The granule size distribution in an anammox-based granular sludge reactor affects the conversion--implications for modeling.
Mathematical models are useful tools to optimize the performance of granular sludge reactors. In these models, typically a uniform granule size is assumed for the whole reactor, even though in reality the granules follow a size distribution and the granule size as such affects the process performance. This study assesses the effect of the granule size distribution on the performance of a granular sludge reactor in which autotrophic nitrogen removal is realized through one-stage partial nitritation-anammox. A comparison is made between different approaches to deal with particle size distributions in one-dimensional biofilm models, from the use of a single characteristic diameter to applying a multiple compartment model. The results show a clear impact on the conversion efficiency of the way in which particle size distribution is modeled, resulting from the effect of the granule size on the competition between nitrite oxidizing and anammox bacteria and from the interaction between granules of different sizes in terms of the exchange of solutes. Whereas the use of a uniform granule size is sufficient in case only the overall reactor behavior needs to be assessed, taking into account the detailed granule size distribution is required to study the solute exchange between particles of different sizes. For the latter purpose, the application of the widespread software package Aquasim is limited and the development of dedicated software applications is required.


Cannabis intoxication inhibits avoidance action tendencies: a field study in the Amsterdam coffee shops.
Experimental laboratory studies suggest that the approach bias (relatively fast approach responses) toward substance-related materials plays an important role in problematic substance use. How this bias is moderated by intention to use versus recent use remains unknown. Moreover, the relationship between approach bias and other motivational processes (satiation and craving) and executive functioning remains unclear. The aim of this study was to investigate the cannabis approach bias before and after cannabis use in real-life setting (Amsterdam coffee shops) and to assess the relationship between approach bias, craving, satiation, cannabis use, and response inhibition. Cannabis, tobacco, and neutral approach and avoidance action tendencies were measured with the Approach Avoidance Task and compared between 42 heavy cannabis users with the intention to use and 45 heavy cannabis users shortly after cannabis use. The classical Stroop was used to measure response inhibition. Multiple regression analyses were conducted to investigate relationships between approach bias, satiation, craving, cannabis use, and response inhibition. In contrast to the hypotheses, heavy cannabis users with the intention to use did not show a cannabis approach bias, whereas intoxicated cannabis users did show an approach bias regardless of image category. This could be attributed to a general slowing of avoidance action tendencies. Moreover, craving was negatively associated with the approach bias, and no relationships were observed between the cannabis approach bias, satiation, prior cannabis use, and response inhibition. Cannabis intoxication in a real-life setting inhibited general avoidance. Expression of the cannabis approach bias appeared not to be modulated by satiation or response inhibition.


DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: probably a different origin for infantile and adolescent germ cell tumours.
The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile cell germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.


Position of poly(methyl methacrylate) and silicone intraocular lenses after phacoemulsification.
To compare the positional change of poly(methyl methacrylate) (PMMA) and silicone intraocular lenses (IOLs) in vivo after phacoemulsification. Taipei Municipal Yang-Ming Hospital, Taipei, Taiwan. A prospective study of 70 cataractous eyes treated by phacoemulsification with IOL implantation was carried out. The eyes were randomized into 2 groups based on IOL type: 1-piece PMMA IOL; 3-piece silicone IOL. The amount of IOL tilt and decentration was measured and anterior chamber depth (ACD) determined by Scheimpflug photography using an anterior eye segment analysis system (EAS-1000, Nidek). All eyes were examined 1 week and 1 to 6 months after surgery. No statistically significantly differences were found in the amount of tilt and decentration between 2 IOL types throughout the study. The ACDs were relatively constant in both groups through the early postoperative periods. The stability of PMMA and silicone IOLs were the same after phacoemulsification.


Extracorporeal shock wave lithotripsy in children: evaluation of the results considering the need for auxiliary procedures.
To retrospectively evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) in children with renal stones, with regard to ability of ureters to transport the fragments, and need for adjunctive procedures. Between January 2000 and November 2004, 60 children (24 girls and 36 boys) with a total of 72 stones of the upper urinary tract were treated by ESWL using a PCK V5 lithotriptor. Patients with anatomical abnormalities and staghorn stones were excluded from the study. Stone size ranged from 4 to 28 mm. Mean number of shock waves was 1430 (range 600-2000) per ESWL session and mean energy used for stone disintegration was 12 kV (range 6-18). At 24-48 h after ESWL, a plain film or renal ultrasound was obtained to evaluate stone fragmentation. Our stone-free rate after one session of ESWL was 92.8% and 81.2% for patients with stones smaller than 10mm and stones between 10 and 28 mm, respectively. Seven (11.6%) patients developed distal ureteral steinstrasse, and the stone size was 15-20 mm and 20-28 mm in two and five patients, respectively. The steinstrasse completely cleared under meticulous follow-up. No patient needed an adjunctive procedure, such as a double-J stent or nephrostomy tube placement, or ureteroscopic stone manipulation. A child's ureter is capable of transporting the fragments after lithotripsy. Interventional procedures should be a last resort. Expectant management is usually adequate even in patients who develop steinstrasse after ESWL.


Octopus microvasculature: permeability to ferritin and carbon.
The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.


[New foetopathological section of the heart. Correlated to the ultrasonographic 4 Chamber view in fetuses].
Our findings on hearts of trisomic 21 fetuses of a new minor cardiac anomaly, belonging to the atrioventricular septal defect (AVSD) spectrum and the improved performances of the fetal ultrasound screening lend us to propose a new section, complementary to the standard cardiopathological examination. It would enable us to test the anatomic level of insertion of the atrioventricular valves of the crux of the heart. It consists of a section of the fetal hearts, fixed in formaldehyde, in a plane correlated to the plane of the fetal ultrasonographic four chamber view. Three hallmarks have been chosen because of their relevance and of their reproductibility in ultra sonography as well as in fetopathology: the apex and the inferior pulmonary veins. This additional section was realized on fetal hearts, regarded as "normal" with the standard pathologic examination, because of a lack of defect. It allowed us to detect a minor cardiac abnormality of the AVSD spectrum, frequent in the trisomic 21 fetuses, which we called: linear insertion of the atrio ventricular valves( LIAVV) without defect. Initially described on a series of Trisomic 21 fetal hearts, the LIAVV without defect has also been found in other fetuses with another pathology often associated with an anomaly of the AVSD spectrum. The possible detection of this abnormality in fetal cardiac ultrasound scanning justifies the use of this new anatomical technique. It also has to be included it in the full standard pathologic examination of the fetal hearts of all the abnormal fetuses.


A morphometric anatomical and comparative study of the foramen magnum region in a Greek population.
The foramen magnum (FM), a complex area in craniocervical surgery, poses a challenge for neurosurgeons. The knowledge of the detailed anatomy of the FM, occipital condyles (OC) and variations of the region is crucial for the safety of vital structures. This study focuses on the FM and OC morphometry, highlights anatomical variability and investigates correlations between the parameters studied. One hundred and forty-three Greek adult dry skulls were examined using a digital sliding calliper (accuracy, 0.01 mm). Mean FM width and length were found 30.31 ± 2.79 and 35.53 ± 3.06 mm, respectively. The commonest FM shape was two semicircles (25.9 %), whereas the most unusual was irregular (0.7 %). The OC minimum width, maximum width and length were 5.71 ± 1.61, 13.09 ± 1.99 and 25.60 ± 2.91 mm on the right, and 6.25 ± 1.76, 13.01 ± 1.98 and 25.60 ± 2.70 mm on the left side. The commonest OC shape was S-like and the most unusual was ring, bilaterally. The mean anterior and posterior intercondylar distances were 19.30 ± 3.25 and 51.61 ± 5.01 mm, respectively. The OC protruded into the FM in 86.7 % of the skulls. Variations such as a third OC existed in 5.6 % and basilar processes in 2.8 %. Posterior condylar foramina were present in 75.5 %. The gender was correlated with FM width and length, OC length, bilaterally, anterior intercondylar distance (AID) and posterior intercondylar distance (PID). The OC protrusion and existence of posterior condylar foramina were correlated. Bilateral asymmetry for OC shape was statistically significant. Our results provide useful information that will enable effective and reliable surgical intervention in the FM region with the maximum safety and widest possible exposure.


Aberrant sense of agency in patients with schizophrenia: forward and backward over-attribution of temporal causality during intentional action.
Self-disturbances in schizophrenia have been explained and studied from the standpoint of an abnormal sense of agency. We devised an agency-attribution task that evaluated explicit experiences of the temporal causal relations between an intentional action and an external event, without any confounding from sense of ownership of body movement. In each trial, a square piece appeared on the bottom of a computer screen and moved upward. Subjects were instructed to press a key when they heard a beep. When the key was pressed, the piece jumped with various temporal biases. Subjects were instructed to make an agency judgment for each trial. We demonstrated that an excessive sense of agency was observed in patients with schizophrenia compared with normal controls. Moreover, patient groups had a greater tendency to feel a sense of agency even when external events were programmed to precede their action. Therefore, patients felt both forward and backward exaggerated causal efficacy in the temporal event sequence during the intentional action. Confusion in the experience of temporal causal relations between the self and the external world may underlie self-disturbances in schizophrenia.


Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy.
Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 +/- 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 +/- 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.


Analysis of intrinsic and extrinsic factors influencing the dynamics of bovine Eimeria spp. from central-eastern Poland.
Eimeria infections are common in cattle worldwide, however, little is known about the invasion dynamics of this unicellular parasite. Therefore, the aim of this study was to analyze intrinsic (host age) and extrinsic (herd size and management system) factors influencing the dynamics of Eimeria spp. found in calves from CE Poland. Fecal samples were collected from 356 calves from different types of management systems and from different herd sizes. Flotation and McMaster method were used for parasitological investigation. Oocysts were differentiated on the basis of morphological criteria. Eight Eimeria species were identified and mean species richness (MSR) was significantly affected by host age. The highest MSR was noted for middle age animals. There was an association between species, with a highly significant co-occurrence of Eimeria bovis with Eimeria zuernii. The presence of E. bovis significantly increased the percentage of individuals carrying E. zuernii. The presence of E. bovis significantly increased the percentage of individuals carrying Eimeria canadensis. The overall prevalence of Eimeria spp. reached 52.8% and was significantly affected by the age of cows, with the highest prevalence in animals between 5-10 months old. The most prevalent species were E. bovis (37.4%), E. zuernii (19.9%) and E. canadensis (12.1%). The prevalence of E. bovis was affected by host age (the highest prevalence in age class 2 animals) and management type (the highest prevalence in individuals raised in groups). The prevalence of E. zuernii was affected by age (the lowest prevalence was noted in the oldest individuals) and herd size (individuals infected were present only in the middle and large size herds), whereas the prevalence of E. canadensis was affected by all three factors. Overall, mean OPG of the combined Eimeria spp. was 458.84 (37.93) and differed significantly between age classes. Mean OPGs were generally low for young and mature animals but high for middle age class animals. There was no significant influence of extrinsic factors on OPG. Taking into consideration the presented results, it is necessary to underline the role of intrinsic and extrinsic factors affecting the prevalence and abundance of Eimeria spp. in calves. Understanding the dynamics of Eimeria infections in calves may help to overcome this most common bovine parasite.


The value of flexibility in conservation financing.
Land-acquisition strategies employed by conservation organizations vary in their flexibility. Conservation-planning theory largely fails to reflect this by presenting models that are either extremely inflexible-parcel acquisitions are irreversible and budgets are fixed-or extremely flexible-previously acquired parcels can readily be sold. This latter approach, the selling of protected areas, is infeasible or problematic in many situations. We considered the value to conservation organizations of increasing the flexibility of their land-acquisition strategies through their approach to financing deals. Specifically, we modeled 2 acquisition-financing methods commonly used by conservation organizations: borrowing and budget carry-over. Using simulated data, we compared results from these models with those from an inflexible fixed-budget model and an extremely flexible selling model in which previous acquisitions could be sold to fund new acquisitions. We then examined 3 case studies of how conservation organizations use borrowing and budget carry-over in practice. Model comparisons showed that borrowing and budget carry-over always returned considerably higher rewards than the fixed-budget model. How they performed relative to the selling model depended on the relative conservation value of past acquisitions. Both the models and case studies showed that incorporating flexibility through borrowing or budget carry-over gives conservation organizations the ability to purchase parcels of higher conservation value than when budgets are fixed without the problems associated with the selling of protected areas.


Percutaneous cryoablation of metastatic renal cell carcinoma for local tumor control: feasibility, outcomes, and estimated cost-effectiveness for palliation.
To assess complications, local tumor recurrences, overall survival (OS), and estimates of cost-effectiveness for multisite cryoablation (MCA) of oligometastatic renal cell carcinoma (RCC). A total of 60 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 72 tumors in 27 patients (three women and 24 men). Average patient age was 63 years. Tumor location was grouped according to common metastatic sites. Established surgical selection criteria graded patient status. Median OS was determined by Kaplan-Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. Total number of tumors and cryoablation procedures for each anatomic site are as follows: nephrectomy bed, 11 and 11; adrenal gland, nine and eight; paraaortic, seven and six; lung, 14 and 13; bone, 13 and 13; superficial, 12 and nine; intraperitoneal, five and three; and liver, one and one. A mean of 2.2 procedures per patient were performed, with a median clinical follow-up of 16 months. Major complication and local recurrence rates were 2% (one of 60) and 3% (two of 72), respectively. No patients were graded as having good surgical risk, but median OS was 2.69 years, with an estimated 5-year survival rate of 27%. Cryoablation remained cost-effective with or without the presence of systemic therapies according to historical cost comparisons, with an adjunctive cost-effectiveness ratio of $28,312-$59,554 per LYG. MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, with apparent increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic RCC.


Treat-to-Target in Pediatric Inflammatory Bowel Disease: What Does the Evidence Say?
The traditional management of inflammatory bowel disease, based on treatment intensification guided by clinical activity alone, has been revised in the last 10 years and a treat-to-target approach has been proposed and is currently under evaluation as a disease-modifying strategy. Treat-to-target focuses on objective and scheduled measures to monitor intestinal damage, with consequent therapeutic adjustments in case of failure to achieve pre-defined targets. Identification of targets has been set out by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) committee in 2015. Mucosal healing is universally accepted as the main target both in Crohn's disease and ulcerative colitis, given its proven association with better long-term outcomes than clinical remission alone. Equally important is to ensure patients' clinical remission and improve patient-reported outcomes. Transmural healing (for Crohn's disease) and histological remission (for ulcerative colitis), listed as adjunctive targets, are likely to become primary targets in the near future. The ultimate goal of this approach is to modify the natural history of inflammatory bowel diseases by trying to block bowel damage progression, with interventions in the pre-clinical stage. In this review, we will discuss the current recommended therapeutic targets, as well as those that are considered adjunctive targets, with a focus on the limited pediatric literature available. Prospective long-term trials are warranted in order to identify the most appropriate target for the pediatric population and its specific issues. Identification of reliable predictors of disease course, outcome, and response to treatment will help to individually adapt each step of this monitoring algorithm and consequent therapeutic decision.


The use of fluorescence resonance energy transfer to monitor dynamic changes of lipid-DNA interactions during lipoplex formation.
Fluorescence resonance energy transfer (FRET) was used to monitor interactions between Cy3-labeled plasmid DNA and NBD-labeled cationic liposomes. FRET data show that binding of cationic liposomes to DNA occurs immediately upon mixing (within 1 min), but FRET efficiencies do not stabilize for 1-5 h. The time allowed for complex formation has effects on in vitro luciferase transfection efficiencies of DOPE-based lipoplexes; i.e., lipoplexes prepared with a 1-h incubation have much higher transfection efficiencies than samples with 1-min or 5-h incubations. The molar charge ratio of DOTAP to negatively charged phosphates in the DNA (DOTAP+/DNA-) also affected the interaction between liposomes and plasmid DNA, and interactions stabilized more rapidly at higher charge ratios. Lipoplexes formulated with DOPE were more resistant to high ionic strength than complexes formulated with cholesterol. Taken together, our data demonstrate that lipid-DNA interactions and in vitro transfection efficiencies are strongly affected by the time allowed for complex formation. This effect is especially evident in DOPE-based lipoplexes, and suggests that the time allowed for lipoplex formation is a parameter that should be carefully controlled in future studies.


Complications in Neurosurgery: General Ethical Principles for Minimizing Them and Subsequent Legal Action.
Medicine and surgery carry inherent risks of inadvertent and unintended harm to the patient. Training, experience, and skill help ensure smooth recovery in most cases. However, there are circumstances beyond the control of the neurosurgeon that may predispose to complications. This review discusses steps that may help to diminish risks to the patient and can be taken before their admission to hospital, in the operating theater, and after surgery. When a complication does occur despite all care, it is essential to maintain total transparency with the patient and his or her family. It is important that they are active witnesses to the care and treatment being lavished on the individual to minimize the harm from the mishap. Should legal action follow despite such efforts, the neurosurgeon must be prepared to defend with the help of a wise, experienced lawyer and to provide evidence of his or her professional competence and the appropriateness of care offered to the patient. In any case, it is counterproductive to view every patient as a potential legal threat or indulge in defensive medical practice.


Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen.
To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells. Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H(2)O(2). HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining. Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H(2)O(2) through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin's effect on the reduction of ROS was mediated by the increase in HO-1 expression. Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.


Unusual trend of increasing selectivity and decreasing flux with decreasing thickness in pervaporation separation of ethanol/water mixtures using sodium alginate blend membranes.
Pervaporation membranes were produced comprising a 4:1 sodium-alginate:poly(vinyl-alcohol) polymer blend selective layer with a plasticizing agent (glycerol). Membranes were supported on a poly(acrylonitrile) mesoporous support layer and non-woven fabric base. Pervaporation separation of ethanol/water mixtures was carefully followed as a function of film thickness and time. It was found, contrary to what might be expected from literature, that these films showed increased selectivity and decreased flux as film thickness was reduced. It is argued that the morphology and structure of the polymer blend changes with thickness and that these structural changes define the efficiency of the separation in these conditions.


Pharmacokinetic study of matrine, oxymatrine and oxysophocarpine in rat plasma after oral administration of Sophora flavescens Ait. extract by liquid chromatography tandem mass spectrometry.
A rapid, sensitive and selective high-performance liquid chromatography tandem mass spectrometric method (HPLC-MS) has been developed and validated for the simultaneous determination of matrine (MT), oxymatrine (OMT) and oxysophocarpine (OSP) in rat plasma after oral administration of Sophora flavescens Ait. extract using pseudoephedrine hydrochloride as an internal standard (I.S.). The three analytes were extracted from the plasma samples by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Kromasil C18 column (150 mm x 4.6 mm). Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The total run time was 12 min between injections. The assay had a lower limit of quantification of 1.0 ng/ml for MT, 2.0 ng/ml for OMT and 2.0 ng/ml for OSP using 200 microl of plasma. The calibration curves were linear in the measured range. The overall precision and accuracy for all concentrations of quality controls and standards was better than 15%. The proposed method enables unambiguous identification and quantification of MT, OMT and OSP in vivo. This was the first report on determination of the major quinolizidine alkaloids in rat plasma after oral administration of Sophora flavescens Ait. extract. The results provided a meaningful basis for evaluating the clinical applications of the herbal medicine.


[Immunoglobulin genes in lymphoid cells and regulation of their transcription].
The hybridoma genomes contain polyploid sets of immunoglobulin genes. We have shown, that the hybridoma PTF-02 genome contains three genes of heavy chains and two genes of light chains. The genes responsible for antibody synthesis were cloned and their structure were determined. Investigation of the kappa gene transcription and its fragments which contain regulatory sequences revealed a nuclear factor. The latter interacts with the octanucleotide localized at the promoter region of the kappa gene. The purified factor activates the transcription of the kappa gene in a heterologous cell-free system. Together with the tissue-specific factor there is also an universal factor interacting with the octanucleotide sequence. We have shown an additional factor in lymphoid cells interact with the protein which binds to the octanucleotide sequence. We have shown an additional factor in lymphoid cells interacting with the protein which binds to the octanucleotide sequence. As a result, there is a family of factors which interact with ATTTGCAT sequence. One major factor (m.w. 60 +/- 2 kDa) is an obligatory component for the initiation of immunoglobulin genes transcription.


Utility of the Asperger Syndrome Diagnostic Scale in the Assessment of Autism Spectrum Disorders.
Investigated internal consistency reliability and criterion validity of the Asperger Syndrome Diagnostic Scale (ASDS) in a well-characterized sample of 120 children ([Formula: see text] = 9.91; autism [AUT] n = 54; non-autism [NOT] n = 66) who completed comprehensive outpatient evaluations with a gold-standard measure, the Autism Diagnostic Observation Schedule-2. With the exception of a low Cognitive alpha in the AUT group, internal consistency reliabilities ranged from moderate to high. Significant between-group mean differences were observed for all scores. Receiver operating characteristic analyses indicated Area Under the Curve in the fair range (.71). Cutoff points and interpretation are discussed. The ASDS appears most useful in cases of either low or high scores or as an adjuvant to gold-standard measures.


Optimum illumination for ground squirrel activity.
The locomotor activity of four antelope ground squirrels was monitored in an activity-wheel enclosure at illuminance levels from 1.1 to 30000 lux and color temperatures from 1950 to 2860°K. The time spent running, speed of running, and length of non-stop running sessions were found to be sensitive to ambient light conditions. Time showed the greatest dependence and appears to peak between 1300 and 17000 lux, the latter value corresponding roughly to light conditions attained within 30 minutes after natural sunrise and before sunset. Running speed was influenced least but in the most highly consistent manner, appearing to peak between 2600 and 17000 lux. Session lengths were quite variable and showed the most complex changes with light level. The overall findings suggest that the squirrels also were influenced by color temperature. There were large individual differences in various aspects of the responses.


Can external and subjective information ever be used to reduce the size of randomised controlled trials?
In the design of randomised trials in rare cancers, a Bayesian approach has been advocated, which allows for external and subjective information to be formally incorporated. We explore whether this can be extended more generally to allow for smaller trials to be conducted using a case study involving a trial of nasopharyngeal carcinoma. The external information available at various points during the trial is first summarised in the form of 'prior distributions'. Each of these is then combined with the accumulated data from the trial at that point in time to form 'posterior distributions', from which conclusions are drawn. We have argued that such a framework for the design, analysis and interpretation of a randomised trial in the light of external evidence is particularly useful in situations such as trials in rare cancers. But more generally, it may potentially also allow for smaller trials to be conducted. Although, at this point in time, we are hesitant to recommend the full implementation of the Bayesian methodology to modify the (conventionally) planned trial size we submit that a formal synthesis of the external evidence bearing on the question of concern is a valuable exercise in itself.


Differential degradation of extraplastidic and plastidic lipids during freezing and post-freezing recovery in Arabidopsis thaliana.
Changes in membrane lipid composition play important roles in plant adaptation to and survival after freezing. Plant response to cold and freezing involves three distinct phases: cold acclimation, freezing, and post-freezing recovery. Considerable progress has been made toward understanding lipid changes during cold acclimation and freezing, but little is known about lipid alteration during post-freezing recovery. We previously showed that phospholipase D (PLD) is involved in lipid hydrolysis and Arabidopsis thaliana freezing tolerance. This study was undertaken to determine how lipid species change during post-freezing recovery and to determine the effect of two PLDs, PLDalpha1 and PLDdelta, on lipid changes during post-freezing recovery. During post-freezing recovery, hydrolysis of plastidic lipids, monogalactosyldiacylglycerol and plastidic phosphatidylglycerol, is the most prominent change. In contrast, during freezing, hydrolysis of extraplastidic phospholipids, phosphatidylcholine and phosphatidylethanolamine, occurs. Suppression of PLDalpha1 decreased phospholipid hydrolysis and phosphatidic acid production in both the freezing and post-freezing phases, whereas ablation of PLDdelta increased lipid hydrolysis and phosphatidic acid production during post-freezing recovery. Thus, distinctly different changes in lipid hydrolysis occur in freezing and post-freezing recovery. The presence of PLDalpha1 correlates with phospholipid hydrolysis in both freezing and post-freezing phases, whereas the presence of PLDdelta correlates with reduced lipid hydrolysis during post-freezing recovery. These data suggest a negative role for PLDalpha1 and a positive role for PLDdelta in freezing tolerance.


Quality of life considered as well-being: views from philosophy and palliative care practice.
The main measure of quality of life is well-being. The aim of this article is to compare insights about well-being from contemporary philosophy with the practice-related opinions of palliative care professionals. In the first part of the paper two philosophical theories on well-being are introduced: Sumner's theory of authentic happiness and Griffin's theory of prudential perfectionism. The second part presents opinions derived from interviews with 19 professional palliative caregivers. Both the well-being of patients and the well-being of the carers themselves are considered in this empirical exploration. In the third part the attention shifts from the description of "well-being" to prescriptions for the promotion of well-being. Our interview data are analysed in light of the theories of Sumner and Griffin for clues to the promotion of "well-being." The analysis (1) underscores the subject-relativity of well-being, (2) points out that values that are considered important in every life still seem to be relevant (at least in palliative care practice), and (3) shows the importance of living a certain sort of life when aiming to enhance dying patients' well-being.


Computer technology in detection and staging of prostate carcinoma: a review.
After two decades of increasing interest and research activity, computer-assisted diagnostic approaches are reaching the stage where more routine deployment in clinical practice is becoming a possibility [Kruppinski, E.A., 2004. Computer-aided detection in clinical environment: Benefits and challenges for radiologists. Radiology 231, 7-9]. This is particularly the case in the analysis of mammographic images [Helvie, M.A., Hadjiiski, L., Makariou, E., Chan, H.P., Petrick, N., Sahiner, B., Lo, S.C., Freedman, M., Adler, D., Bailey, J., Blane, C., Hoff, D., Hunt, K., Joynt, L., Klein, K., Paramagul, C., Patterson, S.K., Roubidoux, M.A., 2004. Sensitivity of noncommercial computer-aided detection system for mammographic breast cancer detection: pilot clinical trial. Radiology 231, 208-214] and in the detection of pulmonary nodules [Reeves, A.P., Kostis, W.J., 2000. Computer-aided diagnosis for lung cancer. Radiol. Clin. North Am. 38, 497-509]. However, similar approaches can be applied more widely with the promise of increasing clinical utility in other areas. We review how computer-aided approaches may be applied in the diagnosis and staging of prostatic cancer. The current status of computer technology is reviewed, covering artificial neural networks for detection and staging, computerised biopsy simulation and computer-assisted analysis of ultrasound and magnetic resonance images.


Surgical management of diseases of the adolescent female breast: a clinicopathologic study.
Sixty-three patients, ages 10 to 20 years with diseases of the breast were operated on during a 10 year period. A variety of pathologic entities were found. The most common were diagnoses fibroadenoma, cystic disease, and cellulitis with abscess formation. Malignancy was found in three patients: lobular carcinoma in situ in one, angiosarcoma in the second, and lymphosarcoma in the third.


Minimally invasive radio-guided surgery for primary hyperparathyroidism: From preoperative to intraoperative localization imaging.
The introduction and successful implementation of minimally invasive radio-guided parathyroidectomy (MIRP) has revolutionized the surgical approach to remove parathyroid adenomas. A prerequisite for such success is an accurate localization of the offending adenoma. To achieve this goal, a multimodality approach is commonly employed using a combination of anatomical and functional imaging. Of the anatomical cross-sectional techniques, ultrasonography is the most widely available but is operator-dependent and has reduced sensitivity, specially in the presence of thyroid nodules. Similarly, computed tomography and magnetic resonance imaging have low sensitivities but provide value in detecting retrotracheal, retro-oesophageal and mediastinal adenomas. Functional imaging with ⁹⁹(m)Tc-Sestamibi is currently the most vital imaging procedure in this respect with variable protocols including dual-phase and dual isotope imaging. The sensitivity and specificity can improve by acquiring in single photon emission tomography (SPECT) mode and using co-registration with low dose CT to provide anatomical data (SPECT/CT). The current recommended approach is the combination of functional imaging with ⁹⁹(m)Tc-Sestamibi and high-resolution ultrasound (US), supplemented with intraoperative gamma probe in certain cases and quick persurgical measurement of parathyroid hormone. This review aims to explore the utility of various imaging modalities, alone and in combination, in detecting parathyroid adenoma and facilitating the current approach of MIRP.


30 years follow-up and increased risks of breast cancer and leukaemia after long-term low-dose-rate radiation exposure.
The current study followed-up site-specific cancer risks in an unique cohort with 30 years' follow-up after long-term low-dose-rate radiation exposure in Taiwan. Six thousand two hundred and forty two Taiwanese people received extra exposure in residential and school buildings constructed with Co-60-contaminated steel from 1982 until informed and relocated in early 1990s. The additional doses received have been estimated. During 1983-2012, 300 cancer cases were identified through the national cancer registry in Taiwan, 247 cases with minimum latent periods from initial exposure. The hazard ratios (HR) of site-specific cancers were estimated with additional cumulative exposure estimated individually. Dose-dependent risks were statistically significantly increased for leukaemia excluding chronic lymphocytic leukaemia (HR100mSv 1.18; 90% CI 1.04-1.28), breast cancers (HR100mSv 1.11; 90% CI 1.05-1.20), and all cancers (HR100mSv 1.05; 90% CI 1.0-1.08, P=0.04). Women with an initial age of exposure lower than 20 were shown with dose response increase in breast cancers risks (HR100mSv 1.38; 90% CI 1.14-1.60; P=0.0008). Radiation exposure before age 20 was associated with a significantly increased risk of breast cancer at much lower radiation exposure than observed previously.


In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain.
Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 micrograms/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.


No evidence for a relationship between MHC heterozygosity and life history strategy in a sample of North American undergraduates.
Although allelic diversity at the major histocompatibility complex (MHC) has implications for adaptive immunity, mate choice, and social signalling, how diversity at the MHC influences the calibration of life history strategies remains largely uninvestigated. The current study investigated whether greater MHC heterozygosity was associated with markers of slower life history strategies in a sample of 789 North American undergraduates. Contrary to preregistered predictions and to previously published findings, MHC heterozygosity was not related to any of the psychological life history-relevant variables measured (including short- vs. long-term sexual strategy, temporal discounting, the Arizona life history battery, past and current health, disgust sensitivity, and Big Five personality traits). Further, no meaningful effects emerged when analysing women and men separately. Possible reasons for why the current results are inconsistent with previous work are discussed.


The relationship between 3',5'-cyclic adenosine monophosphate and calcium in mediating follicle-stimulating hormone signal transduction in Sertoli cells.
FSH signal transduction in Sertoli cells involves the generation of cAMP and calcium as second messengers; however, the relationship between these two signals is not clear. In order to determine whether these were serial or parallel signals, we studied cytosolic calcium levels in freshly isolated rat Sertoli cells using maneuvers to dissociate generation of endogenous cAMP from cytosolic calcium. Pretreatment with 1 mM MDL 12,330A, an adenylate cyclase inhibitor, reduced by greater than 90% increases in cytosolic calcium induced by FSH (97 +/- 6 vs. 213 +/- 16 nM), whereas, despite adenylate cyclase blockade, 1 mM (Bu)2cAMP continued to elevate cytosolic calcium (from 87 +/- 6 to 182 +/- 23 nM), indicating the involvement of adenylate cyclase in the FSH-induced rise of cytosolic calcium. A cAMP antagonist, 1 mM Rp-cAMP, reduced by 75% the FSH-induced rise of cytosolic calcium (115 +/- 14 vs. 213 +/- 16 nM), suggesting that endogenous cAMP levels generated by FSH are sufficient to activate the cytosolic calcium response to FSH. Pretreatment with pertussis toxin (1 mg/liter) to dissociate the FSH-receptor interaction from its G-protein-mediated linkage to adenylate cyclase also suppressed the FSH-induced rise in cytosolic calcium (97 +/- 11 vs. 213 +/- 16 nM). Sertoli cells preincubated with 1 mM staurosporine, an inhibitor of protein kinases, exhibited a reduced calcium response to FSH (125 +/- 14 vs. 213 +/- 16 nM), suggesting that FSH-induced calcium flux might be mediated by protein kinase, presumably cAMP-dependent protein kinase A. The present findings therefore strengthen the premise that the cytosolic calcium response to FSH in Sertoli cells is predominantly attributable to serial signaling after the generation of endogenous cAMP.


Clinical and psychosocial factors associated with needs for care: an Arab experience with a sample of treated community-dwelling persons with schizophrenia.
To (1) highlight the profile of the needs for care among a sample of persons with schizophrenia, using the Camberwell Assessment of Needs (CAN-EU), in comparison with the international data; (2) assess the association of patients' needs with socio-demographics, clinical characteristics and objective quality of life (QOL); and (3) compare the perceptions of patients with those of the staff. Consecutive outpatients in stable condition were interviewed with the CAN-EU and measures of QOL and psychopathology. There were 130 patients (68.5% men, mean age 36.8). The highest frequency of unmet needs was for money (29.2%). About a fifth of the subjects expressed unmet needs for six other items, including accommodation. The mean total needs was 8.67(7.1), the total met needs was 5.29 and total unmet needs was 3.38. The dimension with the highest frequency (40%) of unmet needs (functioning) is constituted by items that are related to family care at home. Staff identified significantly more needs than patients. Higher levels of needs were significantly associated with severity of psychopathology and negative affect, and not participating in outdoor activities. The mean number of needs was similar to reports from developing countries and higher than those from European countries. The met/unmet need ratio was similar to European data. Despite free health services and family support, a number of our treated community-dwelling persons with schizophrenia had problems meeting basic and health-care needs. The findings call for a consideration of techniques for enhancing the capability of families to cope with the care of patients.


[Change in body weight and mandibular development in rats from fluoride administration].
The body weights evolution and the development of mandible were analyzed in rats that received 0.25 mg F contained into a commercial product, during 30 and 60 days consecutively, beginning at birth. The study presented the following conclusions: 1. The treated animals showed body weights always inferior to the controls, with more evident difference at 60 days period; 2. Analysis showed a reduction in the horizontal linear measurements, but not in the length of the mandibular diastem. No influence was observed in relation to the verticals.


Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.
Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.


Aneurysm of the posterior inferior cerebellar artery: nonselective endovascular treatment. One case.
The authors report a case of aneurysm of the right posterior inferior cerebellar artery which was successfully treated by endovascular occlusion of the vertebral artery at C1 level. This treatment was justified by the failure of neurosurgery.


Exercise facilities and the prevalence of obesity and type 2 diabetes in the city of Madrid.
We aimed to study the association between the availability of exercise facilities and the likelihood of obesity and type 2 diabetes in the adult population of Madrid, Spain. We analysed the electronic medical records of all 1,270,512 residents of Madrid aged 40-75 years in 2017. Exercise facility availability was defined as the count of exercise facilities in a 1000 m street network buffer around each residential building entrance. Poisson regression with standard errors clustered at census tract level was used to assess prevalence ratios of exercise facility availability tertiles and obesity and type 2 diabetes. We also examined stratified results by tertiles of area-level socioeconomic status (SES) and sex. People living in areas with lower availability of exercise facilities had a higher prevalence of obesity (prevalence ratio [PR] 1.22 [95% CI 1.20, 1.25]) and diabetes (PR 1.38 [95% CI 1.34, 1.43]). We observed effect modification by area-level SES (p<0.001), with stronger associations for residents living in low-SES areas and no association for residents living in high-SES areas. Associations with type 2 diabetes were stronger among women compared with men, while associations with obesity were similar by sex. People living in areas with low availability of exercise facilities had a higher prevalence of obesity and type 2 diabetes, and this association was strongest in low-SES areas and for women. Understanding the potential role of exercise facilities in driving inequities in obesity and type 2 diabetes prevalence may inform interventions to reduce health inequities.


Protein kinase Cδ regulates nuclear export of FOXO1 through phosphorylation of the chaperone 14-3-3ζ.
Forkhead box protein O1 (FOXO1) is a transcription factor essential for beta cell fate. Protein kinase B-dependent phosphorylation of FOXO1 at S256 (P-FOXO1) enables its binding to 14-3-3 dimers and nuclear export. Dephosphorylated FOXO1 enters nuclei and activates pro-apoptotic genes. Since our previous observations suggest that protein kinase C delta (PKCδ) induces nuclear accumulation of FOXO1, the underlying mechanism was examined. In human islets, genetically modified mice and INS-1E cells apoptosis was assessed by TUNEL staining. Subcellular translocation of proteins was examined by confocal microscopy and signalling pathways were analysed by western blotting and overlay assay. In PKCδ-overexpressing (PKCδ-tg) mouse islet cells and INS-1E cells FOXO1 accumulated in nuclei, surprisingly, as P-FOXO1. PKCδ-tg decelerated IGF-1-dependent stimulation of nuclear export, indicating that changes in export caused nuclear retention of P-FOXO1. Nuclear accumulation of P-FOXO1 was accompanied by increased phosphorylation of 14-3-3ζ at S58 and reduced dimerisation of 14-3-3ζ. Palmitic acid further augmented phosphorylation of 14-3-3ζ and triggered nuclear accumulation of FOXO1 in both INS-1E and human islet cells. Furthermore, the overexpression of a phosphomimicking mutant of 14-3-3ζ (S58D) enhanced nuclear FOXO1. In accordance with the nuclear accumulation of P-FOXO1, PKCδ overexpression alone did not increase apoptotic cell death. Additionally, insulin secretion and glucose homeostasis in PKCδ-overexpressing mice remained unaffected. These results suggest that PKCδ-mediated phosphorylation of 14-3-3ζ contributes to the nuclear retention of FOXO1, even when FOXO1 is phosphorylated as under non-stress conditions. P-FOXO1 does not induce pro-apoptotic genes, but may rather exert beneficial effects on beta cells.


Potentiation of radiotherapy by a localized antiangiogenic gene therapy.
We hypothesized that electrotransfer of a plasmid encoding an antiangiogenic factor, the recombinant disintegrin domain of ADAM-15, (pRDD) could modify the tumor microenvironment and radiosensitize tumor. pRDD was injected in the TLT tumor or FSaII fibrosarcomas before electroporation. pO2 in tumors and oxygen consumption in vitro were measured by electronic paramagnetic resonance (EPR) oximetry. Tumor perfusion was assessed by laser doppler imaging and patent blue assay. pRDD electrotransfer caused a significant delay in TLT growth and an anti-angiogenic effect. It significantly increased tumor pO2 in TLT and FSaII for at least 4 days. pRDD electrotransfer and radiotherapy were more effective than either treatment alone. Modifications of tumor microenvironment were evaluated: tumor perfusion and interstitial fluid pressure were not modified. Oxygen consumption by the cells was decreased resulting both from a decrease in oxygen consumption rate and from a decrease in cell viability. The combination of localized antiangiogenic gene therapy and radiotherapy applied in the time of maximal oxygenation could be a promising alternative for cancer treatment.


Identification of Environmental Risk Factors Associated With the Development of Inflammatory Bowel Disease.
Multiple genetic and environmental factors are involved in the aetiology of inflammatory bowel disease [IBD] including Crohn's disease [CD] and ulcerative colitis [UC], but data on these exposome factors are difficult to identify. Several exposome factors such as smoking have been shown to be involved; as for other environmental factors, eg stress, results have been conflicting. We performed a case-control study including 674 IBD patients of the 1000IBD cohort, frequency-matched based on sex and age with 1348 controls from the population-based Lifelines Cohort Study. Exposome data were obtained using the validated Groningen IBD Environmental Questionnaire [GIEQ], capturing exposome factors through different stages of life using 844 items, of which 454 were applicable to study the role of 93 exposome factors in disease aetiology. Logistic regression [LR] modelling with Bonferroni correction for multiple testing was applied to estimate the multivariable-adjusted effect of each exposome factor. For IBD, we identified four novel factors: stressful life events (CD odds ratio [OR] 2.61/UC OR 2.92), high perceived stress [2.29/2.67], alcohol use [0.40/0.43], and bronchial hyper-reactivity [3.04/2.36]. Four novel factors were associated with only CD: prenatal smoke exposure [1.89], having a bed partner [0.53], allergies [2.66], and cow's milk hypersensitivity [5.87]; and two solely with UC: carpet flooring [0.57] and neuroticism [1.32]. Nine factors were replicated. In this study we identified 10 novel, and replicated nine previously reported, exposome factors associated with IBD. Identifying these factors is important for both understanding disease aetiology and future prevention strategies to decrease the development of IBD in genetically susceptible persons.


Toxicokinetics of plasmatic VX in a swine model: comparison of a simple enzymatic titration method with a mass spectrometry method.
Recent events have shown that organophosphorus nerve agents (OPNAs) are a serious threat. Cholinesterase inhibition by OPNAs results in acetylcholine accumulation, a cholinergic crisis leading to death if untreated. Efficacy assessment of new medical countermeasures against OPNAs relies on translational animal models. We developed a swine model of percutaneous VX intoxication and a simple plate reader-based enzymatic method to quantify plasmatic VX over time. Juvenile pigs anesthetized with sevoflurane were poisoned with a single supralethal (n = 5; 1200 μg/kg) or sublethal (n = 6; 320 μg/kg) percutaneous dose of VX. These intoxicated animals were compared to 7 control animals. Repeated blood sampling was performed up to 6 h post-intoxication. Blood cholinesterase activities were measured using the Ellman assay. Nanomolar plasma concentrations of VX were measured by exogenous butyrylcholinesterase added to an aliquot of plasma. As expected, we observed a steady increase in plasma concentration of VX over time concomitant to a decrease in blood cholinesterase activities for all intoxicated pigs. Despite the simplicity of the enzymatic method, the results obtained are in good agreement with those of the liquid chromatography-mass spectrometry method. This method is also applicable to other OPNAs such as novichoks with minor adaptations.


Retracted: Comprehensive Evaluation of Tourism Resources Based on Multispecies Evolutionary Genetic Algorithm-Enabled Neural Networks.
[This retracts the article DOI: 10.1155/2021/1081814.].


Quantitative assessment of the ecological effects of land use/cover change in the arid region of Northwest China.
In light of ongoing changes in how humans interact with the environment, it is of great importance to quantitatively assess the impact of land use and cover change (LUCC) on ecosystems. Using a variety of methods, we analyzed land-use patterns and ecosystem service values (ESV) in 1990, 2000, and 2010; normalized difference vegetation index (NDVI) from 1982 to 2010 in the arid region of Northwest China; and quantitatively assessed the effects of LUCC on changes in NDVI and ESV. The results indicate the following: (1) From 1990 to 2010, the rate of increase in the amount of cropland and urban land was highest at 19.13% and 18.25%, respectively, followed by the rate for water cover (5.10%) and forest land (3.55%), while grassland experienced a reduction of 2.25%. (2) From 1990 to 2010, the total ESV increased by 1.82%. Changes in the amount of water cover and cropland were responsible for an increase in ESV of 1.42% and 1.10%, respectively, while the change in the amount of grassland was responsible for a decrease of 1.09%. Based on this, it seems likely that climate variability is a substantial cause of change in ESV. (3) From 1982 to 2010, NDVI showed an overall increase, first increasing significantly between 1982 and 2002 and then decreasing somewhat from 2002 to 2010. From 1990 to 2010, the contribution rate of LUCC to change in total NDVI was 26.74%, indicating that the contribution rate of climate variability to NDVI change was up to 73.26%. Therefore, over those 20 years, climate warming and humidification had an important impact on the development of ecosystems in the arid region of Northwest China.


Organic Supramolecular Zippers with Ultralong Organic Phosphorescence by a Dexter Energy Transfer Mechanism.
Ultralong organic phosphorescence (UOP) materials glow persistently in the dark, which offers new exciting possibilities in the fields of anti-counterfeiting, photoelectric devices and biological imaging. However, the development of single-component UOP materials remains a great challenge. Herein, we develop a single component organic supramolecular zipper system with a lifetime up to 0.77 s. Owing to the introduction of a pyrazole ring into the diphenylsulfone group, the "V" shaped molecules were artfully self-assembled into supramolecular zippers via π-π and C-H⋅⋅⋅π interactions, that is not only of significance in highly efficient generation of triplet excitons but also facilitates a Dexter energy transfer process within supramolecular zippers, that are responsible for alleviating radiative and non-radiative deactivation decay of triplet excitons, to finally boost the UOP. This finding not only gives a new set of guidelines for the design of single-component UOP molecules but also reveals the UOP mechanism from a new perspective.


Effects of hypothermic hypoxia on anaerobic energy metabolism in isolated anuran livers.
Many lower vertebrates (reptilian and amphibian species) are capable of surviving natural episodes of hypoxia and hypothermia. It is by specific metabolic adaptations that anurans are able to tolerate prolonged exposure to harsh environmental stresses. In this study, it was hypothesized that livers from an aquatic frog would possess an inherent metabolic ability to sustain high levels of ATP in an isolated organ system, providing insight into a metabolic system that is well-adapted for low temperature in vitro organ storage. Frogs of the species, R. pipiens were acclimated at 20 degrees C and at 5 degrees C. Livers were preserved using a clinical preservation solution after flushing. Livers from 20 degrees C-acclimated frogs were stored at 20 degrees C and 5 degrees C and livers from 5 degrees C-acclimated frogs were stored at 5 degrees C. The results indicated that hepatic adenylate status was maintained for 96 h during 5 degrees C storage, but not longer than 4-10 h during 20 degrees C storage. In livers from 5 degrees C-acclimated animals subjected to 5 degrees C storage, ATP was maintained at 100% throughout the 96-h period. Warm acclimation (20 degrees C) and 20 degrees C storage resulted in poorer maintenance of ATP; energy charge values dropped to 0.50 within 2 h and by 24 h, only 24% of control ATP remained. Lactate levels remained less than 25 mumol/g dry weight in all 5 degrees C-stored livers; 20 degrees C-stored livers exhibited greater accumulation of this anaerobic endproduct (lactate reached 45-50 mumol/g by 10 h). The data imply that hepatic adenylate status is largely dependent on exposure to hypothermic hypoxia and although small amounts of ATP were accounted for by anaerobic glycolysis, there must have been either a substantial reduction in cellular energy-utilization or an efficient use of low oxygen tensions.


Impact of a structured older persons health assessment on herpes zoster vaccine uptake in Australian primary care.
Vaccine uptake in adult immunisation programs is often suboptimal. We aimed to assess the impact of the structured older persons health assessment (health assessment) on herpes zoster (zoster) vaccine uptake in Australia. We used national general practice electronic medical records (MedicineInsight) of encounters with patients aged 75-79 years because these patients were age-eligible for both free zoster vaccines and health assessments in the two years following the addition of zoster vaccine to the national immunisation program (Nov 2016-Dec 2018). Due to repeated encounters, we used generalized estimating equations with each patient treated as a clustering variable to analyse the comparison of rates of zoster vaccine administration during encounters where a health assessment was provided versus encounters where the health assessment was not provided. In analyses there were 31,876 patients with a total of 266,204 eligible general practice encounters. Of the 5018 encounters where a health assessment was provided, 592 zoster vaccinations also occurred on the same day (118.0/1000 encounters); for the 261,186 encounters where no health assessment was provided, 9226 zoster vaccinations occurred (35.3/1000 encounters). Zoster vaccine was more likely to be administered during a general practice encounter with a health assessment compared to encounters without one (adjusted odds ratio 2.99; 95% CI: 2.76-3.23). In conclusion, the structured older persons health assessment, which acts as both an incentive and a reminder for healthcare providers to recommend vaccinations in adults improves uptake of zoster vaccine in eligible adults. Such interventions may have a role in improving vaccine uptake among older adults.


Agomelatine: AGO 178, AGO178, S 20098.
Novartis and Servier are developing agomelatine for the treatment of depression. Agomelatine is a specific melatonin (MT1 and MT2) receptor agonist that also has antagonistic activities at serotonin-(2C) (5-HT(2C)) receptors. Novartis believes agomelatine is comparable to current standard therapies for depression with improved tolerability, including a low propensity to cause sexual dysfunction and weight gain. Clinical development is being conducted in the US for the treatment of depression; approval for this indication was declined in the EU, apparently due to insufficient data. Servier has also conducted a trial of the agent in patients with generalized anxiety disorder in France, South Africa and Finland, and a phase II trial in sleep disorders in France. In March 2006, Servier and Novartis signed a licensing agreement for agomelatine. Novartis obtained the exclusive rights for the development and marketing of agomelatine in the US and several other countries. Servier retained the rights to the product in the rest of the world. The clinical development plan for agomelatine includes phase III trials being conducted under the parAGOn clinical trial programme. One US-based trial that began in March 2007 (NCT00463242) is recruiting 490 patients with depression who will receive placebo or agomelatine 25 or 50 mg for 8 weeks and will then receive open-label agomelatine for 52 weeks. Novartis is also conducting an 8-week phase III trial (NCT00411099) comparing the safety and efficacy of agomelatine 25 and 50 mg in patients with major depressive disorder. A follow-up, 52-week open-label extension study (CAGO178A2301E) will also be conducted. Another phase III study underway is NCT00411242, which has the same design and is also followed by a 52-week open-label extension study (CAGO178A2302E). These studies are all expected to be completed by January 2009. In July 2006, the Committee for Medicinal Products for Human Use recommended the refusal of marketing authorisation for agomelatine for the treatment of depression. Servier had applied for a re-examination of the finding but withdrew the request in November 2006. Servier's MAA was not supported due to insufficient data and no recent development has been reported in this indication in the EU. Agomelatine prevented relapse in patients with depression compared with placebo and was well tolerated in an international phase III trial.


Draft Genome Sequence of Lactobacillus salivarius L28 Isolated from Ground Beef.
In this report, we describe the draft genome sequence of a newly discovered probiotic strain, Lactobacillus salivarius L28. L. salivarius L28 demonstrates antagonistic effects against human foodborne pathogens, including Escherichia coli O157:H7, Salmonella spp., and Listeria monocytogenes, in coculture experiments and food matrices.


Effect of exercise training on endothelial function in men with coronary artery disease.
The objective of this study was to investigate the effects of 12 weeks of standard cardiac rehabilitation on endothelial function, oxidative stress, and antioxidant defenses in patients with coronary artery disease. Twelve weeks of endurance exercise training led to an improvement in endothelial function as measured by brachial artery flow-mediated dilation (7.9% at baseline vs 11.1% at 12 weeks). Exercise training resulted in increased plasma nitrite and nitrate levels, increased plasma superoxide dismutase activity, and decreased oxidative stress.


These terrifying three words: A qualitative, mixed methods study of students' and mentors' understandings of 'fitness to practise'.
There is little empirical published research pertaining to fitness to practise and pre-registration nursing students. Much of the existing fitness to practise literature focuses on medical students and there is a preponderance of literature reviews and descriptive or discursive papers. The multicentre study aimed to explore students' and mentor's understandings of fitness to practise processes in pre-registration nursing programmes. A qualitative study in the interpretive paradigm with interpretive analysis involving 6 focus groups and 4 face-to-face interviews with nursing students and mentors. Eleven Higher Education Institutions providing pre-registration nursing education in the UK. Data were collected January 2014-March 2015 following ethical approval. Purposive sampling was used to recruit mentors and nursing (but not midwifery) students from pre-registration nursing programmes at different stages of educational preparation. Qualitatively driven semi-structured focus groups (n=6) and interviews (n=4) were conducted with a total of 35 participants (17 pre-registration nursing students and 18 nursing mentors). Three themes identified from the student and mentor data are considered: Conceptualising Fitness to Practise; Good Health and Character; and Fear and Anxiety Surrounding Fitness to Practise Processes. Uncertainty about understandings of fitness to practise contributed to a pervasive fear among students and reluctance among mentors to raise concerns about a student's fitness to practise. Both students and mentors expressed considerable anxiety and engaged in catastrophic thinking about fitness to practise processes. Higher Education Institutes should reinforce to students that they are fit to practise the majority of the time and reduce the negative emotional loading of fitness to practise processes and highlight learning opportunities.


Revival of electron crystallography.
Since the structure determination of bacteriorhodopsin in 1990, much progress has been made in the further development and use of electron crystallography. In this review, we provide a concise overview of the new developments in electron crystallography concerning 2D crystallization, data collection and data processing. Based on electron crystallographic work on bacteriorhodopsin, the acetylcholine receptor and aquaporins, we highlight the unique advantages and future perspectives of electron crystallography for the structural study of membrane proteins. These advantages include the visualization of membrane proteins in their native environment without detergent-induced artifacts, the trapping of different states in a reaction pathway by time-resolved experiments, the study of non-specific protein-lipid interactions and the characterization of the charge state of individual residues in membrane proteins.


Clinically evident polyvascular disease and regression of coronary atherosclerosis after intensive statin therapy in patients with acute coronary syndrome: serial intravascular ultrasound from the Japanese assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) trial.
To clarify whether the effects of statin treatment on plaque regression vary according to the presence or absence of polyvascular disease (PVD) in patients with acute coronary syndrome (ACS). 307 patients with ACS who underwent percutaneous coronary intervention for the culprit lesion at 33 centers were treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was defined as coexistent, clinically recognized arterial disease other than coronary artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at baseline and at 8-12 months follow-up. Serial IVUS examinations were obtained in 252 patients. Atheroma volume and percent change in atheroma volume of the target plaque was assessed. Patients of the CAD+PVD (n = 19) were older (68 vs. 62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels at baseline (116 vs. 134 mg/dL, p=0.03) than those of the CAD-only group (n = 233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although the baseline plaque volume was similar in the two groups (59 vs. 57 mm(3)), patients of the CAD+PVD group showed milder regression of atherosclerosis than those of the CAD-only group (-8.9% vs. -18.2%, p = 0.005). This difference remained significant even after adjustment for coronary risk factors including age and serum LDL-C (p = 0.047). Statin treatment results in milder regression of coronary atherosclerosis in CAD patients with polyvascular disease compared to those with CAD only.


Developmental validation of an efficient differential separation method incorporating the i-sep® DL spin column with high sperm DNA recovery for the processing of sexual assault samples.
The differential separation method is key to recovering a DNA profile of the sperm donor from sexual assault samples. However, low numbers of spermatozoa from the perpetrator are often swamped by the victim's epithelial cells or lost during the separation process, with the separation process labor-intensive, time-consuming, and operator-dependent. The self-sealing filter of the i-sep® DL spin column allows direct lysis of the substrate throughout the differential separation process while preventing intact sperm cells from passing through, maximizing DNA recovery, and separation of non-sperm and sperm cells present. This study investigated the efficacy of a modified differential separation method, which incorporated the i-sep® DL spin column in comparison with the conventional pellet-based differential separation method. Using semen dilution series and mock post-coital samples, the sensitivity, reproducibility, repeatability, and efficiency of sperm DNA recovery of the pellet-based differential to the i-sep® method were evaluated side by side. The i-sep® differential method was more sensitive in capturing sperm fraction DNA, with informative semen donor alleles detected from high dilutions of semen inputs where the pellet method has been unsuccessful. The i-sep® differential method reduces manual handling, generating repeatable, and reproducible results between operators. Re-extraction of samples previously processed by the pellet or i-sep® differential method showed that the pellet method failed to recover 15-88% of sperm fraction DNA, while the i-sep® differential method was able to recover >99% in the initial extraction. The i-sep® method is robust for processing sexual assault samples, overcoming the challenges of sperm DNA losses encountered by pellet-based methods.


Rapid separation of urinary acids by high-performance liquid chromatography.
Over a hundred acidic urinary constituents were separated within 30 min by using 5-micron octadecyl-silica columns and gradient elution with increasing acetonitrile concentration in dilute aqueous phosphoric acid solution at 70 degrees. The column effluent was monitored with a UV detector at 280 nm or with a fluorescence detector at 260 nm excitation and 340 nm emission wavelengths. The high sensitivity and speed of analysis, the excellent reproducibility and adequate resolution obtained suggest that this technique may be useful to obtain metabolic profiles in routine clinical work.


Vessel wall imaging features of Moyamoya disease in a North American population: patterns of negative remodelling, contrast enhancement, wall thickening, and stenosis.
This study characterized vessel wall imaging (VWI) features of Moyamoya disease (MMD) in a predominantly adult population at a North American center. Consecutive patients with VWI were included. Twelve arterial segments were analyzed for wall thickening, degree and pattern of contrast enhancement, and remodeling. Overall, 286 segments were evaluated in 24 patients (mean age = 36.0 years [range = 1-58]). Of 172 affected segments, 163 (95%) demonstrated negative remodeling. Complete vessel wall obliteration was most frequent in the proximal M1 (17/48, 35%). Affected segments enhanced in 72/172 (42%) (n = 15 for grade II; n = 54 for concentric and n = 18 for eccentric); 20 of 24 (83%) patients had at least one enhancing segment. Both enhancing and non-enhancing segments were present in 19/20 (95%) patients. Vessel wall enhancement was most common in the proximal segments and correlated to the degree of stenosis (p < 0.001), and outer wall diameter (p < 0.001), but not disease duration (p = 0.922) or Suzuki score (p = 0.477). Wall thickening was present in 82/172 (48%) affected segments and was associated with contrast enhancement (p < 0.001), degree of stenosis (p < 0.001), and smaller outer wall diameter (p = 0.004). This study presents VWI findings in North American patients with MMD. Negative remodeling was the most common finding. Most patients had both enhancing and non-enhancing abnormal segments. Vessel wall enhancement was most common in proximal segments, variable in pattern or degree and was correlated to the degree of stenosis and smaller outer wall diameter.


Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts.
The nonenzymatic condensation of glucose with albumin results in the formation of albumin modified by Amadori glucose adducts, the principal form in which glycated albumin exists in vivo. This review focuses on (a) the utility of measurement of Amadori-modified glycated albumin (AGA) as a biomarker in diabetes, where elevated levels attend the hyperglycemic state; (b) the role of AGA as a causal factor in the pathogenesis of complications of diabetes; (c) effects on transport properties; and (d) structural and functional consequences of the modification of albumin by Amadori glucose adducts. It does not discuss counterparts with respect to Advanced Glycation Endproducts (AGE), which may be found in other publications. Nonenzymatic glycation of albumin, which is increased in diabetes, has clinical relevance and pathophysiologic importance, with ramifications for the management of this disease, the development of its complications, and the transport of endogenous and exogenous ligands. Appreciation of the manifold consequences of AGA has afforded new avenues for assessing clinical management of diabetes, awareness of the impact of nonenzymatic glycation on albumin biology, insights into the pathogenesis of vascular complications of diabetes, and avenues of investigation of and intervention strategies for these complications. This article is part of a Special Issue on albumin. This article is part of a Special Issue entitled Serum Albumin.


Association Between HLA Polymorphisms and Sympathetic Ophthalmia in Han Chinese.
Sympathetic ophthalmia (SO) is considered as an autoimmune disease with unclear mechanisms. This study investigated the relationship between HLA polymorphisms and SO. HLA typing was performed using the LABType reverse SSO DNA typing method. The allele and haplotype frequencies were assessed using the PyPop software. Statistical significance of genotype distributions between 116 patients and 84 healthy individuals (control) was determined using Fisher's exact test or Pearson's chi-squared test. The SO group had a higher frequency of HLA-DRB1 * 04:05, HLA-DQB1 * 04:01, DRB1 * 04:05-DQB1 * 04:01 haplotype as compared to the control group (Pc < 0.001 for all). This study revealed that DRB1 * 04:05 and DQB1 * 04:01 alleles, as well as DRB1 * 04:05-DQB1 * 04:01 haplotye could be potential risk factors for SO.


Ectopic transglutaminase 1 and 3 expression accelerating keratinization in oral lichen planus.
Oral lichen planus (OLP) characterized by interface mucositis frequently shows hyper-keratinization. To clarify mechanisms of excess keratinization, we investigated key molecules for cornified cell envelope (CE). Involucrin (IVL), loricrin (LOR), transglutaminase 1 (TGase 1) and transglutaminase 3 (TGase 3) were immunohistochemically examined in 20 specimens of OLP; five specimens of buccal mucosa served as controls. Subsequently, the data were statistically analyzed. IVL in OLP was localized in the cell membrane, in contrast to its localization in the cytoplasm in controls. No positive reaction indicative of LOR was noted in any specimens. Although the TGase 1 localization in controls was restricted to the upper three-quarters of the membrane, the localization in OLP was in both membrane and in the cytoplasm of full thickness mucosal layers. The TGase 3 localization pattern was dramatically altered from cytoplasmic to membranous in OLP. Our data suggest that aberrant TGase 1 and TGase 3 localization and distribution are closely related to hyper-keratinization in OLP. This is the first report of ectopic transglutaminase localization in OLP.


Fate of the liver in the survivors of adult heart transplant for a failing Fontan circulation.
The Fontan circulation has inherent long-term vulnerabilities such that adult Fontan patients now comprise the largest, most rapidly growing subgroup of adult congenital heart disease referred for transplant assessment. Almost all have Fontan Associated Liver Disease (FALD). There is an absence of mid to late hepatic outcome data after heart transplant alone. Therefore, we analyzed outcomes of survivors of heart only transplant in patients with failing Fontan circulation. Including all 10 of our adult Fontan patients surviving >1 year after isolated heart transplant, we report evolution of their clinical features, bloodwork, hemodynamic data, and liver ultrasound findings over a median of 4.7 years. Nonprogression of FALD, resolution of ascites and freedom from hepatocellular carcinoma in the mid-term highlight the outcomes in this selected group once normal cardiac output and venous pressures are established by heart transplant.


Reverse liaison rounds with a burn unit case.
A liaison rounds is presented, one attended by all members of a consultation-liaison (C-L) team along with the medical director of a burn unit. This structure is designated as a "reverse liaison rounds," as it is the opposite of the conventional liaison meeting, which consists of one C-L consultant and the total nonpsychiatric team. The content centered on a self-inflicted burn case in which countertransference issues involved a nonpsychiatrist. The unconventional format of the reverse liaison rounds provided all parties with new knowledge, perspectives, and insights into the interactions between the C-L consultant and the burn unit team.


trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling.
Discussed herein is the development and advancement of trans-cyclooctene as a tool for facilitating bioorthogonal labeling through reactions with s-tetrazines. While a number of strained alkenes have been shown to combine with tetrazines for applications in bioorthogonal labeling, trans-cyclooctene enables fastest reactivity at low concentration with rate constants in excess of k2=10(6) M(-1) s(-1). In the present article, we describe advances in computation and synthesis that have enabled applications in chemical biology and nuclear medicine.


Utilizing HapMap and tagging SNPs.
Advancements in our understanding of variation in the human genome and rapid improvements in high-throughput genotyping technology have made it feasible to study most of the human genetic diversity that is due to common variations in relation to observable phenotypes. Over the past few years, public SNP databases have matured and empirical genome-wide SNP data, such as that generated by the International HapMap Project, have shown the utility and efficiency of selecting and testing informative markers ("tag SNPs") that exploit redundancies among nearby polymorphisms due to linkage disequilibrium (LD). In this chapter, we will demonstrate how to use the HapMap resource and the Haploview program to process and analyze genetic data from HapMap, to evaluate LD relations between SNPs, and to select tagging SNPs to be examined in disease association studies.


Human monocyte-derived dendritic cells are deficient in prostaglandin E2 production.
Monocyte-derived dendritic cells (moDCs) are increasingly used in clinical settings to stimulate tumor immunity. Prostaglandin E2 (PGE2), which is a member of the eicosanoid family of oxygenated arachidonic acid derivatives generated through the action of cyclooxygenases (COXs), is frequently used to enhance the tumor necrosis factor-alpha-induced terminal maturation of moDCs. We show here that one effect of interleukin (IL)-4, which is used together with GM-CSF to generate moDCs, is the suppression of endogenous PGE2 production in moDCs. IL-4 inhibits the cytoplasmic form of phospholipase A2, the enzyme that specifically liberates arachidonic acid from membrane phospholipids. Although moDCs failed to mobilize endogenous arachidonic acid, they converted exogenous arachidonic acid into PGE2 in a COX-1- and COX-2-dependent fashion. IL-4-mediated suppression of PGE2 biosynthesis in human moDCs explains the previously reported maturation-enhancing effect of exogenous PGE2. The general suppression of eicosanoid biosynthesis may, however, limit the immunological efficacy of moDCs generated with IL-4.


Iodine 123-labeled metaiodobenzylguanidine imaging in heart disease.
Scintigraphic images of myocardial iodine 123-labeled metaiodobenzylguanidine (MIBG) reflect the relative distribution of adrenergic neurodensity and function in the myocardium. In patients with hypertrophic cardiomyopathy or after infarction, MIBG uptake in hypertrophied myocardium and the infarct-related myocardium was found to be decreased in comparison to blood flow distribution, delineated with thallium 201. Most intriguingly, semiquantitative measurements in patients with congestive heart failure demonstrated reduced myocardial MIBG uptake. This reduction correlated directly with indexes of left ventricular function. Decreases in neuronal density, dysfunction of adrenergic neurons, or chronically elevated circulating norepinephrine levels may account for this diminished myocardial uptake, which, as demonstrated in a pilot study of 90 patients with congestive heart failure, was found to be of predictive value for survival.


Developing and implementing a complex Complementary and Alternative (CAM) nursing intervention for breast and gynecologic cancer patients undergoing chemotherapy--report from the CONGO (complementary nursing in gynecologic oncology) study.
The purpose of this study was to develop a complex nursing intervention including complementary and alternative medicine (CAM) for breast and gynecologic cancer patients during chemotherapy to improve quality of life. Data sources Theoretical framework and concepts, practical nursing knowledge, and evidence-based studies were compiled in interprofessional meetings. Data synthesis The final complex intervention consists of three autonomous, but interacting components: (1) CAM nursing package, (2) resource-oriented counseling, and (3) evidence-based information material on CAM. CAM interventions include acupressure, aromatherapy, compress, and massage, targeting 14 clinically relevant symptoms during chemotherapy. Participants receive these interventions during chemotherapy with instructions for self care. During a counseling interview, the patient's needs and preferences are assessed by trained nurses. Furthermore, participants are equipped with evidence-based information material (booklet and DVD). Prior to study start, nurses attended training modules for administering CAM therapies and for communicating and counseling within the salutogenic approach. It was possible to design a multimodal CAM nursing intervention based on a theoretical concept, evidence-based studies, and practical nursing experience targeting the prevention or relief of side-effects women suffer during chemotherapy. The systematic analysis of the CONGO study will contribute to evidence-based CAM nursing care within supportive cancer care. Oncology nurses play an important role in supportive CAM care of breast and gynecologic cancer patients in daily clinical practice. Within oncology outpatient services, the implementation of evidence-based CAM nursing interventions and counseling may contribute to understand the impact of nursing on patient quality of life and symptom relief. This can lead to a new understanding of the nurse's professional role.


Exploring a public database to evaluate consumer preference and aroma profile of lager beers by comprehensive two-dimensional gas chromatography and partial least squares regression discriminant analysis.
In this paper is reported a proof of concept study to evaluate the usage of a public metadata base about beers to guide chemical interpretation of volatile organic compounds (VOC) profiling. 1,569,641 consumers' evaluations were collected from Untappd® platform and used to define a property of interest according to beer preference. 14 brands of beers from lager family were divided in two groups, first one containing samples with low consumers' ratings and the second with brands that exhibited high evaluations. VOC profiles were extracted by headspace solid phase microextraction (HS-SPME) and analyzed using comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC × GC-MS). To correlate the VOC profile and consumers' preference, unfolded-partial least squares discriminant analysis (U-PLS-DA) with orthogonal signal correction (OSC) were employed. The mathematical model successfully classified all the beer samples. Furthermore, a template match protocol identified 31 compounds related to consumers' preference. This proof of concept paper revealed the potential usage of public metadata bases for comprehensive chemical interpretation of VOC profiling in foodomics.


Impact of Coronavirus Disease-19 "Stay-At-Home" Orders on Preterm Birth in Colorado.
In this retrospective cohort analysis of Colorado birth certificate records from April to December 2015-2020, we demonstrate that Colorado birthing individuals experienced lower adjusted odds of preterm birth after issuance of coronavirus-19 "stay-at-home" orders. However, this positive birth outcome was experienced only by non-Hispanic white and Hispanic mothers.


Vitrectomy for chronic aphakic cystoid macular edema. Results of a national, collaborative, prospective, randomized investigation.
A five-year (1979-1984) prospective, randomized, controlled, collaborative study was performed by 27 experienced vitrectomy surgeons in 15 medical centers on 136 surgically aphakic eyes without lens implants but with vitreous adherent to the corneoscleral wound and with chronic aphakic cystoid macular edema (ACME). One hundred fifteen eyes completed the entire course of investigation. The purpose of the study was twofold: to determine the effectiveness of vitrectomy in eliminating established ACME and to determine the natural history of this condition. Following criteria contained within the study protocol, 68 eyes were randomized to surgery (RAN-S) or control (RAN-C), and 47 eyes were observed in the long-term observation group (LTO). Twenty-one eyes were eliminated from the investigation for reasons stated in the text. The RAN-S group proved to have a significantly better visual course than the RAN-C group (P = less than 0.01). An analysis of the LTO group revealed that if central vision did not decline to a level of 20/80 or worse, 27% of the eyes had a chance of spontaneously improving to a level of 20/50 or better. However, if central vision declines to or beyond this point, spontaneous visual improvement to 20/50 or better only occurred in 8% of eyes. Also reported are other important clinical findings such as the role of systemic diseases in ACME, the incidence of vitreous traction on the macula, prognostic value of pre-surgical medical therapy, a comparison of limbal versus pars plana surgical approach, the timing of surgery, and the effectiveness of fluorescein angiography as an objective monitor of visual function.


Maternal smoking during pregnancy is associated with a higher risk of non-syndromic orofacial clefts in infants.
Medline and Embase were searched to 2002 using the search terms "cleft lip", "cleft palate", "smoking", "tobacco", "cigarette", "mother" and "maternal". Reference lists from retrieved articles and a monograph on neural tube defects were also examined for more studies. Case-control and cohort studies that reported data on smoking by women during pregnancy were included. The outcomes were orofacial clefts (OFC) in infants, specifically cleft lip with or without cleft palate (CL+/-P) and cleft palate only (CP). Isolated or multiple defects were included, but syndromic cases were excluded wherever possible. Meta-analyses were carried out for CL+/-P, CP and total clefts. The analyses of CL+/-P and CP were repeated following stratification by the presence or absence of malformations in addition to the cleft, after the exclusion of studies that used malformed controls. Heterogeneity was assessed using the Q test and a random effect model was used if the P value was less than 0.1. Tests for publication bias and presence of a linear dose-response effect were also carried out when suitable data were available. The search identified 32 articles, of which 24 met the inclusion criteria (15 case-control and nine cohort studies). Statistically significant associations were found between maternal smoking and CL+/-P (relative risk, 1.34; 95% confidence interval, 1.25-1.44), and between maternal smoking and CP (relative risk, 1.22; 95% confidence interval, 1.10-1.35). There was evidence of a modest dose-response effect for CL+/-P, but the evidence was not clear for CP. No strong evidence of publication bias could be found. This study showed a consistent, moderate association between maternal tobacco smoking during pregnancy and nonsyndromic OFC in infants. The effect was observed for both isolated and multiple clefts, and was stronger and more consistent for CL+/-P than for CP.