Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.
Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease. Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and functional status of the pNET.


Minimally traumatic extraction techniques in nonrestorable endodontically treated teeth: A comparative study.
The goal of this study was to assess the effectiveness of piezotome as compared to periotome extractions of nonrestorable endodontic treatment of teeth in terms of operational time, pain control, and postoperative bone loss considering the prosthetic rehabilitation in future. A double-blind, randomized controlled trial was conducted with 100 patients who wanted single-rooted teeth to be extracted (which failed endodontically). The participants have been randomized into two equal groups named as - (i) a periotome group (ii) and a piezotome group. Duration of the surgery, postoperative pain within 7 days, complications (if any) associated with the extraction process were performed as a part of clinical assessment. Bone loss has been analyzed 6 months after the surgery radiographically. The data have been recorded and analyzed using the version 22.0 of the SPSS software package. All parameters in the periotome category (P < 0.05) were statistically significant except for bone loss and gingival laceration in comparison to piezotome group. In the piezotome group, a longer time was observed for surgery and delayed pain control was achieved. In our study, we found statistically significant more marginal bone loss in piezotome group in comparison with periotome group. The findings of this study indicate that for intraoperative and postoperative comfort periotome could be used as a safer and cheaper option for atraumatic extractions but piezosurgery may prove as a better choice soon for surgeries in the maxillofacial region to maintain soft-tissue integrity.


Correction to: GASAL2: a GPU accelerated sequence alignment library for high-throughput NGS data.
Following publication of the original article [1], the author requested changes to the figures 4, 7, 8, 9, 12 and 14 to align these with the text. The corrected figures are supplied below.


Femoral shortening osteotomy in total hip arthroplasty for severe dysplasia: a comparison of two fixation techniques.
The purpose of this study was to compare two distinct fixation methods for a total hip replacement performed via transverse femoral shortening osteotomy for patients with severe hip dysplasia. In this retrospective study we compared two fixation methods for total hip replacement of 78 hips in 76 patients exhibiting Crowe type IV developmental hip dysplasia (DDH). The hip replacements were performed via a transverse femoral shortening osteotomy and carried out between September 2009 and December 2013. Group I patients underwent fixation of the shortened femoral segment via a cable attached to the osteotomied segment, and group II patients underwent fixation with a plate and screw. We compared the two techniques based on operating time, osteotomy site union time, Harris hip score, hip loosening signs, and overall clinical outcomes. The mean operating time for groups I and II was determined to be 116.5 ± 12.8 min and 137.7 ± 14 min, respectively (p < 0.05), while the average union time was 113 ± 51 days for group I and 152 ± 37 days for group II (p < 0.05). Fixation of the femur with a cable (group I) is therefore faster and results in more rapid union time when compared to plate osteosynthesis at the osteotomy site (group II). We observed only one non-union in group I compared with three in group II (p = 0.49). Harris hip scores at the final patient follow-up were 82.8 ± 7.8 and 80.8 ± 6.7 for groups I and II, respectively (p = 0.23). Thus, notably no significant differences were observed between the groups with regard to clinical outcomes such as the Harris hip score or loosening of the replacement components. Fixation of the removed femoral segment with a cable provided adequate rotational stability and decreased the operating time, leading to early union at the osteotomy site.


Serum acute phase protein concentrations after hysterectomy with and without low-molecular-weight heparin thrombosis prophylaxis.
Background. Low-molecular-weight heparin (LMWH) is recommended for venous thrombosis prophylaxis. There are several lines of evidence that heparins exhibit anti-inflammatory properties in addition to their anticoagulant activity. Therefore, we decided to estimate the concentrations of C-reactive protein (CRP) and haptoglobin, as acute-phase proteins, in the blood serum of patients who underwent total abdominal hysterectomy with and without the LMWH administration. Method. Forty-two women were studied, including 26 patients treated with enoxaparin and a group of 16 women without thrombosis prophylaxis. Haptoglobin and CRP concentrations were measured in serum samples obtained before the operation and also 8, 24, 48, 72, 96, and 192 hr after surgery. Results. Serum CRP level measured 8 hr after the operation was significantly higher in the group without thrombosis prophylaxis, however, no statistically significant differences in the concentration of CRP between studied groups in the other time periods were found. There were no statistically significant differences in serum haptoglobin levels between the groups of patients in all time periods. Conclusion. Administration of low-molecular-weight heparin may affect CRP production, however, further studies are still needed in order to clarify the exact immunosuppressive action of heparins.


Clinical and neuroimaging findings in children with gray matter heterotopias: A single institution experience of 36 patients.
To describe the clinical spectrum and neuroimaging features of childhood gray matter heterotopias in a single tertiary hospital in Taiwan. We retrospectively reviewed the medical records and magnetic resonance images (MRI) of 36 patients with gray matter heterotopias, 19 females and 17 males, between July 1999 and June 2014. The MRI morphologic findings of gray matter heterotopias were recorded along with the presence of associated cerebral malformations. The clinical, electrophysiological and associated systemic malformation data were also recorded. A total of 36 patients were included in the study. Their ages ranged from 1 month to 18 years with a mean age of 3 years 6 months. According to the location of gray matter heterotopias, patients were classified into two groups: periventricular (26) and band (10). The phenotypic spectrum in our population differed from that described previously. In the periventricular group, additional cerebral malformations were found in 18/26 (69%) and systemic malformations in 14/26 (54%). In the band group, additional cerebral malformations were found in 5/10 (50%) and systemic malformations in 2/10 (20%). The majority of patients had developmental delay and intellectual deficit. Twenty-two patients suffered from epileptic seizures with 12 developing refractory epilepsy. In periventricular heterotopias, the most common associated cerebral malformation was ventriculomegaly, followed by agenesis of corpus callosum. Congenital heart disease was the most common additional systemic malformation. However, the most common associated cerebral malformation was pachygyria in band form. The majority of patients had developmental delay, intellectual deficit, especially in band heterotopias.


Intra- and extrarenal factors of oedema formation in the nephrotic syndrome.
The role of intra- and extrarenal factors in oedema formation in children with nephrotic syndrome is reviewed. Oedema reflects an abnormal accumulation of fluid within the interstitial tissue. At the capillary level oedema develops when increased lymph flow is no longer effective for the removal of interstitial fluid and the maintenance of intravascular volume. Alterations of intrarenal haemodynamics and tubular sodium reabsorption contribute to sodium retention. Recent studies suggest that during oedema formation reduced effective circulatory volume triggers changes in various hormonal systems, such as renin-angiotensin-aldosterone, noradrenaline, dopamine, vasopressin, prostaglandins and natriuretic factors, which contribute to sodium and water retention. It appears that the release of atrial natriuretic peptide following central volume expansion is responsible for the increased urine flow and natriuresis after intravenous administration of albumin.


Discrimination by freshwater zooplankton between single algal cells differing in nutritional status.
Grazing rates of a freshwater copepod (Diaptomus kenai) and a freshwater cladoceran (Daphnia rosea) on the green alga Selenastrum minutum were determined to be dependent on the nutritional status of individual cells. Cells that were less nitrogen limited were ingested at a greater rate than cells reared under more nitrogen limited conditions. Diaptomus displayed active discrimination, possibly via chemodetection, while Daphnia expressed passive selection, probably via differential retention on filters. These results suggest that the impact of grazing zooplankton varies with the physiological state of components of the phytoplankton community.


Successful treatment with antivenin of marked thrombocytopenia without significant coagulopathy following rattlesnake bite.
We cared for two rattlesnake bite victims who developed platelet counts of 21,000/mm3 and 22,000/mm3. Both had only mild defibrination without evidence of intravascular clotting. In both cases, the administration of antivenin was followed promptly by a sustained rise in platelet counts.


Endoscopic Transcanal and Transmastoid Laser-Assisted Resection of Middle Ear Capillary Hemangioma.
To present a rare case of a middle ear capillary hemangioma in an adult. A 31-year-old woman with a 6-month history of left ear fullness, pressure, tinnitus, and progressive hearing loss. Endoscopic laser-assisted resection. Clinical, radiographic, and histopathological findings of a capillary hemangioma. Otoscopy revealed an erythematous and slightly pulsating multilobulated middle ear retrotympanic mass. Her audiogram demonstrated a left-sided mixed hearing loss with air-conduction thresholds in the severe-to-profound range. Computed tomography (CT) imaging was significant for total opacification of the left middle ear and mastoid air cells. She underwent a combined endoscopic transcanal and transmastoid excision of the mass with ossicular chain reconstruction. A KTP laser was used to ablate and shrink down the periphery of the lesion. Pathology of the specimen was consistent with a capillary hemangioma. The patient's pulsatile tinnitus and spontaneous vertigo resolved postoperatively. Capillary hemangiomas are an uncommon cause of vascular middle ear lesions in adults and typically present with symptoms of aural fullness, pulsatile tinnitus, conductive hearing loss, otalgia, and vertigo. Surgery resection provides definitive treatment and the use of laser ablation techniques can allow for hemostasis and excellent visualization.


Prediction of 1-Year Mortality from Acute Myocardial Infarction Using Machine Learning.
Risk stratification at hospital discharge could be instrumental in guiding postdischarge care. In this study, the risk models for 1-year mortality using machine learning (ML) were evaluated for guiding management of acute myocardial infarction (AMI) patients. From the Korea Acute Myocardial Infarction Registry (KAMIR) dataset, 22,182 AMI patients were selected. The 1-year all-cause mortality was recorded at 12-month follow-up periods. Anomaly detection was conducted for removing outliers; principal component analysis for dimensionality reduction, recursive feature elimination algorithm for feature selection. Model selection and training were conducted with 70% of the dataset after the creation and cross-validation of hundreds of models with decision trees, ensembles, logistic regressions, and deepnets algorithms. The rest of the dataset (30%) was used for comparison between the ML and KAMIR score-based models. The mean age of the AMI patients was 64 years, 71.8% were male, and 56.7% were eventually diagnosed with ST-elevation myocardial infarction. There were 1,332 patients suffering from all-cause mortality (6%) during a median 338 days of follow-up. The ML models for 1-year mortality were well-calibrated (Hosmer-Lemeshow p >0.05) and showed good discrimination (area under the curve for test cohort: 0.918). Compared with the performance of the KAMIR score model, the ML model had a higher area under the curve, net reclassification improvement, and integrated discrimination improvement. The ML model for 1-year mortality was well-calibrated and had excellent discriminatory ability and higher performance. In a comprehensive clinical evaluation process, this model could support risk stratification and management in postdischarge AMI patients.


Cancer Care Delivery Research: A Path to Improving the Quality of Oncologic Surgical Care.
The goal of cancer care delivery research (CCDR) is to inform sustainable practice changes that will provide better clinical outcomes and patient experience guided by patient values. CCDR encompasses salient concepts from other well-established research approaches and spans the continuum of research from hypothesis generation to effectiveness studies to policy development. CCDR incorporates pertinent attributes, such as saliency to stakeholders, inclusion of diverse participants, and implementation into real-world settings. This article provides examples of CCDR studies, focusing specifically on how CCDR can improve the quality of oncologic surgical care.


Environmental contamination of SARS-CoV-2 on surfaces, air-conditioner and ventilation systems.
COVID-19 can be transmitted directly through respiratory droplets or indirectly through fomites. SARS-CoV-2 has been detected on various environmental surfaces, air samples and sewage in hospital and community settings. Environmental samples were collected from a ferryboat during a COVID-19 ongoing outbreak investigation and a nursing home and from three COVID-19 isolation hospital wards and a long-term care facility where asymptomatic COVID-19 cases were isolated. Samples were tested by real-time reverse transcriptase-polymerase chain reaction. SARS-CoV-2 was detected on swab samples taken from surfaces of food preparation and service areas, hospital isolation wards, an air exhaust duct screen, air-conditioning filter, sewage treatment unit and air sample during investigations conducted in response to COVID-19 outbreaks on a ferryboat, nursing home, isolation facility and COVID-19 hospital wards. Food preparation areas and utensils can be contaminated during COVID-19 outbreaks. Respiratory droplets/nuclei from infected persons can be displaced by the air flow and deposited on surfaces. It can be assumed that in the same manner, air flow could transfer and deposit infected respiratory droplets/nuclei from infected persons to the mucous membranes of persons standing against the air flow direction.


The protective effect of co-administration of platelet-rich plasma (PRP) and pentoxifylline (PTX) on cyclophosphamide-induced premature ovarian failure in mature and immature rats.
Cyclophosphamide (CP), as an antineoplastic agent, causes premature ovarian failure (POF) due to ovarian toxicity and subsequent infertility in women. Platelet-rich plasma (PRP) has accumulated significant attention in regenerative medicine. Pentoxifylline (PTX) as a methylxanthine derivative has been shown to have antioxidant and antiapoptotic properties. The aim of this study was to evaluate the protective effect of PRP and PTX on CP-induced POF. Fifty mature and immature female rats were assigned into five groups: control, CP (75 mg/kg, intraperitoneal [ip] on days 1 and 10 to induce POF), CP + PRP (200 μl, ip, half an hour after CP injection on day 1 and 10), CP + PTX (50 mg/kg, orally, half an hour after CP injection daily for 21 day), and CP + PRP + PTX. At the end of experiments on day 21, measurement of body weight, ovarian parameters (ovarian volume, follicular granulosa cell layers diameter, oocyte diameter, and the number of granulosa cells), measurement of ovarian hormone in sera for estradiol (E2), and anti-Mullerian hormone (AMH), as well as biochemical assessment were performed.The results showed that CP significantly reduced the ovarian parameters, E2, AMH, superoxide dismutase (SOD) activity and increased Malondialdehyde (MDA) levels compared to the control group (p < 0.001). Our results also indicated that all histomorphometric parameters and biochemical markers in CP-induced POF, were preserved close to normal by PRP and PTX treatments in both mature and immature rats (p < 0.001). Therefore, it is concluded that the co-administration of PRP and PTX can protect the ovary from CP-induced POF.


Histochemical demonstration of mouse submandibular esterproteases with a new chromogenic substrate.
A new method for the histochemical demonstration of mouse submandibular esterproteases has been developed. The substrate is N-acetyl-L-methionine alpha-naphthyl ester. The main enzyme reaction was found in the apical region of the secretory tubules with a marked sex difference as expected. First attempts were made to differentiate histochemically between the various esterproteolytic enzymes.


Expression pattern and functional studies of matrix degrading proteases and their inhibitors in the mouse corpus luteum.
The formation of the corpus luteum (CL) is accompanied with angiogenesis and tissue remodeling and its regression involves tissue degradation. Matrix degrading proteases such as plasminogen activators (PAs) and matrix metalloproteinases (MMPs) are thought to play important roles in such controlled proteolytic processes. In this study, in situ hybridization has been used to examine the regulation and expression pattern of mRNAs coding for proteases and protease inhibitors belonging to the PA- and MMP-systems during the life cycle of the CL in an adult pseudopregnant mouse model. Of the nine proteases and five protease inhibitors that were studied, the majority were found to be temporally expressed during the formation and/or the regression of the CL. However, the mRNAs coding for urokinase type PA (uPA), membrane-type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type-3 (TIMP-3) were constantly expressed in the mouse CL throughout its whole life span. To study the functional role of uPA in the CL, we analyzed luteal formation and function in uPA deficient mice. Our results revealed no significant difference in ovarian weight, serum progesterone levels, and blood vessel density in the functional CL between uPA deficient and wild type control mice. The temporal and spatial expression pattern of proteases and protease inhibitors during the CL life span suggests that members of the PA- and MMP-systems may play important roles in the angiogenesis and tissue remodeling processes during CL formation, as well as in the tissue degradation during luteal regression. However, the absence of reproductive phenotypes in mice lacking uPA and several other matrix degrading proteases indicates that there are redundancies among different matrix degrading proteases or that tissue remodeling in the ovary may involve other additional unique elements.


Isolation of secondary metabolites of Aspergillus ochraceus by HPLC.
A method is described for the isolation and purification of ochratoxin A, ochratoxin B, ochratoxin ß mellein, 4-hydroxymellein and penicillic acid produced byAspergillus ochraceus in a synthetic liquid medium. Ochratoxin α, which was not found in the culture medium, was obtained by acid hydrolysis of ochratoxin A. A high pressure liquid Chromatograph equipped with Lichrosorb 100 and Lichrosorb RP-18 columns and UV and/or Refractive Index detectors was used.


Dataset of human EDEM2 melanoma cells proteomics, affinity proteomics and deglycoproteomics.
EDEM2 (Endoplasmic reticulum Degradation-Enhancing alpha-Mannosidase-like protein 2) is one of the key-proteins suggested to be involved in the selection and degradation of misfolded proteins from the endoplasmic reticulum. The datasets discussed in this article are related to experiments covering affinity proteomics, label-free quantitative proteomics, deglycoproteomics and SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) proteomics data of A375 melanoma cells with modified expression of EDEM2. Our first aim was to affinity-enrich EDEM2 alongside its potential interaction partners and analyse the obtained samples by nanoLC-MS/MS to identify novel EDEM2 associated proteins. The dataset was substantiated by SDF (Sucrose Density Fractionation)-nanoLC-MS/MS experiments, in an integrated workflow to validate EDEM2 identified partners and corroborate these with previous data. Our second aim was to delineate novel EDEM2 substrate candidates using a two-step strategy. The first one refers to the deglycoproteomics dataset, which covers nanoLC-MS/MS analysis of Concanavalin A enriched glycopeptides released by endoglycosidase digestion from A375 melanoma cell lysates. This allowed us to map the fraction of glycoproteins with non-matured N-glycans from A375 melanoma cells and find or validate N-glycosylation sites of proteins from the secretory pathway. The same dataset was also used to define glycoproteins altered by the down-regulation of endogenous EDEM2, which should contain its candidate-substrates. In a second step we delineate the degradation kinetics of some of these proteins using a pulse SILAC strategy (pSILAC) thus complementing our initial findings with a fourth dataset. Beside nanoLC-MS/MS analysis our findings were also validated by various biochemical experiments. All the data described are associated with a research article published in Molecular and Cellular Proteomics [1].


First report on autochthonous urease-positive Trichophyton rubrum (T. raubitschekii) from South-east Europe.
Trichophyton raubitschekii is a dermatophyte belonging to the T. rubrum complex and is differentiated principally by its positive urease activity and production of profuse macroconidia and microconidia in culture. It is classically isolated from African, South-east Asian and Australian aboriginal patients with tinea corporis or tinea cruris. This study was undertaken to screen Greek and Bulgarian clinical isolates identified as T. rubrum for T. raubitschekii and to delineate these strains by two molecular methods used for the first time in T. rubrum epidemiological studies. Ninety-five Greek and 10 Bulgarian strains, originating from various body sites, initially identified as T. rubrum, were screened for urease activity. The biochemical properties and morphology of the urease-positive strains were determined. Strains were delineated with polymerase chain reaction (PCR)-ribotyping amplifying repeat elements of the intergenic spacer region and by PCR fingerprinting. Five Greek and one Bulgarian T. raubitschekii strains were identified comprising isolates from patients with tinea manuum (one), tinea corporis (one), tinea cruris (one) and tinea unguium (three). Only one strain had the classical T. raubitschekii microscopic morphology, whereas the remaining five presented a dominant arthroconidial phenotype. Both typing methods clustered all T. raubitschekii and T. rubrum isolates together in the same group, indicating strain homogeneity in the genetic regions examined. The reported isolation of T. raubitschekii in the Balkan and South-eastern Mediterranean regions extends the geographical distribution of this species. As the more primitive T. raubitschekii probably represents the parental population of T. rubrum, the Greek and Bulgarian T. raubitschekii strains could represent a remnant of the T. rubrum spread that took place after the First World War, rather than being a recent epidemiological event.


Relationship between dissolution and bioavailability for nimodipine colloidal dispersions: the critical size in improving bioavailability.
To compare the dissolution and bioavailability for nimodipine microcrystals and nanocrystals, and to determine the critical size range in improving the oral absorption of nimodipine. Nimodipine microcrystals and nanocrystals were prepared using a microprecipitation method. The particle size was determined with a laser diffraction method. X-ray powder diffraction was applied to inspect the potential crystal form transition. The aqueous solubility was determined by shaking flasks, and the dissolution behavior was evaluated using the paddle method. The pharmacokinetics was performed in beagle dogs in a crossover experimental design. Three nimodipine colloidal dispersions (16296.7, 4060.0 and 833.3 nm) were prepared, respectively. Nimodipine had undergone crystal form transition during microprecipitation process, but experienced no conversion under the high-pressure homogenization. The colloidal dispersions did not show any difference in aqueous equilibrium solubility. Additionally, the three formulations also displayed similar dissolution curves in purified water and 0.05% SDS. The AUC for dispersions of 4060.0 and 833.3 nm sizes was 1.69 and 2.59-fold higher than that for 16296.7 nm system in dogs. To sum up, the critical particle size was found to be within the range of 833.3-4060.0 nm (average volume-weighted particle size) in improving the bioavailability of nimodipine, and dissolution performance was not an effective index in evaluating the bioavailability for nimodipine colloidal dispersions.


Clinical and histological features of idiosyncratic liver injury: Dilemma in diagnosis of autoimmune hepatitis.
Drug-induced liver injury (DILI) is becoming a worldwide problem with its still unexplained properties. The data of patients who were diagnosed with DILI between January 2008 and December 2013 were assessed. Five patients had been diagnosed with intrinsic and 82 patients with idiosyncratic DILI. The most common causative agents were antimicrobial drugs. The most common injury pattern was hepatocellular. When patients with bilirubin levels of more than 5 mg/dL were divided into two groups according to receiving steroid therapy (n = 11) or not (n = 40), there was not any significant difference according to their clinical results (P > 0.05). Five of the idiosyncratic DILI patients were diagnosed with drug-induced autoimmune hepatitis (DI-AIH). In histopathological examination, hepatic rosette formation and emperipolesis were observed to be more common among patients with DI-AIH when compared with ones without (P < 0.05). Interestingly, in the remaining patients with DILI (n = 77), three of them were diagnosed with classic autoimmune hepatitis during long-term follow up (range, 11-51 months). The most common causes were antimicrobials, but any agents that have not been defined to cause DILI can induce DILI. The efficacy of steroids in DILI has not been observed but all deaths were observed in the steroid-free group. The association of DILI and AIH was observed in two different types in terms of diagnosis in our study. The first association was DI-AIH. The second one is the classical AIH which developed in three patients after a few months following spontaneous recovery of DILI.


Stabilization and Transdermal Delivery of an Investigational Peptide Using MicroCor® Solid-State Dissolving Microstructure Arrays.
The formulation of biotherapeutics presents unique challenges especially with regard to physical and chemical stability and often requires refrigerated storage conditions of final drug products. Peptide A is an example of a developmental compound which showed significant stability challenges when prepared as a liquid formulation for a subcutaneous injection. The aim of the present study was to evaluate whether Peptide A can be successfully formulated in MicroCor® microstructure arrays (MSAs) as an alternative delivery option. MSAs contain a high density of dissolving microstructures allowing for transdermal delivery. In the present work, a 5600-needle MSA (~200 μm long microstructures, 2 cm2 array) was prepared with a therapeutically-relevant dose of Peptide A. The array was shown to be stable under room-temperature storage conditions for 3 months. On in vivo application to Yucatan minipigs, Peptide-A-loaded MSAs demonstrated only mild and transient skin irritation and a very high efficiency of peptide transfer from dissolving microstructures into the skin resulting in absolute bioavailability of 74%. This transdermal bioavailability was very similar to the 73% bioavailability obtained from a subcutaneous injection. This technical feasibility study demonstrated that MicroCor® technology represents a viable option for delivery of Peptide A with significant improvements in peptide stability.


The needs of the abused child in the community.
The development of community awareness of child abuse has followed medical awareness and is specifically concerned with prevention and early intervention. Contact between community services and 304 infants from a birth cohort in a poor socio-economic status, multi-ethnic urban municipality was documented to investigate how these services could provide effective community approaches to the problem. While perinatal and medical services provided fragmented care, the Maternal and Child Health Service was the only agency to contact all families, including those of the 21 abused or "at risk" infants. It is suggested that such local universal services should form the basis of a community approach to the needs of the abused or "at risk" child.


Real-time PCR assay for the detection of tanapox virus and yaba-like disease virus.
The yatapoxvirus genus contains three members: tanapox virus (TPV), yaba-like disease virus (YLDV) and yaba monkey tumor virus (YMTV), two of which (TPV and YLDV) may infect humans. However, only a very small number of patients have been diagnosed with TPV outside Africa. Given the increased international travel and the similarity of clinical signs during the early stages of a TPV/YLDV infection as compared to diseases caused by agents of potential biological warfare, such as smallpox, monkeypox, tularemia and anthrax, the rapid and reliable recognition of a TPV/YLDV infection is crucial. A real-time PCR assay using TaqManchemistry was developed in order to identify unambiguously TPV/YLDV. Primers and probe targeting a 101bp region of the PstI L fragment of TPV, initial optimisations steps were carried out with YLDV DNA as template. Using probit regression analysis, the lower limit of detection was calculated to be ca. 8 copies per assay. A total of five TPV strains, one YDLV strain and scab-derived DNA from a patient with a TPV infection yielded specific amplification, whereas the DNA of YMTV was not amplified. Various viral and bacterial pathogens (n=29) associated with rash-causing illnesses were not detected using this assay.


New Pyrano-4H-benzo[g]chromene-5,10-diones with Antiparasitic and Antioxidant Activities.
New pyranonaphthoquinone derivatives were synthesized and investigated for their activity against Trypanosoma brucei, Leishmania major, and Toxoplasma gondii parasites. The pentafluorophenyl derivative was efficacious against T. brucei with single digit micromolar EC50 values and against T. gondii with even sub-micromolar values. The 3-chloro-4,5-dimethoxyphenyl derivative showed an activity against amastigotes of Leishmania major parasites comparable to that of amphotericin B. In addition, antioxidant activities were observed for the bromophenyl derivatives, and their redox behavior was studied by cyclovoltammetry. Anti-parasitic and antioxidative activities of the new naphthoquinone derivatives appear uncorrelated.


[Not Available].
Using the long term rumen simulation technique RUSITEC a possible relationship between Mucor racemosus and Ulocladium chartarum and cerebrocortical necrosis (CCN) in cattle was investigated. In phase one only M. racemosus or U. chartarum and in phase two M. racemosus or U. chartarum in combination with thiamine were tested. The following differences between test groups and controlls could be noted: sVFA -7,5%, cellulase activity +62,1%, protein concentration -16,4%, thiamine -11% (only phase two). Thus, although a clear influence of M. racemosus and U. chartarum on rumen fermentation could be shown, a relation to CCN was not detected.


Incidence rates, risk factors, and outcomes of aspiration pneumonia after gastric endoscopic submucosal dissection: A systematic review and meta-analysis.
The risk and prognosis of aspiration pneumonia (AP) after endoscopic submucosal dissection (ESD) are inconsistent among studies. We aim to estimate the incidence, risk factors, and outcome of AP in patients after gastric ESD. PubMed, EMBASE, Cochrane Library, and Web of Knowledge were searched for relevant articles from inception until April 2020. Data involving the incidence, risk factors, and outcomes were extracted. Pooled incidence, odds ratios (ORs), or standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated. Forty records involving 48 674 subjects were finally included. The pooled incidence of AP after gastric ESD was 1.9% (95% CI, 1.2-2.7) via the double arcsine transformation method and 1.6% (1.1-2.5%) via the logit transformation method. Risk factors analyses revealed that old age (OR, 2.52; 95% CI, 1.99-3.18), comorbid pulmonary disease (2.49; 1.66-3.74), comorbid cerebrovascular disease (2.68; 1.05-6.85), remnant stomach (4.91; 1.83-13.14), sedation with propofol (2.51; 1.48-4.28), and long procedural duration (count data: 5.20, 1.25-21.7; measurement data: 1.01, 1.01-1.02) were related to the occurrence of AP. Patients with AP had a longer hospital stay (SMD, 0.56; 95% CI, 0.25-0.87) than those without AP. About 1.9% (1.2-2.7%) of the patients who receive gastric ESD may develop AP, resulting in prolonged hospital stay. More attention should be paid in patients who are older; have comorbidities such as pulmonary diseases, cerebrovascular diseases, or gastric remnant; or require a long procedural duration or deep sedation with propofol.


Chemotaxonomic variability in Zizyphus mouritiana varieties and its pharmacological properties in relation to human health.
Twenty varieties of ber (Zizyphus mouritiana), namely umaran, katha, bilayati, kaithli, ZG-3, gola, safeda rohtak, takadi, tikari, banarasi karaka, seo, sonaur-2, sonaur-3, ilaichi, mundia murahra, pathan, kakrola gola, seb, golden yellow and chhuhara, were investigated for the presence of phenolic acids in stem bark, leaves and fruits using high performance liquid chromatograph. Results indicated the presence of tannic (retention time (Rt.) 2.76 min), gallic (Rt. 2.86 min), caffeic (Rt. 3.12 min), vanillic (Rt. 3.26 min), ferulic (Rt. 3.42 min), chlorogenic (Rt. 4.16 min) and cinnamic acids (Rt. 4.45 min) in varying amounts in different parts in of these varieties. In fruits of seven varieties, namely, kaithly, sonaur-2, sonaur-3, mundia murahra, pathan, golden yellow and chhuhara, oxalic acid (Rt. 3.00 min) was also detected. Pharmacological properties of phenolic acids of fruits in relation to human health and the possible implications of different phenolic acids in chemotaxonomy of different varieties of ber are discussed.


Immunomodulating effects of synthetic polyribonucleotides.
The polynucleotide complexes are a class of compounds whose activities to date deserve close scrutiny with respect to their potential role as biological response-modifying agents in human disease. The challenge for the future lies in directing and controlling their activity with respect to a single desired effect, such that intelligent interference in patients with immunological aberrancies might occur.


Enantioselective N-heterocyclic carbene-catalyzed nucleophilic dearomatization of alkyl pyridiniums.
NHC-catalyzed nucleophilic dearomatization of alkyl pyridiniums has been achieved to generate 1,4-dihydropyridines with high enantioselectivity. This is a rare example of catalytic, asymmetric addition of a nucleophile to the activated pyridinium that prefers C-4 functionalization leading to the 1,4-dihydropyridine with high selectivity.


Musculoskeletal problems in Parkinson's disease: neglected issues.
To identify the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. 400 PD patients and 138 age- and sex-matched controls were interviewed by physicians about their musculoskeletal problems. The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (66.3% vs. 45.7%, P < 0.001). Commonly involved body sites were the low back, knee, and shoulder in that order. The low back was more frequently involved in the PD group than in the control group (44.3% vs. 24.6%, P < 0.001), and the shoulder tended to be more involved in the PD group than in the control group (15.0% vs. 8.7%, P = 0.061). However, the knee was similarly involved in both group (12.3% vs. 18.0%, P = 0.121). Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in the PD group than in the control group (P < 0.05). Older age, female, and a higher score on the Unified Parkinson's Disease Rating Scale I & II were associated with musculoskeletal problems in the PD group. Only 26.8% of the PD patients and 52.5% of the controls with musculoskeletal problems answered that their musculoskeletal problems were recovering. Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group (P = 0.052). Musculoskeletal problems were more common in the PD group than in the controls. Furthermore, despite PD patients having a higher prevalence, they did not receive adequate treatment.


Hypo-osmolar stimulation of transepithelial Cl- secretion in cultured human T84 intestinal epithelial layers.
Intact epithelial monolayers of T84 human colonic adenocarcinoma cells were exposed from the basolateral surfaces to hypo-osmotic media; in responsive tissues this resulted in a transient stimulation of inward short-circuit current (SCC) to a peak of 12.9 +/- 1.5 (S.E., n = 10) microA/cm2 which declined to prestimulation values of SCC (2.1 microA/cm2) within 5 min. Exposure of T84 cells to hypo-osmotic media results in an increase in cytosolic [Ca2+]i, dependent on extracellular Ca2+ influx. The cell-swelling activated SCC is abolished upon medium Cl- replacement and by 100 microM bumetanide applied to the basal-surfaces, consistent with the inward SCC resulting from transepithelial Cl- secretion. 100 microM DIDS (4,4'-diisothiocyanantostilbene-2,2'-disulphonic acid) also abolished the cell-swelling activated increase in SCC; DIDS is without effect upon the VIP-stimulated SCC, suggesting distinct Cl- channels are involved in the two responses.


Approach for the structural reliability analysis by the modified sensitivity model based on response surface function - Kriging model.
The sensitivity analysis model is widely used to describe the impacts of condition parameters on structural reliability. However, the classical sensitivity analysis model is limited to the small number of influence parameters and has no high prediction accuracy. Integrating the response surface function - Kriging model with Sobol sensitivity algorithm, a revised sensitivity model is proposed in this paper. And the quantitative sensitivity analysis for the influence of condition parameters on structural reliability are achieved through combining the revised sensitivity model with the experimental design of coupling parameters, range verification, the multi-body dynamics analysis and the structural statics analysis. The proposed analysis model is mainly applied in large structures with multiple influence parameters. Finally, a typical port crane is adopted to verify the accuracy and effectiveness of the proposed model. The results reveal that among the multiple parameters, the biggest sensitivity influence is the trolley position, while the least one is the lifting speed. The average prediction accuracy of the quantitative structural reliability index for the influencing parameters is up to 95.91%. The revised sensitivity model enables the accurate assessment of structural relativity with plenty of coupling condition parameters.


Pituitary adenylate cyclase-activating polypeptide protects against β-amyloid toxicity.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophin. However, its role in human Alzheimer's disease (AD) is largely unknown. We examined PACAP expression in postmortem human AD and triple transgenic mouse (3xTG, Psen1/APPSwe/TauP301L) brains. We established an in vitro model of primary neuronal cell culture to study the protective effects of PACAP against β-amyloid (Aβ) toxicity. We further studied the PACAP-Sirtuin 3 (Sirt3) pathway on mitochondrial function. PACAP expression was reduced in AD and 3xTG mouse brains. This reduction was inversely correlated with Aβ and tau protein levels. Treatment with PACAP effectively protected neurons against Aβ toxicity. PACAP stimulated mitochondrial Sirt3 production. Similar to PACAP, Sirt3 was reduced in AD and 3xTG brains. Knocking down Sirt3 compromised the neuroprotective effects of PACAP, and this was reversed by over-expressing Sirt3. PACAP is reduced in AD and may represent a novel therapeutic strategy.


Limited humoral immunity in hepatitis C virus infection.
The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV. A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays. Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection. The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.


Laminar Subnetworks of Response Suppression in Macaque Primary Visual Cortex.
Cortical inhibition plays an important role in information processing in the brain. However, the mechanisms by which inhibition and excitation are coordinated to generate functions in the six layers of the cortex remain unclear. Here, we measured laminar-specific responses to stimulus orientations in primary visual cortex (V1) of awake monkeys (male, Macaca mulatta). We distinguished inhibitory effects (suppression) from excitation, by taking advantage of the separability of excitation and inhibition in the orientation and time domains. We found two distinct types of suppression governing different layers. Fast suppression (FS) was strongest in input layers (4C and 6), and slow suppression (SS) was 3 times stronger in output layers (2/3 and 5). Interestingly, the two types of suppression were correlated with different functional properties measured with drifting gratings. FS was primarily correlated with orientation selectivity in input layers (r = -0.65, p < 10-9), whereas SS was primarily correlated with surround suppression in output layers (r = 0.61, p < 10-4). The earliest SS in layer 1 indicates the origin of cortical feedback for SS, in contrast to the feedforward/recurrent origin of FS. Our results reveal two V1 laminar subnetworks with different response suppression that may provide a general framework for laminar processing in other sensory cortices.SIGNIFICANCE STATEMENT This study sought to understand inhibitory effects (suppression) and their relationships with functional properties in the six different layers of the cortex. We found that the diversity of neural responses across layers in primary visual cortex (V1) could be fully explained by one excitatory and two suppressive components (fast and slow suppression). The distinct laminar distributions, origins, and functional roles of the two types of suppression provided a simplified representation of the differences between two V1 subnetworks (input network and output network). These results not only help to elucidate computational principles in macaque V1, but also provide a framework for general computation of cortical laminae in other sensory cortices.


In vitro octaploid induction of Populus hopeiensis with colchicine.
Autopolyploids, especially artificial lines, provide model systems for understanding the mechanisms of gene dosage effects on trait variation owing to their relatively uniform genetic background. Here, a protocol for in vitro octaploid induction of Populus hopeiensis from leaf blades with colchicine treatment was established through investigation of the effects of different pre-culture durations, colchicine concentrations, and exposure times. We found that pre-culture duration, colchicine concentration, and exposure time had significant effects on the survival rate, shoot regeneration rate, and octaploid induction rate of P. hopeiensis leaf blades. The highest octaploid induction rate (8.61%) was observed when leaf blades pre-cultured for 9 days were treated for 4 days with 100 μM colchicine. The ploidy level of all regenerated plantlets was analyzed by flow cytometry and further confirmed by chromosome counting. A total of 14 octaploids were obtained. The stomatal length, width, and density of leaf blades significantly differed between tetraploid and octaploid plants. Compared with diploid and tetraploid plants, octaploids had a slower growth rate, smaller leaf blade size, and shorter internodes. We established an effective protocol for inducing octaploids in vitro from autotetraploid P. hopeiensis leaf blades by colchicine treatment.


Comparative hormonal and metabolic profile analysis based on mass spectrometry provides information on the regulation of water-deficit stress response of sunflower (Helianthus annuus L.) inbred lines with different water-deficit stress sensitivity.
Water-deficit stress is the most important abiotic stress restricting plant growth, development and yield. The effects of this stress, however, depend on genotypes, among other factors. This study assembles morpho-physiological and metabolic approaches to assess hormonal and metabolic profile changes, upon water-deficit stress, in the shoot and roots of two contrasting sunflower inbred lines, B59 (water-deficit stress sensitive) and B71 (water-deficit stress tolerant). The analyses were carried out using mass spectrometry and performing a multivariate statistical analysis to identify relationships between the analyzed variables. Water-deficit stress reduced all morpho-physiological parameters, except for root length in the tolerant inbred line. The hormonal pathways were active in mediating the seedling performance to imposed water-deficit stress in both lines, although with some differences between lines at the organ level. B59 displayed a diverse metabolite battery, including organic acids, organic compounds as well as sugars, mainly in the shoot, whereas B71 showed primary amino acids, organic acids and organic compounds predominantly in its roots. The discrimination between control and water-deficit stress conditions was possible thanks to potential biomarkers of stress treatment, e.g., proline, maleic acid and malonic acid. This study indicated that the studied organs of sunflower seedlings have different mechanisms of regulation under water-deficit stress. These findings could help to better understand the physio-biochemical pathways underlying stress tolerance in sunflower at early-growth stage.


Outcomes of partial intussusception and endo-to-side vasoepididymostomy in men with epididymal obstructive azoospermia.
Vasoepididymostomy is an ideal surgical approach for epididymal obstructive azoospermia. The aim of the present study was to compare reproductive outcomes of vasoepididymostomy with several anastomotic techniques, including end-to-side and longitudinal intussusception vasoepididymostomy, and partial intussusception and endo-to-side vasoepididymostomy. A case-control study including 110 infertile men with epididymal obstructive azoospermia with mean age of 35 years was carried out. Univariate and multivariate analyses using clinical factors were carried out to predict patency and non-assisted reproductive technology pregnancy. Johnsen score count and proliferating cell nuclear antigen expression were used as surrogates for spermatogenic function. Operative time, number of 10-0 sutures and late failure rates were also compared. The overall patency and non-assisted reproductive technology pregnancy rates were 70% and 32%, respectively. Multivariate analyses showed that the presence of motile sperm in the epididymis and a higher spermatogenic function (P < 0.05) were independent predictors for patency, and that a higher spermatogenic function and anastomosis at the caput/corpus (P < 0.001) were predictors for non-assisted reproductive technology pregnancy. The operative time was significantly shorter with partial intussusception and endo-to-side than with the other techniques (P < 0.001), and the number of 10-0 sutures was significantly less with partial intussusception and endo-to-side than with longitudinal intussusception vasoepididymostomy (P < 0.01). Partial intussusception and endo-to-side as well as end-to-side and longitudinal intussusception vasoepididymostomy are feasible vasoepididymostomy techniques for epididymal obstruction. Spermatogenic function plays important roles in patency and non-assisted reproductive technology pregnancy after vasoepididymostomy. Depending on the surgeon's expertise, partial intussusception and endo-to-side provides similar functional outcomes to those of more established vasoepididymostomy techniques, such as end-to-side and longitudinal intussusception vasoepididymostomy, and it could therefore be considered an effective technique for seminal reconstruction in patients with epididymal obstructive azoospermia.


A case of a bronchogenic cyst in a rare location.
Bronchogenic cysts occur as a result of a developmental fault during the division and budding of the tracheobronchial tree in the embryonic period. They are usually located in the mediastinum and intrapulmonary regions. They may cause serious respiratory distress in childhood; they present less commonly in adults and often present with a variety of symptoms, including recurrent infections. We report the case of an adult female patient who presented with recurrent pulmonary infections and swelling of the neck because of a bronchogenic cyst that was unusually located in the cervical region.


Tumor suppressor and oncogene actions of TGFbeta1 occur early in skin carcinogenesis and are mediated by Smad3.
Interactions between TGFbeta1 and ras signaling pathways play an important role in cancer development. Here we show that in primary mouse keratinocytes, v-ras(Ha) does not block the early biochemical events of TGFbeta1 signal transduction but does alter global TGFbeta1 mediated gene expression in a gene specific manner. Expression of Smad3 dependent TGFbeta1 early response genes and the TGFbeta1 cytostatic gene expression response were not altered by v-ras(Ha) consistent with an intact TGFbeta1 growth arrest. However, TGFbeta1 and v-ras(Ha) cause significant alteration in genes regulating matrix remodeling as the TGFbeta1 induction of extracellular matrix genes was blocked by v-ras(Ha) but specific matrix proteases associated with cancer progression were elevated. Smad3 deletion in keratinocytes repressed normal differentiation maker expression and caused expression of Keratin 8 a simple epithelial keratin and marker of malignant conversion. Smad3 was required for the TGFbeta1 cytostatic response in v-ras(Ha) keratinocytes, but also for protease induction, keratinocyte attachment and migration. These results show that pro-oncogenic activities of TGFbeta1 can occur early in carcinogenesis before loss of its tumor suppressive function and that selective regulation rather than complete inactivation of Smad3 function may be crucial for tumor progression.


Effects of HU binding on the equilibrium cyclization of mismatched, curved, and normal DNA.
The effects of HU, the histone-like protein from Escherichia coli, on the equilibrium cyclization of duplex DNAs have been observed as a function of protein concentration and DNA sequence. The results indicate that the presence of HU significantly enhances the extent of cyclization and increases the melting temperature, T(m), of the cyclized form of the DNA by >10 K. The stabilization of equilibrium cyclization by HU binding is at least -1.2 kcal/mol. The results are consistent with two HU homotypic dimers binding to each of the three 29-mer duplexes studied. One of the 29-mer duplexes contains a central dA tract, one contains mismatched sites, and one a conventional sequence. Stepwise or microscopic association constants, determined from the fluorescence data, range from 1.5 to 0.6 micro M(-1). The binding affinity of the HU dimer is strongest for the mismatched duplex and lowest for the dA tract, consistent with HU dimers having a preference for flexible DNA substrates. These results demonstrate the utility of the equilibrium cyclization approach to monitor DNA-protein interactions. These results have been considered along with those previously obtained to refine a model for the interaction of HU with duplex DNA.


Detailed evaluation of functional recovery following laparoscopic or open surgery for colorectal cancer within an enhanced recovery programme.
Evidence demonstrating improved short-term outcomes with laparoscopic surgery compared with open surgery for colorectal cancer is accumulating. In addition, programmes optimising peri-operative care for major abdominal surgery are becoming widespread. Evaluating laparoscopic surgery and enhanced recovery programmes usually focuses on short-term recovery. The aim of this study was to compare recovery after laparoscopic and open surgery for colorectal cancer up to 1 year post-operatively, using a combination of self-report and observer data. From January 2002 to March 2004, 62 patients were randomised (2:1) to receive laparoscopic (n=43) or open surgery (n=19) within an enhanced recovery programme. Functional outcomes up to 1 year were assessed using interview-administered questionnaires. Questionnaire and health-related quality of life data were obtained in over 85% of patients. Patients undergoing laparoscopic surgery felt fully recovered and resumed driving more quickly than those having open surgery (p=0.016 and p=0.048 respectively). Fifty-eight percent of patients having open surgery felt fully recovered by 12 months versus 88% of laparoscopic patients. Within an enhanced recovery programme, patients undergoing laparoscopic surgery recovered more quickly than after open resection. Both approaches however, were associated with slow recovery despite a relatively short hospital stay.


Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig model.
Lacking a blood supply and having a low cellular density, articular cartilage has a minimal ability for self-repair. Therefore, wide-ranging cartilage damage rarely resolves spontaneously. Cartilage damage is typically treated by chondrocyte transplantation, mosaicplasty or microfracture. Recent advances in tissue engineering have prompted research on techniques to repair articular cartilage damage using a variety of transplanted cells. We studied the repair and regeneration of cartilage damage using layered chondrocyte sheets prepared on a temperature-responsive culture dish. We previously reported achieving robust tissue repair when covering only the surface layer with layered chondrocyte sheets when researching partial-thickness defects in the articular cartilage of domestic rabbits. The present study was an experiment on the repair and regeneration of articular cartilage in a minipig model of full-thickness defects. Good safranin-O staining and integration with surrounding tissues was achieved in animals transplanted with layered chondrocyte sheets. However, tissue having poor safranin-O staining-not noted in the domestic rabbit experiments-was identified in some of the animals, and the subchondral bone was poorly repaired in these. Thus, although layered chondrocyte sheets facilitate articular cartilage repair, further investigations into appropriate animal models and culture and transplant conditions are required.


Development of a database of functional assessment measures related to work disability.
The development of the Functional Assessment Measures Database is described. The database provides a method to organize and search for measures that are used to assess the functional abilities of people with medical impairments to determine work disability. The project identified 4,200 different measures that are used in the functional assessment of persons with disability across the life span, 812 of which are used to evaluate adults in terms of work disability. The database has 3,033 scales that are found in 633 measures. In the database, each measure is described and is linked to at least one functional assessment construct. The use of the database in the Social Security Administration Redesign Project is described. Other possible uses for the database are presented.


Nudging to improve hand hygiene.
Hand hygiene is paramount to prevent healthcare-associated infections, but improving compliance is challenging. When healthcare workers seldom encounter healthcare-associated infections, they will consider the odds of causing infections through poor hand hygiene negligible. Cognitive biases such as these may induce non-compliance. Nudging, 'a friendly push to encourage desired behaviour', could provide an easily implemented, inexpensive measure to address cognitive biases and thus support hand hygiene interventions. To investigate whether behavioural nudges, displayed as posters, can increase the use of alcohol-based hand rub. We developed nudges based on a systematic review of previously described cognitive biases, and tested these through a cross-sectional survey among the target audience. We then conducted a controlled before-after trial on two hospital wards, to assess the effect of these nudges on the use of alcohol-based hand rub, measured with electronic dispensers. Poisson regression analyses adjusted for workload showed that nudges displayed next to dispensers increased their overall use on one ward [poster 1: relative risk: 1.6 (95% confidence interval: 1.2-2.2); poster 2: 1.7 (1.2-2.5)] and during doctor's rounds on both wards [poster 1: ward A: 1.7 (1.1-2.6); ward B: 2.2 (1.3-3.8)]. Use of dispensers without adjacent nudges did not increase. Nudges based on cognitive biases that play a role in hand hygiene, and displayed as posters, could provide an easy, inexpensive measure to increase use of alcohol-based hand rub. When applying nudges to change behaviour, it is important to identify the right nudge for the right audience.


The San Francisco Syncope Rule vs physician judgment and decision making.
To compare a clinical decision rule (San Francisco Syncope Rule [SFSR]) and physician decision making when predicting serious outcomes in patients with syncope. In a prospective cohort study, physicians evaluated patients presenting with syncope and predicted the chance (0%-100%) of the patient developing a predefined serious outcome. They were then observed to determine their decision to admit the patient. All patients were followed up to determine whether they had a serious outcome within 7 days of their emergency department visit. Analyses included sensitivity and specificity to predict serious outcomes for low-risk patients and comparison of areas under the receiver operating characteristic curve for the decision rule, physician judgment, and admission decisions. During the study period, there were 684 visits for syncope with 79 visits resulting in serious outcomes. The area under the receiver operating characteristic curve was 0.92 (95% confidence interval [CI], 0.88-0.95) for the SFSR compared with physician judgment 0.89 (95% CI, 0.85-0.93) and physician decision making 0.83 (95% CI, 0.81-0.87). Physicians admitted 28% of patients in a low-risk group, with a median length of stay of 1 day (interquartile range, 1-2.5 days). The SFSR had the potential to absolutely decrease admissions by 10% in this low-risk group and still predict all serious outcomes. Physician judgment is good when predicting which patients with syncope will develop serious outcomes, but contrary to their judgment, physicians still admit a large number of low-risk patients. The SFSR performs better than current physician performance and has great potential to aid physician decision making.


Pyrimidine nucleosides enhance the efficacy of inhibitors of pyrimidine biosynthesis in cultured hepatocellular carcinoma cells.
Inhibition of colony formation in cultured hepatocellular carcinoma cells of the rat was used to test the efficacy of inhibitors of de novo pyrimidine biosynthesis as potential anticancer drugs. N-(phosphonacetyl)-L-aspartic acid (PALA) (10 and 100 micrograms/ml) and 5-aza-5,6-dihydroorotic acid (DHOX) (100 micrograms/ml) inhibited the formation of colonies and these inhibitions were completely reversed by inclusion of 0.1 mM uridine, the end product of de novo pyrimidine biosynthesis, in the culture medium. With some lots of fetal bovine serum where PALA and DHOX had little effect on inhibiting colony formation, addition of 0.1 mM cytidine restored the inhibitory characteristics of PALA and, to some extent, DHOX. The results demonstrate that cytidine levels modulate the inhibitions of hepatoma colony formation by both PALA and DHOX and that co-administration of these drugs together with cytidine provides a simple expedient to increase drug efficacy.


Plasma vasopressin levels during cardiopulmonary bypass with and without profound haemodilution.
In cardiopulmonary bypass the effect on plasma vasopressin levels of the addition of whole blood to the pump priming solution was measured. Six patients (Group I) had blood added to the lactated Ringer's solution for the prime, and six patients (Group II) had only lactated Ringer's solution. Neither group had significant changes in plasma vasopressin levels until surgical stimulation occurred. Comparable significant elevations occurred during bypass in both groups. Greater decreases in haematocrit and urinary K+ and greater increases in urinary Na+ occurred in Group II. The degree of haemodilution does not appear to effect plasma vasopressin levels but may alter the degree of electrolyte shift.


Re-amputation occurrence in the diabetic population in South Wales, UK.
The incidence of re-amputation following lower extremity amputations (LEA) among the diabetic patients referred to the Artificial Limb and Appliance Centers (ALAC) in South Wales, UK, was investigated. Manual and electronic data-gathering systems were used to extract the medical records of 473 people with various causes of LEA referred to the ALAC in South Wales during 2001-2003. The data included demographic information, causes of amputation and occurrence of various levels of re-amputation. Two hundred and five subjects with diabetes underwent 316 amputations, 44 were foot amputations and 272 major amputations on the ipsilateral and contra-lateral sides. Of the diabetic patients, 45.9% with single LEA underwent re-amputations with 22% incidence of contra-lateral LEA within 2 years. In comparison, 15% underwent re-amputations in the non diabetic dysvascular patients. Ipsilateral re-amputations occurred much earlier (average 21 weeks) compared with the contra-lateral amputations which took an average of 82 weeks following the first amputation. Nearly half of the diabetic patients with single LEA referred for rehabilitation underwent re-amputations within 2 years; out of which 22% of the patients underwent contra-lateral LEA. Although the progression of level of amputations does not follow a particular pattern, re-amputation on the contra-lateral side occurred almost four times later than that on the ipsilateral side.


Alternative Proteins for Fish Diets: Implications beyond Growth.
Aquaculture has been challenged to find alternative ingredients to develop innovative feed formulations that foster a sustainable future growth. Given the most recent trends in fish feed formulation on the use of alternative protein sources to decrease the dependency of fishmeal, it is fundamental to evaluate the implications of this new paradigm for fish health and welfare. This work intends to comprehensively review the impacts of alternative and novel dietary protein sources on fish gut microbiota and health, stress and immune responses, disease resistance, and antioxidant capacity. The research results indicate that alternative protein sources, such as terrestrial plant proteins, rendered animal by-products, insect meals, micro- and macroalgae, and single cell proteins (e.g., yeasts), may negatively impact gut microbiota and health, thus affecting immune and stress responses. Nevertheless, some of the novel protein sources, such as insects and algae meals, have functional properties and may exert an immunostimulatory activity. Further research on the effects of novel protein sources, beyond growth, is clearly needed. The information gathered here is of utmost importance, in order to develop innovative diets that guarantee the production of healthy fish with high quality standards and optimised welfare conditions, thus contributing to a sustainable growth of the aquaculture industry.


Local intense mosaic pattern at site of flail mitral leaflet: report of a new color Doppler sign.
Color flow Doppler has been useful in diagnosing the presence and severity of mitral regurgitation (MR). We noted a hitherto unreported sign of MR due to flail mitral leaflet: intense local mosaic pattern at the site of the flail leaflet. This sign was seen well in 11 of 14 patients (79%) with the two-dimensional echocardiographic features of flail mitral leaflet, all with moderate or severe MR. In 3 other patients, the sign was absent; two of those had flail mitral leaflet with severe MR. No local mosaic pattern was seen on color Doppler in 20 other patients with MR but no flail mitral leaflet. We speculate that the focal intense mosaic color Doppler morphology may have been caused by intrusion of the flail leaflet into the MR stream, or to a Coanda-like effect of the MR jet "adhering" to the flail leaflet.


Catecholamine metabolism in rat brain following the intracerebroventricular administration of cyclic nucleotides.
The dibutyryl analogues of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were administered into the lateral ventricles and catecholamine metabolites were determined in brain 40 min later. Dibutyryl cAMP elevated the level of homovanillic acid in whole brain and dihydroxyphenyl acetic acid levels in striatum, the dopamine-rich part of the limbic system and hemispheres but neither affected the accumulation of 3-methoxytyramine following inhibition of MAO with pargyline nor dopamine and noradrenaline levels. Normetanephrine accumulating after MAO inhibition was elevated markedly by dibutyryl cAMP. Dibutyryl cGMP was without effect on the catecholamine metabolites investigated. Dibutyryl cAMP appears to stimulate dopamine metabolism within dopaminergic nerve endings but does not stimulate dopamine release. Dibutyryl cAMP-induced activation of noradrenaline metabolism, however, appears to coincide with a stimulation of noradrenaline release.


Establishment of a chronic activity-based anorexia rat model.
Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this psychiatric illness. We systematically manipulated the extent and length of starvation and animal age to find the optimal parameters to study chronic starvation. Wistar rats had 24h/day running wheel access and received 40% of their baseline food intake until a 20% or 25% weight reduction was reached (acute starvation). This body weight was then maintained for two weeks (chronic starvation). The rats of different ages of 4 or 8 weeks were used to represent early and late adolescent animals, respectively. The complete absence of a menstrual cycle was defined as the primary outcome parameter. Acute starvation caused a disruption of the oestrous cycle in 58% of the animals. During chronic starvation, a complete loss of the oestrous cycle could be found. Furthermore, 4-week-old rats exhibited higher levels of hyperactivity and amenorrhoea than 8-week-old animals. A 20% starvation level led to 90% loss of cycle, while a 25% starvation level triggered complete loss. Most current ABA models focus on acute starvation, while most patients are chronically ill. The optimal parameters to achieve complete amenorrhoea included early adolescence, chronic starvation and 25% weight loss. The new ABA model allows studying the effects of chronic AN on underlying behavioural, hormonal and brain pathobiology.


Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation.
A fundamental question in developmental biology is how morphogens, such as bone morphogenetic protein (BMP), form precise signaling gradients to impart positional and functional identity to the cells of the early embryo. We combine rigorous mutant analyses with quantitative immunofluorescence to determine that the proteases Bmp1a and Tolloid spatially restrict the BMP antagonist Chordin in dorsoventral (DV) axial patterning of the early zebrafish gastrula. We show that maternally deposited Bmp1a plays an unexpected and non-redundant role in establishing the BMP signaling gradient, while the Bmp1a/Tolloid antagonist Sizzled is surprisingly dispensable. Combining computational modeling and in vivo analyses with an immobile Chordin construct, we demonstrate that long-range Chordin diffusion is not necessary for BMP gradient formation and DV patterning. Our data do not support a counter-gradient of Chordin and instead favor a Chordin sink, established by Bmp1a and Tolloid, as the primary mechanism that drives BMP gradient formation.


Eosinophilic Inflammation and Equine Herpesvirus-1 Associated With Haemorrhagic Cystitis in a Horse. Case Report.
Equine idiopathic haemorrhagic cystitis (EIHC) is a recently described form of aseptic cystitis in horses in which there is no discernible underlying cause. This case report describes a 9-year-old Thoroughbred gelding that presented with stranguria, pollakiuria, and haematuria. Cystoscopy revealed ulceration and haemorrhage of the bladder mucosa, diffuse mural hyperaemia and marked urine sedimentation. Histopathological evaluation of the bladder revealed chronic active ulcerative neutrophilic, lymphoplasmacytic, and eosinophilic cystitis. There was no bacterial or fungal growth upon culture but polymerase chain reaction (PCR) testing and sequencing for equine herpesvirus-1 (EHV-1) on bladder mucosa was positive. Conservative therapy with broad spectrum antimicrobials and non-steroidal anti-inflammatory therapy yielded complete resolution of clinical signs with significant improvement of macroscopic lesions in 14 days. Although a positive EHV-1 PCR suggests a viral cause, the horse's clinical signs, histology and recovery rate are more consistent with equine idiopathic haemorrhagic cystitis (EIHC). Neutrophilic and lymphoplasmacytic inflammation is a known feature of EIHC but eosinophilic infiltrates have not been previously described. The significance of the eosinophilic involvement is not certain; however, their presence has been associated with fungal, viral, parasitic, and immune-mediated aetiologies in other body systems. This is the first report of a horse with possible EIHC in Australia, as well as the first case with eosinophilic infiltrates and testing positive for EHV-1.


Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis.
Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome) at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter), endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. Considering the significantly lower number of vials/patient and the slight (although non-significant) increase in the delivery rate with r-FSH, the cost-minimization analysis showed a 9.4% reduction in the overall therapy cost per born baby in favor of r-FSH.


Case report: metastatic germ cell tumor presenting with thromboembolism and bilateral pneumothorax.
Germ cell tumors usually present with symptoms that are attributed to their location. This article describes a patient who had an extragonadal tumor that was not discovered until he experienced several tumor-related complications.


Lipolytic activities against trioctanoin and monoolein in rat intestinal mucosa.
The hydrolysis of trioctanoin and of monoolein by rat intestinal homogenates, catalyzed by the previously described "trioctanoin hydrolase" and "monoglyceride lipase" [Ref. 6 and 11], was shown to be entirely due to the action of the intestinal glycerol-ester hydrolase [Ref. 1 and 2] and to contaminating pancreatic lipase firmly bound to the intestinal cells. These conclusions are supported by experiments based on the chromatographic behaviour of the different lipolytic activities, the use of an immunoserum directed against rat pancreatic juice and the relief of bile salt inhibitions by pancreatic colipase. The results are in favour of the existence of a single lipolytic enzyme in the rat intestinal mucosa, i.e. glycerol-ester hydrolase, active against short- and medium chain mono-, di- and triglycerides and against long chain monoglycerides.


Giant sperm cells with accessory macrotubules in a neuropteran insect.
The flagellar axoneme of the atypical spermatozoa (paraspermatozoa) of Mantispa perla (Neuroptera, Planipennia) contains accessory microtubules or rather macrotubules that are 55 nm in diameter and that has a wall consisting of about 40 protofilaments. The sperm tail further contains two giant mitochondrial derivatives, which during spermiogenesis store an electron dense material. The mature spermatozoon has a flattened acrosome and a elliptical nucleus. These giant spermatozoa may furnish nutrients to the functional spermatozoa (euspermatozoa) when they reach the female genital tracts or/and they function in sperm competition filling the spermatheca.


Arachidonic acid supplementation attenuates adipocyte inflammation but not adiposity in high fat diet induced obese mice.
Obesity is associated with low-grade chronic inflammation and has a remarkable role in the pathophysiology of metabolic complications. In triggering these inflammatory responses, the arachidonic acid (AA) cascade plays a key role. However, there is a lack of data on how supplementary AA would affect obesity, adipose tissue inflammation, and the AA cascade in obesity. This study aims to investigate how AA supplementation affects obesity, adipocyte morphology, inflammation, and AA cascade signaling. Male Swiss Albino mice were used in our experiment. The mice were fed high-fat diets to induce obesity, and these obese mice were treated with two different doses of AA for 3 weeks. A normal diet non-obese group and an untreated obese group were kept as controls. Bodyweight and daily food intake data were recorded during that period. After the treatment period, blood serum and white adipose tissue of the experimental mice were collected for colorimetric lipid profile tests, histology, and mRNA extraction. The ΔΔCT method was employed for calculating the relative mRNA expression of target genes. The findings of our study suggest that AA has no significant effects on body weight, visceral adiposity, adipose tissue morphology, and serum lipid profile. However, AA treatment has resulted in a significant down-regulation of pro-inflammatory markers as well as the COX pathway. Besides, up-regulation of 12/15-LOX has been observed, indicating the metabolism pathway of supplementary AA through the LOX pathway. Our findings indicate that AA treatment may not provide significant benefits in terms of body weight, visceral fat mass, or serum lipid profile. However, it has effectively alleviated obesity-induced adipocyte inflammation in high-fat diet-induced obese mice.


Comparison of Sense of Humor and Burnout in Surgeons and Internal Medicine Physicians.
We aimed to evaluate humor styles in surgeons and internists and investigate the association between humor and burnout. A cross-sectional survey of physicians in surgical and medicine departments was conducted, assessing sense of humor and burnout using the Humor Styles Questionnaire and the Emotional Exhaustion subscale of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel. For 131 surgeons and 72 internists, no differences in humor styles were found. A sense of personal accomplishment was more common among surgeons (P = 0.03) and rates of burnout were lower for surgeons (P = 0.02). Physicians with a higher-than-average score in affiliative and self-enhancing humor were less likely to suffer from burnout (P < 0.0001 and P = 0.03, respectively). Surgeons and internists have similar styles of humor. Surgeons suffer less from burnout. Affiliative and self-enhancing humor styles are associated with reduced burnout.


Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis.
In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. Patients demonstrated increased AVP levels compared to controls (p = 0.01). Higher AVP levels were associated with greater positive symptoms (r = 0.58, p = 0.03) and worse verbal learning (r = -0.63, p = 0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia.


Effect of the diglyceride lipase inhibitor, RG80267, on epithelial chloride secretion induced by various agents.
We previously reported that a diglyceride lipase inhibitor, RG80267, inhibits chloride secretion stimulated by adenosine agonists, stimuli whose effects appear unrelated to cAMP, cGMP or cytosolic calcium. Here, the effect of RG80267 on Cl- secretory responses to agents which do utilize these messengers was examined. RG80267 inhibited responses to vasoactive intestinal polypeptide, forskolin (cAMP-dependent) and E. coli heat stable enterotoxin (cGMP-dependent), but not to prostaglandin E1 or cholera toxin (cAMP-dependent). RG80267 enhanced responses to histamine (calcium-dependent). The inhibitory effect of RG80267 was not due to inhibition of cAMP accumulation. Arachidonic acid release may participate in chloride secretion. Vasoactive intestinal polypeptide, but not prostaglandin E1, released radiolabel from cells preloaded with [3H]arachidonic acid. There may thus be differences between mechanisms of various cyclic nucleotide-dependent chloride secretory responses. Arachidonic acid release may modulate the extent of secretion elicited by some secretagogues.


New insights into the effects of alloying Pt with Ni on oxygen reduction reaction mechanisms in acid medium: a first-principles study.
The effects of alloying Pt with transition metal Ni on oxygen reduction reaction (ORR) mechanisms was investigated based on a systematic density functional theory (DFT) calculation explored in the present work. New insights into the ORR mechanisms were reported at the atomic level on Pt-segregated Pt3Ni(111). Only one molecular chemisorption state with the end-on OOH configuration was identified through geometry optimization and minimum energy path (MEP) analysis; top-bridge-top configuration as observed on pure Pt(111) was not identified on Pt-segregated Pt3Ni(111), indicating that alloying Pt with Ni influences the intermediates of ORR, and leads to only the dissociation mechanism of chemisorption state OOH species being involved in acid medium on Pt-segregated Pt3Ni(111). By contrast, the dissociation mechanisms of chemisorbed O2 molecule with top-bridge-top configuration and OOH species both were involved on pure Pt(111). The rds of the entire four-electron ORR was changed after Pt alloying with Ni. The rds of the entire ORR is the proton and electron transfer to O2 to form OOH on Pt-segregated Pt3Ni(111), whereas it is the reaction of O atom protonation to form OH species on pure Pt(111), indicating that sublayer Ni strongly influences the rds of ORR. The comparison of the ORR mechanisms explained that Pt3Ni alloy enhanced the ORR electrocatalytic activity more than pure Pt. The effect of electrode potential on ORR pathway on the pure Pt and Pt3Ni alloy was considered to obtain further insights into the electrochemical reduction of O2. Results showed that the proton and electron transfer becomes difficult at high potential. The ORR can easily proceed when the electrode potential lowers. For pure Pt- and Pt-based alloys, this phenomenon may imply the origin of the overpotential.


Complaint and disciplinary systems in dentistry in Sweden: a presentation and discussion of their efficacy in preventing malpractice.
The Swedish systems for complaints and supervision with many possibilities of claiming on different levels may lead to prevention of future problems in medical and dental care. The systems are corrective, preventive and compensatory, and are important in the process of quality assurance. However, some elements need improvement. The present paper gives as a background an overview of the Swedish systems and discusses a few cases. Comparisons with systems in other countries, especially the USA, are made, and new measures are discussed. There is a need for smooth, preventive measures as well as strong, punitive and corrective measures. Recidivist doctors/dentists must be stopped.


Clinical assessment of serum myosin light chains in the diagnosis of acute myocardial infarction.
Serum myosin light chain levels were quantitated with radioimmunoassay in patients admitted to the coronary care unit. In this study there were 29 patients with acute myocardial infarction, 84 with chest pain but without myocardial infarction and 5 with chest pain but with preexisting electrocardiographic abnormalities that could not be interpreted using standard criteria. Values for human cardiac light chains in normal human sera averaged less than 2 ng/ml, and values in the 84 patients without myocardial infarction fell into this category. The 29 patients with myocardial infarction all had elevated light chain concentrations (average 10.9 +/- 1.3 ng/ml; range 4 to 35 ng/ml). In this study there were no false positive or false negative results. Use of this assay has permitted separation of patients with and without myocardial infarction. The assay for cardiac light chains provides a biochemical marker of high sensitivity and specificity that is useful in the diagnosis of infarction.


[Critically ill pediatric hemato-oncology patient: What we do is what we should do?].
Primary objective, to describe the management and monitorization of critically ill pediatric hemato-oncology patient (CIPHO) in the Spanish pediatric intensive care units (PICU). Secondary objective, through a literature review, to identify possible areas of improvement. Observational transversal descriptive study. An anonymous web-based survey was sent to 324 Spanish pediatric intensivists from April 2011 to May 2011. None of them were pediatric residents. The survey was answered by 105 intensivists, 59/105 always agreed their treatment with the oncologist. In case of hemodynamic instability, non-invasive blood pressure monitoring is always done by 85/105 and almost always optimized by intra-arterial measuring (85/105) and central venous pressure (70/105). If respiratory failure the use of non-invasive ventilation (NIPPV) is always (36/105) or frequently (60/105) established prior to conventional mechanical ventilation. To replace or withdraw non-invasive ventilation only 44/96 of the respondents to this question use a clinical protocol. Before the instauration of conventional mechanical ventilation the oncological prognosis is considered by 72/105. In case of acute oliguric renal failure the renal replacement techniques are widely used (74/105). The withdrawal of sustaining life support is frequently discussed (75/103) and agreed with the oncologist (91/103) and caregivers (81/103). In our study, despite there is not a defined standard-of-care, the respondents showed similar therapeutics and monitorization choices. The use of NIPPV as first respiratory assistance is extended. Prospective, observational and multicenter studies should be developed to establish the results of this management in this population.


Paramyosin gene (unc-15) of Caenorhabditis elegans. Molecular cloning, nucleotide sequence and models for thick filament structure.
Paramyosin is a major structural component of thick filaments isolated from many invertebrate muscles. The Caenorhabditis elegans paramyosin gene (unc-15) was identified by screening with specific antibodies an "exon-expression" library containing lacZ/nematode gene fusions. Short probes recovered from the library were used to identify bacteriophage lambda and cosmid clones that encompass the entire paramyosin (unc-15) gene. From these clones, numerous subclones containing epitopes reacting with anti-paramyosin sera were obtained, providing strong evidence that the initial cloned fragment was, in fact, derived from the structural gene for paramyosin. The complete nucleotide sequence of a 12 x 10(3) base-pair region spanning the gene was obtained. The gene is composed of ten short exons encoding a protein of 866 [corrected] amino acid residues. Paramyosin is highly similar to residues 267 to 1089 of myosin heavy chain rods. For most of its length, paramyosin appears to form an alpha-helical coiled-coil and shows the expected heptad repeat of hydrophobic amino acid residues and the 28-residue repeat of charged amino acids characteristic of myosin heavy chain rods. However, paramyosin differs from myosin in having non-helical extensions at both the N and C termini and an additional "skip" residue that interrupts the 28-residue repeat. The distribution of charges along the length of the paramyosin rod is also significantly different from that of myosin heavy chain rods. Potential charge-mediated interactions between paramyosin rods and between paramyosin and myosin rods were calculated using a model successfully applied previously to the analysis of the myosin rod sequences. Myosin rods aligned in parallel show optimal charge-charge interactions at multiples of 98 residue staggers (i.e. at axial displacements of multiples of 143 A). Paramyosin rods, in contrast, appear to interact optimally at parallel staggers of 493 residues (i.e. at axial displacements of 720 A) but show only weak interaction peaks at 98 or 296 residues. Similar calculations suggest optimal interactions between paramyosin molecules and myosin rods and in their anti-parallel alignments. The implications of these results for the structure of the bare zone and the assembly of nematode thick filaments are discussed.


Point of care ultrasound for rapid assessment and treatment of palliative care patients in acute medical settings.
The combination of an ageing population with improving survival in malignant and non-malignant disease processes results in a growing cohort of patients with advanced or end-stage chronic diseases who require acute medical care. Emergency care has historically been stereotyped as the identification and treatment of acute life-threatening problems. Although palliative care may be considered to be new to the formal curriculum of emergency medicine, in many domains the ultrasound skillset of a physician in acute medical care can be efficaciously deployed the benefit of patients with both malignant and non-malignant disease processes that require palliative care in the full breadth of acute healthcare settings. In diagnostic domains (abdominal pain, urinary tract obstruction, dyspnoea, venous thromboembolism and musculoskeletal pain) and for specific intervention guidance (thoracentesis, paracentesis, venous access, regional anaesthesia and musculoskeletal interventions) we suggest that POCUS has the potential to streamline improve patient satisfaction, streamline diagnostic strategies, optimise patient length of stay, expedite timely symptomatic relief and reduce complications in this important patient population. POCUS is a mandatory competence in the European curriculum of internal medicine, and specific training programs which cover applications in the domains of palliative care in acute care settings are available. Supervision, quality assurance and appropriate documentation are required. We expect that as the availability of mobile units suitable for point of care applications increases, these applications should become standard of care in the acute management of patients who require palliative care.


Relationship Between Interpregnancy Interval and Adverse Perinatal and Neonatal Outcomes in Northern Alberta.
Birth outcomes are known to be associated with birth spacing, but there are population differences. The purpose of this study was to examine the association between interpregnancy intervals and perinatal and neonatal outcomes in a Canadian population during the era of mandatory folate fortification of food. We conducted a study of 46 243 women who had two consecutive singleton births in northern Alberta between 1999 and 2007, using a linked provincial dataset. Perinatal outcomes of interest were preterm birth, low birth weight (LBW), small for gestational age, and perinatal death. Neonatal outcomes were low Apgar score, low arterial blood gas pH, need for neonatal resuscitation or admission to NICU, and neonatal death. Multivariable logistic regression was used to control for maternal demographic and obstetrical characteristics. The risk of preterm birth was increased for multiple interpregnancy intervals: for an interval of 0 to 5 months, the adjusted odds ratio (aOR) was 1.37 (95% CI 1.18 to 1.59), for 6 to 11 months the aOR was 1.18 (95% CI 1.04 to 1.34), for 24 to 35 months the aOR was 1.16 (95% CI 1.02 to 1.31), and for 36+ months the aOR was 1.36 (95% CI 1.20 to 1.53), compared with the reference interval of 12 to 17 months. The risk of LBW was increased with interpregnancy intervals of 0 to 5 months (aOR 1.48; 95% CI 1.23 to 1.80), 6 to 11 months (aOR 1.21; 95% CI 1.03 to 1.42), 24 to 35 months (aOR 1.21; 95% CI 1.03 to 1.41) and 36+ months (aOR 1.48; 95% CI 1.27 to 1.73). The risk of SGA was increased with intervals 0 to 5 months (aOR 1.29; 95% CI 1.09 to 1.52), 24 to 35 months (aOR 1.15; 95% CI 1.01 to 1.31), and 36+ months (aOR 1.26; 95% CI 1.11 to 1.44). The risk of perinatal death was increased with an interval of 36+ months (aOR 1.60; 95% CI 1.06 to 2.43). Similar associations were also observed for neonatal outcomes. This study suggests that both short and long interpregnancy intervals are associated with adverse perinatal and neonatal outcomes, and it provides risk estimates for a Canadian population in the era of folate fortification of food.


Further evidence for the role of inferential reasoning in forward blocking.
Previous studies on human causal learning (De Houwer & Beckers, 2003; De Houwer, Beckers, & Glautier, 2002) showed that secondary task difficulty (performing an easy vs. a difficult secondary task during the main causal learning task) and ceiling information (outcome occurs with a maximal vs. submaximal intensity) had an influence on forward blocking (i.e., lower causal ratings for cue T when AT+ trials are preceded by A+ trials than when no A+ trials are presented). We extended these studies by also examining self-reports of participants about the reasons behind their causal ratings. Blocking was found only for participants who reported an appropriate blocking inference. Furthermore, secondary task difficulty and ceiling information influenced the number of participants who reported an appropriate blocking inference. These findings point to a major impact of inferential reasoning in human causal learning.


Antimicrobial resistance and plasmid profiles of Campylobacter jejuni and Campylobacter coli from human and animal sources.
The purpose of this study was to determine the susceptibility of Campylobacter jejuni and Campylobacter coli isolates to antimicrobial agents and to investigate the presence of plasmid DNA. A total of 15 clinical isolates from children faeces, and 29 animal isolates of Campylobacter jejuni (n=22) and Campylobacter coli (n=22) were tested for susceptibility to 9 antimicrobial agents using a disc diffusion method, and screened for the presence of plasmid DNA by agarose gel electrophoresis. Of the 44 isolates, 56.8% were resistant to sulphonamide, 25% to norfloxacin, 18.2% to erythromicin, ciprofloxacin and ampicillin, and 13.6% to tetracycline. All isolates were susceptible to gentamicin, chloramphenicol and cefotaxime. Plasmids were detected in one Camp. jejuni (4.54%) strain isolated from sheep and in six (27.27%) Camp. coli strains isolated from rhesus monkey(3), swine(2), and poultry(1) with sizes ranging from 3.4 to 50 kb. The majority of the human isolates were susceptible to antibiotics commonly used for the treatment of campylobacteriosis. The origin and spread of Campylobacter resistance to antibiotics are discussed, with particular respect to the current situation in Brazil.