Tungiasis infestation in Tanzania.
Tungiasis is caused by the jigger flea Tunga penetrans. We describe a case of severe infestation from Kigoma region, Western Tanzania. A 19-year-old male with epilepsy and mental disability presented with ulcerated and inflamed toes. Clinical examination revealed the presence of approximately 810 embedded jigger fleas on the feet, and another 60 lesions on the hands. The patient presented with fissures on the feet, hands and soles. He had difficulty walking and erythematous, oedematous, ulcerated and inflamed skin around the feet. Living conditions were precarious. The patient was assisted to extract the embedded fleas and his feet were washed with disinfectants. Oral antibiotics were given. The case shows that the disease may reach high parasite loads in Tanzanian individuals, with consequently severe pathology. There have been single reports of returning tourists from Tanzania with tungiasis, but the epidemiological situation and the geographic occurrence of the disease in this country are not known. Systematic studies are needed to increase knowledge on the epidemiological situation of tungasis in Tanzania and to identify endemic areas.


Vascular tissue adaptations in end-to-end autologous arterial grafts in rats: a morphometric analysis.
Autologous vein grafts are employed extensively to bypass stenoses in the arterial circulation. More recently arterial segments have been used for such bypass surgery. In this study the adaptation of regenerating vascular tissues in experimental autologous artery grafts (4 mm long and 1 mm in diameter) in 20 adult male Wistar rats was analysed. At 1, 2, 4, 8 and 16 wk after insertion, 4 grafts per time interval were removed, processed for high resolution light microscopy and the thicknesses of the media and neointima, as well as the area fractions of smooth muscle cells, were analysed morphometrically. All grafts were reendothelialised by 2 wk. Neointimal hyperplasia (a subendothelial layer of smooth muscle cells) developed in all grafts and reached its maximal thickness (40.4 +/- 4.7 microns) at 2 wk. The area fraction of smooth muscle cells in the neointima of the artery grafts did not change significantly at any time from 2 to 16 wk. The media underlying the neointima of the artery grafts remained relatively constant throughout the 16 wk duration of the experiment. Whilst the total wall thickness of the grafts reduced significantly between 2 and 4 wk after insertion, at all times the grafts were thicker than the host artery.


Management of pneumococcal meningitis.
During the past decade antibiotic resistance among Streptococcus pneumoniae isolates has complicated the empiric approach to and treatment of pneumococcal meningitis. Standard empiric therapy for suspected bacterial meningitis for infants and children older than 1 month of age is the combination of cefotaxime or ceftriaxone and vancomycin. Treatment is modified after antimicrobial susceptibilities are available. The optimal treatment of pneumococcal meningitis caused by strains with a cefotaxime/ceftriaxone MIC >2 microg/ml is unknown, although the addition of rifampin to the initial combination is generally recommended. The role of newer agents including quinolones is under investigation. Dexamethasone remains the only adjunctive antiinflammatory therapy to consider. The empiric approach to the child with suspected bacterial meningitis who has received the pneumococcal conjugate vaccine currently remains unchanged.


Assessment of sperm mitochondrial activity by flow cytometry and fluorescent microscopy: a comparative study of mitochondrial fluorescent probes in bovine spermatozoa.
While conventional semen analysis is a simple, time-saving, and economical means to evaluate sperm quality, it leaves biochemical and metabolic characteristics of spermatozoa aside. To address this issue, the use of fluorescent probes assessing functional sperm parameters, such as JC-1, DiOC6 (3) and MitoTracker, has increased over the last decades. Apparently contradictory observations have nevertheless fostered an ongoing debate on their sensitivity and ability to evaluate the mitochondrial membrane potential (MMP) of sperm cells, thus warranting a re-examination of these probes. The present study aims to elucidate the suitability and sensitivity of each probe to evaluate the MMP of bovine spermatozoa by flow cytometry. Cryopreserved spermatozoa from ten bulls were thawed, stained with JC-1/SYTOXRed, DiOC6 (3)/propidium iodide (PI) or MitoTracker Deep Red (MTDR)/PI, and evaluated with flow cytometry and fluorescence microscopy. DiOC6 (3), JC-1 and MTDR can be simultaneously co-stained with a viability marker. The results of the present study support the ability of DiOC6 (3)/PI and JC-1/SYTOXRed, but not that of MTDR/PI, to monitor the MMP of spermatozoa. JC-1/SYTOXRed assessed by flow cytometry was found to be the most sensitive and robust fluorescent probe to assess MMP. Moreover, DiOC6 (3)/PI could be a suitable alternative when the flow cytometer is not equipped with a red laser and/or an adequate optical filter. Both DiOC6 (3) and JC-1, but not MTDR, could be used as probes to assess the mitochondrial membrane potential of bovine spermatozoa.


Bonding of restorative resins to dentine: status of dentine adhesives and impact on cavity design and filling techniques.
In conjunction with the acid etch technique for bonding of restorative resins to enamel, an effective bonding to dentine would eliminate the need for retentive undercuts and ensure a tight marginal seal. Bonding to dentine can be achieved through dentine adhesives. These may be divided into Ca2+-bonding and collagen-bonding types. Several Ca2+-bonding adhesives are based on phosphate methacrylates. Adhesives of this type mediate a bond strength to dentine not exceeding 10 MPa. In contrast, Bowen's bonding system and the Gluma system yield bond strengths higher than 10 MPa. The two latter systems have recently been conceived in simplified versions. In general, the higher the bond strength to dentine mediated by an adhesive, the smaller are the marginal gaps formed by a composite resin polymerizing in a dentine cavity treated by the adhesive. The size and the shape of the cavity influence the width of the marginal gaps. A cavity having a V-shape gives rise to smaller gaps than box-shaped cavities. A filling technique with two 'inclining' layers reduces the width of marginal gaps. Combination of certain Ca2+-bonding and collagen-bonding adhesives results in increased bond strength and smaller marginal gaps.


[Antagonism of lovastatin on oxidative stress and apoptosis in primary rat hippocampal neurons induced by β-amyloid peptide].
Objective: To investigate the effect of lovastatin on oxidative stress and apoptosis in neurons induced by β-amyloid peptide (Aβ). Methods: Primary culture of rat hippocampal neuron was treated with Aβ oligomers alone or combined with lovastatin. The levels of OH(-), H(2)O(2), O(2)·(-), malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were measured by biochemical methods and protein expression of caspase-3 and bcl-2 was detected by Western blot. Results: As compared with the control group, treatment of 0.5 μmol/L Aβ oligomers for 48 h led to significant increase of OH(-), H(2)O(2), O(2)·(-) and malondialdehyde content, inhibition of SOD and GSH-PX activities, enhanced caspase-3 expression and decreased bcl-2 expression. Interestingly, these neurotoxic modifications on the levels of OH(-), H(2)O(2), O(2)·(-) and malondialdehyde content, SOD and GSH-PX activities, and the protein expression of cleaved caspase-3 and bcl-2 were significantly attenuated when the cells were pretreated with 0.1 μmol/L lovastatin for 24 h before exposure of Aβ oligomers. Conclusion: Lovastatin may play an important role in antagonizing the neurotoxicity of Aβ through a mechanism likely related to the inhibition of oxidative stress.


The role of 99mTc-MIBI SPECT-CT in reoperation therapy of persistent hyperparathyroidism patients.
To compare the role of 99mTc-MIBI SPECT-CT image and US in reoperation of persistent secondary hyperparathyroidism patients. A total of 8 persistent secondary hyperparathyroidism patients underwent parathyroidectomy. The sensitivity and accuracy of US and 99mTc-MIBI images before operation were determined. 9 of 14 surgical resection tissues from 8 persistent secondary hyperparathyroidism patients were confirmed to parathyroid hyperplasia. The results showed that the sensitivities were 77.8% and 100%, respectively, for US and 99mTc-MIBI SPECT-CT images. And the accuracies of US and 99mTc-MIBI dual time planar image and SPECT-CT were 50%, 78.6%, respectively. There was significantly difference between two procedures (P=0.021). The superior and inferior localization of glands were both detected by the ultrasound and scintigraphy. Two ectopic parathyroidism nodules were found by 99mTc-MIBI SPECT-CT imaging, while US provided no consistent findings. There was no significantly difference between two procedures (P=0.3). Although two cases of them were not confirmed by pathology, the iPTH of them (800 and 1429 respectively) were much higher than other four cases (<400) pg/ml. PTX is a safe and effective treatment for the patients with persistent SHPT. 99mTc-MIBI planar and SPECT-CT imaging may provide more helps for clinician's localization the hyperparathyroidism glands accurately.


Purification and characterization of a repressor for the Bacillus cereus glnRA operon.
We report the overexpression, purification, and properties of the regulatory protein, GlnR, for glutamine synthetase synthesis of Bacillus cereus. The protein was found to be a dimer with a molecular weight of approximately 30,000, and its subunit molecular weight was 15,000 in agreement with that (15,025) of deduced amino acid sequence of GlnR. The purified GlnR protein bound specifically to the promoter region of the glnRA operon of B. cereus and Bacillus subtilis. The binding of the GlnR protein to the DNA fragment was enhanced by the presence of glutamine synthetase, the product of glnA, of B. cereus or B. subtilis, although the affinity of the GlnR protein for DNA was not affected in the presence of glutamate, glutamine, Mg2+, Mn2+, or ammonia. These results indicate the existence of an interaction between GlnR and glutamine synthetase, and support the hypothesis that the regulation of glnA expression requires both GlnR protein and glutamine synthetase in Bacillus.


The dynamic lift of developmental process.
What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.


Investigation of the mouse serum proteome.
With the rapid assimilation of genomic information and the equally impressive developments in the field of proteomics, there is an unprecedented interest in biomarker discovery. Although human biofluids represent increasingly attractive samples from which new and more accurate disease biomarkers may be found, the intrinsic person-to-person variability in these samples complicates their discovery. One of the most extensively used animal models for studying human disease is mouse because, unlike humans, they represent a highly controllable experimental model system. Unfortunately, very little is known about the proteomic composition of mouse serum. In this study, a multidimensional fractionation approach on both the protein and the peptide level that does not require depletion of highly abundant serum proteins was combined with tandem mass spectrometry to characterize proteins within mouse serum. Over 12 300 unique peptides that originate from 4567 unique proteins-approximately 16% of all known mouse proteins-were identified. The results presented here represent the broadest proteome coverage in mouse serum and provide a foundation from which quantitative comparisons can be made in this important animal model.


Endemic Syndromes associated with Diabetes - A call for Awareness, recognition and management in India and beyond.
Diabetes mellitus has reached pandemic proportions throughout the globe. Though hyperglycaemia is the hall mark feature of diabetes, there are several variations in its etiology, clinical presentation, and associated complications. Some of these variations have been distinctly described in specific regions and ethnicities across India and other regions in the world. In this commentary we describe these endemic syndromes associated with diabetes to improve their awareness, recognition and management. A focused attention on these relatively neglected clinical challenges would encourage future discussion and research to address these conditions.


Cunninghamella echinulata a new biosorbent of metal ions from polluted water in Egypt.
Thirty-two fungal species were isolated from a polluted watercourse near the Talkha fertilizer plant, Mansoura Province, Egypt. Aspergillus niger, A. flavus, Cunninghamella echinulata and Trichoderma koningii were isolated frequently. On the basis of its frequency, Cunninghamella echinulata was chosen for biosorption studies. Free and immobilized biomass of C. echinulata sequestered ions in this decreasing sequence is: Pb >Cu >Zn. The effects of biomass concentration, pH and time of contact were investigated. The level of ion uptake rose with increasing biomass. The maximum uptake for lead (45 mg/g), copper (20 mg/g) and zinc (18.8 mg/g) occurred at 200 mg/L biomass. The uptake rose with increasing pH up to 4 in the case of Pb and 5 in the case of Cu and Zn. Maximum uptake for all metals was achieved after 15 min. Ion uptake followed the Langmuir adsorption model, permitting the calculation of maximum uptake and affinity coefficients. Treatment of C. echinulata biomass with NaOH improved biosorbent capacity, as did immobilization with alginate. Immobilized biomass could be regenerated readily by treatment with dilute HCl. The biomass-alginate complex efficiently removed Pb, Zn and Cu from polluted water samples. Therefore,Cunninghamella echinulata could be employed either in free or immobilized form as a biosorbent of metal ions in waste water.


Calcium inhibits epidermal growth factor-induced activation of p21ras in human primary keratinocytes.
Human primary keratinocytes are an elegant model system to study the balance between proliferation and differentiation. Both epidermal growth factor (EGF) and extracellular calcium have been implicated to function in the control of this balance, although the molecular mechanism underlying this process is poorly understood. In this study, we measured the effect of both EGF and calcium treatment on activation of p21ras and ERK2. We found that addition of EGF stimulated the activity of ERK2. This stimulation was dependent on p21ras activity, since it was completely abolished by expression of a dominant negative mutant of p21ras (p21ras(Asn-17)). Raising the level of extracellular calcium (1.8 mM) did not result in activation of ERK2. On the contrary, calcium treatment inhibited EGF-induced stimulation of ERK2 activity. In order to determine the site at which calcium treatment interferes in EGF-induced signaling, we analyzed the effect of calcium on the various steps that are involved in EGF-induced, p21ras-dependent activation of ERK2. We observed that calcium treatment inhibited EGF-induced p21ras activation. Calcium treatment, however, did not interfere with EGF-induced EGF receptor autophosphorylation or association of mammalian SOS with the EGF receptor and Shc. This, together with the observation that calcium treatment alone decreased the basal level of p21ras activity, indicates that calcium treatment interferes in EGF-mediated signaling at the level of p21ras. This type of cross talk may play a role in the decision between proliferation and differentiation in human primary keratinocytes.


Optimization of sire selection based on maximization of guaranteed income and risk associated with sire merit.
A method based on discounted income and risk assessment was developed to aid in the selection of dairy sires. The discounted profit generated from milk production of daughters was proposed as the suitable composite selection criterion to combine estimates of predicted transmitting ability (PTA) for yields of milk, fat, and protein and estimates of sire evaluations for dystocia or expected progeny difference. Steps are described to derive discounted profit (defined as expected income) for a sire with known PTA and evaluation for dystocia. The derivation of profit considered costs for semen, dystocia, heifer raising, production and maintenance of the daughter, and income from milk. Variance of income from a sire depended on the reliability of his PTA and evaluation for dystocia. Total variance from a selected set of sires was defined as the risk. A quadratic programming procedure was developed to identify the best set of sires from a given pool of sires that met a desired expected income goal with minimum risk. Combinations of sires with minimum risk for all possible levels of expected income were defined by the expected income variance frontier. The set of sires at the maximum lower boundary for 95% confidence of the expected income variance frontier was defined as the optimum set of sires to be selected; the optimum set maximized the 95% guaranteed expected income. The quadratic programming procedure provided the optimum percentage of cows to be mated to each sire in the selected set.


Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli.
Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS oxidation of DNA potentially regulated by ROS regulators.


Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory.
The exposure-excretion relationship to carbon disulfide (CS2) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS2 in urine samples from the latter was: 0.23 microgram/l (95% upper limit = 0.52 microgram/l) when log-normal distribution was assumed. Among the exposed workers, the CS2 level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS2 vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS2 concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS2 vapor at concentrations of up to 64 mg/m3 and the levels of CS2 measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 micrograms CS2/l urine (95% confidence range, 13.8-17.1 micrograms/l) was excreted following an exposure to CS2 at 31 mg/m3 (the current occupational exposure limit).


Is there an optimal organ acceptance rate for pediatric heart transplantation: "A sweet spot"?
Despite a limited supply of donors, potential donor hearts are often declined for subjective concerns regarding organ quality. This analysis will investigate the relationship between donor heart AR and patient outcome at pediatric transplant centers. The UNOS database was used to identify all match runs for pediatric candidates (age < 18 years) from 2008 through March 2015 in which a heart offer was ultimately placed. Centers which received ≥10 offers/y were included (10 634 offers, 38 centers). Transplant centers were stratified based on their AR: low (<20%, n = 13), medium (20%-40%, n = 16), or high (>40%, n = 9). Low AR centers experienced worse negative WL outcome compared with medium (P = .022) and high (P = .004) AR centers. Low AR centers had similar post-transplant graft survival to medium (P = .311) or high (P = .393) AR centers; however, medium AR centers had better post-transplant graft survival than high AR centers (P = .037). E-F survival from listing regardless of transplant was worse for low AR centers compared with medium (P < .001) or high (P = .001) AR centers. Low AR centers experience worse WL outcomes without improvement in post-transplant outcomes. High AR centers experience higher post-transplant graft failure than medium AR centers. AR of 20%-40% appears to have optimal WL and post-transplant outcomes.


Impact of the surgical experience on cochleostomy location: a comparative temporal bone study between endaural and posterior tympanotomy approaches for cochlear implantation.
The goal of this study was to evaluate, in the hands of an inexperienced surgeon, the cochleostomy location of an endaural approach (MINV) compared to the conventional posterior tympanotomy (MPT) approach. Since 2010, we use in the ENT department of Nice a new surgical endaural approach to perform cochlear implantation. In the hands of an inexperienced surgeon, the position of the cochleostomy has not yet been studied in detail for this technique. This is a prospective study of 24 human heads. Straight electrode arrays were implanted by an inexperienced surgeon: on one side using MPT and on the other side using MINV. The cochleostomies were all antero-inferior, but they were performed through an endaural approach with the MINV or a posterior tympanotomy approach with the MPT. The positioning of the cochleostomies into the scala tympani was evaluated by microdissection. Cochleostomies performed through the endaural approach were well placed into the scala tympani more frequently than those performed through the posterior tympanotomy approach (87.5 and 16.7 %, respectively, p ≤ 0.001). This study highlights the biggest challenge for an inexperienced surgeon to achieve a reliable cochleostomy through a posterior tympanotomy, which requires years of experience. In case of an uncomfortable view through a posterior tympanotomy, an inexperienced surgeon might be able to successfully perform a cochleostomy through an endaural (combined approach) or an extended round window approach in order to avoid opening the scala vestibuli.


A Bioinspired NiII Superoxide Dismutase Catalyst Designed on an ATCUN-like Binding Motif.
Nickel superoxide dismutase (NiSOD) is an enzyme that protects cells against O2·-. While the structure of its active site is known, the mechanism of the catalytic cycle is still not elucidated. Its active site displays a square planar NiII center with two thiolates, the terminal amine and an amidate. We report here a bioinspired NiII complex built on an ATCUN-like binding motif modulated with one cysteine, which demonstrates catalytic SOD activity in water (kcat = 8.4(2) × 105 M-1 s-1 at pH = 8.1). Its reactivity with O2·- was also studied in acetonitrile allowing trapping two different short-lived species that were characterized by electron paramagnetic resonance or spectroelectrochemistry and a combination of density functional theory (DFT) and time-dependent DFT calculations. Based on these observations, we propose that O2·- interacts first with the complex outer sphere through a H-bond with the peptide scaffold in a [NiIIO2·-] species. This first species could then evolve into a NiIII hydroperoxo inner sphere species through a reaction driven by protonation that is thermodynamically highly favored according to DFT calculations.


[The genetic control of mouse coat color and its applications in genetics teaching].
Mice are the most commonly used mammalian model. The coat colors of mice are typical Mendelian traits, which have various colors such as white, black, yellow and agouti. The inheritance of mouse coat color is usually stated as an example only in teaching the knowledge of recessive lethal alleles. After searched the related literatures and summarized the molecular mechanisms of mouse coat color inheritance, we further expanded the application of this example into the introduction of the basic concepts of alleles and Mendelian laws, demonstration of the gene structure and function, regulation of gene expression, gene interaction, epigenetic modification, quantitative genetics, as well as evolutionary genetics. By running this example through the whole genetics-teaching lectures, we help the student to form a systemic and developmental view of genetic analysis. At the same time, this teaching approach not only highlights the advancement and integrity of genetics, but also results in a good teaching effect on inspiring the students' interest and attracting students' attention.


The siam photon laboratory.
A synchrotron radiation research project, the Siam Photon Project, is underway in Thailand. The light source used in the project is the modified SORTEC storage ring. The project and simple aspects of the light source are described. The detailed design of the building to accommodate the experimental hall and the light source has been accomplished and the construction will start soon. The engineering design work of the machine components necessary for the modifications to reduce the beam emittance and to make the installation of insertion devices possible is underway.


Calcium supplementation: cardiovascular risk?
Adequate dietary calcium intake and appropriate sunlight exposure ensuring adequate vitamin D availability are basic measures for the prevention of osteoporosis. Calcium and vitamin D supplementation increases bone density. Vitamin D plus calcium supplementation prevents hip fractures and other nonvertebral fractures in institutionalised persons 70 years of age or older. A meta-analysis of clinical trials showed an increase in myocardial infarction in patients taking calcium supplementation alone, with a relative risk of about 1.3. Epidemiological studies have not shown an increase in the cardiovascular risk. Conflicting results have also been reported in postmenopausal women taking both calcium and vitamin D. In an epidemiological study, hypercalcaemia was associated with increased mortality, particularly cardiovascular mortality. In practice, caution dictates that not all patients should routinely take calcium and vitamin D supplements. When calcium supplements are nonetheless used, the dose should be adjusted to dietary intake in order to avoid hypercalcaemia.


[Vulvar intra-epithelial neoplasms. Development of ideas and facts].
The authors report their personal experience concerning the recent increase in the frequency of VINs and demonstrate how the mean age of the patients has decreased. They advocate "vulvoscopy" and guided biopsy for screening. VIN I and II may be treated with local chemotherapy and/or laser vaporisation. VIN III must be treated surgically (superficial tailored resection).


Cognitive inhibition and working memory in unipolar depression.
Over the past decade, evidence has accumulated to suggest that people suffering from Major Depressive Disorder (MDD) present impairment in attention, working memory, executive function, including cognitive inhibition, problem- and task-planning. The aim of the current study was to assess inhibitory mechanisms within working memory with emotionally neutral material in a group of patients suffering from MDD. We hypothesized that impairment in cognitive inhibition is global and not only due to the emotional valence of the stimuli employed for the tasks. Twenty patients with MDD (DSM-IV) and 20 healthy controls were recruited. To assess cognitive inhibition, we used neutral material, in the form of the Prose Distraction Task (PDT) (Connelly SL, 1991), Trail Making Test (TMT), Modified Card Sorting Test (MCST), Rule Shift Cards (RSC), Stroop test and Hayling Sentence Completion test (HSC). The Modified 6 elements test, the Brixton Spatial Anticipation test, the dual task performance and the verbal fluencies test were also used to assess other executive function such as flexibility, planning tasks and memory. Individuals with depression showed impairment in cognitive inhibition. They made more errors on the PDT, alongside slower response times. Slower response times were also observed on the Stroop, TMT and RSC. The MDD group made more errors in HSC and performed worse than controls in the semantic part of verbal fluency and Modified 6 elements tasks. The impairment of access function was significantly associated with the level of depression. Depressed patients showed inability to inhibit neutral information access to working memory, restrain and delete irrelevant information. This impairment in cognitive inhibition could underlie cognitive slowness and attentional deficits in depression.


[The effect of sorphoridine on neuron ultrastructure in CA3 of hippocampus in rats].
To observe the effect of sorphoridine (SR) on electroencephalograph (EEG) and ethological changes as well as neurons ultrastructure alterations in CA3 of hippocampus in rats. Tiny electrodes were embedded into hippocampus of male SD rats. The EEG and behavior changes were observed simultaneously and ultrastructure of morphological deformation of neurons in CA3 of hippocampus were observed with electron microscope at 0.5, 1.5, 8 hours after SR were injected intraperitoneally on freely moving rats. There were no epileptiform discharges and seizure activities observed in control group. There was no abnormality seen on neuron in hippocampus of CA3 in control group. While there were epileptiform discharges and convulsions observed simultaneously when SR were administrated at the dose of 55 mg/kg intraperitoneally. 0.5, 1.5, 8 hours after SR, mitochondrion showed swelling cristae and ruptured membrane. Organelle burst and degeneration of synapses were seen with electromicroscope in CA3 of hippocampus ,especially at 1.5 hours after SR administration. Sophoridine can induce acute seizure activity on rats and cause mitochondrion ultrastructural damage. The ultrastructural damage of mitochondrion occurs in the early period after SR administration. It indicates that the injury of mitochondria could be critical in neuron damage caused by sorphoridine.


Identification of the extracellular loop 2 as the point of interaction between the N terminus of the chemokine MIP-1alpha and its CCR1 receptor.
Macrophage inflammatory peptide-1alpha (MIP-1alpha)/CC-chemokine receptor ligand 3 is an 8-kDa peptide that induces chemotaxis of various lymphocytes to sites of inflammation through interaction with the G protein-coupled chemokine receptors CCR1 and CCR5. We recently described the preparation of a photoactivatable derivative of MIP-1alpha labeled with a benzophenone group at the extreme N-terminal end, which is a determinant for the agonist character of chemokines. Benzophenone-MIP-1alpha is a full agonist that specifically and covalently labels CCR1 and CCR5 receptors upon irradiation. In the present study, we use enzymatic and chemical cleavage methods on wild-type and mutated CCR1 receptors to show that the N terminus of the chemokine MIP-1alpha interacts in a specific manner with the second extracellular loop of the CCR1 receptor, within a segment comprising amino acids 178 to 194. This is the first report on the direct identification of a contact point between the N terminus of a chemokine and its membrane-bound receptor. The work shows that the part of chemokines that is endowed with agonist properties interacts with extracellular parts of the receptor rather than the transmembrane core of the protein.


Accurate and efficient cleavage of the human insulin proreceptor by the human proprotein-processing protease furin. Characterization and kinetic parameters using the purified, secreted soluble protease expressed by a recombinant baculovirus.
Maturation of the insulin proreceptor in a late Golgi compartment requires cleavage at an Arg-Lys-Arg-Arg processing site, suggesting involvement of furin, a transmembrane serine protease of the Kex2 family of processing enzymes. A genetically engineered secreted, soluble form of human furin (ss-furin), expressed by infection of insect cells with a recombinant baculovirus, was purified to near homogeneity. ss-Furin exhibited rapid and efficient cleavage of both isoforms of the human insulin proreceptor in solubilized extracts of cultured mammalian cells expressing preproreceptor cDNA. Proreceptor cleavage occurred at the physiological processing site as judged by the effects of mutations in this site on cleavage by purified ss-furin. Moreover, purified ss-furin exhibited specificity for proreceptor cleavage identical to that of the endogenous insulin proreceptor-processing enzyme. Furin thus displays the properties expected of an insulin proreceptor-processing enzyme in that it (i) cleaves the proreceptor efficiently and at the correct site; (ii) exhibits the same specificity in processing variant proreceptors as the endogenous enzyme; (iii) appears to be localized in the correct secretory compartment; and (iv) has the same broad pattern of tissue distribution as the insulin proreceptor.


Decision-making during initiation of medication therapy.
Individuals' frequent and consistent interaction with medications can serve as a unifying element to help coordinate individuals' health care services. Despite its potential to improve coordination of heath care, initiation of medication therapy from the perspective of individuals' experiences remains largely unexamined. The objectives for this study were to describe the viewpoints of consumers, physicians, pharmacists, and social workers regarding initiation of medication therapy in terms of: (1) activation and engagement, (2) information processing, and (3) economic factors. Data were collected via mailed survey methodology from random samples of 400 adults, 400 physicians, 400 pharmacists, and 400 social workers residing in Minnesota. Responses to open-ended questions were coded using content analysis and summarized with descriptive statistics. The findings showed that consumer views of (1) activation and engagement, (2) information processing, and (3) economic factors differed from the views of physicians, pharmacists, and social workers. Consumers typically view initiation of medication therapy within the context of their overall lives. Physicians view it as a biomedical puzzle in which diagnosis, drug product selection, and risk assessment are main concerns. Pharmacists view it as a health care systems puzzle in which insurance coverage, cost, and risk management are main concerns. Social workers view it as a social systems puzzle in which access to care, cost, and social support are main concerns. Initiation of medication therapy is a disjointed experience for many consumers. The best timing for providing information about prescription drugs to individuals depends largely on what kinds of thoughts and impressions they have about a new therapy at various stages of the medication use process. The findings from this study can be useful for (1) developing consumer-centered approaches for medication use and (2) coordinating health care through the integration of the medication experience using consumer viewpoints.


A case of optic neuritis complicating herpes zoster ophthalmicus in a child.
Here we report a case of optic neuritis in the setting of herpes zoster ophthalmicus (HZO) in a child. A six-year-old girl presented with HZO in the right eye. During the hospitalization, her visual acuity decreased. Fluorescein angiography (FAG) and optical coherence tomography revealed optic neuritis in the affected eye. Visual acuity improved with one month of treatment with acyclovir and steroids. FAG analysis showed no evidence of leakage at the optic disc. At one year post treatment, the patient's fundus exam and vision were normal. Therapy with antivirals and steroids may be effective in patients with childhood HZO optic neuritis.


[Expression evaluation of in loco coagulation system in colorectal cancer].
Colorectal cancer is the third most often cause of morbidity and mortality due to cancer in Poland. Thromboembolic complications are common events during the course of the disease. It is well known that hemostatic proteins play an important role in cancer progression. The purpose of the study was to evaluate the in loco interactions among colorecatal cancer and coagulation factors. 21 cases of G2 colorectal adenocarcinoma obtained during surgical resection were examined. Immunohistochemical procedures according to ABC method were employed. Tissue factor (TF) and coagulation factors II, VII, X, IX were observed in cancer cells and except factors II and IX--in tumor associated macrophages. TF was also demonstrated in endothelial cells of small blood vessels. Strong expression of fibrinogen was observed among connective tissue at some distance around malignant tumor while weaker expression was found in tumor stroma. Expression of F(1+2), the by-product of thrombin generation, was revealed in cancer cells, macrophages and in the tumor stroma. The results indicate extravascular activation of blood coagulation in loco in colorectal cancer that is TF-dependent.


Does believing in "use it or lose it" relate to self-rated memory control, strategy use, and recall?
After an oral free recall task, participants were interviewed about their memory. Despite reporting similar levels of perceived personal control over memory, older and young adults differed in the means in which they believed memory could be controlled. Older adults cited health and wellness practices and exercising memory, consistent with a "use it or lose it" belief system, more often than young adults who were more likely to mention metacognition and flexible strategy use as means of memory control. Young adults reported using more effective relational strategies during study for a free recall test. Use of relational strategies predicted recall in both age groups, but did not materially affect age differences in performance. Metacognitive beliefs, including implicit theories about aging and memory decline, memory self-concept, and perceived control over memory functioning, did not systematically correlate with strategy use or recall.


Studying morphological variations across single fibres using an X-ray waveguide.
Waveguide and glass capillary optics have been used to study morphological variations across single as-spun poly(p-phenylene benzobisoxazole) (PBO) fibres. The waveguide provides a beam with a submicrometre dimension perpendicular to the fibre axis. The glass capillary optics provide a beam of a few micrometres in diameter. By directly comparing results obtained with both optics it is possible to assess the influence of beam size on experimental observations. The study demonstrates that submicrometre beams are invaluable for detailed morphological studies across single fibres. The greater morphological averaging inherent to data collected using glass capillary optics reduces the variation between skin and core measurements, as well as obscuring other important features. Crystalline domain orientation, (200) crystal plane spacings and reflection intensities can be determined from data generated using a submicrometre beam. All parameters are found to vary significantly across the diameter of single PBO fibres. In terms of orientation, both skin and core regions exhibit a lower degree of crystalline domain orientation than an intermediate zone. In terms of (200) crystal plane spacing, the observed variations suggest residual stresses within the fibre structure following manufacture.


Stress-reducing effect of physician's tape-recorded support on cardiac surgical patients in the intensive care unit.
Staying in an intensive care unit (ICU) is very stressful for patients after heart surgery. Although it is a general belief that support from doctors is important to reduce patients' tension, no quantitative data are available. We investigated the stress-reducing effects of a tape-recorded message from the physician which provided information regarding the surgery and emotional support for heart surgery patients postoperatively in the ICU. Sixty patients who underwent cardiac surgery were randomly allocated to two equal groups. The patients in the experimental group listened to a tape-recorded message from their attending surgeon soon after they recovered from anesthesia, while the control group rested during the study period. The effectiveness of the tape-recorded support program was evaluated by the influence on heart rate, blood pressure, and finger skin temperature, as well as the degree of subjective pain, tension, anxiety, depression, and anger. The pain and tension levels of the patients were measured using a visual analogue scale, while the severity of anxiety, depression, and anger was evaluated using the Brief Symptom Rating Scale. Patients' evaluation of the usefulness of the program was also assessed. After listening to the physician's recorded message, the mean increase in the skin finger temperature in the experimental group was higher than in the control group (0.44 degree C vs 0.25 degree C, p = 0.0513). The experimental group had significant decreases in their mean scores of pain (-1.11 vs 0.36, p = 0.0043), tension (-2.26 vs -0.25, p = 0.0001), anxiety (-1.3 vs -0.57, p = 0.0473), and depression (-2.24 vs -0.37, p = 0.0253). The patients showed a high need for this support program (mean need score 8.4). These findings show that a physician's tape-recorded message providing information and emotional support can reduce stress in heart surgery patients in the ICU postoperatively.


Robust real-time myocardial border tracking for echocardiography: an information fusion approach.
Ultrasound is a main noninvasive modality for the assessment of the heart function. Wall tracking from ultrasound data is, however, inherently difficult due to weak echoes, clutter, poor signal-to-noise ratio, and signal dropouts. To cope with these artifacts, pretrained shape models can be applied to constrain the tracking. However, existing methods for incorporating subspace shape constraints in myocardial border tracking use only partial information from the model distribution, and do not exploit spatially varying uncertainties from feature tracking. In this paper, we propose a complete fusion formulation in the information space for robust shape tracking, optimally resolving uncertainties from the system dynamics, heteroscedastic measurement noise, and subspace shape model. We also exploit information from the ground truth initialization where this is available. The new framework is applied for tracking of myocardial borders in very noisy echocardiography sequences. Numerous myocardium tracking experiments validate the theory and show the potential of very accurate wall motion measurements. The proposed framework outperforms the traditional shape-space-constrained tracking algorithm by a significant margin. Due to the optimal fusion of different sources of uncertainties, robust performance is observed even for the most challenging cases.


Positive non-invasive tests in the chest pain unit: importance of the clinical profile for estimating the probability of coronary artery disease.
We studied 100 consecutive patients with coronary angiography performed after a positive result of a non-invasive test in the chest pain unit. Mean age was 66 years. The percentage of patients without significant coronary artery disease, 1-vessel disease and multivessel disease was 35, 33, and 32%, respectively. The CPU-65 index that combines four clinical variables (comorbidity: diabetes, pain: typical, use of: aspirin, 65 years old or more) was associated with the presence of coronary artery disease, multivessel disease, and coronary revascularization. We conclude that in the chest pain unit, patients with a positive non-invasive test the rate of false positive results, one-vessel disease and multivessel disease is similar. However, important changes in these percentages are seen, according to the clinical profile. The CPU-65 index is useful to determine the pre-test probability of significant coronary artery disease and patients with intermediate scores are the ones that benefit most of non-invasive tests.


Extraocular Muscle Findings in Myasthenia Gravis Associated Treatment-Resistant Ophthalmoplegia.
We report the histopathological and ultrastructural tissue analysis of extraocular muscle (EOM) obtained from a patient with seronegative myasthenia gravis (MG) with treatment-resistant ophthalmoplegia for 3.5 years. The EOM demonstrated predominantly myopathic features and ultrastructural evidence of mitochondrial dysfunction, but the most striking features were increased endomysial collagen and adipocyte replacement of muscle fibers. By contrast, control EOM from a patient undergoing strabismus surgery for a sensory exotropia in a nonseeing eye and a similar duration of deviation, showed normal muscle histology. Although the histopathological and ultrastructural findings largely resemble those of limb muscle in MG, the abundant endomysial collagen may be nonspecific and secondary to poor force generation as a result of chronic ophthalmoplegia.


Nuclear translation or nuclear peptidyl transferase?
It is widely accepted that protein synthesis occurs in the cytoplasms of eukaryotic cells, but some investigators believe that it also occurs in the nucleus. In spite of experiments performed in several labs over many years, the issue of nuclear translation remains unresolved. Advocates assert that it would serve as an economical and convenient way to explain how cells monitor the quality of newly made mRNAs or ribosomes. Skeptics argue that regardless of its esthetic appeal, compelling evidence for nuclear translation has been absent. The key question--also central to the debate more than 30 years ago--is whether alleged nuclear translation can be proven to represent "genuine polypeptide synthesis that is a function of the nuclear compartment".


Microbial degradation of phenol in a modified three-stage airlift packing-bed reactor.
Phenol degradation was carried out by using a modified three-stage airlift packing-bed bioreactor. A laboratory-scale airlift packing-bed reactor, with hydrodynamic flexible packing material in the three-stage bioreactor, was constructed and operated for phenol removal from synthetic wastewater. The airlift packing-bed reactor successfully degraded phenol and lowered the chemical oxygen demand (COD) of wastewater. High COD removal was observed, and much lower sludge effluent was obtained in this investigation. This airlift bioreactor showed a superior hydrodynamics performance and broad operating conditions for phenolic material removal. Different operating modes were discussed to obtain the optimal condition for phenol degradation (i.e., hydraulic retention time [HRT] and gas flowrate of airlift). The HRT and feed phenol concentration of wastewater dominated the removal efficiency of phenol and COD. In this bioreactor, surface loading up to 2.84 g phenol/ m2 x d, almost 100% phenol removal, and over 90% COD removal was achieved. The lower operating cost combined with higher phenol-removal efficiency and a low sludge effluent concentration can be achieved by using this reactor for phenol wastewater treatment.


Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study.
Low bone mineral density (BMD) and osteoporosis remain frequent problems in patients with inflammatory bowel diseases (IBDs). Several guidelines with nonidentical recommendations exist and there is no general agreement regarding the optimal approach for osteoporosis screening in IBD patients. Clinical practice of osteoporosis screening and treatment remains insufficiently investigated.In the year 2014, a chart review of 877 patients included in the Swiss IBD Cohort study was performed to assess details of osteoporosis diagnostics and treatment. BMD measurements, osteoporosis treatment, and IBD medication were recorded.Our chart review revealed 253 dual-energy x-ray absorptiometry (DXA) scans in 877 IBD patients; osteoporosis was prevalent in 20% of tested patients. We identified widely differing osteoporosis screening rates among centers (11%-62%). A multivariate logistic regression analysis identified predictive factors for screening including steroid usage, long disease duration, and perianal disease; even after correction for all risk factors, the study center remained a strong independent predictor (odds ratio 2.3-21 compared to the center with the lowest screening rate). Treatment rates for patients with osteoporosis were suboptimal (55% for calcium, 65% for vitamin D) at the time of chart review. Similarly, a significant fraction of patients with current steroid medication were not treated with vitamin D or calcium (treatment rates 53% for calcium, 58% for vitamin D). For only 29% of patients with osteoporosis bisphosphonate treatment was started. Treatment rates also differed among centers, generally following screening rates. In patients with longitudinal DXA scans, calcium and vitamin D usage was significantly associated with improvement of BMD over time.Our analysis identified inconsistent usage of osteoporosis screening and underuse of osteoporosis treatment in IBD patients. Increasing awareness of osteoporosis as a significant clinical problem in IBD patients might improve patient care.


Eigenvector determination by iterative optical methods.
Three power methods to compute the eigenvalues and eigenvectors of a matrix on an iterative optical processor (IOP) are analyzed. Each is appropriate for a different eigenvalue and eigenvector application. When implementation on an IOP and the processing speed are considered, the second method is found to be preferable to others recently described.


Rapid adaptive divergence of life-history traits in response to abiotic stress within a natural population of a parthenogenetic nematode.
Sexual reproduction is acknowledged to facilitate adaptation to novel environments while asexual eukaryotes are often regarded as having low adaptive potential. This view has been challenged in a number of studies, but the adaptive potential of asexual populations in the field is poorly documented. We investigated the response of natural populations of the parthenogenetic nematode Acrobeloides nanus to imposed divergent selective pressures. For this purpose, we employed a replicated evolution experiment in the field. After 20 years of evolution under abiotic stress and control conditions, life-history traits were assessed in reaction norm- and reciprocal transplant experiments. Both these experiments indicated adaptive divergence within the population of A. nanus. Namely, the transplant experiment demonstrated that in the stressed soil environment, body growth rate was more reduced in the nematodes originating from the control treatment. In the reaction norm experiment, survival and reproduction were higher under test conditions corresponding to the native environment of the nematodes. The differences in the analysed traits are discussed in the context of life-history theory. Overall, our results strongly support high adaptive potential of A. nanus and suggest that population structure and distribution of asexual species is shaped by local adaptation events.


Long-term follow-up of endoscopic papillectomy and the value of preventive pancreatic stent placement (with videos).
Early-stage ampullary adenomas have only been reported in a small case series on endoscopic management. Hence, this study aimed to evaluate the long-term outcomes of early ampullary adenoma with endoscopic management and identify the risk factors for acute pancreatitis after endoscopic papillectomy (EP). In this study, 115 patients who underwent EP at Changhai Hospital (Shanghai, China) between January 2012 and December 2018 were retrospectively analysed. Endoscopy was performed at 1, 3, 6, and 12 months after EP. Data were statistically analysed using the t-test or the Mann-Whitney U test. A total of 107 patients were included in this study and the follow-up period was 75 ± 43 months. The average age of the 107 patients was 54.6 years and the average tumor size was 17 mm. The average age of the patients (53.7 ± 10.7 years vs 55.2 ± 10.5 years, P = 0.482), minimum tumor size (13 vs 19 mm, P = 0.063), and complete resection rate (84.78% vs 85.25%, P = 0.947) did not differ significantly between the stent placement and non-stent placement groups. Post-EP acute pancreatitis rates in the non-stent placement and stent placement groups were 11.48% and 4.35%, respectively. The risk of post-EP acute pancreatitis was significantly associated with the preoperative carcinoembryonic antigen level in univariate analysis, but not in multivariate analysis. The risk of post-EP acute pancreatitis was not significantly associated with the placement of the pancreatic stent in either univariate or multivariate analysis. Moreover, delayed proximal pancreatic duct stenosis was not noted in either group during long-term follow-up. EP is a satisfactory option for treating adenomas of the ampulla of the duodenum.


High RIPK3 expression is associated with a higher risk of early kidney transplant failure.
Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.


Pathogenesis of the anemia of Shay Chloroleukemia.
The pathogenesis of anemia of the Shay chloroleukemia (SCL) was studied in rats following SC, IP and IV inoculation of chloroma cells. Little difference in survival was noted regardless of the route of inoculation. A decrease in hamatocrit occurred in all SCL rats during approximately the final 48 hours of the disease; however, the anemia was more severe in SC- and IP-inoculated terminal rats than in SCL rats inoculated IV. A reduction in the numbers of normal cellular elements was noted in the femoral bone marrow of most terminal rats studied which was found to correlate inversely with the leukemic blast cell content of the marrow. No correlation was observed between the erythroblast content of the marrow and the degree of anemia. The number of erythroblasts varied from greatly reduced to normal in terminal SCL rats despite severe anemia. Moreover, the greatest reduction of both normal marrow cellularity and erythroblast numbers was observed in IV inoculated rats which consistently displayed the highest hematocrits in the terminal stage of the disease. Thus, the terminal anemia appears to be due primarily to excessive red cell loss. The decrease in erythroblasts, when observed, was most striking in the orthochromatophilic and polychromatophilic stages of erythroid maturation.


Facile synthesis of novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole.
Novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole have been synthesized starting from tetra-tert-butylated 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles, which were prepared via an efficient tert-butylation of 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles.


[Efficacy and safety of a salsobromoiodic gel solution in proctological surgery].
Surgical procedures for ano-rectal pathologies are always conditioned by an high percentage of side-effects. Indeed, the prevention of probable complications such as the non tissue-recovery or infection is a fundamental topic to guarantee an adequate follow-up. The aim of this comparative study is to assess the short-term outcomes of the use of a solution salsobromoiodic gel solution in postoperative period of patients undergoing proctological surgery. The authors selected retrospectively a population of 80 patients, undergoing surgery for Milligan-Morgan hemorrhoidectomy. Based on the recommended medications postoperatively, patients were divided into two groups: the Group A applied the salsobromoiodic solution gel on the perianal surgical wound in the postoperative period, the Group B did not use any medical facility with the exception of a soap at neutral pH. The clinical features assessed at 5, 10, 15 and 30 days after surgery were: pain, burning and itching lenght, the healing time, the presence or absence of early or late superinfection, the time of re-epithelization, the need for surgical curettage. The subjective evaluation of quality of life was assessed using a Visual Analogue Scale (VAS). There was a statistically significant reduction in length of postoperative pain in patients of Group A compared to Group B (5.6 vs 10.4 days respectively; p<0.005). There was a more rapid wound healing and re-epithelialization in group A, 15 and 21,3 days, respectively, as compared to Group B, 22.9 and 31.7 days (p<0.005). There were no differences between the two groups in terms of burning, itching and early and late bacterial infection. Two patients in Group B required a surgical debridement of the wound. Patients who used postoperatively salsobromoiodic solution declared a better quality of life. The use of salsobromoiodic gel solution in the postoperative proctological surgery, resulted safe and was effective in reducing postoperative pain, in contributing wounds healing and improving the quality of life, as subjectively assessed by each patient.


Healing following implantation of periodontitis affected roots into bone tissue.
The aim of the present experiment was to study whether new connective tissue attachment can occur to root surfaces which have been exposed to the oral environment and subsequently implanted into bone tissue. Twelve teeth in three beagle dogs were subjected to progressive periodontal breakdown to half the root length by placing cotton floss ligatures around the neck of the teeth. Following crown resection and root hemisection, the teeth were root filled and the roots thoroughly scaled and planed. Each root was extracted and implanted into bone cavities prepared in edentolous areas of the jaws in such a way that epithelial migration into the wound and bacterial infection were prevented during healing. Root implantation and sacrifice of the animals were scheduled to allow for observation periods of 1, 2 and 3 months. The results demonstrated that new connective tissue attachment did not occur to root surfaces which had been exposed to the oral environment, but healing was characterized by repair phenomena, i.e. mainly root resorption and ankylosis. In those areas of the roots where periodontal ligament tissue was preserved following tooth extraction, a functionally oriented attachment apparatus was reformed. The results indicate that in addition to apical migration of junctional epithelium and regrowth of subgingival plaque, the type of cells which repopulate the wound area may jeopardize new connective tissue attachment.


Highly precarious general and sexual health conditions of young domestic servants: results from a qualitative exploratory study and perspectives for community-based research in Bamako, Mali.
Most domestic servants (DS) in Mali are very young female migrants living in precarious conditions. We aimed to understand their living and working conditions in relation to their general and sexual health. Seven focus groups (53 participants) were conducted by the DS community-based organization ADDAD. Narratives were thematically analyzed using an inductive method. The dominant emerging theme was DS' strong dependence on their employers. Employers' attitudes regarding DS workload, the provision of food, water and hygiene products, housing conditions, and healthcare cover, appeared decisive for DS' physical and mental health, and the type of healthcare they used (self-medication, traditional care, healthcare facilities). Psychological, physical and sexual violence in employers' households was frequent. HIV/STI prevention knowledge was poor. These results highlight the serious risks for DS in terms of HIV/STI and unwanted pregnancies. DS were interested in receiving healthcare from ADDAD; this was motivated by the organization's trusting and understanding community-based environment, and DS' fear of discrimination in healthcare facilities. This study highlights the relevance of tackling the defense of rights and sexual health promotion for DS at the community level. Its findings can help identify research questions to evaluate the extent to which DS constitute a key HIV population.


Transition from traveling to standing waves as a function of frequency in a reaction-diffusion system.
The addition of polyethylene glycol to the Belousov-Zhabotinsky reaction increases the frequency of oscillations, which in an extended system causes a transition from traveling to standing waves. A further increase in frequency causes another transition to bulk oscillations. The standing waves are composed of two domains, which oscillate out of phase with a small delay between them, the delay being smaller as the frequency of oscillations is increased.


Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.
We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.


Synovial sarcoma of the heart.
Primary synovial sarcomas of the heart are exceptionally rare tumours, only five being previously documented. We report a sixth case and review published data. Ages ranged from 13-53 (mean 40.8) years. There were four men and two women who characteristically presented with syncope or dyspnoea. Most of the tumours arose in the right atrium where they formed pedunculated or polypoid masses. In the previously documented cases, all patients died within 9 months. However in our case, local excision was felt to have been complete and the patient remains disease free at 10 months.


Postoperative use of epidurally administered morphine in children and adolescents.
Epidurally administered narcotics are increasingly used to provide relief of pain in adults after major surgical procedures. This report describes the use of epidurally administered morphine for postoperative analgesia in nine pediatric patients after 15 major surgical procedures. The mean dose of morphine was 0.12 +/- 0.03 mg/kg of body weight, and the mean duration of analgesia per dose was 10.8 +/- 4.0 hours. Catheters remained in place for a mean duration of 50.3 +/- 16.0 hours. Increasing the dose of morphine to more than 0.1 mg/kg did not prolong the duration of analgesia but it did increase the frequency of side effects. No complications from placement of the catheter and no serious side effects were encountered. The postoperative requirements for narcotics were significantly less in the patients who received morphine epidurally than in those who received narcotics parenterally. Epidurally administered morphine can provide reliable postoperative analgesia in pediatric patients. The potential benefits include improved quality of pain relief at low total requirements, improved pulmonary function, and early ambulation.


New marks on the block: Set5 methylates H4 lysines 5, 8 and 12.
The methylation of lysine residues in the N-terminal tails of histones is a highly conserved mechanism that regulates critical functions of chromatin, such as the control of gene expression. Using a biochemical approach, we recently identified new methylation marks on the histone H4 tail in budding yeast at lysines 5, 8 and 12, catalyzed by the previously-uncharacterized enzyme Set5. Genetic studies revealed that Set5 functions in cellular processes that also rely on the global chromatin modifying complexes COMPASS and NuA4, which methylate H3 lysine 4 and acetylate H4 lysines 5, 8 and 12, respectively. The identification of new methylation events on the H4 tail raises many intriguing questions regarding their function and their interaction with known histone modifications. Here, we analyze the insights gained about the new enzyme Set5 and the implications for new functionality added to the H4 tail.


A charge-transfer salt composed of methyl viologen and hexacyanidoferrate(II).
The methyl viologen dication, used under the name Paraquat as an agricultural reagent, is a well-known electron-acceptor species that can participate in charge-transfer (CT) interactions. The determination of the crystal structure of this species is important for accessing the CT interaction and CT-based properties. The title hydrated salt, bis(1,1'-dimethyl-4,4'-bipyridine-1,1'-diium) hexacyanidoferrate(II) octahydrate, (C12H14N2)2[Fe(CN)6]·8H2O or (MV)2[Fe(CN)6]·8H2O [MV2+ is the 1,1'-dimethyl-4,4'-bipyridine-1,1'-diium (methyl viologen) dication], crystallizes in the space group P21/c with one MV2+ cation, half of an [Fe(CN)6]4- anion and four water molecules in the asymmetric unit. The FeII atom of the [Fe(CN)6]4- anion lies on an inversion centre and has an octahedral coordination sphere defined by six cyanide ligands. The MV2+ cation is located on a general position and adopts a noncoplanar structure, with a dihedral angle of 40.32 (7)° between the planes of the pyridine rings. In the crystal, layers of electron-donor [Fe(CN)6]4- anions and layers of electron-acceptor MV2+ cations are formed and are stacked in an alternating manner parallel to the direction of the -2a + c axis, resulting in an alternate layered structure.


A contemporary survey of bumble bee diversity across the state of California.
Bumble bees (genus Bombus) are important pollinators with more than 260 species found worldwide, many of which are in decline. Twenty-five species occur in California with the highest species abundance and diversity found in coastal, northern, and montane regions. No recent studies have examined California bumble bee diversity across large spatial scales nor explored contemporary community composition patterns across the state. To fill these gaps, we collected 1740 bumble bee individuals, representing 17 species from 17 sites (~100 bees per site) in California, using an assemblage monitoring framework. This framework is intended to provide an accurate estimate of relative abundance of more common species without negatively impacting populations through overcollection. Our sites were distributed across six ecoregions, with an emphasis on those that historically hosted high bumble bee diversity. We compared bumble bee composition among these sites to provide a snapshot of California bumble bee biodiversity in a single year. Overall, the assemblage monitoring framework that we employed successfully captured estimated relative abundance of species for most sites, but not all. This shortcoming suggests that bumble bee biodiversity monitoring in California might require multiple monitoring approaches, including greater depth of sampling in some regions, given the variable patterns in bumble bee abundance and richness throughout the state. Our study sheds light on the current status of bumble bee diversity in California, identifies some areas where greater sampling effort and conservation action should be focused in the future, and performs the first assessment of an assembly monitoring framework for bumble bee communities in the state.


Real-World Outcomes of DMEK: A Prospective Dutch registry study.
This study analyzed real-world practice patterns, graft survival, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in the Netherlands. Population-based interventional clinical study. In this prospective registry study, all consecutive primary DMEK procedures registered in the Netherlands Organ Transplant Registry were identified. Short-term graft survival and outcomes of primary transplants for Fuchs' endothelial dystrophy (FED) were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Linear mixed model analyses were used for best spectacle-corrected visual acuity (BSCVA), spherical equivalent, hyperopic shift, and endothelial cell density. 752 DMEKs were identified between 2011 and 2018. In 90% of cases, the indication for DMEK was FED. Graft survival measured 87% at 3 months, 85% at 6 months, 85% at 1 year, and 78% at 2 years. DMEK procedures after 2015 showed better survival compared to previous years (Hazard ratio = 0.4; P < .001). Baseline BSCVA in primary transplants with FED measured on average 0.45 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.41-0.49), and significantly improved (overall P < .001) to 0.17 logMAR (95% CI, 0.14-0.21) at 3 months, 0.15 logMAR (95% CI, 0.11-0.18) at 6 months, 0.12 logMAR (95% CI, 0.08-0.16) at 1 year, and 0.08 (95% CI, 0.05-0.12) at 2 years. At 3 months, a hyperopic shift of +0.36 diopters (P < .001) was observed and endothelial cell loss measured 33%. Our findings provide real-world support that DMEK is an effective treatment for FED with respect to vision restoration, inducing a small hyperopic shift with an acceptable endothelial cell loss. Graft survival improved over time, suggesting a learning curve on a national level.


Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy.
Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool.


Off-label use of ondansetron in pregnancy in Western Australia.
Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. There is an increasing trend to prescribe ondansetron although its safety for use in pregnancy has not been established. Exposed pregnancies were all births in Western Australia, 2002-2005, where the mother was dispensed ondansetron under the Australian Pharmaceutical Benefits Scheme, compared with all other births during the same period. Outcomes investigated include maternal and child characteristics, birth defects, pregnancy, and delivery characteristics. There were 96,968 births from 2002 to 2005. Ondansetron was dispensed to 251 pregnant women during this period. The women dispensed ondansetron were more likely to be privately insured (OR: 5.8; 95% CI: 4.3-7.9), to be Caucasian (3.3; 1.9-5.7), not to smoke during their pregnancy (2.9; 1.8-4.7), to have a multiple birth (2.7; 1.5-5.0), and to have used fertility treatment (1.8; 1.0-3.4). There was a small but not significantly increased risk of a major birth defect with first trimester exposure (1.2; 0.6-2.2). Our study did not detect any adverse outcomes from the use of ondansetron in pregnancy but could not conclude that ondansetron is safe to use in pregnancy.


Isokinetic leg strength of institutionalized older adults with mental retardation with and without Down's syndrome.
This study compared isokinetic leg strength of aged individuals with mental retardation (MR) with and without Down's syndrome (DS). Nine subjects with MR and DS (mean age = 61) and 16 subjects with MR but without DS (mean age = 63) performed a leg strength test on a Biodex dynamometer. Parameters measured were peak torque, peak torque percent body weight (ratio displayed as a percentage of the maximum torque production to the subject's body weight), and average power percent body weight. In addition, anthropometric measurements (height, weight, skinfolds, and body mass index) and intelligence quotient (IQ) were also analyzed and compared. The results indicate a significant increase of scores for isokinetic knee extension and flexion in the group with MR but without DS over the subjects in the group with MR and DS. As a group, the individuals with MR and DS tended to be smaller and fatter. No significant difference in IQ was observed between the 2 groups with MR. It was concluded that the strength of individuals with MR but without DS is greater than the group of subjects with MR and DS. When comparing their results to aged individuals without MR, a significant decline in muscle strength can be observed among people with MR.


Human immunoglobulins in intraocular inflammation.
Chronic intraocular inflammation (IOI) is a heterogeneous group of rare diseases, which represents one of the leading causes of acquired and treatable blindness in adults. The main anatomical site of inflammation is the uveal tract, which is the vascular organ of the eye, but uveitis is now used to describe IOI more globally. In around 40% of the cases of uveitis an underlying systemic disease, often of autoimmune origin, can be identified. In autoimmune diseases with IOI, uveitis may be the first clinical manifestation and may represent the most severe sign. Studies in animal models, especially in experimental autoimmune uveitis (EAU), offer the opportunity to investigate the pathogenicity of these disorders. The conventional treatment of IOI includes corticosteroids and immunosuppressive agents, which are efficient in around one-half of the patients, but their effectiveness is also limited by their iatrogenicity. The effects of intravenous immunoglobulins (IVIGs) on ocular inflammation have been investigated in a wide spectrum of autoimmune/systemic diseases. Most of the publications are case series or open trials. They show favorable results in a subset of indications, including mainly ocular cicatricial pemphigoid (OCP), Vogt-Koyanagi-Harada (VKH) syndrome, or birdshot disease. Efficacy results are more debated in other conditions such as inflammatory demyelinating optic neuritis. In other diseases with IOI only case reports are available, suggesting that IVIGs may be of some interest. These observations support the need for controlled trials to demonstrate the efficacy of IVIGs and assess their potential steroid-sparing effect.


Time to positivity of neonatal blood cultures: fast and furious?
The aim of this study was to determine the time to positivity (TTP) of neonatal blood cultures, to investigate differences between early onset versus late-onset sepsis, and non-proven versus proven sepsis, and to examine differences in TTP by organism type using a retrospective observational study at the Neonatal Intensive Care Unit, Antwerp University Hospital, Belgium. The subjects were 1828 neonates with suspected sepsis who were treated with antimicrobials for at least 3 days. The TTP was recorded for all episodes of suspected sepsis in an approximately 6.5 year period. A total of 2916 blood cultures were collected, of which 437 (15%) became positive. The overall TTP was 21.33 h (Q1-Q3 13.17-32.46). The difference between the median TTP in early onset versus late-onset sepsis was 0.83 h (22.00 versus 21.17 h, P=0.75). The median TTP for Gram-negative organisms was 11.17 h (Q1-Q3 8.84-15.67), whereas the median TTP for Gram-positive organisms was 23.59 h (Q1-Q3 15.29-34.58, P<0.001). In Gram-positive isolates, the median TTP for coagulase-negative staphylococci (CNS) was 26.67 h (Q1-Q3 19.00-38.17), whereas the median TTP for non-CNS was 12.83 h (Q1-Q3 10.50-18.17, P<0.001). The median TTP in proven sepsis was 20.17 h (Q1-Q3 13.00-30.37), whereas it was 29.67 h (Q1-Q3 21.17-50.63, P<0.001) in non-proven sepsis. TTP of neonatal blood cultures was significantly shorter for Gram-negative organisms. We suggest shortening the total incubation time of neonatal blood cultures to a maximum of 3 days. However, blood cultures collected in infants<72 h of age might require a longer incubation time. According to our results, it may be safe to narrow the antimicrobial spectrum to solely target Gram-positive bacteria when the culture is still negative after 48 h, and to cease antimicrobial therapy when the culture is still negative after 72 h in clinically well infants.


A Review of Biologically Active Oxime Ethers.
Oxime ethers are a class of compounds containing the >C=N-O-R moiety. The presence of this moiety affects the biological activity of the compounds. In this review, the structures of oxime ethers with specific biological activity have been collected and presented, and bactericidal, fungicidal, antidepressant, anticancer and herbicidal activities, among others, are described. The review includes both those substances that are currently used as drugs (e.g., fluvoxamine, mayzent, ridogrel, oxiconazole), as well as non-drug structures for which various biological activity studies have been conducted. To the best of our knowledge, this is the first review of the biological activity of compounds containing such a moiety. The authors hope that this review will inspire scientists to take a greater interest in this group of compounds, as it constitutes an interesting research area.


Protein production by stationary phase induction (SPI).
An alternative method for expressing the recombinant proteins in Escherichia coli is proposed. Unlike the ordinary induction protocol where the cells in the early- to mid-log phase are induced for the protein production, this alternative protocol utilizes the cells in the stationary phase. By using a glutathione S-transferase fusion protein as an example, the protocol proposed in this report yielded a higher amount of the desired protein than that from the ordinary protocol. This protocol also suppressed the proteolytic cleavage of the desired protein in the Escherichia coli cytoplasm, thus it should be particularly useful to produce proteins that undergo unwanted cleavages.


[Bioinformatics analysis, prokaryotic expression and biological activity of HSP70 domain-containing proteins derived from pollen of Populus deltoides].
Objective To study the bioinformatics characteristics of HSP70 domain proteins derived from pollen of Populus deltoides (P. deltoides), optimize the prokaryotic expression methods, and identify the biological activity of these proteins. Methods Physicochemical characteristics of three kinds of HSP70 domain-containing proteins were analyzed by bioinformatics software. The T/B cell epitopes of these proteins were predicted by Immune Epitope Database and Analysis Resource (IEDB). According to the amino acid sequence provided by Uniprot database, their nucleotide sequences were synthesized and cloned into pET28a(+) plasmid for prokaryotic expression. Protein expression was detected by SDS-PAGE, then the expressed products were purified by nickel column and identified by Western blotting. The protein concentration was measured by protein quantitative kit. Then the three proteins were used as antigens to prepare mouse asthma models, and the concentration of serum total IgE antibody was determined by ELISA. Results The bioinformatics analysis showed that the relative molecular mass (Mr) of B9N9W6, B9GX02 and A0A2K2AYN8 were 71 900, 94 600 and 75 200, respectively. The 13 T-cell epitopes and 14 B-cell epitopes were identified in the three proteins which had high hydrophilia and stability. SDS-PAGE analysis revealed that the genes encoding the three proteins were expressed with three specific bands of approximately Mr 72 000, 95 000 and 75 000, respectively. Western blotting showed the specific bands at the corresponding sites. ELISA showed that the IgE level in the extract group and the A0A2K2AYN8 group were higher than that in the PBS group. Compared with the A0A2K2AYN8 group, the IgE concentration in the B9N9W6 group and B9GX02 group increased significantly. Conclusion The soluble HSP70 domain-containing proteins A0A2K2AYN8, B9GX02 and B9N9W6 derived from pollen of P. deltoides can be expressed as well as purified, and have the biological activity of producing IgE antibodies.


Early Tracheostomy May Be Performed Safely in Obese COVID-19 Patients Supported on VV-ECMO.
Obese patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory failure (ARDS) often require prolonged intubation. However, data are sparse regarding optimal tracheostomy timing in obese adults with COVID-19 requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). This study retrospectively describes the course of obese patients with COVID-19 who underwent tracheostomy on VV-ECMO between March 2020 and December 2022. There were 62 participants with a median age of 43 (interquartile range [IQR] 33 to 53) years and a median body mass index of 42 (IQR 34 to 50) kg/m2 who received VV-ECMO for COVID-19-associated ARDS. Of those, 42 underwent tracheostomy on VV-ECMO, and 50% (n = 21) of the 42 patients underwent early (within 14 days of initiated ventilatory support) tracheostomy. Among patients who received tracheostomies, the combined respiratory tract and lung parenchymal bleeding rate was 29% (n = 12), but only 7% required surgical intervention for bleeding from the tracheostomy site (n = 3). The hospital length of stay (LOS) was 42 (IQR 36 to 57) days, and mortality rate was 38% (n = 16). Tracheostomy timing was not associated with differences in respiratory tract bleeding, mechanical ventilatory support duration, VV-ECMO support duration, intensive care unit LOS, hospital LOS, mortality, or survival probability. Although an individualized and holistic approach to clinical decision making continues to be necessary, the findings of this study suggest that early tracheostomy may be performed safely in obese patients with COVID-19 on VV-ECMO.


Contrast sensitivity and disability glare in the middle years.
Spatial contrast sensitivity and disability glare were measured in a large sample (n = 90, 30 per decade) of middle-aged subjects, aged 21-50 years, who had clear media and were ophthalmologically normal. We found no significant differences in the contrast sensitivities as a function of age in the middle years for (1) gratings generated on a monitor; (2) interference gratings generated in the retinal plane; (3) gratings in the presence of glare; and (4) mesopic increment thresholds with and without glare. The large sample size provides sufficient statistical power (0.8) for one to conclude that contrast sensitivity, optical quality, and foveal neural sensitivity are unlikely to vary more than 0.1 log unit between the ages of 21 and 50 in ophthalmologically normal subjects with clear media.


Limit of resolution of flow cytometry for the detection of selected bacterial species.
The enumeration of bacteria in dental plaque samples is a vital but time-consuming procedure that uses standard cultural methods. Flow cytometry has proven to be a useful tool for the analysis of eukaryotic cells. In the present investigation, the utility of this technology for the enumeration of bacteria in mixtures was explored. Rabbit antisera were produced against the putative periodontal pathogens A. actinomycetemcomitans, B. intermedius, B. gingivalis, E. corrodens, W. recta, B. forsythus, as well as the frequently isolated supragingival species S. sanguis. Cross-reactive antibodies were removed by absorption, and the specificity of each antiserum was confirmed by being tested against a panel of 235 oral microbial strains (79 genera; 94 species) by means of ELISA. Conditions were established for the indirect immunofluorescent labeling of cells without agglutination with use of a goat anti-rabbit Ig-FITC second antibody. When an internal bead standard was used, it was found that unstained bacteria were enumerated by light-scattering parameters with poor efficiency (less than 3%). However, cells exposed to FITC either in the presence of specific or non-specific first antibody were enumerated with high efficiency (102.6 +/- 29.3%), indicating that a small amount of non-specific binding of fluorochrome facilitates bacterial detection. Clear discrimination between specifically- and non-specifically-stained bacteria was achieved with all six rabbit antisera. Mixtures of known composition were made (1) with pure cultures or (2) with a known species and supragingival plaque devoid of that species by culture. The results from both approaches with various species combinations revealed that the limit of resolution for accurate quantitation of a selected species was approximately 5%, although specific organisms could be detected qualitatively when present at approximately 1%.


Delayed interval delivery of preterm multiples: experience from a large specialized twin center.
Preterm delivery is a recognized complication of twins and higher order multiple pregnancies. Delayed interval delivery is a rarely used management option for pre- or peri-viable preterm labor in these pregnancies. We describe the management and outcomes of 7 delayed interval deliveries over an 8-year period in a large specialized twin center. A retrospective cohort study of all delayed interval deliveries of preterm multiples from 2009 to 2016, defined as >24 h between deliveries of twins 1 and 2. During the study period there were 68,845 deliveries with 1377 multiple pregnancies comprising 1331 sets of twins and 46 sets of higher-order multiples. 7 of these were identified as being delayed interval deliveries - 6 twin pregnancies and 1 triplet pregnancy. The mean gestation of delivery of the first infant was 23 + 4 weeks (range 22 + 3 to 30 + 0 weeks) with a mean interval of 10 days (range 1.5-39 days). Outcomes for the first infant delivered were poor, with 5 out of 7 (71%) dying from extreme prematurity. However, out of the remaining twins or triplets, 5/8 (62%) survived. The mean gestation of delivery of the remaining infant (or infants in the triplets) was 25 + 0 weeks (range 23 + 0 to 30 + 2 weeks). Only one mother (16%) developed clinical chorioamnionitis requiring iatrogenic delivery of the remaining infant with subsequent neonatal death due to extreme prematurity. There were no cases of severe maternal morbidity - however, there was one maternal death in the cohort due to an amniotic fluid embolism. The neonatal follow up of the surviving infants to date is mostly normal. Delayed interval deliveries can offer hope for survival for the remaining infant(s) with an acceptable risk profile to the mother. Close clinical and laboratory monitoring is essential to reduce the risk of severe maternal morbidity.


Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene.
Inflammatory myofibroblastic tumor (IMT) is clinically and histologically characterized by inflammation. Some populations of IMT have anaplastic large cell lymphoma kinase (ALK) gene rearrangements. Infection with Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV-8) in tumor cells of IMT has been reported; these reports, however, have been limited to ALK-negative IMT. The purpose of the present paper was to evaluate 21 cases of IMT for the presence of EBV and HHV-8. Immunohistochemically, 15 cases were ALK positive and six were negative. Of eight cases analyzed using reverse transcription-polymerase chain reaction, tropomyosin 3 (TPM3)-ALK, TPM4-ALK and clathrin heavy chain-ALK fusion genes were detected in one, two and two cases, respectively. All 21 IMT, irrespective of ALK expression, were negative for EBV by in situ hybridization for EBV-encoded RNA and immunohistochemical stain for latent membrane antigen-1. HHV-8 was also negative in all IMT by PCR for HHV-8 DNA sequence (KS330/233) and immunohistochemical stain for latent nuclear antigen. These results suggest that IMT may be a heterogeneous group in terms of pathogenesis, and EBV and HHV-8 do not play a major role in the pathogenesis of ALK-positive tumor.


Management and prevention of bacterial diarrhea.
The etiology, pathogenesis, transmission and communicability, diagnosis, and management of infectious diarrhea are reviewed. Infectious diarrhea is common in both industrialized and unindustrialized areas of the world. Better understanding of the etiology and pathogenesis and identification of "new" enteric pathogens has resulted in the use of a variety of drugs to relieve symptoms or to effect a clinical cure. Both host and microbial virulence factors are key in the acquisition of diarrheal illness. Host factors such as extreme age, a dysfunctional gastrointestinal tract, or underlying immunodeficiency enhance the risk of illness after ingestion of a pathogen or its toxins. Microbial virulence factors (the pathogen's ability to invade or produce enterotoxins, neurotoxins, or cytotoxins) characterize the type of illness manifested and the symptom complex (e.g., acute watery diarrhea versus chronic dysentery). Supportive care is indicated in the majority of cases of infectious enteritis, and rehydration is considered the mainstay of therapy in any diarrheal illness accompanied by dehydration. Antimicrobial therapy is beneficial in the treatment of severe diarrhea caused by Shigella, Campylobacter spp., Vibrio cholerae, Escherichia coli, and Clostridium difficile. Infectious diarrhea is common but is often self-limited and of short duration. Therapy frequently consists of symptomatic relief and fluid replacement.


Structural diversity in the coordination of amidines and guanidines to monovalent metal halides.
A series of structurally characterised, monovalent metal-halide complexes incorporating neutral amidine and guanidine ligands is reported. N,N'-diphenylbenzamidine reacted with copper(I) chloride to afford the bis-ligand complex [CuCl(PhC[NPh][NHPh])2]2 (1), that exists as a chlorine bridged dimer in the solid state, with a non-symmetrical distribution of NH...Cl interactions within the 'Cu2Cl2' metallacycle. In contrast, only one equivalent of the guanidine, Me2NC[NiPr][NHiPr] (2), is coordinated in the copper(I) iodide complex [CuI(Me2NC[NiPr][NHiPr])]2 (3), which was also isolated as the dimer with bridging halide atoms. The molecular structure of the bicyclic guanidine, 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-alpha]pyrimidine (hppH), is reported, revealing a hydrogen bridged dimer with extensive delocalisation throughout the ligand framework. Coordination of hppH to lithium chloride afforded the dimeric bis-ligand complex [LiCl(hppH)2]2 (4) in which each hppH molecule interacts with a different chlorine atom of the central 'Li2Cl2' core of the molecule via NH...Cl hydrogen bonding. In contrast the 2:1 ligand to metal complex is formed with silver(I) chloride to afford AgCl(hppH)2 (5), a unique example of a monomeric, three-coordinate silver chloride supported by nitrogen-based ligands. The series of mixed ligand complexes [CuX(hppH)(PPh3)]n (6, X = Cl, n= 1; 7, X = Br, n= 2; 8 X = I, n= 2) have also been synthesised and structurally characterised, allowing comparisons of the relative coordinating behaviour of hppH and PPh3 as neutral donors at copper(I) centres to be made.


Brain-derived neurotrophic factor modulates GABAergic synaptic transmission by enhancing presynaptic glutamic acid decarboxylase 65 levels, promoting asynchronous release and reducing the number of activated postsynaptic receptors.
Brain-derived neurotrophic factor is known to modulate the function of GABAergic synapses, but the site of brain-derived neurotrophic factor action is still a matter of controversy. This study was aimed at further dissecting the functional alterations produced by brain-derived neurotrophic factor treatment of GABAergic synaptic connections in cultures of the murine superior colliculus. The functional consequences of long-term brain-derived neurotrophic factor treatment were assessed by analysis of unitary evoked and delayed inhibitory postsynaptic currents in response to high frequency stimulation of single axons. It was found that brain-derived neurotrophic factor facilitated the asynchronous release, but had no effect on the probability of evoked release, the size of the readily releasable pool, and the paired-pulse behavior of evoked inhibitory postsynaptic currents. However, the amplitudes of evoked inhibitory postsynaptic currents, delayed inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents were significantly reduced. Non-stationary fluctuation analysis revealed a decrease in the open channel number at the miniature/evoked inhibitory postsynaptic current peak, but no effect on the mean GABA(A) receptor single channel conductance. Quantitative immunocytochemistry uncovered a significant elevation of presynaptic levels of glutamic acid decarboxylase 65. Together, these findings indicate that brain-derived neurotrophic factor treatment induces pre- as well as postsynaptic changes. What effect predominates will depend on the presynaptic activity pattern: at low activation rates brain-derived neurotrophic factor-treated synapses display a pronounced postsynaptic depression, but at high frequencies this depression is fully compensated by an enhancement of asynchronous release.