so as to tune the control of peripheral energy metabolism. In order to characterize the nature of a possible link between sleep and peripheral energy metabolism, we have investigated the relationship between sleep parameters [wakefulness (W), slow wave sleep (SWS), paradoxical sleep (PS)] and the intensity of peripheral lipid and protein deposition processes. To achieve this, by manipulating the amount and quality of food available to rats, we induced states of energy or protein depletion/repletion which would specifically affect lean or fat body mass, which was quantified by an analysis of body composition. In parallel, using a permanently implanted cortical electrode, we measured electroencephalogram signals (EEG) to quantify the time spent in W, SWS and PS. Analysis of EEG changes in relation to the changes induced in body composition, showed that (1) the amount of sleep (PS and SWS) followed the evolution of energy supply levels, and (2) the time spent in PS relative to SWS varied to a considerable degree (14-23.5%) and followed the same trend as the ratio of lean body mass to fat mass. These results suggest the possible existence of quantitative and qualitative interactions between sleep quality and the anabolic and catabolic processes of peripheral fat and protein deposition.


Borderzone strokes and transcortical aphasia.
Borderzone infarcts (BZIs) are anatomically defined as ischemic lesions occurring at the junction between two arterial territories, accounting for 2% to 10% of strokes. Three types of hemispheric BZIs are described according to topography (ie, superficial anterior, posterior, and deep). Although published series on related aphasia are rare in the setting of BZI, aphasia is of transcortical (TCA) type, characterized by the preservation of repetition. TCA can be of motor, sensory, or mixed type depending on whether expression, understanding, or both are impaired. Recent studies have reported specific aphasic patterns. BZI patients initially presented with mixed TCA. Aphasia specifically evolved according to the stroke location, toward motor or sensory TCA in patients with respectively anterior or posterior BZI. TCA was associated with good long-term prognosis. This specific aphasic pattern is interesting in clinical practice because it prompts the suspicion of a BZI before the MRI is done, and it helps in the planning of rehabilitation and in providing adapted information to the patient and family concerning the likelihood of language recovery.


Histamine via histamine H1 receptor enhances the muscarinic receptor-induced calcium response to acetylcholine in an enterochromaffin cell model.
As a prerequisite for serotonin secretion, the P-STS ileal enterochromaffin cell line responds to acetylcholine (ACh) stimulation with an increase in intracellular calcium mediated by the muscarinic ACh receptor M3 (M3R). Histamine increases intracellular calcium via histamine H1 receptor (H1R) in P-STS cells and pre-incubation with histamine specifically augments the response to ACh but not to epinephrine or nicotine. We aimed to elucidate whether histamine receptors are involved in this synergism. Astonishingly, HEK-293 T cells-known to express M3R, but only a very low amount of histamine receptor messenger RNA-showed a similar enhancement of the calcium response to ACh by pre-incubation with histamine. Despite the much lower level of H1R protein detected in HEK-293 T cells as compared to P-STS cells, in both cell lines pre-treatment with H1R antagonists inhibited the synergism between histamine and ACh. No indication for an involvement of histamine H2 or H4 receptors in the synergism was found. Furthermore, pre-incubation with the cAMP-inducing compound forskolin had no influence on the intracellular calcium response to ACh. Serotonin secretion from P-STS cells was increased after challenge with ACh and histamine added simultaneously compared to ACh alone, suggesting that histamine increases ACh-induced serotonin secretion from enterochromaffin cells. In conclusion, our data suggest that histamine enhances the M3R-mediated intracellular calcium response to ACh via activation of H1R. This probably increases serotonin secretion from enterochromaffin cells and thereby affects intestinal motility in histamine intolerance, food allergies and irritable bowel syndrome.


Gout and organ transplantation.
Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use.


[Possible use of DNA cytophotometry and karyometry for the cytological diagnosis of human prostate cancer].
Karyometric and cytophotometric parameters of the prostate epithelium are examined on the pattern of aspiration biopsy under benign hyperplasia and carcinoma of different grades of differentiation. The results obtained suggest that the distribution of the nuclei, according to their volume and DNA values, and the calculated index of DNA accumulation per cell may be used for differential diagnostics of the prostate cancer and for making the morphological type of tumor more precise.


Isolation and characterization of cDNA clones encoding ADP-glucose pyrophosphorylase (AGPase) large and small subunits from chickpea (Cicer arietinum L.).
Four cDNA clones encoding two large subunits and two small subunits of the starch regulatory enzyme ADP-glucose pyrophosphorylase (AGPase) were isolated from a chickpea (Cicer arietinum L.) stem cDNA library. DNA sequence and Southern blot analyses of these clones, designated CagpL1, CagpL2 (large subunits) and CagpS1 and CagpS2 (small subunits), revealed that these isoforms represented different AGPase large and small subunits. RNA expression analysis indicated that CagpL1 was expressed strongly in leaves with reduced expression in the stem. No detectable expression was observed in seeds and roots. CagpL2 was expressed moderately in seeds followed by weak expression in leaves, stems and roots. Similar analysis showed that CagpS1 and CagpS2 displayed a spatial expression pattern similar to that observed for CagpL2 with the exception that CagpS1 showed a much higher expression in seeds than CagpS2. The spatial expression patterns of these different AGPase subunit sequences indicate that different AGPase isoforms are used to control starch biosynthesis in different organs during chickpea development.


[Transposons coding beta-lactamase with an extended spectrum of effects and resistance to other antibiotics].
The authors present contemporary knowledge concerning the transposition of resistance genes to penicillins, cephalosporins and carbapenems, and transposons and integrins coding resistance to other antibacterial substances. Transposition is, together with bacterial conjugation and transduction with bacteriophages, another mechanism of mobility and restructuring of resistance genes in bacterial strains of the same and also in other bacteria.


Molecular Imaging of Cardiac Amyloidosis.
The aim of this review is to give an update on the molecular imaging tools currently available as well as to discuss the potential roles and limitations of molecular imaging in cardiac amyloidosis. Molecular imaging plays a central role in the evaluation of patients with suspected cardiac amyloidosis. It can be used to diagnose and distinguish between the different types of cardiac amyloidosis. The diagnostic properties of bone scintigraphy are such that it allows reliable diagnosis of transthyretin cardiac amyloidosis without the need of endomyocardial biopsy in a significant proportion of patients. Furthermore, molecular tracers assessing amyloid plaque burden and sympathetic innervation may be useful for the non-invasive evaluation diagnosis and risk stratification of patients with suspected cardiac amyloidosis. Cardiac amyloidosis is an under-recognized cause of left ventricular hypertrophy and heart failure in the elderly. The role of molecular imaging in cardiac amyloidosis is expected to grow considering the arrival of new therapies and molecular imaging probes.


Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease.
Alpha-synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.


Living related and unrelated donors for kidney transplantation. A 28-year experience.
The objective of this study was to analyze a single center's 28-year experience with 1000 living donor transplants. The number of potential renal transplant recipients far exceeds the number of cadaveric donors. For this reason, living related donors (LRDs) and, more recently, living unrelated donors (LURDs) have been used to decrease the cadaveric donor shortage. From November 15, 1966, until August 5, 1994, 1000 living donor transplants were performed; 906 were living related and 94 were living unrelated transplants. Results were divided into precyclosporine (1966-1986, era I) and cyclosporine (1986-1994, era II) eras. Patient and graft survivals were compared between diabetic and nondiabetic recipients, between LRDs and LURDs, and according to human leukocyte antigen (HLA) matching. Donor mortality, morbidity, and postoperative renal function were also analyzed. The 5-, 10-, and 20-year graft survivals were 78.8%, 64.8%, and 43.4%, respectively. Patient and graft survival improved in era II (patient = 87.0% vs. 81.7%, p = 0.03; graft = 72.9% vs. 67.7%, p = 0.04). Nondiabetic patient and graft survivals were better than diabetic patient survivals in both eras. However, diabetic patient survival improved in era II (78.0% vs. 66.9%, p = 0.04). In era II, HLA-identical recipients had better graft survival than haploidentical or mismatched recipients (91.7% vs. 67.3% and 66.1%, p = 0.01). No difference between haploidentical LRDs and LURDs was seen. One donor death occurred in 1970, and 17% of donors developed postoperative complications. Living related and unrelated renal donation continues to be an important source of kidneys for patients with end-stage renal disease.


[Effect of fatty acids on the antibacterial activity of butylated hydroxytoluene (BHT)].
This study deals with the effect of the association of certain fatty acids with butylhydroxytoluene (BHT) on the antibacterial activity of this antioxidant. Evidence is drawn from the results as to an increase of the inhibitory effect of the antioxidant towards a few bacterial strains when it is associated with either lauric acid or palmitoleic acid.


Aflatoxin-macromolecular adducts in the hepatic and nonhepatic tissues of F-344 male rats.
In order to understand the resistance of nonhepatic organs to aflatoxin-induced aberrations, subcellular contents of 3-HAF and its covalent binding in liver, kidney and testes were determined. The amount of incorporated radioactivity into nonhepatic fractions was significantly lower. Protein deficiency also caused a decrease in the 3-HAF content in the liver, but showed no change in other two organs.


Changes in soil organic carbon status and microbial community structure following biogas slurry application in a wheat-rice rotation.
Biogas slurry is widely used as a crop fertilizer due to its available nitrogen content. However, it remains unclear how biogas slurry application affects soil organic carbon (SOC) status and soil microbial community under typical agricultural systems. Here, under a wheat-rice field experiment, we examined the responses of SOC and soil bacterial and fungal communities to biogas slurry application, both with (BSS) and without (BS) straw return, relative to chemical nitrogen fertilizer with (CFS) and without (CF) straw return. The BS treatment significantly increased total organic carbon (TOC) at all soil depths (0-60 cm), compared to CF. Greater TOC occurred at 20-40 cm depth under BSS relative to all other treatments. However, straw return had no impact on soil TOC content under the CF and CFS treatments. Labile organic carbon (LOC) in the topsoil and recalcitrant organic carbon (ROC) at 20-60 cm depth was significantly greater under BS relative to CF. The bacterial class Gammaproteobacteria and family Hyphomicrobiaceae were found to be specifically abundant under biogas slurry application after one year of wheat-rice double cropping. Network analyses showed that the soil bacterial community under biogas slurry application was more complex than under chemical fertilizer application, while the opposite was true for the fungal community. Correlations between network modules and the SOC fractions indicated that biogas slurry application stimulated soil bacteria and fungi to participate in SOC cycling. The module functionality supports our speculation that soil microorganisms degraded the biogas slurry derived-ROC in the topsoil. Overall, we conclude that substitution of chemical fertilizer with biogas slurry can be beneficial for increasing SOC stocks and, in systems with straw return, enhancing straw decomposition.


An equation of growth of a single species with realistic dependence on crowding and seasonal factors.
Various biological phenomena lead to single species models where the relative rate of increase is a non-monotone function of the density, i.e. depensation models. A brief survey of the literature and some new models are given. A nonlinear nonautonomous O.D.E. is proposed as a general depensation model in a periodically fluctuating environment. Results on existence, multiplicity and global stability of periodic solutions are given.


Comparisons of high versus low emergency department utilizers in sickle cell disease.
Patients with sickle cell disease often receive a substantial amount of their health care in the emergency department (ED) and some come to the ED frequently, seeking treatment for pain. As a result, patients with sickle cell disease are often stigmatized as opioid-seeking ED overutilizers. We describe the proportion of sickle cell disease patients who are high utilizers of the ED and compare them with other sickle cell disease patients on demographics, pain characteristics, health data, psychosocial characteristics, and quality of life. Two hundred thirty-two patients completed baseline data and at least 30 days of daily diary data. Baseline data included demographics, health data, and quality of life (Medical Outcome Study 36 Item Short Form). Daily diary data included ED utilization for sickle cell pain and descriptors of pain and distress. Eighty-two (35.5%) patients were found to be high ED utilizers. Clinically important and statistically significant differences were found between high ED utilizers and all other sickle cell disease patients: lower hematocrit level, more transfusions, more pain days, more pain crises, higher mean pain and distress, and worse quality of life on Medical Outcome Study 36 Item Short Form physical function summary scales. After controlling for severity and frequency of pain, high ED utilizers did not use opioids more frequently than other sickle cell disease patients. A substantial minority of sickle cell disease patients are high ED utilizers. However, high ED utilizers with sickle cell disease are more severely ill as measured by laboratory variables, have more pain, more distress, and have a lower quality of life.


B.K.'s Story: His Path to Becoming an Inner-City Custodial Father.
African American males are regularly cast as deadbeat dads and non-contributors to family life. However, a growing literature has been documenting that African American males do contribute in many ways, including as custodial fathers. 5% of African American children live in single-parent father-only households. This paper presents B.K.'s story which describes his overcoming drug abuse and his becoming a custodial father. His story illustrates the powerful contribution African American males can make in their families and thereby in their communities. His story also describes how social outreach sustained him during his most troubled periods and supported his path to responsibility.


Comparative analysis of neurological disorders focuses genome-wide search for autism genes.
The behaviors of autism overlap with a diverse array of other neurological disorders, suggesting common molecular mechanisms. We conducted a large comparative analysis of the network of genes linked to autism with those of 432 other neurological diseases to circumscribe a multi-disorder subcomponent of autism. We leveraged the biological process and interaction properties of these multi-disorder autism genes to overcome the across-the-board multiple hypothesis corrections that a purely data-driven approach requires. Using prior knowledge of biological process, we identified 154 genes not previously linked to autism of which 42% were significantly differentially expressed in autistic individuals. Then, using prior knowledge from interaction networks of disorders related to autism, we uncovered 334 new genes that interact with published autism genes, of which 87% were significantly differentially regulated in autistic individuals. Our analysis provided a novel picture of autism from the perspective of related neurological disorders and suggested a model by which prior knowledge of interaction networks can inform and focus genome-scale studies of complex neurological disorders.


The jensen symposium; a tribute to a pioneer in the field of nuclear receptor biology.
The Jensen Symposium was held at the University of Cincinnati in December 2003 to honor the pioneering contributions of Dr. Elwood Jensen to the field of nuclear hormone action. Those in attendance were treated to an outstanding scientific program that served as an update of recent progress and illustrated the breadth of activity in the nuclear receptor field. Here we highlight recent findings presented at the Symposium that provide new insights into the mechanisms of nuclear receptor action and the diverse roles of members of the nuclear receptor superfamily in development and homeostasis.


Prosthetic vascular graft infection imaging.
We are reporting our experience with imaging of vascular graft infections using computed tomography angiography (CTA), white blood cell (WBC) scintigraphy and software-based fusion imaging. Institutional review board approval was obtained. We performed a retrospective review of patients who had clinical signs and symptoms of vascular graft infection in whom both WBC single photon emission computed tomography (SPECT) and CTA was performed between 2005 and 2010. We performed fusion imaging with available data using software coregistration technique and analyzed outcome of the patients. We had 20 patients; 11 had grafts of the aorta, five had peripheral vascular grafts, three had aortic and peripheral vascular grafts, and one had a thoracic aortic graft. WBC imaging was positive in 10 patients, negative in six patients and indeterminate in 4 patients. CTA was positive in six patients, negative in four patients and indeterminate in 10 patients. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value (NPV) for WBC, CTA and WBC SPECT/CTA fusion were 75/100/80/100/50%, 88/50/80/88/50% and 94/50/85/88/67% respectively. The use of CTA, WBC scintigraphy, and image co-registration influenced the diagnostic confidence of graft infection and the outcome of the patients. Software-based fusion imaging of both modalities resulted in improved sensitivity, accuracy, and NPV.


Shear bond strengths between alumina-toughened zirconia cores and veneering ceramics and their susceptibility to aging.
To evaluate the shear bond strength (SBS) between alumina-toughened zirconia (ATZ) cores and veneering ceramics, investigate the effect of aging in artificial saliva on SBS and compare it with that of yttria-stabilized tetragonal zirconia polycrystals(Y-TZP). Bars of ATZ and Y-TZP were layered with veneering ceramics in accordance to the recommendation of the manufacturer. Half of each group (n = 10) was aged at 134 °C (under 2 bar pressure) in an autoclave for 48 h. Subsequently, all specimens were subjected to shear force in a universal testing machine. The interface and fractured surface of the specimens were evaluated using scanning electron microscopy and X-ray energy dispersive spectroscopy. The initial mean SBS values in MPa±SD were 28.9±8.0 for ATZ and 26.2±7.6 for Y-TZP. After aging, the mean SBS values for ATZ and Y-TZP were 22.9±4.9 MPa and 22.8±6.9 MPa, respectively. Neither the differences between the SBS values of the ATZ and Y-TZP groups nor the influence of aging on all groups were statistically significant. The SBS between the ATZ core and the veneering ceramics was not affected by aging. The SBS of ATZ to veneering ceramics was not significantly different compared with that of Y-TZP.


Grey platelet syndrome: studies on platelet alpha-granules, lysosomes and defective response to thrombin.
The platelets of a young man with the grey platelet syndrome were severely depleted of all seven alpha-granule proteins assayed as well as partially deficient in alpha-mannosidase and alpha-fucosidase; four other lysosomal enzymes were present in normal concentrations. Total platelet 5-hydroxytryptamine (5HT) and adenine nucleotides were normal, and 14C-5HT uptake reached normal levels only slightly more slowly than a control. Aggregation and dense body secretion occurred normally in response to ADP, adrenaline, collagen, PAF-acether, sodium arachidonate, A23187, Ionomycin, TPA and U44069, but were very delayed in response to thrombin. The increase in cytosolic free calcium in response to thrombin was very slow and much reduced in amplitude, whether in the presence or absence of extracellular Ca2+. These defects in response to thrombin were not corrected by the separate addition of purified alpha-granule proteins or by a whole releasate from normal platelets. It is suggested that these platelets, in addition to their alpha-granule deficiency, may have a specific defect of thrombin receptor-mediated activation of phospholipase C.


Effects of insulin on the metabolism of the isolated working rat heart perfused with undiluted rat blood.
Working rat hearts were perfused with either buffer or with defibrinated, undiluted rat blood dialyzed to remove vasoconstrictor factors. With precautions taken for sterility in the preparation of the perfusate and the apparatus, hearts were obtained which were stable as judged by stroke rate and cardiac output. In these hearts, cardiac output and coronary flow averaged 46.0 and 1.7 ml/g heart per min, respectively. Perfusion with erythrocyte-free buffer depressed cardiac output by 30%, while coronary flow averaged 8.8 ml/g of heart per min. The mean stroke rate of blood-perfused hearts was 300 beats/min but only 240 beats/min during buffer perfusion. In blood-perfused hearts, insulin did not alter stroke rate but significantly lowered coronary flow. The hormone caused a transient increase in cardiac output in hearts perfused with buffer. Insulin did not alter glucose uptake in buffer-perfused hearts but increased lactate release in perfusions with blood. Both serum fatty acids and triacylglycerol fatty acids were significant metabolic fuels in hearts perfused with undiluted blood. The preparation described would appear to be potentially useful for the study of myocardial metabolism in vitro.


CCR2-overexpressing biomimetic carrier-free nanoplatform for enhanced cascade ferroptosis tumor therapy.
Ferroptosis-based nanoplatforms have shown great potential in cancer therapy. However, they also face issues such as degradation and metabolism. Carrier-free nanoplatforms consisting of active drugs can effectively avoid the security issues associated with additional carrier ingredients. Herein, a biomimetic carrier-free nanoplatform (HESN@CM) was designed to treat cancer by modulating cascade metabolic pathways of ferroptosis. CCR2-overexpressing macrophage membrane-modified HESN can target cancer cells via the CCR2-CCL2 axis. The acidic tumor microenvironment (TME) can disrupt the supramolecular interaction of HESN, releasing hemin and erastin. Then, erastin could induce cancer cells ferroptosis by inhibiting system XC- pathways, while hemin, a vital component of blood to transport oxygen, could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to induce cancer cells' ferroptosis further. Meanwhile, erastin could enhance the activity of HO-1, further promoting the release of Fe2+ from hemin. As a result, HESN@CM demonstrated superior therapeutic efficacy in both primary and metastatic tumors in vitro and in vivo. The carrier-free HESN@CM provided cascade ferroptosis tumor therapy strategies for potential clinical application. STATEMENT OF SIGNIFICANCE: CCR2-overexpressing biomimetic carrier-free nanoplatform (HESN@CM) was designed for cancer treatment by modulating metabolic pathways of ferroptosis. HESN modified with CCR2-overexpressing macrophage membrane can target tumor cells via the CCR2-CCL2 axis. HESN was composed of hemin and erastin without additional vectors. Erastin could directly induce ferroptosis, while hemin could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to enhance ferroptosis further. Meanwhile, erastin could improve the activity of HO-1, promoting the release of Fe2+ from hemin. Therefore, HESN@CM with good bioavailability, stability, and simple preparation can realize cascade ferroptosis tumor therapy and have the potential prospect of clinical translation.


Efficacy of balloon tamponade in treatment of bleeding gastric and esophageal varices. Results in 151 consecutive episodes.
The efficacy and complications of esophageal tamponade as the first procedure in the routine management of acute variceal hemorrhage were evaluated in 151 consecutive bleeding episodes treated at a specialized unit. The Sengstaken-Blakemore tube was employed in the 118 cases in which emergency endoscopy demonstrated bleeding esophageal varices, and the Linton-Nachlas balloon in the 33 cases with bleeding from gastric varices. Hemostasis lasting at least 24 hr was obtained in 91.5% of cases treated with the Sengstaken-Blakemore balloon and in 88% of those treated with the Linton-Nachlas balloon. Permanent hemostasis was obtained in 47.7% of all cases. The only severe complication noted in these 151 episodes of bleeding treated by tamponade was pulmonary aspiration, which was detected in 10% of cases. This complication was related to the presence and degree of encephalopathy (P less than 0.001) and was prevented by orotracheal intubation prior to tamponade. These results indicate that balloon tamponade continues to be a reliable and valuable method to arrest bleeding from esophagogastric varices.


Pancreaticogastrostomy decreased relaparotomy caused by pancreatic fistula after pancreaticoduodenectomy compared with pancreaticojejunostomy.
Pancreaticogastrostomy (PG) is associated with a lower relaparotomy rate following pancreaticoduodenectomy (PD) than pancreaticojejunostomy (PJ). Retrospective clinical trial. Department of digestive surgery and transplantation. Between 1987 and 2001, 250 consecutive patients underwent PD in our institution. Among them, 83 patients underwent PJ and 167, PG. Preoperative clinicopathological features, intraoperative parameters, in-hospital mortality, postoperative morbidity, pancreatic fistula (PF), relaparotomy rates, and length of hospital stay were analyzed and compared between 2 reconstructive methods, PJ and PG, after PD. The morbidity rate, including PF, was lower in the PG group (38.3%) than in the PJ group (53.0%; P =.02). The mortality rate did not differ between the PG group (2.9%) and PJ group (2.4%). Conversely, the incidence of PF and the mean +/- SD length of hospital stay were significantly lower in the PG group (2.3% and 17.2 +/- 7.7 days) than in the PJ group (20.4% and 23.3 +/- 11.7 days; P<.001 for both variables). Moreover, the overall relaparotomy rate was significantly lower in the PG group (4.7%) than in the PJ group (18.0%; P =.001). Nine (52.9%) of 17 patients with PF in the PJ group underwent relaparotomy. These 9 patients underwent subsequent completion pancreatectomy (n = 7) or removal of peripancreatic necrotized tissue (n = 2) with a postoperative mortality rate of 22.2%. However, no patient required relaparotomy for PF in the PG group because medical therapy succeeded in all 4 patients with PF. Moreover, no mortality related to PF occurred in the PG group. The PG procedure is a safe method of reconstruction after PD, with a significantly lower rate of PF and relaparotomy.


The T-peak-to-T-end interval: a novel ECG marker for ventricular arrhythmia and appropriate ICD therapy in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death (SCD) primarily due to ventricular arrhythmia (VA). In patients (pts.) with a high risk of SCD, the implantation of an intracardiac cardioverter defibrillator (ICD) is thus indicated. Previous studies suggest that a prolonged interval between the peak and the end of the T wave, T-peak to T-end (TpTe), is associated with an elevated risk of VA and SCD in various clinical settings. The aim of our study was to evaluate the association between TpTe and VA in HCM pts. with a previously implanted ICD. In 40 HCM pts. (51.4 ± 16.4 years; 62.5% men), TpTe was measured using the baseline digital standard resting 12-lead ECG during sinus rhythm. VA was assessed by device follow-up. Within 41.8 ± 35.1 months, 7 (17.5%) pts. had VA leading to appropriate therapy (AT), 7 pts. (17.5%) had non-sustained VA, and 26 pts. (65.0%) had no VA. The maximum TpTe was significantly prolonged in pts. with VA leading to AT compared to pts. without VA (101.3 ± 19.6 vs. 79.9 ± 15.3 ms; p = 0.004). Maximum TpTe was associated with an elevated risk of VA leading to AT (hazard ratio per 10 ms increase 1.63; 95% CI 1.04-2.54; p = 0.031) and pts. with a maximum TpTe ≤ 78 ms were without any VA leading to AT during follow-up. There was no correlation of maximum TpTe to other clinical parameters in our patient cohort. A prolonged TpTe is associated with VA and AT in HCM. Our findings suggest that TpTe can possibly serve as a marker for ventricular arrhythmogenesis in pts. with HCM and assessment of TpTe might, therefore, optimize SCD risk stratification.


Socio-economic burden of disease: Survivorship costs for bladder cancer.
In this cost-of-illness study, we analysed the socio-economic burden of bladder cancer survivorship for the ten years after initial treatment in Germany during 2000, 2010 and 2020. Bladder cancer follow-up guidelines were extracted from the European Association of Urology. Per patient costs were estimated with a micro-costing approach considering direct and indirect medical expenses derived from literature and official scales of tariffs. Three perspectives covering costs for patients, providers, and insurers were included to estimate societal costs. Mean 10-year follow-up costs per patient amounted to EUR 2214 for low-risk, EUR 4758 for medium-risk, and EUR 11,325 for high-risk non-muscle invasive bladder cancer (NMIBC) in 2020. The mean economic burden of muscle-invasive and metastatic bladder cancer (MIBC) was EUR 8994 per patient. Overall expenditure rose by 65% from 2000 to 2020 across all cancer stages (p < 0.001). While insurers covered 38% of costs in 2000, only 31% of costs were reimbursed in 2020 (p < 0.001). 58% of high-risk NMIBC follow-up resources were consumed by physician-patient visits and 17% by medical imaging (x-ray, CT-IVU, ultrasound). Spending was unevenly distributed across follow-up years (years 1-2: 43%, years 3-5: 29%, years 5-10: 28%). The rising socio-economic burden of follow-ups signifies the relevance of cancer survivorship for the healthcare system and society. This burden must be evenly distributed across stakeholders and considered in cost-effectiveness evaluations of novel anti-cancer drugs. Policy summary Personalized, equitable, and effective follow-up schedules covered by insurance funds are necessary to care for cancer survivors.


Next-generation sequencing and bioinformatic approaches to detect and analyze influenza virus in ferrets.
Conventional methods used to detect and characterize influenza viruses in biological samples face multiple challenges due to the diversity of subtypes and high dissimilarity of emerging strains. Next-generation sequencing (NGS) is a powerful technique that can facilitate the detection and characterization of influenza, however, the sequencing strategy and the procedures of data analysis possess different aspects that require careful consideration. The RNA from the lungs of ferrets infected with influenza A/California/07/2009 was analyzed by next-generation sequencing (NGS) without using specific PCR amplification of the viral sequences. Several bioinformatic approaches were used to resolve the viral genes and detect viral quasispecies. The genomic sequences of influenza virus were characterized to a high level of detail when analyzing the short-reads with either the fast aligner Bowtie2, the general purpose aligner BLASTn or de novo assembly with Abyss. Moreover, when using distant viral sequences as reference, these methods were still able to resolve the viral sequences of a biological sample. Finally, direct sequencing of RNA samples did not provide sufficient coverage of the viral genome to study viral quasispecies, and, therefore, prior amplification of the viral segments by PCR would be required to perform this type of analysis. the introduction of NGS for virus research allows routine full characterization of viral isolates; however, careful design of the sequencing strategy and the procedures for data analysis are still of critical importance.


Effect of irrigation, nitrogen application, and a nitrification inhibitor on nitrous oxide, carbon dioxide and methane emissions from an olive (Olea europaea L.) orchard.
Drip irrigation combined with nitrogen (N) fertigation is applied in order to save water and improve nutrient efficiency. Nitrification inhibitors reduce greenhouse gas emissions. A field study was conducted to compare the emissions of nitrous oxide (N2O), carbon dioxide (CO2) and methane (CH4) associated with the application of N fertiliser through fertigation (0 and 50kgNha(-1)), and 50kgNha(-1)+nitrification inhibitor in a high tree density Arbequina olive orchard. Spanish Arbequina is the most suited variety for super intensive olive groves. This system allows reducing production costs and increases crop yield. Moreover its oil has excellent sensorial features. Subsurface drip irrigation markedly reduced N2O and N2O+N2 emissions compared with surface drip irrigation. Fertiliser application significantly increased N2O+N2, but not N2O emissions. Denitrification was the main source of N2O. The N2O losses (calculated as emission factor) ranging from -0.03 to 0.14% of the N applied, were lower than the IPCC (2007) values. The N2O+N2 losses were the largest, equivalent to 1.80% of the N applied, from the 50kgNha(-1)+drip irrigation treatment which resulted in water filled pore space >60% most of the time (high moisture). Nitrogen fertilisation significantly reduced CO2 emissions in 2011, but only for the subsurface drip irrigation strategies in 2012. The olive orchard acted as a net CH4 sink for all the treatments. Applying a nitrification inhibitor (DMPP), the cumulative N2O and N2O+N2 emissions were significantly reduced with respect to the control. The DMPP also inhibited CO2 emissions and significantly increased CH4 oxidation. Considering global warming potential, greenhouse gas intensity, cumulative N2O emissions and oil production, it can be concluded that applying DMPP with 50kgNha(-1)+drip irrigation treatment was the best option combining productivity with keeping greenhouse gas emissions under control.


Three-dimensional reconstruction of protein networks provides insight into human genetic disease.
To better understand the molecular mechanisms and genetic basis of human disease, we systematically examine relationships between 3,949 genes, 62,663 mutations and 3,453 associated disorders by generating a three-dimensional, structurally resolved human interactome. This network consists of 4,222 high-quality binary protein-protein interactions with their atomic-resolution interfaces. We find that in-frame mutations (missense point mutations and in-frame insertions and deletions) are enriched on the interaction interfaces of proteins associated with the corresponding disorders, and that the disease specificity for different mutations of the same gene can be explained by their location within an interface. We also predict 292 candidate genes for 694 unknown disease-to-gene associations with proposed molecular mechanism hypotheses. This work indicates that knowledge of how in-frame disease mutations alter specific interactions is critical to understanding pathogenesis. Structurally resolved interaction networks should be valuable tools for interpreting the wealth of data being generated by large-scale structural genomics and disease association studies.


Thoracic applications of dual-source CT technology.
Among the various imaging modalities available, CT has remained over time the core imaging technique for the evaluation of respiratory disorders. The recent advent of dual-source CT offers innovative approaches to investigate thoracic diseases, based on the use of one or two tubes as well as single or dual energy to scan the entire thorax. Two major options can be used in clinical practice with promising results. Dual source, single-energy scanning allows scanning of the entire thorax with ultra-high temporal resolution which opens the field of integrated cardiothoracic imaging without ECG gating as well as optimized evaluation of pediatric and adult patients with limited ability to cooperate. Dual-source, dual-energy acquisitions represent another very innovative means of investigating respiratory disorders, adding tissue characterization and functional analysis to morphological evaluation. The purpose of this review article is to provide results on preliminary experiences with the above-mentioned scanning conditions with dual-source CT and to envisage potential forthcoming applications in the field of thoracic imaging.


Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium.
We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.


Crystal structure, Hirshfeld surfaces and DFT computation of NLO active (2E)-2-(ethoxycarbonyl)-3-[(1-methoxy-1-oxo-3-phenylpropan-2-yl)amino] prop-2-enoic acid.
Nonlinear optical (NLO) activity of the compound (2E)-2-(ethoxycarbonyl)-3-[(1-methoxy-1-oxo-3-phenylpropan-2-yl)amino] prop-2-enoic acid is investigated experimentally and theoretically using X-ray crystallography and quantum chemical calculations. The NLO activity is confirmed by both powder Second Harmonic Generation (SHG) experiment and first hyper polarizability calculation. The title compound displays 8 fold excess of SHG activity when compared with the standard compound KDP. The gas phase geometry optimization and vibrational frequencies calculations are performed using density functional theory (DFT) incorporated in B3LYP with 6-311G++(d,p) basis set. The title compound crystallizes in non-centrosymmetric space group P21. Moreover, the crystal structure is primarily stabilized through intramolecular N-H···O and O-H···O hydrogen bonds and intermolecular C-H···O and C-H···π interactions. These intermolecular interactions are analyzed and quantified using Hirshfeld surface analysis and PIXEL method. The detailed vibrational assignments are performed on the basis of the potential energy distributions (PED) of the vibrational modes.


Characteristics of clients using a community-based drug treatment service ('CAPS-AD') in Brazil: An exploratory study.
Substance use is common in Brazil. In order to improve availability of substance misuse care services, over 400 Psycho-Social Care Centres for Alcohol and Drugs (CAPS-AD) - providing community-based care - have been established following mental health care reform (2001). Information on CAPS-AD clients and outcomes is limited. The present study examined select characteristics of local CAPS-AD clients. N=143 adult CAPS-AD clients in Ceilândia (suburb of Brasília, Federal District) participated in a 1-week 'snapshot' assessment of service users (February 2015). Following consent, descriptive data were collected by a brief, anonymous interviewer-administered questionnaire that included socio-demographic, drug use, treatment history and needs/barriers information. Participants were predominantly male; middle-aged; unemployed; married; with middle-school education; primary problem drugs indicated were alcohol and cocaine/crack; half had prior treatment histories and indicated that treatment was externally motivated; 60% reported ways to improve treatment and possible reasons for treatment discontinuation; in multi-variate analyses, the latter was associated with employment and education status (both p<.05). CAPS-AD services appear to have increased low-barrier substance misuse treatment availability in Brazil, as well as attract individuals new to the treatment system. Various potential barriers to continuing in treatment should be addressed and more research on CAPS-AD clients and outcomes is needed.


In vitro monitoring of GTPase activity and enzyme kinetics studies using capillary electrophoresis.
A capillary electrophoresis (CE)-based method for the in vitro detection and monitoring of nucleotide-triphosphatase activity is described. This robust and reproducible method was used to investigate GTPase activity of a recombinant protein construct containing the catalytic domain of Human SEPT4/Bradeion beta (GST-rDGTPase). This example application demonstrates that the CE technique can replace classical radioactive methods for GTPase activity assays and may be used as a routine analytical tool. Enzyme kinetics of GST-rDGTPase was studied and yielded the following kinetic parameters: v(max) = 1.7 microM min(-1) +/- 0.1, Km = 1.0 mM +/- 0.3, and apKcat = 9 x 10(-3) s(-1). In addition the effect of co-factors such as Mg2+ and Mn2+ on the catalytic activity was investigated. The described analytical method was also shown to be useful to analyze diphosphated and triphosphated forms of other nucleotides.


A new species of the genus Tyrictaca Walker, 1862 (Lepidoptera: Sesiidae) from West Malaysia with a catalogue of the genus.
A new species, Tyrictaca pulchra O. Gorbunov sp. nov., is described and illustrated from West Malaysia. The female and the larval host plant are still unknown. Ceratocorema woodstocki Liang Hsu, 2017 is transferred from the genus Tyrictaca Walker, 1862 to the genus Entrichella Bryk, 1947. An annotated catalogue of the genus Tyrictaca is provided.


Emergency pancreaticoduodenectomy: When is it needed? A dual non-trauma centre experience and literature review.
Emergency pancreaticoduodenectomy (EPD) has been very rarely reported in literature as a lifesaving procedure for complex pancreatic injury, uncontrollable hemorrhage from ulcers and tumors, descending duodenal perforations, and severe infection. The aim of this study was to analyze the experience of two non-trauma centers and to review the literature concerning emergency pancreaticoduodenectomy. From January 2005 to December 2014, from a population of 169 PD (92 females and 77 males; mean age: 61.3, range 23-81) 5 patients (3%; 2 females and 3 males; mean age: 57.8, range: 42-74) underwent EPD for non-traumatic disease performed at two Academic Units of the University of Bari. The emergency pancreaticoduodenectomy subgroup of patients showed an overall morbidity of 80%, and mortality of 40%. In 80% (4/5) of patients treated by emergency pancreaticoduodenectomy, the pancreatic remnant was not reconstructed, and in 20% (1/5) a pancreaticojejunostomy was performed. Emergency pancreaticoduodenectomy is an effective life-saving operation reservable to pancreatoduodenal trauma, perforations, and bleeding, unmanageable by a less invasive approach. It should be preferentially approached by surgeons with a high level of experience in hepatobiliary and pancreatic surgery and in trauma centers too, but it should also be in the armamentarium of general surgeons performing hepato-pancreato-biliary surgery.


Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors.
In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.


Effects of ethanol and acetaldehyde on cultured pre-implantation mouse embryos.
Pre-implantation 2-cell stage mouse embryos, obtained from superovulated CF-1 mice, were exposed to ethanol and acetaldehyde through the culture medium for 60 min followed by a 105-h incubation period. Control and ethanol exposed embryos survived equally well in ethanol concentrations as high as 800 mg/100 ml medium and acetaldehyde levels up to 10 mg/100 ml medium.


Fast reconstruction of an original continuous series from a recurrence plot.
We propose an algorithm to refine the reconstruction of an original time series given a recurrence plot, which is also referred to as a contact map. The refinement process calculates the local distances based on the Jaccard coefficients with the neighbors in the previous resolution for each point and takes their weighted average using local distances. We demonstrate the utility of our method using two examples.


Systematic review and meta-analysis of electrocautery versus scalpel for surgical skin incisions.
The creation of surgical skin incisions has historically been performed using a cold scalpel. The use of electrocautery for this purpose has been controversial with respect to patient safety and surgical efficacy. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare skin incisions made by electrocautery and a scalpel. A systematic electronic literature search was performed using 2 electronic databases (MEDLINE and PubMed), and the methodological quality of included publications was evaluated. Six RCTs were identified comparing electrocautery (n = 606) and a scalpel (n = 628) for skin incisions. No significant difference in wound infection rates or scar cosmesis was identified between the treatment groups. Electrocautery significantly reduced the incision time and postoperative wound pain. A trend toward less incisional blood loss from skin incisions made with electrocautery was noted. Electrocautery is a safe and effective method for performing surgical skin incisions.


A review of electrocardiogram filtering.
Analog filtering and digital signal processing algorithms in the preprocessing modules of an electrocardiographic device play a pivotal role in providing high-quality electrocardiogram (ECG) signals for analysis, interpretation, and presentation (display, printout, and storage). In this article, issues relating to inaccuracy of ECG preprocessing filters are investigated in the context of facilitating efficient ECG interpretation and diagnosis. The discussion covers 4 specific ECG preprocessing applications: anti-aliasing and upper-frequency cutoff, baseline wander suppression and lower-frequency cutoff, line frequency rejection, and muscle artifact reduction. Issues discussed include linear phase, aliasing, distortion, ringing, and attenuation of desired ECG signals. Due to the overlapping power spectrum of signal and noise in acquired ECG data, frequency selective filters must seek a delicate balance between noise removal and deformation of the desired signal. Most importantly, the filtering output should not adversely impact subsequent diagnosis and interpretation. Based on these discussions, several suggestions are made to improve and update existing ECG data preprocessing standards and guidelines.


Coherence between one random and one periodic signal for measuring the strength of responses in the electro-encephalogram during sensory stimulation.
Coherence between a pulse train representing periodic stimuli and the EEG has been used in the objective detection of steady-state evoked potentials. This work aimed to quantify the strength of the stimulus responses based on the statistics of coherence estimate between one random and one periodic signal, focusing on the confidence limits and power of significance tests in detecting responses. To detect the responses in 95% of cases, a signal-to-noise ratio of about -7.9 dB was required when using 48 windows (M) in the coherence estimation. The ratio, however, increased to -1.2 dB when M was 12. The results were tested in Monte Carlo simulations and applied to EEGs obtained from 14 subjects during visual stimulation. The method showed differences in the strength of responses at the stimulus frequency and its harmonics, as well as variations between individuals and over cortical regions. In contrast to those from the parietal and temporal regions, results for the occipital region gave confidence limits (with M = 12) that were above zero for all subjects, indicating statistically significant responses. The proposed technique extends the usefulness of coherence as a measure of stimulus responses and allows statistical analysis that could also be applied usefully in a range of other biological signals.


"To nitrous oxide, chloroform gives way": Was Dr. W.J.A. DeLancey's poetic license in advertising…inspired?
Born in New Hampshire but raised in Massachusetts, 14-year-old William J.A. DeLancey became "the man of the house" after the accidental death of his father. Amiable and good humored, young DeLancey supported his widowed mother and his three sisters until the girls all reached maturity. After he married, DeLancey moved to Illinois and took up dentistry, eventually settling in Centralia. Following anesthesia training back east at Manhattan's Colton Dental Association, DeLancey returned to Centralia. There he practiced the Coltonian method of testing freshly made nitrous oxide upon himself before using the gas upon patients. Before his training at Colton Dental, DeLancey had advertised in Centralia newspapers only in prose. After he began administering laughing gas to his patients and to himself, DeLancey waxed poetic and began advertising in heroic couplets in local newspapers.


Interviewing For Residency as an LGBTQ+ Applicant: Compounded Problems With Virtual Interviewing.
Applying to and interviewing for residency positions can be challenging tasks for LGBTQ+ applicants. Resident and faculty surgeons have expressed challenges in disclosing their sexual orientation and/or gender identity throughout the recruitment process. Discrimination and lack of LGBTQ+ inclusion in the recruitment process may have been exacerbated by virtual interviews in response to the COVID-19 pandemic. The authors describe their experiences interviewing virtually for academic general surgery programs, and academic and university-affiliated/community residency programs as LGBTQ+ applicants. Several recommendations are offered to help reduce LGBTQ+ discrimination and to help make institutions more inclusive with the overall aim of making resident recruitment more inclusive for LGBTQ+ applicants.


A monopartite sequence is essential for p45 NF-E2 nuclear translocation, transcriptional activity and platelet production.
p45 NF-E2 is a bZIP transcription factor crucial for thrombopoiesis, as indicated by the fact that loss of p45 NF-E2 function results in dramatic embryonic lethal thrombopoietic defects and its overexpression boosts platelet release. In the present study, we set out to identify the sequences responsible for p45 NF-E2 nuclear import, evaluate its transport mechanism and ascertain its functional significance. A series of p45 NF-E2 deletion constructs fused to green fluorescent protein (GFP) was created and their cellular localization examined in mammalian cells, with the factor responsible for nuclear import identified using an in vitro transport assay. A p45 NF-E2 derivative mutated in the nuclear targeting sequence (NLS) was generated and its biological activity compared with wild type (wt) in luciferase assays, and proplatelet and platelet production measured in murine megakaryocytes transduced with a retroviral vector. Here we show that residues 271-273 are essential for nuclear import of p45 NF-E2 in COS-7 and in primary bone marrow cells. The p45 NF-E2 NLS facilitates nuclear import specifically via importin (IMP) 7. Although within the DNA-binding domain of p45 NF-E2, the NLS is not essential for DNA-binding, but is crucial for transcriptional activation and biological activity; where, in contrast to wt, a mutant derivative with a mutated NLS failed to promote proplatelet and platelet production in murine megakaryocytes. The NLS is critical for p45 NF-E2 function, with the present study being the first to demonstrate the importance of NLS-dependent nuclear import of p45 NF-E2 for platelet development.


Mathematical, numerical and experimental study in the human aorta with coexisting models of bicuspid aortic stenosis and coarctation of the aorta.
Coarctation of the aorta is an obstruction of the aorta and is usually associated with other concomitant cardiovascular abnormalities especially with bicuspid aortic valve stenosis. The objectives of this study are, (1) to investigate the effects of coarctation on the hemodynamics in the aorta to gain a better understanding of the cause of certain post-surgical coarctation problems, (2) to develop and introduce a new lumped parameter model, mainly based on non-invasive data, allowing the description of the interaction between left ventricle, coarctation of the aorta, aortic valve stenosis, and the arterial system.


Symposium on trauma for the general surgeon. 1. An accident health care program: the organization and development of regional trauma units.
Fifteen thousand deaths, 3 million hospital bed--days and billions of dollars per year are the cost of dealing with accidents in Canada. Our present methods of caring for the seriously injured need revision. The available data on accidents, although extensive, are not sufficiently complete to allow clear definition of the Canadian accident profile. We are unable to explain why Canadians are subject to a 25% greater risk of motor vehicle accidents than are Americans. The development of a Canadian accident health care delivery and audit system is proposed that would provide an improved standard of health care and supply a data base for the advancement of effective programs for accident prevention. The system would include radio-equipped ambulance stations strategically located between regional trauma units, which would be equipped to care for the majority of injured patients. Those severely injured patients who could not be handled by the regional trauma units would be transferred to comprehensive trauma units established in the major referral centres. A trauma registry set up in every province would collect data on each patient and accident to provide an accurate provincial accident profile and a national trauma institute would correlate provincial data.


Characterization of miR-200 family members as blood biomarkers for human and laying hen ovarian cancer.
MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. We evaluated the levels of family members relative to the internal control miR-103a in ovarian cancer and control blood specimens collected from American and Hong Kong Chinese institutions, as well as from a laying hen spontaneous ovarian cancer model. The levels of miR-200a, miR-200b and miR-200c were significantly elevated in all human cancer versus all control blood samples. Further analyses showed significantly higher miR-200 levels in Chinese control (except miR-429) and cancer (except miR-200a and miR141) samples than their respective American counterparts. Subtype-specific analysis showed that miR-200b had an overall elevated level in serous cancer compared with controls, whereas miR-429 was significantly elevated in clear cell and endometrioid cancer versus controls. MiR-429 was also significantly elevated in cancer versus control in laying hen plasma samples, consistent with the fact that endometrioid tumor is the prevalent type in this species. A neural network model consisting of miR-200a/200b/429/141 showed an area under the curve (AUC) value of 0.904 for American ovarian cancer prediction, whereas a model consisting of miR-200b/200c/429/141 showed an AUC value of 0.901 for Chinese women. Hence, miR-200 is informative as blood biomarkers for both human and laying hen ovarian cancer.


Panic disorder and agoraphobia: fear of fear or fear of the symptoms produced by hyperventilation?
Two versions of the fear-of-fear hypothesis of panic disorder are discussed. The fear-of-the-somatic-effects-of-fear version, which is distinguished from the classical conditioning version, is compared with the hyperventilation theory of panic disorder and agoraphobia. The fear-of-the-somatic-effects-of-fear hypothesis is criticized on the basis of its inability to explain adequately (a) the initiation of panic attacks, (b) the growth in intensity of panic attacks, and (c) the termination of panic attacks. The tenability of the hyperventilation theory is supported by evidence from programs of treatment derived from the basic assumptions of the theory.


Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients.
Most patients with dengue experience mild disease, dengue fever (DF), while few develop the life-threatening diseases dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). No laboratory tests predict DHF or DSS. We evaluated whether the serum chymase level can predict DHF or DSS in adult and pediatric patients and the influence of preexisting conditions (PECs) on chymase levels. Serum chymase levels were measured in patients presenting with undifferentiated fever to hospitals in Colombo District, Sri Lanka. The value of serum the chymase concentration and clinical signs and symptoms as predictors of DHF and/or DSS was evaluated by multivariate analysis. We assessed the influence of age, PECs, and day after fever onset on the robustness of the chymase level as a biomarker for DHF and/or DSS. An elevated chymase level in acute phase blood samples was highly indicative of later diagnosis of DHF or DSS for pediatric and adult patients with dengue. No recorded PECs prevented an increase in the chymase level during DHF. However, certain PECs (obesity and cardiac or lung-associated diseases) resulted in a concomitant increase in chymase levels among adult patients with DHF. These results show that patients with acute dengue who present with high levels of serum chymase consistently are at greater risk of DHF. The chymase level is a robust prognostic biomarker of severe dengue for adult and pediatric patients.


Emergency versus delayed hepatectomy following transarterial embolization in spontaneously ruptured hepatocellular carcinoma survivors: a systematic review and meta-analysis.
Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Recent trends in surgical treatments avoid emergency hepatectomy (EH) and favor emergency transarterial embolization (TAE) followed by delayed hepatectomy (DH). Still, there is debate on which is the better treatment option and whether delaying hepatectomy increases peritoneal metastasis. To provide evidence-based references for the optimal management of patients with spontaneously ruptured HCC by comparing the outcomes of EH and DH. Literature on postoperative outcomes of EH and DH in patients with spontaneously ruptured HCC published between the date of the database establishment and May 2022, was identified in the PubMed, EMBASE, and Cochrane Library databases. Revman 5.3 software was used for statistical analyses. Nine publications were identified, including a total of 681 patients. Of those, 304 underwent EH, and 377 underwent TAE followed by DH. The meta-analysis results indicated that the in-hospital mortality rate in the EH patient group was significantly higher than that in the DH patient group (relative risk (RR) = 2.17, 95% confidence interval (CI) 1.03-4.57, p =0.04). There was no significant differences in the rates of postoperative complications (RR = 1.21, 95% CI 0.77-1.90, p = 0.40), postoperative hospital stay (WMD = - 0.64, 95% CI - 5.61-4.34, p = 0.80), recurrence (RR = 1.09, 95% CI 0.94-1.25, p = 0.27), peritoneal metastasis (RR = 1.06, 95% CI 0.66-1.71, p = 0.80), 1-year survival (RR = 0.91, 95% CI 0.80-1.02, p = 0.11), or 3-year survival (RR = 0.81, 95% CI 0.61-1.09, p = 0.17) in survivors between the two patient groups. The postoperative outcomes of the spontaneously ruptured HCC survivors who received EH were similar to those who received emergency TAE followed by DH. However, the in-hospital mortality rate was higher in EH patients. Based on the findings, DH with TAE first strategy might be considered over EH as the first line treatment modality. However, these findings await further validation by future high-quality studies.


Pharmacy students' medication history taking competency: Simulation and feedback learning intervention.
Obtaining accurate patient medication histories and performing medication reconciliation are core pharmacy practice skills that optimize patient safety at transitions of care. Competency-based learning and assessment of medication reconciliation skills are essential methods in undergraduate pharmacy education. The aim of this study was to investigate the impact of an in-classroom simulation- and feedback-driven training activity on pharmacy students' medication reconciliation skills, self-perceived confidence, and overall student satisfaction. Over a three-day learning activity in 2016, pharmacy students from a private university in Jordan were assessed by roleplay on their ability to conduct a simulated patient medication interview, obtain the Best Possible Medication History, reconcile the history against a hospital medication chart, identify discrepancies, and document findings. Students received immediate feedback and observed peers undergo the assessment process. Pre- and post-simulation questionnaires and supplementary focus groups enabled collection of quantitative and qualitative data pertaining to student self-perceived confidence, perceptions, experiences, and usefulness of the course. Assessment-based competency scores demonstrated significant improvement in student performance during the activity. Self-perceived confidence scores significantly improved after the medication reconciliation training intervention. Focus group content analysis yielded positive responses such as students valuing receiving feedback on performance and recommendations for future training. Simulation with feedback was a useful tool to teach pharmacy students medication reconciliation in Jordan. Subsequent to the study, medication reconciliation and interactive teaching methods were added to curriculum to supplement traditional teaching modalities.


Drainage of the rectum: a simple maneuver to improve the accuracy of colon examinations.
In double contrast enemas, the rectum and distal sigmoid can easily be examined with a high degree of accuracy. This requires adequate drainage and good air distension of this segment of the colon. Methods are outlined by which this can easily be accomplished.


A computer program for the analysis of dental arch form using the cubic spline function.
This paper presents the details and logic of a FORTRAN computer program which fits a cubic interpolatory spline to a set of data points digitized from an exact size photographic reproduction of a dental model. It also measures the length of the arc and computes a set of normals to the curve to be used in evaluating the error in the fit of the spline. The program is used in studies of dental arch form and is useful in evaluating changes in the form of the arches due to orthodontic treatment. The measurement of the arc length provides an adequate assessment of space available in the dental arch, which is of importance to the orthodontist.


Analysis of ROS-Triggered Changes in the Transcriptome.
RNA sequencing is routinely used for determining transcriptome-wide expression changes during various conditions, including oxidative stress conditions. In this chapter, a basic workflow to determine differentially expressed genes between two conditions of interest is provided. After providing brief guidelines for experimental design, we provide step-by-step instructions for genome alignment of reads and differential expression analysis.


Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.
Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated. This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells. The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry. The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles. These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair.


[Inhibition effect of aspirin on the growth of gastric cancer and the mechanism there-in involved].
To investigate the effect of aspirin on the growth of gastric cancer in vitro and the relevant mechanism. The effect of aspirin on proliferation of SGC-7901 cells was measured by 3H-thymidine incorporation into DNA; the cell cycle was analyzed by flow cytometry. COX-2 protein was examined in SGC-7901 cells by immunohistochemistry. The expression of c-fos and the AP-1 activity were detected by immunoblotting and EMSA respectively. Aspirin decreased 3H-thymidine incorporation into SGC-7901 cells. The inhibition effect showed a good correlation with aspirin over a range of concentrations from 1 x 10(-1) mol/L to 1 x 10(-5) mol/L (r = 0.9, P < 0.01). Immunohistochemistry and immunoblotting indicated that aspirin effectively decreased COX-2 and c-fos expression in SGC-7901 cell. Aspirin could inhibit the AP-1 binding activation stimulated by fetal calf serum. Aspirin is effective for inhibiting the growth of gastric cancer. The anti-neoplastic effect aspirin produces may involve the inhibition of COX-2 expression and AP-1 activity.


Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.
The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.


Protein uptake into E. coli during Bdellovibrio infection. A process of reverse secretion?
Bdellovibrio bacteriovorus is a small bacterial parasite that infects other Gram-negative bacteria, resides in the periplasm of the host cell, and utilizes host macromolecules as a source of nutrients. Evidence is summarized suggesting that B. bacteriovorus secretes proteases and nucleases synthesized in its own cytoplasm that are targeted to the cytoplasm of the host cell. Possible mechanisms for this trans-trimembrane protein transport process are discussed.