Improved insulin action and glycemic control after long-term angiotensin-converting enzyme inhibition in subjects with arterial hypertension and type II diabetes.
To determine the long-term effects of the angiotensin-converting enzyme inhibitor captopril on insulin sensitivity in subjects with type II diabetes and arterial hypertension. The chronic effects of angiotensin-converting enzyme inhibition on insulin-sensitive individuals are presently controversial. Sixteen subjects, with type II diabetes (on diet and/or diet plus oral hypoglycemic agents) and arterial hypertension, were studied. During a 1-mo run-in period no antihypertensive drugs were administered, but oral hypoglycemic agents were continued in subjects already in therapy. The subjects were then randomly assigned to two 3-mo treatment periods, with either captopril or placebo (single blind, cross-over design). At the end of each treatment period, insulin sensitivity was assessed by means of a euglycemic-hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1 mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3-3H]glucose (for calculation of hepatic glucose output and peripheral glucose utilization, rates of glucose disappearance), and indirect calorimetry (for calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid oxidation). The percentage of HbA1c was measured to assess long-term glycemic control. Comparing data at the end of placebo and captopril treatment, captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3 mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in hyperglycemic conditions (total amount of insulin infused and time of insulin infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58 +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater insulin sensitivity in euglycemic conditions at liver level (hepatic glucose output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp), muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1 mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately 29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/- 0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2 vs. 7.3 +/- 0.2%, P < 0.05). Long-term captopril administration in type II diabetic subjects improves insulin sensitivity in the postprandial state, not in the fasting state, and improves glycemic control.


A comparative study of laser posterior cordotomy and combined laser posterior cordotomy with suture lateralization in bilateral vocal cords abductor paralysis.
A prospective randomized study was conducted on 40 patients with true bilateral vocal fold abductor paralysis. The patients under the study were divided into 2 groups, group (A) including 20 patients who underwent laser posterior cordotomy and another group (B) including 20 patients who underwent combined laser posterior cordotomy with suture lateralization, the patients under the study presented at otorhinolaryngology outpatient clinic at faculty of medicine, Cairo University. The study was conducted in the period from January 2018 till January 2021. No significant difference between both surgeries regarding respiratory efficiency, voice handicap index (VHI) scores, and presence of postoperative aspiration. A significant difference was found regarding some Computerized Speech Lab (CSL) measures (there is a statistically significant difference between the 2 groups in favor of group (b) regarding N to H ratio in week 2 postoperatively and maximum phonation time in 4-week postoperatively) and granuloma formation (granuloma formation was more common in the group (A) than group (B)). Combined laser posterior cordotomy with suture lateralization in bilateral vocal folds abductor paralysis showed fewer complications and better maximum phonation time and a comparable effect to laser cordotomy regarding respiration.


Cortical spreading depolarization: Pathophysiology, implications, and future directions.
Cortical spreading depolarization (CSD) is a spreading loss of ion homeostasis, altered vascular response, change in synaptic architecture, and subsequent depression in electrical activity following an inciting neurological injury. First described by Leão in 1944, this disturbance in neuronal electrophysiology has since been demonstrated in a number of animal studies, and recently a few human studies that examine the occurrence of this depolarizing phenomenon in the setting of a variety of pathological states, including migraines, cerebrovascular accidents, epilepsy, intracranial hemorrhages, and traumatic brain injuries. The onset of CSD has been demonstrated experimentally following a disruption in the neuronal environment leading to glutamate-induced toxicity. This initial event leads to pathological changes in the activity of ion channels that maintain membrane potential. Recovery mechanisms such as sodium-potassium pumps that aim to restore homeostasis fail, leading to osmolar shifts of fluid, swelling of the neuron, and ultimately a measurable depression in cortical activity that spreads in the order of millimeters per minute. Equally important is the resulting change in vascular response. In healthy tissue, increased electrical activity is coupled with release of vasodilatory factors such as nitric oxide and arachidonic acid metabolites that increase local blood flow to meet increased energy expenditure. In damaged tissue, not only is the restorative vascular response lacking but a vasoconstrictive response is promoted and the ischemia that follows adds to the severity of the initial injury. Tissue threatened by this ischemic response is then at elevated risk for CSD propagation and falls into a vicious cycle of electrical and hemodynamic disturbance. Efforts have been made to halt this spreading cortical depression using N-methyl-D-aspartate receptor antagonists and other ion channel blockers to minimize the damaging effects of CSD that can persist long after the triggering insult.


Thrombomodulin expression in endothelial cells after contact with bone cement.
The expression of thrombomodulin after contact with CMW 1 bone cement extracts was studied in human umbilical vein endothelial cells. Cement extracts after 1 h and 7-day curing induced no significant variations in thrombomodulin antigen levels and in mRNA expression. Significant increase of thrombomodulin was observed when endothelial cells were treated with all-trans retinoic acid (ATRA). ATRA induced the increase of thrombomodulin also in cells incubated with cement extracts. These results suggest that CMW 1 bone cement does not impair the expression of thrombomodulin in endothelial cells.


Development and comparison of high-performance liquid chromatographic methods with tandem mass spectrometric and ultraviolet absorbance detection for the determination of cyclobenzaprine in human plasma and urine.
Sensitive assays for the determination of cyclobenzaprine (I) in human plasma and urine were developed utilizing high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS-MS) and ultraviolet (UV) absorbance detections. These two analytical techniques were evaluated for reliability and sensitivity, and applied to support pharmacokinetic studies. Both methods employed a liquid-liquid extraction of the compound from basified biological sample. The organic extract was evaporated to dryness, the residue was reconstituted in the mobile phase and injected onto the HPLC system. The HPLC assay with MS-MS detection was performed on a PE Sciex API III tandem mass spectrometer using the heated nebulizer interface. Multiple reaction monitoring using the parent-->daughter ion combinations of m/z 276 --> 215 and 296 --> 208 was used to quantitate I an internal standard (II), respectively. The HPLC-MS-MS and HPLC-UV assays were validated in human plasma in the concentration range 0.1-50 ng/ml and 0.5-50 ng/ml, respectively. In urine, both methods were validated in the concentration range 10-1000 ng/ml. The precision of the assays, as expressed as coefficients of variation (C.V.) was less than 10% over the entire concentration range, with adequate assay specificity and accuracy. In addition to better sensitivity, the HPLC-MS-MS assay was more efficient and allowed analysis of more biological fluid samples in a single working day than the HPLC-UV method.


Scrub typhus mimicking Parkinson's disease.
Scrub typhus is a re-emerging infection in Sri Lanka. It often poses a diagnostic challenge and tends to present as a febrile illness of uncertain origin. Undiagnosed illness may progress to serious multi-systemic complications. Here we report a case of scrub typhus presenting with features of Parkinsonism. A 62-year-old previously healthy Sri Lankan native male from the Western province of Sri Lanka presented with high fever with malaise, myalgia and arthralgia for 17 days. On the 5th day of illness he developed intermittent resting tremor in his right arm and leg associated with stiffness, difficulty in carrying out normal work and difficulty in smiling. He denied similar previous episodes. There were no other associated neurological manifestations. Clinical examination revealed a high amplitude low frequency resting tremor in his right hand, a mask-like face and increased muscle tone limited to the right side with normal reflexes. The rest of the system examination was normal except for an eschar over the abdomen. His investigations revealed lymphocytic leukocytosis, high erythrocyte sedimentation rate and immunofluorescence assay-IgM and IgG against Orientia tsutsugamushi Karp antigen were positive with rising titers. With oral doxycycline and azithromycin his fever settled within 48 h and a complete recovery of Parkinson's features was observed within 2 weeks. Doctors practicing in endemic regions should be familiar with delayed clinical manifestations of scrub typhus and should carefully look for an eschar in order to avoid delay in the diagnosis.


Vitamin D Status and Supplementation in the Critically Ill.
Vitamin D deficiency has recently been recognized as a widespread global disorder. Generally considered a direct extension of malnutrition, even subclinical hypovitaminosis D is now recognized in adequately nourished populations. Compared to the general population, the prevalence of hypovitaminosis D is greater in the critically ill population. In fact, several studies have shown poorer outcomes in critically ill patients discovered to be vitamin D deficient or insufficient. Controversy persists regarding vitamin D measurements, quantity of supplementation, and appropriate target level in various populations. Vitamin D has a vital role in calcium homeostasis and extra-skeletal health, such as immune function. Therefore, vitamin D supplementation may have a role for improving outcomes in critically ill patients. In this review, we will first discuss the metabolism and function of vitamin D under normal physiologic conditions. We will then explore the prevalence and prognostic value of vitamin D deficiency in critical illness. Finally, we will examine recent trials focusing on appropriate dosing, route of administration, and outcomes associated with vitamin D supplementation in the ICU.


Olivanic acids, a family of beta-lactam antibiotics with beta-lactamase inhibitory properties produced by Streptomyces species. I. Detection, properties and fermentation studies.
The screening of soil actinomyces for beta-lactamase inhibitors is described. Using a plate test a number of strains of Streptomyces were found to produce beta-lactamase inhibitory activity designated olivanic acid complex. Factors affecting the production of this complex by Streptomyces olivaceus ATCC 21379 are reported. The complex showed antibacterial activity and also inhibited a number of different types of beta-lactamase in a progressive manner. Certain ampicillin-resistant bacteria are rendered sensitive to ampicillin in the presence of olivanic acid complex at a concentration which alone did not inhibit growth.


Medicinal wild plant knowledge and gathering patterns in a Mapuche community from North-western Patagonia.
Medicinal plant use has persisted as a long standing tradition in the Mapuche communities of Southern Argentina and Chile. An ethnobotanical survey was conducted in the rural Curruhuinca community located near the mountain city of San Martin de los Andes, Argentina. Semi-structured interviews were carried out on 22 families in order to examine the present use of medicinal plants and their reputed therapeutic effects. Ecological variables, such as distance to the gathering site and biogeographical origin were also analyzed. Our results showed that the Curruhuinca dwellers cited 89 plant species for medicinal purposes, both of native and exotic origin. They know about 47 native plants, of which they use 40, and they know of 42 exotic medicinal plants of which they use 34. A differential pattern was observed given that only native species, relevant for the traditional Mapuche medicine, were collected at more distant gathering sites. The interviewees mentioned 268 plant usages. Those most frequently reported had therapeutic value for treating digestive ailments (33%), as analgesic/anti-inflammatory (25%) and antitusive (13%). Native species were mainly cited as analgesics, and for gynecological, urinary and "cultural syndrome" effects, whereas exotic species were mainly cited for digestive ailments. The total number of medicinal plants known and used by the interviewees was positively correlated with people's age, indicating that this ancient knowledge tends to disappear in the younger generations.


Role of ischemia-reperfusion on myocardial cyclic AMP and cyclic AMP phosphodiesterase: effects of amrinone on regional myocardial force and shortening.
This study tested the hypothesis that a reperfused ischemic myocardial region of the dog heart would be unable to increase its function in response to amrinone, a specific cyclic AMP phosphodiesterase (cAMP-PDE) inhibitor, due to loss of cAMP-PDE activity in the region. The global contractility (+dp/dtmax), regional percent shortening (ultrasonic crystals), and developed force (miniature force gauge) were measured on a continuous basis throughout a 6-hour experiment and regional blood flow (radioactive microspheres) in open-chest pentobarbital-anesthetized mongrel dogs. The left anterior descending coronary artery (LAD) was isolated and ligated for 2 hours and allowed to reperfuse for 4 hours. This myocardial region was compared to a nonischemic region supplied by the circumflex artery. At the end of the 4-hour reperfusion period, 9 dogs were treated with amrinone (5 mg/kg) and three dogs were not treated with amrinone. The hearts were rapidly excised and frozen in liquid nitrogen. Cyclic AMP and cAMP-PDE activity was determined in homogenates of myocardial tissue. Blood flow decreased during occlusion in the LAD region and returned toward control with reperfusion. Flow increased nonsignificantly with amrinone. the basal cyclic AMP content of the two regions was not different. The cAMP-PDE activity was reduced 24% in the LAD region compared to the control region. There were no ischemia-induced changes in the enzyme characteristics. These experiments demonstrated increased global function in the ischemic reperfused myocardium after amrinone was administered (dP/dtmax: 2092 +/- 538 to 3277 +/- 688 mmHg/sec).(ABSTRACT TRUNCATED AT 250 WORDS)


Differential expression of benzodiazepine anticonvulsant cross-tolerance according to time following flurazepam or diazepam treatment.
In previous studies in which the anti-pentylenetetrazol (PTZ) effect of benzodiazepines was used to measure tolerance, the results depended on the benzodiazepine used for chronic treatment as well as the benzodiazepine given acutely to test for tolerance. In this study, the time course of tolerance reversal was studied in rats given two treatments known to cause anticonvulsant tolerance, 1-week flurazepam (FZP), and 3-week diazepam (DZP). Neither treatment altered convulsive threshold for IV PTZ, but both treatments decreased the convulsive threshold for bicuculline. Withdrawing DZP, but not FZP, treatment resulted in a loss of body weight. Twelve hours after 1-week FZP treatment, all benzodiazepines were significantly less effective, showing tolerance. Forty-eight hours after the 1-week FZP treatment, tolerance was still observed with DZP, FZP, and zolpidem, but was no longer present with clonazepam or bretazenil. After the 3-week DZP treatment, rats were tolerant to all benzodiazepines tested at 12 h of withdrawal, but had lost tolerance to all the drugs except bretazenil by 48 h. The results suggest differences in the way these benzodiazepines interact with their receptors, allowing differential expression of tolerance, and that chronic DZP and FZP treatments affected interactions of the benzodiazepines with their receptors, but not in the same fashion.


Crystal Structure of β-Arrestin 2 in Complex with CXCR7 Phosphopeptide.
β-Arrestins (βarrs) critically regulate G-protein-coupled receptor (GPCR) signaling and trafficking. βarrs have two isoforms, βarr1 and βarr2. Receptor phosphorylation is a key determinant for the binding of βarrs, and understanding the intricate details of receptor-βarr interaction is the next frontier in GPCR structural biology. The high-resolution structure of active βarr1 in complex with a phosphopeptide derived from GPCR has been revealed, but that of βarr2 remains elusive. Here, we present a 2.3-Å crystal structure of βarr2 in complex with a phosphopeptide (C7pp) derived from the carboxyl terminus of CXCR7. The structural analysis of C7pp-bound βarr2 reveals key differences from the previously determined active conformation of βarr1. One of the key differences is that C7pp-bound βarr2 shows a relatively small inter-domain rotation. Antibody-fragment-based conformational sensor and hydrogen/deuterium exchange experiments further corroborated the structural features of βarr2 and suggested that βarr2 adopts a range of inter-domain rotations.


GlycineB antagonists as potential therapeutic agents. Previous hopes and present reality.
It is not clear what therapeutic application is most likely for agents blocking glycine site of the NMDA receptors (glycineB). Majority of the studies to date used either glycineB antagonists with doubtful brain penetration or partial agonists. Following systemic administration to rats of our newly developed glycineB antagonists (MRZ 2/570; 2/571 and 2/576) and L-701,324 (MSD) as a reference agent the following behavioural effects were observed: weak (if any) antiparkinsonian-like effects, lack of anxiolytic activity, inhibition of physical and motivational aspects of morphine dependence and neuroprotective activity in global ischaemia. The side effects include: sedation, ataxia, and myorelaxation. We detected neither vacuolisation in the cingulate cortex nor impairment of pre-pulse inhibition indicating lack of psychotomimetic potential.


Sclerosing bone disorders.
Sclerosing bone disorders are a diagnostic challenge. However, hereditary sclerosing disorders often have characteristic radiological features that allow their diagnosis. Osteocondensation can result from decreased bone resorption; malignant recessive osteopetroses have been related to mutations in several genes necessary for osteoclast function and also, more recently, to osteoclast differentiation (RANK-L). Albers-Schonberg disease or autosomal-dominant osteopetrosis type II has the characteristic 'sandwich vertebrae' and 'bone within bone' radiological features. It has been related to mutation in chloride channel 7, which is necessary for osteoclast acidification. Osteocondensation can also be related to increased bone formation. Camurati-Engelman dysplasia is a disabilitating disorder with leg pain and weakness, and thickening of the diaphysis of long bones on x ray. It is due to activating mutations in the gene encoding TGF-beta, a growth factor that increases bone formation. Other less common recessive or dominant sclerosing disorders, such as endosteal hyperostosis, sclerostosis, van Buchen disease and high bone mass syndrome, are due to mutations in two genes (LRP5 and SOST) of the Wnt pathway that induce increased osteoblast activity. Recent elucidation of the molecular mechanism responsible for several hereditary diseases with osteocondensation has improved our comprehension of bone remodelling. It has allowed the discovery of new targets for the treatment of postmenopausal osteoporosis, some of which are already being investigated in clinical trials. Molecular mechanism for some hereditary osteocondensation remains to be discovered.


Variation in rates of leaf abscission between plants may affect the distribution patterns of sessile insects.
At Sand Lake, Leon County, Florida, mines of Stilbosis quadricustatella, a leaf-mining moth, occur on sand live oak trees (Quercus geminata) over a broad range of densities. Some trees have fewer than 2% of their leaves mined (lightly infested), others up to 70% (heavily infested). Similar levels of infestation are maintained on the same trees year after year. There are no significant negative correlations of miner density per tree with any mortality factor that might explain miner preferences for certain trees. Nor is there a positive correlation with host leaf quality as measured by foliar nitrogen or by total or individual amino acid concentrations of host leaves. Egg-transfer experiments showed that larvae from eggs transferred to lightly infested trees were more likely to be killed by leaf abscission than were those that were transferred to and developed on heavily infested trees. This is the first demonstration that variation in rates of leaf abscission could be an important cause of the observed distribution pattern of sessile insects between conspecific host plants.


Concentration-dependent specimen shrinkage in iodine-enhanced microCT.
Iodine potassium iodide (I2 KI) solution can be employed as a contrast agent for the visualisation of soft tissue structures in micro-computed tomography studies. This technique provides high resolution images of soft tissue non-destructively but initial studies suggest that the stain can cause substantial specimen shrinkage. The degree of specimen shrinkage, and potential deformation, is an important consideration when using the data for morphological studies. Here we quantify the macroscopic volume changes in mouse skeletal muscle, cardiac muscle and cerebellum as a result of immersion in the common fixatives 10% phosphate-buffered formal saline, 70% ethanol and 3% glutaraldehyde, compared with I2 KI staining solution at concentrations of 2, 6, 10 and 20%. Immersion in the I2 KI solution resulted in dramatic changes of tissue volume, which were far larger than the shrinkage from formalin fixation alone. The degree of macroscopic change was most dependent upon the I2 KI concentration, with severe shrinkage of 70% seen in solutions of 20% I2 KI after 14 days' incubation. When using this technique care needs to be taken to use the lowest concentration that will give adequate contrast to minimise artefacts due to shrinkage.


Inter- and intramolecular disulfide bond formation and related structural changes in the lens proteins. A Raman spectroscopic study in vivo of lens aging.
Raman spectra have been measured for intact rat lens nuclei at various stages of aging in an attempt to gain further insight into age-related structural changes in the lens proteins, especially changes concerning protein sulfhydryl groups. Two Raman bands at 2579 and 2561 cm-1 were observed to be assignable to SH stretching modes of the cysteine residues. These bands have been attributed to "exposed" and "buried" sulfhydryl groups of the lens proteins, respectively, on the basis of a model compound study. The relative intensities of both SH stretching modes decreased with lens aging, and concurrently the intensity of a S-S stretching mode at 509 cm-1 due to disulfide bridges increased, suggesting that not only exposed but also buried protein sulfhydryl groups are converted to disulfide groups as a result of aging. The rate of the intensity decrease in the 2561 cm-1 band was similar to that in the 2579 cm-1 band. Therefore, it seems likely that the sulfhydryl groups in the two distinct environments are nearly equally subjected to the oxidation. Cysteine and cystine residues of the lens proteins gave their C-S stretching modes at 708 cm-1, indicating that they predominantly assume PC and/or PN conformers. The intensity ratio of a tyrosine doublet near 840 cm-1 (I832/I855) changed from approximately 0.86 to approximately 0.81 with the aging of the rat lens. This result implies that some tyrosine residues undergo a change in their hydrogen bonding environments during the course of aging. Of particular importance is that the relative intensity change of the tyrosine doublet with normal aging and that with cataract formation are in opposite directions.


[Listrophorus gibbus, a fur mite in domestic rabbits (author's transl)].
A case of infection with the fur mite of domestic rabbits, Listrophorus gibbus, is reported. Possible methods of treatment of individual rabbits as well as of colonies of rabbits are reviewed. The presence of Listrophorus gibbus in conjunction with Cheyletiella parasitivorax is also discussed.


Cell migration or cytokinesis and proliferation?--revisiting the "go or grow" hypothesis in cancer cells in vitro.
The mortality of patients with solid tumors is mostly due to metastasis that relies on the interplay between migration and proliferation. The "go or grow" hypothesis postulates that migration and proliferation spatiotemporally excludes each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13 melanoma and 10 lung cancer) on both the individual cell and population levels. Following three-day-long videomicroscopy, migration, proliferation and cytokinesis-length were quantified. We found a significantly higher migration in mesothelioma cells compared to melanoma and lung cancer while tumor types did not differ in mean proliferation or duration of cytokinesis. Strikingly, we found in melanoma and lung cancer a significant positive correlation between mean proliferation and migration. Furthermore, non-dividing melanoma and lung cancer cells displayed slower migration. In contrast, in mesothelioma there were no such correlations. Interestingly, negative correlation was found between cytokinesis-length and migration in melanoma. FAK activation was higher in melanoma cells with high motility. We demonstrate that the cancer cells studied do not defer proliferation for migration. Of note, tumor cells from various organ systems may differently regulate migration and proliferation. Furthermore, our data is in line with the observation of pathologists that highly proliferative tumors are often highly invasive.


Findings from a nursing student CPR study: implications for staff development educators.
This article reports a secondary data analysis of a year-long study with 606 nursing students involving brief monthly CPR practice with voice-activated manikins versus no practice. Findings indicate that even with monthly practice and accurate voice-activated manikin feedback, some students could not perform CPR correctly. Implications of these findings for staff educators are discussed.


Polarization-rotating, Bragg-grating filters on silicon-on-insulator strip waveguides using asymmetric periodic corner corrugations.
We report on a wavelength-selective, polarization-rotating filter using a partially etched asymmetric Bragg grating on a compact single-mode, silicon-on-insulator (SOI) strip waveguide. The asymmetric Bragg grating rotates and reflects the fundamental transverse electric (TE) and transverse magnetic (TM) modes at selected wavelengths. Our device offers wavelength-selective, polarization-rotating reflection at its reflection port and wavelength-selective, polarization-independent notch filtering at its through port. The device is fabricated using a CMOS-compatible process with 193 nm-deep ultraviolet lithography on an SOI platform. We present results for a 294.4 μm long device that has a 3 dB bandwidth of 2.63 nm and a low-excess loss of less than 1 dB. This device also has a maximum polarization-extinction-ratio of greater than 27 dB.


Robot-assisted Laparoscopic Excision of Abdominal Wall Endometrioma Utilizing Intraoperative Ultrasound and Transabdominal Needle Placement.
In patients with endometriosis, extra pelvic endometriosis is estimated to have an incidence of 11% and a rare subset of extra pelvic lesions include abdominal wall endometriosis with an incidence of 0.03% to 3.5% [1,2]. Evaluation for and surgical management of abdominal wall endometriosis are an essential skill set for the advanced gynecologic surgeon. In this video, we demonstrate a surgical technique for robot-assisted laparoscopic excision of abdominal wall endometriosis with intraoperative ultrasound-guided needle placement. Description and demonstration of surgical technique. A patient with previous history of 2 cesarean sections and right lower quadrant cyclic abdominal wall pain; a tertiary care, academic center. Intraoperative ultrasound-guided needle placement to map location and boundaries of the lesion followed by minimally invasive resection of the lesion with the intermittent advancement and withdrawal of needles to confirm clear margins. Minimally invasive resection of abdominal wall endometriosis using intraoperative ultrasound-guided needle placement is an effective technique to guide surgical dissection and allow for clear surgical margins and successful treatment of this rare condition.


Patient group directions in nurse-led sexual health clinics.
This article details an audit of the supply of medications by specialist nurses at a genitourinary medicine clinic. The use of patient group directions resulted in a reduced number of prescriptions being required from doctors, thus saving time for them, the nurses and patients.


Cooperation increases robustness to ecological disturbance in microbial cross-feeding networks.
Microorganisms mainly exist within complex networks of ecological interactions. Given that the growth and survival of community members frequently depend on an obligate exchange of essential metabolites, it is generally unclear how such communities can persist despite the destabilising force of ecological disturbance. Here we address this issue using a population dynamics model. In contrast to previous work that suggests the potential for obligate interaction networks to emerge is limited, we find the opposite pattern: ecological disturbance favours both specific network topologies and cooperative cross-feeding among community members. These results establish environmental perturbations as a key driver shaping the architecture of microbial interaction networks.


Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation.
Intracerebral haemorrhage is inadequately controlled by current treatments, requiring new solutions to improve the prognosis. Following the primary injury, a proinflammatory cascade in the perihaematomal region, composed of activated resident microglia and astrocytes and infiltrated leucocytes, propagates neural cell death. The protracted nature of neuroinflammation in intracerebral haemorrhage provides a window of opportunity for therapies to subdue the undesired consequences. In animal models and early clinical trials in intracerebral haemorrhage, several drugs have reduced detrimental neuroinflammation without substantial compromise of the beneficial reparative aspects of an inflammatory response. Potential strategies include controlling excessive harmful neuroinflammation with minocycline, sphingosine-1-phosphate receptor modulators, and statins after a brain haemorrhage. The quick initiation of these drugs, particularly in high systemic doses, could be key to counteracting the evolving secondary injury in people with intracerebral haemorrhage and provides a promising way in which the poor prognosis of intracerebral haemorrhage might one day be counteracted.


Activity rhythms and the tide in a saltmarsh beetle Dicheirotrichus gustavi.
Field observations at Mersea Island, Essex confirm previous observations at Scolt Head Island, Norfolk that the intertidal beetle Dicheirotrichus gustavi Crotch (Coleoptera: Carabidae) has a rhythm of activity on the saltmarsh surface which is suppressed during periods of submerging tides. Although the timing of the tides at the two sites is 180° (6 h) out of phase, the timing of beetle activity at the two sites is the same, with a peak of activity shortly after dusk. Beetle activity therefore shows no special phase relationship with the "critical" tide - the first high tide that covers the beetle zone after a period of emergence. At Mersea, the peak of beetle activity coincides with the critical high tides, but the beetles were observed to escape from the seawater by scrambling up the mud and vegetation.


The relationship of environment size and population parameters Oxytrema proxima (say) (Gastropoda: Pleuroceridae).
Environmental size, as measured by cross-sectional area of the inhabited streams, and population density of Oxytrema proxima are related by the power function Y=8.074X -0.584, where Y=population density and X=cross-sectional area of the stream. Relationships were also found between maximum size and biomass and cross-sectional area, but maximum size and biomass were more closely related to population density by the equations Y=8.832X -0.064 (Y=maximum individual size, X=density) and Y=6.730X 0.459 (Y=biomass (total live weight), X=density). This is interpreted as evidence that environment size acts directly on density, which in turn produces effects on maximum size, total live weight, and to a lesser extent mean size. The inverse relationship between population size and environment has not been previously reported. It is clear that in this case this distribution and abundance of O. proxima are closely related, and that this can be so when populations disperse extremely poorly as well as extremely well. This must mean that dispersal is secondary in importance to population stability as an influence on distribution and abundance.


Selective C-C and C-N bond activation in dopamine and norepinephrine under deep ultraviolet laser irradiation.
Utilizing a customized mass spectrometer, we analyze selective C-C bond and C-N bond activation in neurotransmitters dopamine (DA) and norepinephrine (NE) under deep ultraviolet laser irradiation.


Deep eutectic solvents in sample preparation and determination methods of pesticides: Recent advances and future prospects.
This review summarizes recent advances of deep eutectic solvents (DESs) in sample preparation and determination methods of pesticides in food, environmental, and biological matrices since 2019. Emphasis is placed on new DES categories and emerging microextraction techniques. The former incorporate hydrophobic deep eutectic solvents, magnetic deep eutectic solvents, and responsive switchable deep eutectic solvents, while the latter mainly include dispersive liquid-liquid microextraction, liquid-liquid microextraction based on in-situ formation/decomposition of DESs, single drop microextraction, hollow fiber-liquid phase microextraction, and solid-phase microextraction. The principles, applications, advantages, and limitations of these microextraction techniques are presented. Besides, the use of DESs in chromatographic separation, electrochemical biosensors, fluorescent sensors, and surface-enhanced Raman spectroscopy are discussed. This review is expected to provide a valuable reference for extracting and detecting pesticides or other hazardous contaminants in the future.


Practical methods for improving B1+ homogeneity in 3 Tesla breast imaging.
To improve image contrast and B1+ field homogeneity in 3 Tesla (T) breast MR. Two practical B1+ shimming methods for 3T breast MR are presented; low-cost passive shimming using local pads of high dielectric permittivity (εr from 0 to 100), and two-channel radiofrequency (RF) shimming (adjusting Q-I amplitude ratios and phase differences of 0 to -4 dB and 90 to 45 degrees), as well as a combination of both methods. The technique has been studied both in simulation using a numerical body model with added mammary tissue and in vivo in six subjects. Large improvements are observed with both methods, leading to a decrease in left-right B1+ asymmetry ratio of 1.24 to 1.00 (simulation) and from 1.26 to 1.01 (in vivo). RF safety was not adversely affected. Both RF shimming and dielectric shimming were shown to improve inhomogeneity in the B1+ field in 3T breast MR.


Isolation of Candida dubliniensis in denture stomatitis.
To describe the isolation of Candida dubliniensis from a patient with denture stomatitis and to compare with the presence of yeasts in the oral cavities of denture wearers. One hundred and fifty-two Candida isolates were recovered through oral swabs from denture as well as the underlying mucosa from 100 patients wearing denture. For detection and identification of fungal isolates, standard phenotypic and genotypic methods were used. Forty-five of 100 denture wearers suffered from denture stomatitis. Seventy-three Candida isolates were recovered from 38 denture wearers without denture stomatitis. In this group, Candida albicans was the predominant species (58.9%), followed by Candida tropicalis (15.1%), Candida guilliermondii (13.7%), Candida glabrata (9.6%), and Candida parapsilosis (2.7%). Seventy-nine isolates were yielded from 40 patients suffering from denture stomatitis. C. albicans was also the most frequently isolated species (58 isolates, 73.4%), followed by C. glabrata and C. tropicalis (7 isolates each, 8.9%), and Saccharomyces cerevisiae (2 isolates, 2.5%). One isolate was yielded of the following species: Candida famata, Candida krusei, C. parapsilosis and C. guilliermondii. Moreover 1 isolate was phenotypic and genotypic identified as C. dubliniensis genotype 1. C. albicans is the predominant fungal species isolated from denture wearers. C. dubliniensis could be isolated from adults with denture stomatitis.


Molecular species of glycerophospholipids and sphingomyelins of human plasma: comparison to red blood cells.
In addition to diacyl glycerophosphocholine and sphingomyelin, human plasma also contains small amounts of other glycerophospholipids, which may have special metabolic function. The structure and origin of these minor plasma lipids has not been determined. Knowledge of the detailed composition of the phospholipids of red blood cells (Myher et al., Lipids 24, 1989) permits evaluation of one of the possible sources. This study reports the detailed analyses of plasma glycerophospholipids made in parallel to those of the erythrocyte lipids obtained from the same blood using HPLC and GLC methods. The proportions of the major phospholipid classes in the plasma and erythrocytes were similar to published values, including the essential absence of diradyl glycerophosphoserine from plasma. Plasma diradyl glycerophosphocholine contained 93.0% diacyl, 3.4% alkylkacyl and 3.6% alkenylacyl, whereas the diradyl glycerophosphoethanolamine consisted of 71.8% alkenylacyl, 19.9% diacyl and 8.3% alkylacyl subclasses. The diradyl glycerophosphoinositol was 100% diacyl. The content of the minor subclasses of plasma diradyl glycerophosphocholine is similar to that of the red cells, but the ether content of the diradyl glycerophosphoethanolamine is higher in plasma than in cells. The lipid ether subclasses of plasma glycerophospholipids also contained a higher proportion of the C20, C22 and C24 alkyl and alkenyl chains than those of the cells. Furthermore, the C16 and C18-containing species in diradyl glycerophosphoethanolamine subclasses varied with the nature of the polyunsaturated acid, whereas in diradyl glycerophosphocholine subclasses the polyunsaturated acids were combined with the C16 and C18 acids in equal proportions. The significant differences in the molecular species of glycerophospholipids and sphingomyelin between plasma and red cells would appear to limit any direct transfer or equilibration of their lipid components.


The control of myocardial contraction with skeletal fast muscle troponin C.
The present study describes experiments on the myocardial trabeculae from the right ventricle of Syrian hamsters whose troponin C (TnC) moiety was exchanged with heterologous TnC from fast skeletal muscle of the rabbit. These experiments were designed to help define the role of the various classes of Ca2+-binding sites on TnC in setting the characteristic sensitivities for activations of cardiac and skeletal muscles. Thin trabeculae were skinned and about 75% of their troponin C extracted by chemical treatment. Tension development on activations by Ca2+ and Sr2+ was found to be nearly fully blocked in such TnC extracted preparations. Troponin C contents and the ability to develop tension on activations by Ca2+ and Sr2+ was permanently restored after incubation with 2-6 mg/ml purified TnC from either rabbit fast-twitch skeletal muscle (STnC) or the heart (CTnC, cardiac troponin C). The native (skinned) cardiac muscle is characteristically about 5 times more sensitive to activation by Sr2+ than fast muscle, but the STnC-loaded trabeculae gave response like fast muscle. Attempts were also made to exchange the TnC in psoas (fast-twitch muscle) fibers, but unlike cardiac muscle tension response of the maximally extracted psoas fibers could be restored only with homologous STnC. CTnC was effective in partially extracted fibers, even though the uptake of CTnC was complete in the maximally extracted fibers. The results in this study establish that troponin C subunit is the key in setting the characteristic sensitivity for tension control in the myocardium above that in the skeletal muscle. Since a major difference between skeletal and cardiac TnCs is that one of the trigger sites (site I, residues 28-40 from the N terminus) is modified in CTnC and has reduced affinity for Ca2+ binding, the possibility is raised that this site has a modulatory effect on activation in different tissues and limits the effectiveness of CTnC in skeletal fibers.


Organisation of the equine immunoglobulin constant heavy chain genes. II. Equine cgamma genes.
The number of immunoglobulin G constant heavy chain genes (cgamma genes) varies broadly among mammalian species, reflecting structural and functional differences between expressed immunoglobulin G (IgG) isotypes and allotypes. Up to now equine IgG isotypes have been defined only at the biochemical and serological level. It is still not clear how many IgG isotypes exist in horses and whether there are any allotypes. Here, we describe the isolation and characterisation of equine cgamma genes. An equine genomic lambda phage library was screened with a human cgamma4 probe. Cross-hybridising equine cgamma sequences were cloned twice and characterised by restriction mapping with the human cgamma4 and a murine sgamma1 probe. Genomic equine DNA probes for both, cgamma genes and corresponding switch regions (sgamma), were isolated and used for a more detailed BamHI restriction analysis, comparing genomic DNA of various horses. This analysis reveals the existence of at least five, or probably six cgamma genes in the equine haploid genome. Beside the porcine system, this is the highest number of cgamma genes described for any mammalian species. Moreover, for two of these cgamma genes, BamHI restriction fragment length polymorphism became evident.


3D-3D dentition superimposition for individual identification: A study of an Eastern Chinese population.
Recently, 3D dental intraoral scanning technology has been developed rapidly and applied widely in everyday dental practice. Since 3D dental scanning could provide valuable personal information, it enabled researchers to develop novel procedures for individual identification through 3D-3D dentition superimposition. This study aimed to test the applicability of this method in an Eastern Chinese population and propose a threshold for personal identification. For this purpose, 40 volunteers were recruited, and the initial 80 (upper and lower) 3D intraoral scans (IOS) were collected. After one year, 80 IOS of these volunteers were repeatedly collected. In addition, the other 120 IOS of 60 patients were extracted from the database. The 3D models were trimmed, aligned, and superimposed via Geomagic Control X software, and then the root mean square (RMS) value of point-to-point distance between the two models was calculated. The superimposition of two IOS belonging to the same individual was considered as a match, and superimposition of two IOS belonging to different individuals was considered as a mismatch. Totally, superimpositions of 80 matches and 3120 mismatches were obtained. Intra- and inter-observer errors were assessed through the calculation of relative technical error of measurement (rTEM). Mann-Whitney U test verified possible statistically significant differences between matches and mismatches (P < 0.05). The rTEM of intra- and inter-observer repeatability analyses was lower than 4.7 %. The range of RMS value was 0.05-0.18 mm in matches and 0.72-2.28 mm in mismatches without overlapping. The percentage of accurate identification reached 100 % in blind test through an arbitrary RMS threshold of 0.45 mm. The results indicated that individual identification through the 3D-3D dentition superimposition was effective in Eastern Chinese population. Successful identification could be achieved with high probability when the RMS value of the point-to-point distance of two dentitions is <0.45 mm.


The influence of initial hemoglobin and blood pressure levels on results of radiation therapy for carcinoma of the prostate.
A group of 914 patients with carcinoma of the prostate treated by definitive radiotherapy at Stanford between 1956 and 1985 was studied. Of these, the initial hemoglobin level was recorded in 656 cases and the initial blood pressure in 760 cases. End-points studied in actuarial analyses were survival, disease-specific survival, local control, freedom from distant relapse, and occurrence of late intestinal complications. Although the anemic group (Hb less than 13.5 g/dl) was correlated negatively with survival (p = 0.02), there was no correlation with disease-specific survival or local control. The conclusion was that anemia per se did not affect the outcome of radiation therapy. A pulse pressure greater than or equal to 60 mm Hg was significantly correlated with worse survival (p = 0.01) and local control (p = 0.04), but no correlation was found between systolic and diastolic blood pressure and the end-points measured. Neither anemia nor hypertension were significantly correlated with late intestinal complications.


Mead acid production by disruption of Δ12-desaturase gene in Mortierella alpina 1S-4.
Mead acid (MA; 20:3ω9) is one of the ω9 series of polyunsaturated fatty acids (PUFAs). MA is used to inhibit the inflammation of joints and is applied to the medicinal or health food field. We aimed to construct MA-producing strains with disruption of the Δ12-desaturase gene (Δ12ds) via an efficient gene-targeting system using the lig4-disrupted strain of Mortierella alpina 1S-4 as the host. The transformants showed a unique fatty acid composition that only comprised ω9-PUFAs and saturated fatty acids, while ω6-and ω3-PUFAs were not detected, and the total composition of ω9-PUFAs, including oleic acid (18:1ω9), 18:2ω9, 20:1ω9, 20:2ω9, and MA, was up to 68.4% of the total fatty acids. The MA production in the Δ12ds-disruptant reached 0.10 g/L (8.5%), which exceeded 0.050 g/L (4.6%) in the conventional Δ12ds-defective mutant JT-180.


Hydrodynamic studies of a DNA-protein complex. Dimensions of the complex of single-stranded 145 base DNA with gene 32 protein of phage T4 deduced from quasi-elastic light scattering.
The translational diffusion coefficient of the saturated complex of single-stranded 145 base DNA and the helix-destabilizing protein of phage T4, GP32, can be measured at equilibrium by means of quasi-elastic light scattering. If the complex is considered as a rigid rod one can estimate its dimensions by combining the translational diffusion coefficient with earlier data on rotational diffusion. It was found that the average base-base distance of the 145 base DNA in the complex is between 4.3 and 4.7 A, while the diameter of the complex is between 44 and 68 A. This suggests that the conformation of the complex must be such that a large amount of water is trapped.


Molecular approaches to field studies of malaria.
The third 'Molecular Approaches to Malaria' conference was held in Lorne, Australia, in February 2008 and provided extensive information on the application of molecular tools in field studies on malaria. In recent years, technological advances and capacity building in malaria-endemic countries have permitted molecular tools to be applied much more frequently and successfully with exciting new findings. In this review, Hans-Peter Beck and Kevin Tetteh report on the most recent findings using molecular tools in field studies.


Deglycosylation increases the fibrinolytic activity of a deletion mutant of tissue-type plasminogen activator.
delta 2-89 t-PA is a deletion mutant lacking the finger (F) and epidermal growth factor (EGF) domains; thus, the fibrin interaction of this molecule must be mediated solely by the kringle region. In the present study, the influence of the oligosaccharide side-chains on the activity of delta 2-89 t-PA has been investigated. delta 2-89 t-PA was secreted in two forms, designated I and II, which presumably differ by the lack of one asparagine-linked oligosaccharide in the kringle 2 domain of form II. Forms I and II of delta 2-89 t-PA were purified; form II displayed higher fibrinolytic activity than form I. When form I was partially deglycosylated or treated to remove sialic acid, fibrinolytic activity was increased. Production of delta 2-89 t-PA in the presence of tunicamycin led to secretion of a glycan-free activator with higher activity. These findings suggest that certain oligosaccharide side-chains, particularly those containing sialic acid, can interfere with the interaction between the kringle region of t-PA and fibrin.


First one-dimensional stress-strain experiments inside an aperiodic inclusion compound: evidence of depinning effects.
This Letter reports on the first observation of depinning under hydrostatic pressure of the guest and host sublattices inside the aperiodic nonadecane-urea inclusion compound. This leads to a unique way for a direct determination of the one-dimensional interguest interaction (1 N/m for nonadecane).


Vicinal difunctionalization of carbon-carbon double bond for the platform synthesis of trifluoroalkyl amines.
Regioselective vicinal diamination of carbon-carbon double bonds with two different amines is a synthetic challenge under transition metal-free conditions, especially for the synthesis of trifluoromethylated amines. However, the synthesis of ethylene diamines and fluorinated amine compounds is demanded, especially in the pharmaceutical sector. Herein, we demonstrate that the controllable double nucleophilic functionalization of an activated alkene synthon, originated from a trifluoropropenyliodonium salt with two distinct nucleophiles, enables the selective synthesis of trifluoromethylated ethylene amines and diamines on broad scale with high efficiency under mild reaction conditions. Considering the chemical nature of the reactants, our synthetic approach brings forth an efficient methodology and provides versatile access to highly fluorinated amines.


Cross-sectional point prevalence survey to study the environmental contamination of nosocomial pathogens in intensive care units under real-life conditions.
In intensive care units (ICUs), inanimate surfaces and equipment may be contaminated by nosocomial pathogens, including multi-drug-resistant micro-organisms. To assess the degree of environmental contamination close to and distant from patients, and contamination of healthcare workers' (HCWs) hands with nosocomial pathogens under real-life conditions and to investigate potential transmission events. Over the course of three weeks, agar contact samples were taken close to and distant from patient areas and from HCWs' hands in eight ICUs of a tertiary care hospital in Innsbruck, Austria. Each ICU was visited once without announcement. Species identification and antimicrobial susceptibility testing were performed according to standard methods, and corresponding strains from patient, environment and hand samples were genotyped using pulsed-field gel electrophoresis. Among 523 samples, HCWs' hands were most frequently contaminated with potentially pathogenic bacteria (15.2%), followed by areas close to patients (10.9%) and areas distant from patients (9.1%). Gram-positive bacteria were identified most often (67.8%), with Enterococcus spp. being the most prevalent species (70% vancomycin sensitive and 30% vancomycin resistant) followed by Staphylococcus aureus, of which 64% were classified as meticillin-resistant Staphylococcus aureus. Molecular typing documented identical strains among patient, environment and hand isolates. This study found widespread contamination of the ICU environment with clinically relevant pathogens, including multi-drug-resistant micro-organisms, despite cleaning and disinfection. The bioburden might not be restricted to areas close to patients. The role of extended environmental disinfection of areas distant from patients in order to improve infection prevention needs further discussion.


Incidence of Avoidable 30-Day Readmissions Following Hospitalization for Community-Acquired Pneumonia in France.
Rates of 30-day readmissions following hospitalization for pneumonia are used to publicly report on hospital performance and to set financial penalties for the worst-performing hospitals. However, the rate of avoidable readmission following hospitalization for pneumonia is undefined. To assess how often 30-day readmissions following hospitalization for community-acquired pneumonia (CAP) are avoidable. This cohort study analyzed the results of an independent review of readmissions following hospitalization for CAP within 30 days among patients discharged from 2 large hospitals in France in 2014. Structured clinical records including clinical information (ie, baseline characteristics, physical examination, laboratory findings, x-ray or computed tomography scan findings, discharge plan, and treatments) for both index and readmission stays were independently reviewed by 4 certified board physicians. All consecutive adult patients hospitalized in 2014 with a diagnosis of CAP in our 2 eligible hospitals were eligible. All analyses presented were performed in March 2021. Avoidable readmission within 30 days of discharge from index hospitalization. The likelihood that a readmission was avoidable was quantified using latent class analysis based on the independent reviews. A readmission was considered avoidable if Bayes posterior probability exceeded 50%. The total analytical sample consisted of 1150 index hospital stays with a diagnosis of CAP, which included 651 (56.6%) male patients. The median (IQR) age for all patients was 77.8 (IQR, 62.7-86.4) years. Out of the 1150 index hospital stays, 98 patients (8.5%) died in hospital, and 108 (9.4%) unplanned readmissions were found. Overall, 15 readmissions had a posterior probability of avoidability exceeding 0.50 (13.9% of the 108 unplanned readmissions; 95% CI, 8.0%-21.9%). The median (IQR) delay between the hospital discharge index and readmission was considerably shorter when readmission was deemed avoidable (4 [6-21] days vs 12 [2-18] days; P = .02). Only a small number of readmissions following hospitalization for CAP were deemed avoidable, comprising less than 10% of all readmissions. Shorter time interval between hospitalization discharge and readmission was associated with avoidability.


Forest health effects due to atmospheric deposition: Findings from long-term forest health monitoring in the Athabasca Oil Sands Region.
Oil sands developments release acidifying compounds (SO2 and NO2) with the potential for acidifying deposition and impacts to forest health. This article integrates the findings presented in the Oil Sands Forest Health Special Issue, which reports on the results of 20 years of forest health monitoring, and addresses the key questions asked by WBEA's Forest Health Monitoring (FHM) Program: 1) is there evidence of deposition affecting the environment?, 2) have there been changes in deposition or effects over time?, 3) do acid deposition levels require management intervention?, 4) what are major sources of deposited substances? and 5) how can the program be improved? Deposition of sulphur, nitrogen, base cations (BC), polycyclic aromatic compounds and trace elements decline exponentially with distance from sources. There is little evidence for acidification effects on forest soils or on understory plant communities or tree growth, but there is evidence of nitrogen accumulation in jack pine needles and fertilization effects on understory plant communities. Sulphur, BC and trace metal concentrations in lichens increased between 2008 and 2014. Source apportionment studies suggest fugitive dust in proximity to mining is a primary source of BC, trace element and organic compound deposition, and BC deposition may be neutralizing acidifying deposition. Sulphur accumulation in soils and nitrogen effects on vegetation may indicate early stages of acidification. Deposition estimates for sites close to emissions sources exceed proposed regulatory trigger levels, suggesting a detailed assessment of acidification risk close to the emission sources is warranted. However, there is no evidence of widespread acidification as suggested by recent modeling studies, likely due to high BC deposition. FHM Program evolution should include continued integration with modeling approaches, ongoing collection and assessment of monitoring data and testing for change over time, and addition of monitoring sites to fill gaps in regional coverage.


(SCp)Rhodium-Catalyzed Asymmetric Satoh-Miura Reaction for Building-up Axial Chirality: Counteranion-Directed Switching of Reaction Pathways.
Satoh-Miura reaction is an important method for extending π-systems by forging multi-substituted benzene rings via double aryl C-H activation and annulation with alkynes. However, the development of highly enantioselective Satoh-Miura reaction remains rather challenging. Herein, we report an asymmetric Satoh-Miura reaction between 1-aryl benzo[h]isoquinolines and internal alkynes enabled by a SCpRh-catalyst. Judiciously choosing the counteranion of the Rh-catalyst is crucial for the desired reactivity over the competitive formation of azoniahelicenes. Detailed mechanistic studies support the proposal of counteranion-directed switching of reaction pathways in Rh-catalyzed asymmetric C-H activation.


Botulinum toxin in paediatric urology: a systematic literature review.
The use of botulinum toxin in paediatric urology has become increasingly widespread during recent years; however, the evidence base for its clinical use has been from adult urology centres and trials. The mechanism of action of this potent neurotoxin is discussed and evidence for its efficacy and safety is reviewed in both the adult and paediatric literature. Second, an electronic literature search was performed using the keywords paediatric urology, botulinum toxin, bladder, sphincter, and voiding dysfunction (excluding abstracts, letters and case reports). A total of 225 children in 10 peer-reviewed publications were evaluated with 165 paediatric patients with neurogenic overactivity (6 studies), 21 patients with idiopathic overactivity (1 study) and 39 patients with voiding dysfunction (3 studies). Specifically, we discuss the main indications of intravesical injections for detrusor overactivity and of intrasphincteric injections for refractory voiding dysfunctions in the paediatric population.


Copper protects against galactosamine-induced hepatitis.
Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, D-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 +/- 545 IU/l; normal 64.8 +/- 2.1), ALT (2090 +/- 190 IU/l; normal 18.0 +/- 0.7), and OCT (16.7 +/- 2.6 mmol/min/ml; normal 0.12 +/- 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 +/- 169 micrograms/g (control 18.7 +/- 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 +/- 122 IU/l), ALT (103 +/- 15 IU/l) and OCT (0.27 +/- 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.


Four-wave mixing in silicon coupled-cavity resonators with port-selective, orthogonal supermode excitation.
We propose coupled-cavity triply-resonant systems for degenerate-pump four-wave mixing (FWM) applications that support strong nonlinear interaction between distributed pump, signal and idler modes, and allow independent coupling of the pump mode and signal/idler modes to separate ports based on nonuniform supermode profile. We demonstrate seeded FWM with wavelength conversion efficiency of -54 dB at input pump power of 3.5 dBm, and discuss applications of such orthogonal supermode coupling.


Morphological analysis of tumor cell/endothelial cell interactions under shear flow.
In the process of hematogenous cancer metastasis, tumor cells (TCs) must shed into the blood stream, survive in the blood circulation, migrate through the vascular endothelium (extravasation) and proliferate in the target organs. However, the precise mechanisms by which TCs penetrate the endothelial cell (EC) junctions remain one of the least understood aspects of TC extravasation. This question has generally been addressed under static conditions, despite the important role of flow induced mechanical stress on the circulating cell-endothelium interactions. Moreover, flow studies were generally focused on transient or firm adhesion steps of TC-EC interactions and did not consider TCs spreading or extravasation. In this paper, we used a parallel-plate flow chamber to investigate TC-EC interactions under flow conditions. An EC monolayer was cultured on the lower plate of the flow chamber to model the endothelial barrier. Circulating TCs were introduced into the flow channel under a well-defined flow field and TC cell shape changes on the EC monolayer were followed in vitro with live phase contrast and fluorescence microscopy. Two spreading patterns were observed: radial spreading which corresponds to TC extravasation, and axial spreading where TCs formed a mosaic TC-EC monolayer. By investigating the changes in area and minor/major aspect ratio, we have established a simple quantitative basis for comparing spreading modes under various shear stresses. Contrary to radial spreading, the extent of axial spreading was increased by shear stress.


Genetic mapping of green curd gene Gr in cauliflower.
Gr5.1 is the major locus for cauliflower green curd color and mapped to an interval of 236 Kbp with four most likely candidate genes. Cauliflower with colored curd enhances not only the visual appeal but also the nutritional value of the crop. Green cauliflower results from ectopic development of chloroplasts in the normal white curd. However, the underlying genetic basis is unknown. In this study, we employed QTL-seq analysis to identify the loci that were associated with green curd phenotype in cauliflower. A F2 population was generated following a cross between a white curd (Stovepipe) and a green curd (ACX800) cauliflower plants. By whole-genome resequencing and SNP analysis of green and white F2 bulks, two QTLs were detected on chromosomes 5 (Gr5.1) and 7 (Gr7.1). Validation by traditional genetic mapping with CAPS markers suggested that Gr5.1 represented a major QTL, whereas Gr7.1 had a minor effect. Subsequent high-resolution mapping of Gr5.1 in the second large F2 population with additional CAPS markers narrowed down the target region to a genetic and physical distance of 0.3 cM and 236 Kbp, respectively. This region contained 35 genes with four of them representing the best candidates for the green curd phenotype in cauliflower. They are LOC106295953, LOC106343833, LOC106345143, and LOC106295954, which encode UMP kinase, DEAD-box RNA helicase 51-like, glutathione S-transferase T3-like, and protein MKS1, respectively. These findings lay a solid foundation for the isolation of the Gr gene and provide a potential for marker-assisted selection of the green curd trait in cauliflower breeding. The eventual isolation of Gr will also facilitate better understanding of chloroplast biogenesis and development in plants.


Comparative study on the effect of dietary β-carotene and phycocyanin extracted from Spirulina platensis on immune-oxidative stress biomarkers, genes expression and intestinal enzymes, serum biochemical in Nile tilapia, Oreochromis niloticus.
The current trial investigated the roles of β-carotene and phycocyanin extracted from Spirulina platensis on growth, serum biochemical, digestive enzymes, antioxidant defense, immune responses, and immune gene expression in Nile tilapia (Oreochromis niloticus). Fish (1.52 ± 0.10 g) were randomly stocked to three treatments with three replicates (12 fish per replicate) in nine aquaria (60 L glass aquarium for each), and reared for 70-days. Three tested diets were formulated to be isonitrogenous and isolipidic, and were offered for experimental fish until ad-libitum three times daily at 09:00 a.m., 11.00 a.m. and 3:00 p.m. The first diet (control) was without supplementation. About 50 mg β-carotene and 50 mg phycocyanin kg-1 were supplemented to the other experimental diets, respectively. Results indicated that feed intake was not (P > 0.05) differ among experimental diets. Compared to control diet wight gain and specific growth rate were significantly (P < 0.05) in fish fed diet containing β-carotene, while, the highest weight gain and the best FCR were detected in phycocyanin diet. Survival fish among treatments was significantly (P < 0.05) differ and the highest survival rate was showed in fish fed diet supplemented with phycocyanin. Either β-carotene or phycocyanin significantly (P < 0.05) improved the intestinal digestive enzymes compared with control diet, where the highest values of chymotrypsin, trypsin, lipase and amylase were noticed in fish fed phycocyanin. Diets supplemented with β-carotene and phycocyanin significantly (P < 0.05) improved hematology parameters contents compared with to the control diet, and the best contents were detected in fish fed diet supplemented with phycocyanin. The highest significant (P < 0.05) phagocytic, lysozyme, immunoglobulin M (IgM), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and total antioxidant capacity (T-AOC) activities were recorded in diet supplemented with phycocyanin. The transcripts of interferon gamma and interleukin 1β genes were (P < 0.05) up-regulated in the liver of fish fed diet supplemented with β-carotene and phycocyanin, but expression of HSP70 gene down-regulated in fish fed β-carotene and phycocyanin containing diet compared control. The highest gene expression of the interferon gamma and interleukin 1β was observed in fish fed phycocyanin.


Nanoparticles: New agents toward treatment of leishmaniasis.
Leishmaniasis is a widespread disease that causes 20,000 to 30,000 deaths annually, making it a major health problem in endemic areas. Because of low-performance medications, drug delivery poses a great challenge for better treatment of leishmaniasis. The present study's purpose was to review the application of nanoparticles as a new method in leishmaniasis treatment. To identify all relevant literature, we searched Web of Sciences, Scopus, PubMed, NCBI, Scielo, and Google Scholar, and profiled studies published between 1986 and 2019. In the present study, we tried to identify different research efforts in different conditions that examined the influence of various nanoparticles on different forms of leishmaniasis. In this way, we could compare their results and obtain a reliable conclusion from the most recent studies on this subject. Our review's results indicate that incorporating nanoparticles with chemical drugs improves the quality, efficiency, and sustainability of drugs and reduces their costs. Finally, considering the use of nanoparticles in the destruction of parasites, their inhibitory effect (making drugs more effective and less harmful), and their utility in making effective vaccines to prevent and fight against parasites, further research on this issue is highly recommended.


A radiological study after parenteral nutrition through silicone rubber catheters: fibrin sleeves without thrombosis.
Injection of contrast material through 38 central silicone rubber catheters at the time of withdrawal after a mean catheter life of 55 days (range 5-369) has shown no evidence of occult venous thrombosis despite the presence of a fibrin sleeve around the whole length of the intravascular portion in 37 cases. The presence of this fibrin sleeve appears to have been harmless. The absence of thrombosis suggests that silicone rubber is the material of choice for central venous feeding catheters and that the addition of heparin to the infusion fluid is unnecessary.


Endovascular embolisation is a successful and safe treatment for post-operative arterial complications after total hip arthroplasty and revision surgery.
Arterial complications are rare but clinically critical during or following total hip arthroplasty (THA) surgery. They usually require secondary interventions, either through open or endovascular approaches. In a retrospective study, we analysed indications for, as well as success and safety of, endovascular embolisation for arterial complications after THA. We reviewed all arterial complications that had occurred through THA surgery and been treated by endovascular embolisation. We analysed angiographic findings, endovascular treatment, location in relation to the surgical approach and success of the interventions. Between 1997 and 2013 we performed 3,891 THAs at our hospital. We identified 14 patients with acute arterial complications treated by minimally invasive endovascular embolisation. Clinical findings included swelling of the ipsilateral leg, pain, prolonged wound bleeding, decreased haemoglobin and/or haemodynamic instability. Angiography revealed pseudoaneurysm in 11 patients, arteriovenous fistulas in two and extravasation of contrast media in one. Two patients showed no signs of acute bleeding. Twelve patients were treated, each with a single session of endovascular embolisation; in two additional patients, the haematoma was evacuated. No complications from the endovascular treatment were observed in this series. Endovascular embolisation is a safe and successful minimally-invasive method to treat arterial injuries occurring through THA. Therefore, it should be considered as a first-line option of treatment for those injuries.


Correction to: Neolithic phylogenetic continuity inferred from complete mitochondrial DNA sequences in a tribal population of Southern India.
Unfortunately, the original version of this article was published with an error in the second sentence of the 'Molecular dating' section.


Dual-micropillar-based microfluidic platform for single embryonic stem cell-derived neuronal differentiation.
We developed the dual-micropillar-based microfluidic platform to direct embryonic stem (ES) cell fate. 4 × 4 dual-micropillar-based microfluidic platform consisted of 16 circular-shaped outer micropillars and 8 saddle-shaped inner micropillars in which single ES cells were cultured. We hypothesized that dual-micropillar arrays would play an important role in controlling the shear stress and cell docking. Circular-shaped outer micropillars minimized the shear stress, whereas saddle-shaped innermicropillars allowed for docking of individual ES cells. We observed the effect of saddle-shaped inner micropillars on cell docking in response to hydrodynamic resistance. We also demonstrated that ES cells cultured for 6 days within the dual-micropillar-based microfluidic platform differentiated into neural-like cells. Therefore, this dual-micropillar-based microfluidic platform could be a potentially powerful method for screening of lineage commitments of single ES cells.


Decabromodiphenyl ether induces male reproductive toxicity by activating mitochondrial apoptotic pathway through glycolipid metabolism dysbiosis.
Decabromodiphenyl ether (BDE-209), an extensively used flame retardant, exists widely in the environment. Although male reproductive toxicity induced by BDE-209 has been reported, its mechanisms remain unclear. To explore the role of glycolipid metabolism in male reproductive toxicity and the potential mechanisms, forty male SD rats were divided into four groups and given gavage with BDE-209 at 0, 5, 50, and 500 mg/kg/d for 28 days. In vitro, the spermatogenic cell lines GC-2spd cells were divided into four groups: the control group, 32 μg/mL BDE-209 group, 32 μg/mL BDE-209 + 0.4 μM Fatostatin (the inhibitor of SREBP-1) group, and 0.4 μM Fatostatin group. Our results showed that BDE-209 decreased sperm quality and quantity, which was correlated with glycolipid metabolism dysbiosis of testis. The levels of glucose, triglyceride, and total cholesterol were negatively correlated with sperm concentration, and triglyceride and total cholesterol levels were negatively correlated with sperm motility, while positively correlated with the sperm malformation rate. Moreover, BDE-209 exposure activated the glycolipid metabolism pathways (PPARγ/RXRα/SCAP/SREBP-1) and mitochondrial apoptotic pathway, thereby inducing the apoptosis of spermatogenic cells. In vitro, BDE-209 caused triglyceride and total cholesterol disorder and apoptosis of GC-2spd cells, the lipid metabolism pathways inhibitor fatostain downregulated the elevation of triglyceride and total cholesterol concentrations, and suppressed apoptosis and the activation of the mitochondrial apoptotic pathway in GC-2spd cells caused by BDE-209. Our results indicated that BDE-209 induced male reproductive toxicity by causing glycolipid metabolism dysbiosis of testis resulting in activating of the mitochondrial apoptotic pathway in spermatogenic cells. The study provides new insight into the mechanisms of male reproductive toxicity caused by BDE-209.


Differential function of the alpha2A-adrenoceptor and Phosphodiesterase-3B in human adipocytes of different origin.
Human adipocytes can be obtained in vitro by differentiation of human preadipocytes or mesenchymal stem cells (hMSC). Although functionally similar to freshly isolated cells, no detailed comparison of the different cell types has been performed. The antilipolytic alpha2A-adrenoceptor (AR) and the cAMP-degrading enzyme Phosphodiesterase-3B (PDE3B) have been implicated in the fine-tuning of lipolysis but little is known regarding their role in human adipocytes nor whether their expression and/or function differs in fat cells from different precursors. The effects of alpha2A-AR and PDE3B inhibition in mature adipocytes was determined and compared to that in differentiated preadipocytes and hMSC-derived fat cells. Gene expression was determined by real-time PCR and protein expression by Western blot. Noradrenaline (NA) stimulated lipolysis in preadipocytes and mature adipocytes but markedly reduced lipolysis in differentiated hMSC derived-adipocytes. This was due to a potent stimulation of alpha2A-AR since co-incubation with NA and the alpha2-AR-inhibitor yohimbine restored NA-induced lipolysis. The order of Yohimbine response was hMSC>preadipocytes>mature adipocytes. Although alpha2-AR mRNA expression was highest in mature adipocytes there was no difference in alpha2A-AR protein levels between the cell types. In contrast, Galphai2 mRNA and protein expression was significantly higher in MSC-derived adipocytes, suggesting that differences in the response to alpha2A-AR inhibition reside at the postreceptor level. Incubation with the cAMP-analog 8-bromo(8b) cAMP increased lipolysis in hMSC-derived fat cells while co-incubation with the PDE3-specific inhibitor OPC3911 did not alter the lipolytic effect. In contrast, OPC3911 increased 8bcAMP-induced lipolysis significantly in preadipocytes and mature adipocytes. The response to PDE3B inhibition was; mature adipocytes>preadipocytes>hMSC a finding that correlated significantly with both PDE3B mRNA expression and enzymatic activity. Although differentiated adipocytes of different origins display similar functional characteristics there are important differences in the regulation of lipolysis with a marked alpha2A-AR and less pronounced PDE3B effect in fat cells from MSCs.


Does restoration of focal lumbar lordosis for single level degenerative spondylolisthesis result in better patient-reported clinical outcomes? A systematic literature review.
It is controversial whether the surgical restoration of sagittal balance and spinopelvic angulation in a single level lumbar degenerative spondylolisthesis results in clinical improvements. The purpose of this study to systematically review the available literature to determine whether the surgical correction of malalignment in lumbar degenerative spondylolisthesis correlates with improvements in patient-reported clinical outcomes. Literature searches were performed via Ovid Medline, Embase, CENTRAL and Web of Science using search terms "lumbar," "degenerative/spondylolisthesis" and "surgery/surgical/surgeries/fusion". This resulted in 844 articles and after reviewing the abstracts and full-texts, 13 articles were included for summary and final analysis. There were two Level II articles, four Level III articles and five Level IV articles. Most commonly used patient-reported outcome measures (PROMs) were Oswestery disability index (ODI) and visual analogue scale (VAS). Four articles were included for the final statistical analysis. There was no statistically significant difference between the patient groups who achieved successful surgical correction of malalignment and those who did not for either ODI (mean difference -0.94, CI -8.89-7.00) or VAS (mean difference 1.57, CI -3.16-6.30). Two studies assessed the efficacy of manual reduction of lumbar degenerative spondylolisthesis and their clinical outcomes after the operation, and there was no statistically significant improvement. Overall, the restoration of focal lumbar lordosis and restoration of sagittal balance for single-level lumbar degenerative spondylolisthesis does not seem to yield clinical improvements but well-powered studies on this specific topic is lacking in the current literature. Future well-powered studies are needed for a more definitive conclusion.


Isolated Aortitis: Workup and Management.
The finding of aortitis, often incidentally noted on surgical resection, should prompt evaluation for secondary causes including large-vessel vasculitis. In a large proportion of cases, no other inflammatory cause is identified and the diagnosis of clinically isolated aortitis is made. It is unknown whether this entity represents a more localized form of large-vessel vasculitis. The need for immunosuppressive therapy in patients with clinically isolated aortitis remains unclear. Patients with clinically isolated aortitis warrant imaging of the entire aorta at baseline and regular intervals because a significant proportion of patients have or develop abnormalities in other vascular beds.


A method for measurement of liver iron fractions in needle biopsy specimens and some results in acute liver disease.
Methods are described for measurement of total tissue iron, ferritin iron, haem iron and ferritin protein in approx. 15 mg of tissue obtained by liver biopsy. The validity of these methods is examined by comparison with the values observed in larger samples of the same post-mortem derived liver tissue. Correlation coefficients vary between 0.80 and 0.99 (n = 11--16). It appears that in post-mortem liver tissue the haem iron concentration is higher than in biopsy specimens from patients. Analysis of liver biopsy specimens from patients with hepatitis showed a large variation in the mean iron content of the liver ferritin molecules. Also, the non-ferritin depot iron concentration and ferritin protein concentration is quite variable. It is suggested that in cases of advanced ferritin catabolism during hepatitis the mean percentage of iron in ferritin molecules often increases while at the same time the non-ferritin depot iron fraction decreases, probably because of iron release from the liver.


Acquired resistance to anti-EGFR mAb ICR62 in cancer cells is accompanied by an increased EGFR expression, HER-2/HER-3 signalling and sensitivity to pan HER blockers.
The human epidermal growth factor receptor (EGFR) is an important target for cancer treatment. Currently, only the EGFR antibodies cetuximab and panitumumab are approved for the treatment of patients with colorectal cancer. However, a major clinical challenge is a short-term response owing to development of acquired resistance during the course of the treatment. In this study, we investigated the molecular mechanisms underlying development of acquired resistance in DiFi colorectal cancer cells to the anti-EGFR mAb ICR62 (termed DiFi62) and to the small molecule tyrosine kinase inhibitor (TKI) gefitinib (termed DiFiG) using a range of techniques. Compared with the findings from parental DiFi and DiFiG cells, development of acquired resistance to anti-EGFR mAb ICR62 in DiFi62 cells was accompanied by an increase in cell surface EGFR and increased phosphorylation of HER-2 and HER-3. Interestingly, DiFi62 cells also acquired resistance to treatment with anti-EGFR mAbs cetuximab and ICR61, which bind to other distinct epitopes on the extracellular domain of EGFR, but these cells remained equally sensitive as the parental cells to treatment with pan-HER inhibitors such as afatinib. Our results provide a novel mechanistic insight into the development of acquired resistance to EGFR antibody-based therapy in colorectal cancer cells and justify further investigations on the therapeutic benefits of pan-HER family inhibitors in the treatment of colorectal cancer patients once acquired resistance to EGFR antibody-based therapy is developed.


Spatial frequency and orientation tuning curves of visual neurones in the cat: effects of mean luminance.
Experiments have been performed on unanaesthetized and paralysed cats. The tuning curves for spatial frequency of retinal, lateral geniculate and simple and complex cells of the cortex have been determined in response to sinusoidal gratings of various spatial frequencies at different levels of mean luminance. For all neurones, decreasing the mean luminance leads to a progressive loss of spatial resolution and contrast sensitivity. Retinal ganglion cells of type X show, for scotopic levels of luminance, a flattening of their spatial frequency tuning curves in the low spatial frequency range. For geniculate and cortical neurones, on the contrary, the spatial frequency characteristics at the various levels of luminance remain practically invariant in their bandwidth. On the average, complex cells still respond to mean luminances ten times lower than simple cells. The tuning curves for orientation of cortical cells maintain, to a first approximation, the same shape at the various levels of mean luminance. The results are discussed comparing the electrophysiological with psychophysical data.


Mutational analysis of Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP).
Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP) is a member of the serine/threonine protein phosphatases and shares 29% sequence identity with protein phosphatase 2Calpha (PP2Calpha) in its catalytic domain. To investigate the functional domains of CaMKP, mutational analysis was carried out using various recombinant CaMKPs expressed in Escherichia coli. Analysis of N-terminal deletion mutants showed that the N-terminal region of CaMKP played important roles in the formation of the catalytically active structure of the enzyme, and a critical role in polycation stimulation. A chimera mutant, a fusion of the N-terminal domain of CaMKP and the catalytic domain of PP2Calpha, exhibited similar substrate specificity to CaMKP but not to PP2Calpha, suggesting that the N-terminal region of CaMKP is crucial for its unique substrate specificity. Point mutations at Arg-162, Asp-194, His-196, and Asp-400, highly conserved amino acid residues in the catalytic domain of PP2C family, resulted in a significant loss of phosphatase activity, indicating that these amino acid residues may play important roles in the catalytic activity of CaMKP. Although CaMKP(1-412), a C-terminal truncation mutant, retained phosphatase activity, it was found to be much less stable upon incubation at 37 degrees C than wild type CaMKP, indicating that the C-terminal region of CaMKP is important for the maintenance of the catalytically active conformation. The results suggested that the N- and C-terminal sequences of CaMKP are essential for the regulation and stability of CaMKP.


Anodic oxidation of ciprofloxacin using different graphite felt anodes: Kinetics and degradation pathways.
Ciprofloxacin (CIP) is ubiquitous in the environment which poses a certain threat to human and ecology. In this investigation, the physical and electrochemical properties of graphite felt (GF) anodes which affected the anodic oxidation (AO) performance, and the CIP removal effect of GF were evaluated. The GFs were used as anodes for detection of ·OH with coumarin (COU) as molecule probe and removal of CIP in a 150 mL electrolytic cell with Pt cathode (AO-GF/Pt system). The results showed that hydrophilic GF (B-GF) owned higher sp3/sp2 and more oxygen-containing and nitrogen-containing functional groups than the hydrophobic GF (A-GF). Moreover, B-GF possessed higher oxygen evolution potential (1.12 V), more active sites and stronger ·OH generation capacity. Above mentioned caused that B-GF exhibited more superior properties for CIP removal. The best efficiencies (96.95%, 99.83%) were obtained in the AO-B-GF/Pt system at 6.25 mAcm-2 after 10 min (k1, 0.356 min-1) and 60 min (k2, 0.224 min-1), respectively. Furthermore, nine degradation pathways of CIP in AO-B-GF/Pt system were summarized as the cleavage of the piperazine ring, cyclopropyl group, quinolone ring and F atom by ·OH. It provides new insights into the removal and degradation pathways of CIP with GF in AO system.


Quality and Safety in Healthcare, Part LXXXI: Critical Care Nursing and the Beacon Award for Excellence.
When the "Standards for Establishing and Sustaining Healthy Work Environments" set forth by the American Association of Critical-Care Nurses are met in a health care system, there is enhanced safety and quality care for the patient, better job satisfaction, and less turnover by the staff. The American Association of Critical-Care Nurses started the Beacon Award for Excellence not only to recognize those who have such high standards but also to encourage units who already have achieved this distinction or are applying for it to do better.


Coronary artery bypass surgery in elderly patients.
Seventy-five patients 65 years of age and older had coronary artery bypass surgery during 2 years at Scott and White Memorial Hospital with a 4 per cent mortality rate. An average of 3.1 grafts were placed and 5.1 units of blood were used during 13 days of postoperative hospitalization. Sixty-one patients were in New York Heart Association Class IV, 12 were in Class III, and 2 had other indications for coronary artery bypass. One year following surgery there were 60 patients in Class I, 6 in Class II, 3 in Class III, and 1 in Class IV; 1 patient was dead, and 4 were lost to follow-up. Our conclusion is that coronary artery bypass grafting can be performed with an acceptable mortality rate in the elderly and that age alone should not be considered a contraindication to the operation.


Purification of a derepressible arylsulfatase from Chlamydomonas reinhardti. Properties of the enzyme in intact cells and in purified state.
Arylsulfatase (aryl-sulfate sulfohdydrolase, EC 18.104.22.168) has been purified from SO4-2-minus-starved cells of Chlamydomonas reinhardti. The enzyme was isolated from acetone-powder extract by (NH4)2SO4 precipitation, Sephadex G-200 filtration and ion-exchange chromatography. Only one fraction of aryl-sulfatase was found. The final preparation was homogenous by the criteria of sedimentation, diffusion and polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of about 150 000, estimated by ultracentrifugation and gel filtration, and an isoelectric point of 9.0. The properties of the enzyme as investigated in intact cells and in the purified state were found to be very similar except for the temperature optimum. Imidazole strongly increased the enzyme by increasing the V, but reduced the affinity for the substrate. The enzyme activity was competitively inhibited by borate with a greater affinity for borate than for the substrate. The Chlamydomonas enzyme is a Type I arylsulfatase since it was inhibited by CN-minus, but not SO4-2-minus and phosphate.


Structure of the oligosaccharyl transferase complex at 12 A resolution.
Oligosaccharyl transferase (OT) catalyzes the transfer of a lipid-linked oligosaccharide to the nascent polypeptide emerging from the translocon. Currently, there is no structural information on the membrane-embedded OT complex, which consists of eight different polypeptide chains. We report a 12 A resolution cryo-electron microscopy structure of OT from yeast. We mapped the locations of four essential OT subunits through a maltose-binding protein fusion strategy. OT was found to have a large domain in the lumenal side of endoplasmic reticulum where the catalysis occurs. The lumenal domain mainly comprises the catalytic Stt3p, the donor substrate-recognizing Wbp1p, and the acceptor substrate-recognizing Ost1p. A prominent groove was observed between these subunits, and we propose that the nascent polypeptide from the translocon threads through this groove while being scanned by the Ost1p subunit for the presence of the glycosylation sequon.


Distinguishing the C3 vs SH4 Mass Split by Comprehensive Two-Dimensional Gas Chromatography-High Resolution Time-of-Flight Mass Spectrometry.
The C3 vs SH4 (0.0034 Da) mass split is considered to be one of the most critical mass splits in petroleomics and is relevant because of the regulatory requirements for sulfur in petroleum fractions. To date, there are two ways to resolve mass splits such as C3 vs SH4: (a) ultrahigh resolution Fourier transform mass spectrometry (FT-MS); (b) high-resolution chromatography such as comprehensive two-dimensional gas chromatography (GC×GC). High-resolution chromatography minimizes the mass spectral resolution required to distinguish these key chemical constituents and provides additional sample characterization via isomer separation. High resolution mass spectrometry enables unambiguous chemical formulas determination and structural elucidation. In this paper, we demonstrate the combination of high resolution GC×GC with high resolution time-of-flight mass spectrometry to distinguish the C3 vs SH4 mass split and other common mass splits in a crude oil sample.


Activity of VIP, somatostatin and other peptides in the mouse vas deferens assay.
Non-opiate peptides such as vasoactive intestinal peptide (VIP) and somatostatin were tested for their effects on electrically induced contractions of the vas deferens. VIP(ED50 = 2.7 X 10(-8) M) and to a lesser extent somatostatin (ED50 = 5.2 X 10(-8) M) were found to be in the same general range of activity as enkephalin and the endorphins in this system. Human pancreatic polypeptide (HPP) exerted a biphasic effect, inhibiting the contractions at high concentrations but enhancing them at lower concentrations. A number of other natural occurring brain peptides were ineffective at concentrations of 1 X 10(-6) M. Several somatostatin analogues were tested and their activity on the vas deferens was found to more closely parallel their potency to inhibit the release of gastric acid than of growth hormone. In contrast to the brain opiates, however, the inhibitory effects of VIP, somatostatin and its analogues, and HPP were not reversed by the opiate antagonist naloxone. The results suggest that the vas deferens can be readily used for evaluation of analogues of VIP, somatostatin, and other peptides.


Identification of intermediate risk breast cancer patients with 1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis.
According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/μgDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p < 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Cox's proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.


Evaluation of β-blocker therapy for long-term outcomes in patients with low ejection fraction after cardiac surgery.
Preoperative low left ventricular ejection fraction (LVEF) has been reported as an independent risk factor for in-hospital mortality. However, there were few studies evaluating the long-term mortality in these patients. We, therefore, conducted this study to investigate long-term outcomes of surgery on patients with LVEF≤35% undergoing a broad range of cardiac procedures. We performed a retrospective cohort study in 510 patients from January 1, 2007 to September 1, 2019. These patients were divided into survival group (n = 386) and non-survival group (n = 124). The multivariate Cox analysis was used to estimate the risk factors for survival. In Cox analysis, β-blockers were indicated to be associated with long-term mortality. To further address bias, we derived a propensity score predicting the function of β-blockers on survival, and matched 52 cases to 52 controls with similar risk profiles. Patients were followed for a median period of 24 months (interquartile range: 11-44 months). Multivariate Cox regression analysis indicated that the non-survival group had higher weight, higher EuroSCORE, more smoking patients, longer time of cardiopulmonary bypass (CPB), more intra-aortic balloon pump (IABP) use, and more patients who always used β-blocker (HR: 2.056, 95%CI:1.236-3.420, P = 0.005) compared with survival group. After propensity matching, the group which always used β-blocker showed higher rate of all-cause death compare with the control group (61.54% vs 80.77%, P = 0.030). The risk factors for long-term survival were weight, EuroSCORE, smoking, CPB, IABP, always used β-blockers in patients with LVEF≤35%. The discharge prescription of β-blocker should be cautiously administrated in those patients.


Pterygium combined with corneal perforation: a case report.
Pterygium is a common ocular surface disease. Pterygium combined with corneal perforation is rare. A 28-year-old female patient visited our outpatient clinic due to sudden onset of blurred vision and increased tearing in her left eye. The visual acuity was 1.0 OD and intraocular pressure (IOP) of 19.5 mmHg for the right eye with no significant abnormalities found in the anterior and posterior segments. The visual acuity of her left eye was 0.06, and IOP was 6.2 mmHg. A triangular vascular membranous tissue was seen in her left eye below the nose growing into the cornea and the pupil area was not touched. Slit-lamp examination revealed a tiny round corneal perforation in 8 o'clock position of the lesion area. Hospital diagnosis was given as pterygium combined with corneal perforation. The patient was treated with levofloxacin eye drops and autologous serum-based eye drops. We report a rare case of pterygium combined with corneal perforation. Perforation is a very rare complication of pterygium. This patient received proper treatment and good result was seen. This article aimed to improve clinicians' understanding of pterygium.