Coerced first sexual intercourse and selected reproductive health outcomes among young women in KwaZulu-Natal, South Africa.
Coercion may play an important role in compelling young women to engage in sexual intercourse at an early age. With a decline in age at first intercourse and increased reporting of coercive first sex, concerns of adverse reproductive health outcomes such as unintended pregnancy and sexually transmitted infections (STIs), including HIV, have become important issues, particularly in the context of a high HIV prevalence. This paper uses data collected in 2001 from the second round of a longitudinal study of 1130 sexually experienced young women in KwaZulu-Natal to investigate the relationship between coerced first intercourse and selected reproductive health outcomes and behaviours. Nearly 46% of all sexually experienced young women had reported that their first sexual encounter had been coerced. Young women who reported being coerced at first sex were significantly more likely to be Black and living in an urban area. Those who had been coerced at first sex were also more likely to report having had an STI and having experienced unintended pregnancy, than those who had not been coerced at first sex. Coercion at first sex is an important social and public health problem that has a serious impact on the reproductive health and behaviours of young women. Interventions should directly address the issue of sexual coercion by ensuring young women are aware of their reproductive rights.


Anatomy of the anterolateral ligament of the knee.
In 1879, the French surgeon Segond described the existence of a 'pearly, resistant, fibrous band' at the anterolateral aspect of the human knee, attached to the eponymous Segond fracture. To date, the enigma surrounding this anatomical structure is reflected in confusing names such as '(mid-third) lateral capsular ligament', 'capsulo-osseous layer of the iliotibial band' or 'anterolateral ligament', and no clear anatomical description has yet been provided. In this study, the presence and characteristics of Segond's 'pearly band', hereafter termed anterolateral ligament (ALL), was investigated in 41 unpaired, human cadaveric knees. The femoral and tibial attachment of the ALL, its course and its relationship with nearby anatomical structures were studied both qualitatively and quantitatively. In all but one of 41 cadaveric knees (97%), the ALL was found as a well-defined ligamentous structure, clearly distinguishable from the anterolateral joint capsule. The origin of the ALL was situated at the prominence of the lateral femoral epicondyle, slightly anterior to the origin of the lateral collateral ligament, although connecting fibers between the two structures were observed. The ALL showed an oblique course to the anterolateral aspect of the proximal tibia, with firm attachments to the lateral meniscus, thus enveloping the inferior lateral geniculate artery and vein. Its insertion on the anterolateral tibia was grossly located midway between Gerdy's tubercle and the tip of the fibular head, definitely separate from the iliotibial band (ITB). The ALL was found to be a distinct ligamentous structure at the anterolateral aspect of the human knee with consistent origin and insertion site features. By providing a detailed anatomical characterization of the ALL, this study clarifies the long-standing enigma surrounding the existence of a ligamentous structure connecting the femur with the anterolateral tibia. Given its structure and anatomic location, the ALL is hypothesized to control internal tibial rotation and thus to affect the pivot shift phenomenon, although further studies are needed to investigate its biomechanical function.


Monitoring the electric field in CdSe quantum dots under ultrafast interfacial electron transfer via coherent phonon dynamics.
Coherent phonon dynamics in CdSe quantum dots (QD) under an ultrafast electron transfer (ET) reaction of the (1Se-1S3/2) exciton quenched by methyl viologen (MV2+) adsorbed onto the QD surface was studied by ultrafast pump-probe spectroscopy. Frequency and amplitude modulations (FM, AM) of the transient absorption ΔA(ωprobe,t) in the pure CdSe and coupled CdSe/MV2+ QDs were identified in the bleach band dynamics of the red-edge exciton. The fast Fourier transform (FFT) and continuous wavelet transform analysis of the FM and AM oscillations revealed peaks at 0.51-0.58 THz (17-19 cm-1) and 6.06-6.27 THz (202-209 cm-1) attributed to the longitudinal acoustic (LA) and longitudinal optical (LO) phonons, respectively. The electron transfer to MV2+ proceeded non-exponentially with effective time constants of 164 fs (∼30%) and 540 fs (∼70%). The quantum yield of MV˙+ radical formation was 40 ± 5%. It implies a fast route for the electron-hole pair [h+…MV˙+] recombination that can be rationalized in accordance with the adiabatic ET mechanism at the semiconductor surface. In the coupled CdSe/MV2+ QDs, the amplitude of the FM oscillations rose considerably with time despite the natural attenuation of the phonon amplitude due to decoherence processes. A kinetic model explaining the increase of FM oscillations is proposed. The surprising growth of FM oscillations is elucidated by the kinetic model taking into account the relatively slow damping of LO phonon oscillations (∼1.5 ps), the ultrafast ET to MV2+, and the quantum yield of charge separation [h+…MV˙+] (∼40%). The fast formation of the charge-separated pair [h+…MV˙+] suggests the appearance of an electric field F with a strength of ∼3 × 106 V cm-1. The MV2+ reduction substantially increased the magnitude of LA phonon oscillations. Since the ET time is shorter than the period of LA phonon oscillations (∼1.8 ps), the MV2+ reduction substantially increased the magnitude of LA phonon oscillations due to the inverse piezoelectric effect. The CdSe nanocrystals exposed to the electric field F exhibit the quantum-confined Stark and Franz-Keldysh electro-absorption effects. The proposed kinetic model gives consideration to the dynamic Stark shift of the red-edge exciton and to the increased amplitude of LO phonon oscillations in the bleach band dynamics.


Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.
We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P<.01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8).


[Developmental disorder in girls due to Rett syndrome].
Three girls with Rett syndrome are presented. Patients A and B had initially exhibited normal development, patient C showed severe developmental delay from birth on. In all three stereotypical hand movements arose which led to Rett syndrome being suspected. For patients A and B the clinical diagnosis was further supported by the identification of mutations in the MECP2-gene. In patient C, the mutation found turned out to be a neutral variant. Rett syndrome is a X-linked developmental disorder, which is particularly prevalent in girls. In 70-90% of clinically diagnosed RS patients a mutation is detected. MECP2-mutations result in a far wider range of phenotypes than classic RS. Mutations of this gene also occur in boys, with or without Rett-syndrome type phenotypes.


The use of six sigma in health care management: are we using it to its full potential?
Popular quality improvement tools such as Six Sigma (SS) claim to provide health care managers the opportunity to improve health care quality on the basis of sound methodology and data. However, it is unclear whether this quality improvement tool is being used correctly and improves health care quality. The authors conducted a comprehensive literature review to assess the correct use and implementation of SS and the empirical evidence demonstrating the relationship between SS and improved quality of care in health care organizations. The authors identified 310 articles on SS published in the last 15 years. However, only 55 were empirical peer-reviewed articles, 16 of which reported the correct use of SS. Only 7 of these articles included statistical analyses to test for significant changes in quality of care, and only 16 calculated defects per million opportunities or sigma level. This review demonstrates that there are significant gaps in the Six Sigma health care quality improvement literature and very weak evidence that Six Sigma is being used correctly to improve health care quality.


Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization and efficacy against Francisella tularensis infection in mice.
The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12 commercially available jet nebulizers was evaluated in this study. Aerosol particles containing liposome-encapsulated ciprofloxacin generated by the nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were determined, and the drug contents of the sampling filters from each run onto which aerosolized liposome-encapsulated ciprofloxacin had been deposited were analyzed spectrophotometrically. The aerosol particles of liposome-encapsulated ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 microm, with GSDs ranging from 1.51 to 1.84 microm. The drug contents of the sampling filters exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from 12.7 to 40.5 microg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected on the basis of most desirable MMADs, particle counts, and drug deposition, aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of mice infected with 10 times the 50% lethal dose of Francisella tularensis. All mice treated with aerosolized liposome-encapsulated ciprofloxacin survived the infection, while all ciprofloxacin-treated or untreated control mice succumbed to the infection (P < 0.001). These results suggest that aerosol delivery of liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible and that it may provide an effective therapy for the treatment of respiratory tract infections.


Development and analytical validation of a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity in serum.
Pancreatitis is recognized as an important cause for morbidity and mortality in cats, but diagnosis remains difficult in many cases. As a first step in trying to identify a better diagnostic tool for feline pancreatitis the objective of this project was to develop and analytically validate a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity (fPLI). Feline pancreatic lipase (fPL) was purified from pancreatic tissue and antiserum against fPL was raised in rabbits. Tracer was produced by iodination of fPL using the chloramine T method. A radioimmunoassay was established and analytically validated by determination of sensitivity, dilutional parallelism, spiking recovery, intra-assay variability, and interassay variability. A control range for fPLI in cat serum was established from 30 healthy cats using the central 95th percentile. The sensitivity of the assay was 1.2 microg/L. Observed to expected ratios for serial dilutions ranged from 98.8% to 164.3% for 3 different serum samples. Observed to expected ratios for spiking recovery ranged from 76.9% to 147.6% for 3 different serum samples. Coefficients of variation for intra- and interassay variability for 4 different serum samples were 10.1%, 4.5%, 2.2%, and 3.9% and 24.4%, 15.8%, 16.6%, and 21.3%, respectively. A reference range for fPLI was established as 1.2 to 3.8 microg/L. We conclude that the assay described is sensitive, accurate, and precise with limited linearity in the lower and limited reproducibility in the lower and higher end of the working range. Further studies to evaluate the clinical usefulness of this assay are needed and in progress.


A convenient 3-step synthesis of (R)-7-hydroxycarvone from (S)-alpha-pinene.
A convenient 3-step synthesis of (R)-7-hydroxycarvone (2) has been developed starting from (S)-alpha-pinene (7), using photooxygenation, oxidation, and fragmentation reactions. An improved synthesis of epoxy alcohol 6 and an unusual Ti(OiPr)(4) catalyzed hydroxy epoxide to keto alcohol rearrangement are also described.


Karydakis Flap With Compressing Tie-over Interrupted Sutures Without Drain versus Standard Karydakis for Treatment of Sacrococcygeal Pilonidal Sinus Disease.
Sacroccygeal pilonidal sinus disease is a worldwide health problem, affecting young adults, mainly males, with a tendency for recurrence. Various modalities have been used for treating this condition. The Karydakis procedure is one of most commonly used asymmetric flaps for treating this condition. The study aimed to evaluate the Karydakis procedure with tie-over compressing sutures instead of the routine use of a drain in the treatment pilonidal sinus. This prospective randomized controlled clinical study was conducted between January 2010 and January 2015. The study was conducted at Minia University Hospital. The study included 154 patients. Patients were randomly assigned into 2 equal groups. The patients in group 1 were operated on by the standard Karydakis procedure, and the patients in group 2 were operated on by the Karydakis procedure with tie-over compressing sutures without a drain. The primary outcomes measured were the incidence of seroma formation, wound complications, length of hospital stay, off-work time, and recurrence rate. All patients were discharged on the same day of surgery in group 2 compared with a mean hospital stay of 4.9 ± 2.4 days in group 1. No patients developed seroma in group 2 compared with 7.8% in group 1. In group 2, 1.3% of patients developed wound infection compared with 9.1% in group 1. The average time for return to work in group 2 was 10.2 ± 1.4 days compared with 12.6 ± 4 days in group 1. No recurrences were noted in group 2 compared with 2.6% in group 1. The feedback about postoperative pain and patient satisfaction about the scar were not investigated. The extent of the disease in both groups was not investigated. The duration of follow-up too short to accurately weight recurrence rate. Karydakis flap with tie-over compressing interrupted sutures without a drain is safe, 1-day surgery with the lowest complications rate.


p53 levels in human mammary epithelial cells expressing wild-type and mutant human papillomavirus type 16 (HPV-16) E6 proteins.
Human fibroblast cells must overcome both the M1 and the M2 stages of cellular senescence to immortalize, at which point cells almost always express telomerase activity. The human papillomavirus (HPV) oncoproteins, HPV-16 E6 and E7, can block the progression to senescence in fibroblasts by associations with p53 and pRb, respectively. Human mammary epithelial (HME) cells require only HPV-16 E6 to bypass M1, suggesting that pRb may not have a direct role in HME cells senescence. In the present report, we show that only wild-type HPV-16 E6 allows complete degradation of p53, immortalization and reactivation of telomerase activity in HME cells. These results suggest that the ability of HPV-16 wild-type and mutant E6 proteins to degrade p53 in intact HME cells and keratinocytes does not completely correlate with their ability to degrade p53 in a cell-free system. This discrepancy between in vitro and in vivo p53 degradation may be biologically significant and may provide insight into the susceptibility of certain human cells and tissues for reactivation of telomerase and immortalization.


Enhanced direct binary search algorithm for binary computer-generated Fresnel holograms.
The direct binary search (DBS) algorithm was originally invented for the synthesis of a binary Fourier hologram, and was applied for the generation of a binary Fresnel hologram recently. DBS performs quality evaluation on every pixel. Therefore, both the quality and diffraction efficiency of the generated binary hologram are better among various algorithms of the binary hologram. However, DBS is a time-consuming algorithm and thus is impractical for the generation of high-definition computer-generated holograms. In this paper, we proposed an enhanced DBS (E-DBS) method to speed up the hologram computation. E-DBS is based on the same pixelwise evaluation strategy of DBS, but the diffraction field of a single pixel is precomputed as a lookup table. In evaluating any pixel value, only a small area in the region of interest affected by the diffraction field of single pixel is calculated. In addition, it is also found that qualified results can be obtained by using only 4% of the area of the diffraction field. As a result, the computing complexity of E-DBS can be reduced by at least 2 orders of magnitude in contrast to conventional DBS.


The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos).
Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.


Comparative analysis of the primary transcriptome of Synechocystis sp. PCC 6803.
RNA-seq and especially differential RNA-seq-type transcriptomic analyses (dRNA-seq) are powerful analytical tools, as they not only provide insights into gene expression changes but also provide detailed information about all promoters active at a given moment, effectively giving a deep insight into the transcriptional landscape. Synechocystis sp. PCC 6803 (Synechocystis 6803) is a unicellular model cyanobacterium that is widely used in research fields from ecology, photophysiology to systems biology, modelling and biotechnology. Here, we analysed the response of the Synechocystis 6803 primary transcriptome to different, environmentally relevant stimuli. We established genome-wide maps of the transcriptional start sites active under 10 different conditions relevant for photosynthetic growth and identified 4,091 transcriptional units, which provide information about operons, 5' and 3' untranslated regions (UTRs). Based on a unique expression factor, we describe regulons and relevant promoter sequences at single-nucleotide resolution. Finally, we report several sRNAs with an intriguing expression pattern and therefore likely function, specific for carbon depletion (CsiR1), nitrogen depletion (NsiR4), phosphate depletion (PsiR1), iron stress (IsaR1) or photosynthesis (PsrR1). This dataset is accompanied by comprehensive information providing extensive visualization and data access to allow an easy-to-use approach for the design of experiments, the incorporation into modelling studies of the regulatory system and for comparative analyses.


The EcoRI restriction endonuclease with bacteriophage lambda DNA. Equilibrium binding studies.
The EcoRI restriction endonuclease was found by the filter binding technique to form stable complexes, in the absence of Mg2+, with the DNA from derivatives of bacteriophage lambda that either contain or lack EcoRI recognition sites. The amount of complex formed at different enzyme concentrations followed a hyperbolic equilibrium-binding curve with DNA molecules containing EcoRI recognition sites, but a sigmoidal equilibrium-binding curve was obtained with a DNA molecule lacking EcoRI recognition sites. The EcoRI enzyme displayed the same affinity for individual recognition sites on lambda DNA, even under conditions where it cleaves these sites at different rates. The binding of the enzyme to a DNA molecule lacking EcoRI sites was decreased by Mg2+. These observations indicate that (a) the EcoRI restriction enzyme binds preferentially to its recognition site on DNA, and that different reaction rates at different recognition sites are due to the rate of breakdown of this complex; (b) the enzyme also binds to other DNA sequences, but that two molecules of enzyme, in a different protein conformation, are involved in the formation of the complex at non-specific consequences; (c) the different affinities of the enzyme for the recognition site and for other sequences on DNA, coupled with the different protein conformations, account for the specificity of this enzyme for the cleavage of DNA at this recognition site; (d) the decrease in the affinity of the enzyme for DNA, caused by Mg2+, liberates binding energy from the DNA-protein complex that can be used in the catalytic reaction.


Effects of emotional intensity under perceptual load: An event-related potentials (ERPs) study.
Effects of emotional intensity and valence on visual event-related potentials (ERPs) are still poorly understood, in particular in the context of limited attentional resources. In the present EEG study, we investigated the effect of emotional intensity of different emotional facial expressions on P1, N170, early posterior negativity (EPN) and late positive potential (LPP) while varying the amount of available attentional resources. A new stimulus set comprising 90 full color pictures of neutral, happy (low, high intensity), and angry (low, high intensity) expressions was developed. These facial expressions were presented centrally, superimposed by two horizontal bars, and participants engaged in a focal bars task. Availability of attentional resources was varied in two conditions by manipulating the difficulty of the focal bars task (low vs. high perceptual load). Our findings demonstrate intensity and valence effects of task-irrelevant facial expressions on early (N170) and intermediate processing stages (EPN). In addition, task-related effects of perceptual load evolved at intermediate processing stages and were full blown in the time window of LPP. In line with limited resource accounts, valence effects on N170 and EPN were reduced under high perceptual load. Interestingly, apart from this valence by load interaction no further interactions between stimulus and task-driven factors were obtained: Effects of emotional intensity were not modulated by the perceptual load of the focal bars task, indicating that emotional intensity was processed even though attentional resources were heavily restricted.


Dog ownership, abundance and potential for bat-borne rabies spillover in Chile.
Rabies is a viral infectious disease that affects all mammals, including humans. Factors associated with the incidence of rabies include the presence and density of susceptible hosts and potential reservoirs. Currently, Chile is declared free of canine-related rabies, but there is an overpopulation of dogs within the country and an emergence of rabies in bats. Our objectives are to determine potential areas for bat-borne rabies spillover into dog populations expressed as a risk map, and to explore some key features of dog ownership, abundance, and management in Chile. For the risk map, our variables included a dog density surface (dog/km(2)) and a distribution model of bat-borne rabies presence. From literature review, we obtained dog data from 112 municipalities, which represent 33% of the total municipalities (339). At country level, based on previous studies the median human per dog ratio was 4.8, with 64% of houses containing at least one dog, and a median of 0.9 dog per house. We estimate a national median of 5.3 dog/km(2), and a median of 3680 dogs by municipality, from which we estimate a total population of 3.5×10(6) owned dogs. The antirabies vaccination presented a median of 21% of dogs by municipality, and 29% are unrestricted to some degree. Human per dog ratio have a significant (but weak) negative association with human density. Unrestricted dogs have a negative association with human density and income, and a positive association with the number of dogs per house. Considering dog density by municipality, and areas of potential bat-borne rabies occurrence, we found that 163 (∼48%) of Chilean municipalities are at risk of rabies spillover from bats to dogs. Risk areas are concentrated in urban settlements, including Santiago, Chile's capital. To validate the risk map, we included cases of rabies in dogs from the last 27 years; all fell within high-risk areas of our map, confirming the assertive risk prediction. Our results suggest that the use of dog population parameters may be informative to determine risk areas for bat-rabies spillover events. In addition, we confirm that dog abundance is a neglected and emerging public health concern in Chile, particularly within urban areas, which deserves prompt intervention.


Factors influencing anatomic and visual results in primary scleral buckling.
To identify the factors influencing anatomical and visual results in cases of rhegmatogenous retinal detachment undergoing primary scleral buckling. A retrospective study of 233 eyes of 226 patients was done. The data were evaluated by univariate analysis and stepwise logistic regression analysis. Retinal reattachment was achieved with primary scleral buckling in 197 eyes (84.5%). The extent of retinal detachment, preoperative proliferative vitreoretinopathy (PVR), preoperative visual acuity and relative afferent pupillary defects were identified as influencing anatomical results, by univariate analysis. The predictive roles of extent of retinal detachment (P<0.0001) and preoperative PVR (P=0.0085) were shown to be significant by step-wise logistic regression. As well as the above factors, the patient's age, the duration of symptoms and the status of the macula were predictors of visual results, by univariate analysis. Stepwise logistic regression analysis confirmed the predictive roles of preoperative visual acuity (P<0.0001) and the extent of retinal detachment (P=0.0089). Cases with a larger extent of retinal detachment, more advanced preoperative PVR and poorer preoperative visual acuity have less favorable anatomical and functional results.


Oral morphine for cancer pain.
This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain. To determine the efficacy of oral morphine in relieving cancer pain, and to assess the incidence and severity of adverse events. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9); MEDLINE (1966 to October 2015); and EMBASE (1974 to October 2015). We also searched ClinicalTrials.gov (1 October 2015). Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of oral morphine in adults and children with cancer pain. We excluded trials with fewer than 10 participants. One review author extracted data, which were checked by another review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNTs) for the analgesic effect. We extracted any available data on the number or proportion of participants with 'no worse than mild pain' or treatment success (very satisfied, or very good or excellent on patient global impression scales). We identified seven new studies in this update. We excluded six, and one study is ongoing so also not included in this update. This review contains a total of 62 included studies, with 4241 participants. Thirty-six studies used a cross-over design ranging from one to 15 days, with the greatest number (11) for seven days for each arm of the trial. Overall we judged the included studies to be at high risk of bias because the methods of randomisation and allocation concealment were poorly reported. The primary outcomes for this review were participant-reported pain and pain relief.Fifteen studies compared oral morphine modified release (Mm/r) preparations with morphine immediate release (MIR). Fourteen studies compared Mm/r in different strengths; six of these included 24-hour modified release products. Fifteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Three studies compared MIR with MIR by a different route of administration. Two studies compared Mm/r with Mm/r at different times and two compared MIR with MIR given at a different time. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine.In the previous update, a standard of 'no worse than mild pain' was set, equivalent to a score of 30/100 mm or less on a visual analogue pain intensity scale (VAS), or the equivalent in other pain scales. Eighteen studies achieved this level of pain relief on average, and no study reported that good levels of pain relief were not attained. Where results were reported for individual participants in 17 studies, 'no worse than mild pain' was achieved by 96% of participants (362/377), and an outcome equivalent to treatment success in 63% (400/638).Morphine is an effective analgesic for cancer pain. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration was undertaken with both instant release and modified release products. A small number of participants did not achieve adequate analgesia with morphine. Adverse events were common, predictable, and approximately 6% of participants discontinued treatment with morphine because of intolerable adverse events.The quality of the evidence is generally poor. Studies are old, often small, and were largely carried out for registration purposes and therefore were only designed to show equivalence between different formulations. The conclusions have not changed for this update. The effectiveness of oral morphine has stood the test of time, but the randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Only a few reported how many people had good pain relief, but where it was reported, over 90% had no worse than mild pain within a reasonably short time period. The review demonstrates the wide dose range of morphine used in studies, and that a small percentage of participants are unable to tolerate oral morphine. The review also shows the wide range of study designs, and inconsistency in cross-over designs. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in cross-over design studies. It was not clear if these trials were sufficiently powered to detect any clinical differences between formulations or comparator drugs. New studies added to the review for the previous update reinforced the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence that oral morphine has much the same efficacy as other available opioids.


The nature of suffering and the goals of medicine.
The question of suffering and its relation to organic illness has rarely been addressed in the medical literature. This article offers a description of the nature and causes of suffering in patients undergoing medical treatment. A distinction based on clinical observations is made between suffering and physical distress. Suffering is experienced by persons, not merely by bodies, and has its source in challenges that threaten the intactness of the person as a complex social and psychological entity. Suffering can include physical pain but is by no means limited to it. The relief of suffering and the cure of disease must be seen as twin obligations of a medical profession that is truly dedicated to the care of the sick. Physicians' failure to understand the nature of suffering can result in medical intervention that (though technically adequate) not only fails to relieve suffering but becomes a source of suffering itself.


Dabigatran Reversal with Idarucizumab in an Emergency Lumbar Puncture: A Case Report.
The widespread use of direct oral anticoagulants (DOACs) has been increasing the conditions in which emergency physicians are forced to rapidly reverse anticoagulation in case of life-threatening bleeding or need of urgent surgery or invasive procedures. The recent approval of Idarucizumab, a humanized monoclonal antibody fragment (Fab), offered the opportunity to rapidly and safely neutralize the anticoagulant effect of Dabigatran. However, real-world experience of its effective use in different emergency setting is now required. Lumbar Puncture (LP) is recognized as an invasive procedure at major bleeding risk and is, therefore, contraindicated in anticoagulated patients. We report a successful use of Idarucizumab in an emergency LP of a young woman with a possible diagnosis of encephalitis and a previous history of venous thromboembolism on long-term treatment with Dabigatran 150 mg twice a day.


Laminin matrix promotes hepatogenic terminal differentiation of human bone marrow mesenchymal stem cells.
The application of stem cells holds great promises in cell transplants. Considering the lack of optimal in vitro model for hepatogenic differentiation, this study was designed to examine the effects of laminin matrix on the improvement of in vitro differentiation of human bone marrow mesenchymal stem cells (hBM-MSC) into the more functional hepatocyte-like cells. Characterization of the hBM-MSCs was performed by immunophenotyping and their differentiation into the mesenchymal-derived lineage. Then, cells were seeded on the laminin-coated or tissue culture polystyrene (TCPS). The differentiation was carried out during two steps. Afterward, the expression of hepatocyte markers such as AFP, ALB, CK-18, and CK-19 as well as the expression of C-MET, the secretion of urea, and the activity of CYP3A4 enzyme were determined. Moreover, the cytoplasmic glycogen storage was examined by periodic acid-Schiff (PAS) staining. The results demonstrated that the culture of hBM-MSC on laminin considerably improved hepatogenic differentiation compared to TCP group. A significant elevated level of urea biosynthesis and CYP3A4 enzyme activity was observed in the media of the laminin-coated differentiated cells (P<0.05). Furthermore higher expressions of both AFP and ALB were determined in cells differentiated on laminin matrix. Glycogen accumulation was not detected in the undifferentiated hBM-MSCs, however, both differentiated cells in laminin and TCPS groups demonstrated the intracellular glycogen accumulation on day 21 of hepatogenic differentiation. Taken together, these findings may indicate that laminin matrix can improve terminal differentiation of hepatocyte-like cells from hBM-MSCs. Thus, laminin might be considered as a suitable coating in hepatic tissue engineering designs.


Evaluation of an investigative model in dairy herds with high calf perinatal mortality rates in Switzerland.
The objective of this study was to evaluate an investigative model which encompassed the risk factors, incidence, timing and causes of perinatal mortality (PM) (0-48 h) on high risk dairy farms (PM of >5% in the previous year) in Switzerland. This pilot-study was carried out on 47 predominantly Holstein PM calves from 21 dairy farms, between September 2016 and January 2018. Gross pathological examinations of calves and placentae as well as histopathological examinations of internal organs and placental tissue were performed. Further investigations included microbiological examinations: broad-spectrum bacterial and fungal culture, detection of Chlamydia abortus, Coxiella burnetii, pathogenic Leptospira spp. and Neospora caninum by real-time PCR (qPCR) and of bovine viral diarrhoea virus (BVDV) by Ag-ELISA. Maternal blood samples were used for serology of bovine herpesvirus 1 (BHV-1), Brucella abortus, Chlamydia abortus, Coxiella burnetii and nine pathogenic leptospiral serovars and the evaluation of trace element status. A questionnaire was completed with the farmer, which included general farm characteristics and case-related data. Inbreeding coefficients (IC) were calculated for pure-bred matings. At the farm-level, the PM rate was 10.0% (5.3-28.2%) and at the cow-level, 11.5%. These values, from high-risk farms, were approximately five-times higher than the contemporary national bovine PM rate (2.3%) in Switzerland. The risk factors associated with these high PM rates were the self-selection of high risk herds, the high proportion of primiparae in these herds (45%) and the evidence of widespread pathogenic infections on these farms (exposure: 67% of herds, 53% of dams; infection: 57% of herds, 45% of calves). The majority (68.1%) of calves died intrapartum. The most commonly diagnosed initiating/ultimate cause of death (UCOD) was infection (34%) of which Coxiella burnetii was the most frequently detected pathogen, by antigen. The most frequently diagnosed proximate cause of death (PCOD) was asphyxia (44.7%), though multiple PCOD was also common (21.3%). This study was the first detailed investigation of bovine PM in Switzerland. Infectious causes were diagnosed more frequently than expected. While the findings from these high PM Swiss herds may have limited external validity, the investigative model adopted and the detailed research methodologies employed can be replicated and re-evaluated, respectively, in future studies on PM internationally.


Long-term studies in prevention of food allergy: patterns of IgG anti-cow's milk antibody responses.
Over the past 7 years we have enrolled several hundred families in a study of the prophylaxis of atopic allergy. Initially, control and study patients were at different institutions, but more recently a true double-blind random assignment to control or study group has been instituted. Nevertheless, all of the infants from these highly atopic families can be utilized to obtain the data reported; that is, the rate of change of IgE levels, the appearance of food sensitization (food-specific IgE), the signs and symptoms of atopic allergy diseases and the changes in cow's milk-specific IgG antibody during the first 2 years of life. Some aspects of the first three of these parameters have been presented in the eight references to this paper, but only preliminary data on the use of IgG anti-cow's milk antibody as a measure of compliance has been available. In this paper an analysis is presented of the various patterns of IgG antibody levels in the first 60 infants of the over 200 who have been studied to date. Both the age of onset and the subsequent changes in the foregoing immunologic measurements provide fundamental data with which to measure the success rate of any prophylactic or therapeutic regimen and may improve our capacity to predict the future course of infants and children with a strong familial tendency to allergy.


The efficacy of interprofessional simulation in improving collaborative attitude between nursing students and residents in medicine. A study protocol for a randomised controlled trial.
Effective collaboration among health professionals is an essential component to ensure quality of care. Many adverse events experienced by patients are attributed to misunderstanding or poor communication among members of the interprofessional team. Interprofessional simulation is a learning strategy used to improve collaboration and facilitate communication between medical and nursing students. To determine the efficacy of educational program based on high-fidelity interprofessional simulation aimed at improving collaborative attitude. For this purpose, a protocol for a planned single-center, non-blinded and Randomized Controlled Trial (RCT) was chosen. The present has been approved by the Ethics Committee of Area Vasta Emilia Nord (Italy) (n° 479/2018). All students attending the second and third year of nursing and all resident physicians in anesthesia, reanimation, intensive care and pain management of University of Modena and Reggio Emilia, will be recruited and randomly assigned to two groups. The Experimental Group (EG) will receive an educational intervention based on high-fidelity simulation and the Control Group (CG) will attend a traditional classroom lesson. Jefferson Scale of Attitudes toward Physician-Nurse Collaboration (JSAPNC) and Readiness for Interprofessional Learning Scale (RIPLS) will be administered before and after the educational program in both the EG and CG. Expected outcomes is that, at the end of the study, nursing students and resident physicians who participated in the interprofessional simulation show significantly higher levels of interprofessional collaboration compared to the CG, evaluated through the JSAPNC.


Effects of hyperbaric therapy on liver morphofunctional of rabbits (Oryctolagus cuniculus) after hind limb ischemia-reperfusion injury.
The objective of this research was to study and to prove the effectiveness of hyperbaric oxygen therapy (HBOT) starting time on liver morphofunctional changes after ischemia-reperfusion in the hind limb of rabbits. This research used a complete randomized design with 4 groups and 6 repetitions on each. After 6 h artery femoral is ligation, reperfusion was performed for 100 min (G1), HBOT for 90 min after 10 min reperfusion (G2), 10 min reperfusion (G3), and HBOT 90 min after 60 min reperfusion (G4). Then, all of the rabbits were sacrificed. The liver and blood were taken for histopathological changes examination as well as for measuring the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The statistical test using Kruskal-Wallis and Mann-Whitney showed that the score of degeneration, necrosis, and portal inflammation in groups without HBOT (G1 and G3) were not significantly different, as well as in group with HBOT (G2 and G4) (p>0.05). However, the scores of histopathological changes in G1 and G3 were significantly different from those in G2 and G4 (p<0.05). The levels of AST and ALT in the groups without hyperbaric therapy (G1 and G3) were not significantly different from those in the groups treated with hyperbaric therapy (G2 and G4) (p>0.05). Hind limb ischemia injury reperfusion can trigger damage for liver morphology, but not lead to liver dysfunction. Reperfusion can trigger increased activity of neutrophils, while neutrophil infiltration in the organ will lead to dysfunction. HBOT can inhibit the activity of neutrophils and the dysfunction of organs caused by ischemic reperfusion. HBOT for 90 min, both 10 and 60 min after the reperfusion, can protect hepatocytes from damage.


Patients at Risk for Exceeding CJR Cost Targets After Total Ankle Arthroplasty.
The Comprehensive Care for Joint Replacement (CJR) model includes total ankle arthroplasty (TAA), under which a target reimbursement is established. Whether this reimbursement is sufficient to cover average cost remains unknown. We hypothesized that a substantial number of TAAs still exceed cost targets, and that risk factors associated with exceeding the target cost could be identified preoperatively. Two hundred two primary TAAs performed at a single tertiary referral center under the CJR model from June 2013 to May 2017 were retrospectively reviewed. Patient demographics, comorbidities, outcomes, and costs were extracted from the electronic medical record using a validated structured query language (SQL) algorithm. A comparison cohort of 2084 CJR total hip arthroplasty (THA) and total knee arthroplasty (TKA) cases performed during the same period was also reviewed. Twenty TAAs (10%) exceeded the target cost of care, significantly fewer than CJR THAs/TKAs (29%) performed during the same period (P < .0001). These patients did not differ significantly in age, sex, body mass index, number of Elixhauser comorbidities, or the American Society of Anesthesiologists score. The average cost for these patients was $17 338 higher than those who did not exceed the target cost, and they were less likely to be married or have a partner (45% vs 79%, P = .001). Non-Caucasian status also reached significance (P < .0001). Those exceeding the target cost had a significantly longer length of stay (2.6 vs 1.5 days, P < .0001) and were more likely to be discharged to either skilled nursing or a rehabilitation facility (60% vs 1%, P < .0001). Even high-volume TAA centers still exceed target costs in up to 10% of cases, with length of stay, discharge location, and readmissions driving many of these events. Potential risk factors for excess cost include marital/partner status and non-Caucasian ethnicity, but further work is needed to clarify their effects and whether other risk factors exist. Level III, comparative study.


Do quality improvement organizations improve the quality of hospital care for Medicare beneficiaries?
Quality improvement organizations (QIOs) are charged with improving the quality of medical care for Medicare beneficiaries. To explore whether the quality of hospital care for Medicare beneficiaries improves more in hospitals that voluntarily participate with Medicare's QIOs compared with nonparticipating hospitals. DESIGN, SETTING, AND DATA: Data from 4 QIOs charged with improving the quality of care in 5 states (Maryland, Nevada, New York, Utah, and Washington) and the District of Columbia were used. Hospitals participate with the QIOs on quality improvement on a voluntary basis. A retrospective study was conducted comparing improvement in the quality of care of patients in hospitals that actively participated with the QIOs vs hospitals that did not. The medical records of approximately 750 Medicare beneficiaries per state in each of 5 clinical areas (atrial fibrillation, acute myocardial infarction, heart failure, pneumonia, and stroke) were abstracted at baseline (1998) and follow-up (2000-2001). Fifteen quality indicators associated with improved outcomes in the prevention or treatment of the 5 clinical areas were used as quality of care measures. These 15 indicators were specifically targeted by the QIOs for quality improvement during the study period. Hospitals that voluntarily participate with the QIOs are more likely to be larger than nonparticipating hospitals (P<.05). At baseline, there were statistically significant (P<.05) differences between participating and nonparticipating hospitals on 5 of 15 quality indicators, with participating hospitals performing better on 3 of 5. There was no statistically significant difference in change from baseline to follow-up between participating and nonparticipating hospitals on 14 of 15 quality indicators. The one exception was that participating hospitals improved more on the pneumonia immunization indicator than nonparticipating hospitals (P = .005). Hospitals that participate with the QIO program are not more likely to show improvement on quality indicators than hospitals that do not participate.


[HIV-1 infection changes miRNA expression profile in the whole blood].
To describe the unique miRNA profiles for HIV seropositive individuals and identify significantly differently expressed miRNAs, we determined the expression level of 754 miRNAs of 10 HIV seropositive individuals and 10 HIV seronegative individuals by using the Taqman low density microRNA array. BRB-Array Tool was used to conduct the significance analysis, and the DIANA online tool was used to perform the miRNA target prediction and pathway analysis. A total of 56 significantly differentially expressed miRNAs were identified by microarray between HIV seropositive and seronegative individuals. Among them, 49 miRNAs were down-regulated and 7 were up-regulated, partially overlapped with reported data. Predicted target genes were mainly involved in MAPK, TGF-beta and Wnt pathways. The results shows that miRNA profile changes in HIV-1 seropositive individuals, and the 56 differentially expressed miRNAs may play important role during HIV infection. Further studies on these miRNAs may be helpful for identify key molecules involved in HIV infection and potential diagnostic markers.


The role of glucose in the survival and 'recovery' of the anoxic isolated perfused rat heart.
Studies with the isolated perfused working rat heart were carried out to investigate factors that may enable the heart to recover after periods of anoxia. It was found that the presence of glucose in the perfusion fluid during anoxia was essential for complete post-anoxic recovery and the presence of a high concentration of K(+) increased not only the rate of recovery but also the final extent of recovery. In an attempt to clarify the roles played by glucose and K(+) in aiding the survival and recovery of the anoxic myocardium the concentrations of parameters associated with energy liberation and anaerobic glycolysis (ATP, ADP, AMP, P(i), creatine phosphate, glycogen and lactate) were measured in the presence and absence of glucose during the anoxic phase. Determinations of these parameters were carried out during the working aerobic control period, the anoxic period (K(+) arrest) and the recovery period. The results demonstrated that glucose acted as an energy source during anoxia and thus maintained myocardial concentrations of high-energy phosphates, particularly ATP. These studies have also shown a direct relationship between the ability of the heart to recover and the concentration of myocardial ATP at the time of reoxygenation.


CA125 levels are a weak predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer.
The utility of preoperative CA125 to predict optimal primary tumor cytoreduction in patients with advanced (stages IIIC and IV) epithelial ovarian cancer is controversial. In this paper, we retrospectively review patients with stage IIIC and IV epithelial ovarian cancer who underwent primary cytoreductive surgery from 1989 to 2001. Ninety-nine patients were identified and included in the analysis. All patients had preoperative CA125 levels measured. Operative and pathology reports were reviewed. Optimal cytoreduction was defined as largest volume of residual disease < 1 cm in maximal dimension. Mean values were compared with t-test on a log scale when needed. The optimal cut-point for discriminating between those with vs. without optimal cytoreduction was determined using the receiver operator curve (ROC) method. Optimal cytoreduction was achieved in 73% of patients. Among patients with optimal cytoreductive status the mean CA125 level was 569, while among patients with suboptimal cytoreduction the mean CA125 level was 1520 (P < 0.007). A CA125 level of 912 was identified as the optimal cut-point to distinguish the two groups. Using this CA125 level, the sensitivity of this test in predicting optimal cytoreduction was 58% and the specificity was 54%. The positive predictive value of CA125 for optimal cytoreduction was 78% and the negative predictive value was 31%. We conclude that CA125 level is a weak positive and negative predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer. The CA125 level should not be used as a primary predictor of the outcome of cytoreductive surgery and should be viewed in the context of all other preoperative features.


Risky procedures by nurses in hospitals: problems and (contemplated) refusals of orders by physicians, and views of physicians and nurses: a questionnaire survey.
Occurrence of problems with, refusals of orders and contemplated refusals of orders for risky procedures by nurses in Dutch hospitals and views on the safety of performance was studied using postal questionnaires (600 physicians and 3200 nurses, response 60--71%). Of the respondents, 11--30% experienced problems with and (contemplated) refusals of orders for risky procedures in the previous 12 months. Gynaecologists and internists most frequently mentioned problems concerning the practical performance of the procedure (44% and 30%, respectively). The reason for a problem or a contemplated refusal most frequently given by nurses was that they disagreed with the medication policy (34% and 35%, respectively). The reason for a refusal most frequently given by the gynaecologists, internists, and nurses was that the nurses themselves were of the opinion that they did not have the necessary authorisation (95%, 67%, and 62%, respectively). With regard to certain procedures, the views of professionals are more strict than the current legal regulations.


Characterization of Multiple Regimes of Cardiorespiratory Phase Synchronization in Athletes Undergoing Inspiratory Muscle Training.
Cardiorespiratory phase synchronization (CRPS) is defined as the stable occurrence of n heartbeats within m respiratory cycles according to the n:m phase locking ratio (PLR). Since CRPS is an intermittent phenomenon where different phase synchronization regimes and epochs of phase unlocking can alternate within the same recording, an index of CRPS ideally should assess all potential PLRs present in the recording. However, traditional approaches compute the synchronization index (SYNC%) over a single n:m PLR, namely the one that maximizes CRPS. In the present work, we tested a synchronization index assessing the total percentage of heartbeats coupled to the inspiratory onset regardless of phase locking regimes (SYNC%sum) and we compared its efficacy to the more traditional SYNC%. Analysis was carried out in a cohort of 25 male amateur cyclists (age: 20-40 yrs) undergoing inspiratory muscle training (IMT) at different intensities. CRPS was assessed before and after the IMT protocol, during an experimental condition known to modify CRPS, namely active standing (STAND). We found that after a moderate intensity IMT at 60% of the maximal inspiratory pressure, SYNC%sum could detect the decrease in CRPS following STAND. This result was not visible using the more traditional SYNC%. Therefore, we stress the significant presence of different phase locking regimes in athletes and the importance of accounting for multiple PLRs in CRPS analysis.Clinical Relevance- Multiple phase locking regimes contribute significantly to cardiorespiratory control in amateur cyclists especially after inspiratory muscle training of moderate intensity.


Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss.
Sleep homoeostasis refers to a process in which the propensity to sleep increases as wakefulness progresses and decreases as sleep progresses. Sleep is tightly organized around the circadian clock and is regulated by genetic and epigenetic mechanisms. The homoeostatic response of sleep, which is classically triggered by sleep deprivation, is generally measured as a rebound effect of electrophysiological measures, for example delta sleep. However, more recently, gene expression changes following sleep loss have been investigated as biomarkers of sleep homoeostasis. The genetic background of an individual may affect this sleep-dependent gene expression phenotype. In this study, we investigated whether parental genetic background differentially modulates the expression of genes following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and DBA/2J mouse strains and we show a parent-of-origin effect on the expression of circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus, we further explored, by in silico, specific functions or upstream mechanisms of regulation and we observed that several upstream mechanisms involving signalling pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional regulators (EGR2 and ELK4) may be differentially modulated by parental effects. This is the first report showing that a behavioural manipulation (e.g. sleep deprivation) in adult animals triggers specific gene expression responses according to parent-of-origin genomic mechanisms. Our study suggests that the same mechanism may be extended to other behavioural domains and that the investigation of gene expression following experimental manipulations should take seriously into account parent-of-origin effects.


The Mel 14 antibody binds to the lectin domain of the murine peripheral lymph node homing receptor.
Murine and human leukocytes express surface glycoproteins, termed homing receptors (HRs), containing lectin-like, EGF-like (egf), and complement binding-like domains, that apparently endow these cells with the ability to home to peripheral lymph nodes (pln's) by virtue of an adhesive interaction with the pln postcapillary venule endothelium. The murine pln HR was initially characterized with a rat monoclonal antibody, Mel 14, that was specific for the murine form of the receptor. This work demonstrated that Mel 14 blocked the binding of murine lymphocytes to pln endothelium both in vitro and in vivo, a result consistent with the possibility that this monoclonal antibody recognizes a region of the HR that is involved with endothelium recognition and adhesion. In addition, this antibody also blocked the binding to the HR of PPME, a polyphosphomannan carbohydrate known to inhibit lymphocyte-pln endothelium interactions, suggesting that Mel 14 may recognize the lectin domain of the pln HR. Here we show that, while Mel 14 recognized truncated HR containing both the lectin and egf domains, antibody recognition was lost when the lectin domain alone was expressed. Chimeric molecules, in which regions of the lectin domain of the non-Mel 14-reactive human pln HR were replaced with homologous regions of the murine pln HR, demonstrated that the Mel 14 recognition site is within the NH2-terminal 53 amino acids of the lectin domain. These results suggest that the Mel 14 monoclonal antibody recognizes a determinant within the lectin domain of the pln HR whose conformation may be dependent upon the presence of the egf domain. Since Mel 14 efficiently blocks lymphocyte-endothelial interactions, these results support the hypothesis that the pln HR lectin domain may be directly involved with binding of lymphocytes to a carbohydrate ligand on the pln postcapillary venule endothelium.


[Patient handover involves numerous safety risks].
Modern patient care requires collaboration among health-care workers belonging to various functional units, departments and hospitals. When the responsibility for patients is handed over, information is easily lost. This literature review identifies problems in patient handover situations and proposes solutions to these. We reviewed 417 papers and the analysis comprises 29 papers. The paper points out numerous problems in connection with the transfer of responsibility, showing the importance of focusing on patient handover as a vulnerable phase in patient care.


Efficient computational algorithms for docking and for generating and matching a library of functional epitopes I. Rigid and flexible hinge-bending docking algorithms.
In this, and the next review article (1), we present highly efficient, computer-vision and robotics based algorithms for docking and for the generation and matching of epitopes on molecular surfaces. We start with descriptions of molecular surfaces, and proceed to utilize these in both rigid-body and flexible matching routines. These algorithms originate in the computer vision and robotics disciplines. Frequently used approaches, both in searches for molecular similarity and for docking, i.e., molecular complementarity, strive to obtain highly accurate correspondence of respective molecular surfaces. However, owing to molecular surface variability in solution, to mutational events, and to the need to use modeled structures in addition to high resolution ones, utilization of epitopes might prove to be a judicious approach to follow. Furthermore, through the deployment of libraries of epitopes which represent recurring features, or motifs in a given family of receptors or of enzymes, in principle we a priori focus on the more critical groups of atoms, or amino acids, essential for the binding of the two molecules. Utilization of recurring motifs may prove more robust than single molecule matchings. In addition, via utilization of epitopes one can make use of information derived from evolutionary related molecules. All of the above combine to represent an approach which may be highly advantageous. Combinatorial approaches have proven their immense utility in the wet laboratory. The combination of efficient computational approaches and the utilization of such libraries may well be particularly profitable. Our highly efficient techniques are amenable to such a task. In this review we focus on rigid and flexible docking algorithms. In the second review (1) we address the generation of epitopes in families of molecules. These may be used by the docking algorithms to identify the more likely bound interfaces.


Purified 60-kilodalton Legionella protein antigen with Legionella-specific and nonspecific epitopes.
In a previous study, all convalescent-phase sera from patients with culture-confirmed legionellosis reacted on immunoblots with a Legionella genus-wide 58-kilodalton (kDa) protein antigen (J.S. Sampson, B.B. Plikaytis, and H.W. Wilkinson, J. Clin. Microbiol. 23:92-99, 1986). The present study was done to immunologically characterize and determine the diagnostic relevance of this purified antigen. The antigen was precipitated from enriched cell extracts with ammonium sulfate and purified by high-pressure liquid chromatography. High-titered rabbit antiserum produced to the purified protein was used to show its presence on immunoblots in the 60-kDa range in 38 Legionella serogroups, representing 23 species, and in 39 non-Legionella bacteria. The antiserum was made specific for Legionella strains by sequential absorptions with Bordetella pertussis, Pseudomonas aeruginosa, and Pseudomonas fluorescens whole cells. Serum from legionellosis patients reacted with both specific and nonspecific epitopes. Results of indirect immunofluorescence experiments showed that neither specific nor nonspecific epitopes of the 60-kDa protein were surface exposed on Legionella cells and that cross-reactive epitopes were variably exposed on non-Legionella bacteria. The 60-kDa protein antigen should be useful in diagnostic tests for legionellosis if care is taken to expose cryptic epitopes and if the tests use or measure only the Legionella-specific epitopes.


Sensitivity of peripheral nerve fibres to sodium pentobarbital anaesthesia in rat.
The sensitivity of different classes of peripheral nerve fibres to anaesthesia with sodium pentobarbital in rat was tested. The basic approach was to examine changes in compound action potential (CAP) in a rat sural nerve induced by sodium pentobarbital. Rats were either sacrificed by cervical dislocation (control) or anaesthetized with sodium pentobarbital (100 mg/kg, i.p.), and a 30 mm long sural nerve segment excised and placed on electrodes in a thermostatically controlled recording chamber. CAPs were evoked by electrically stimulating the sural nerve segment with supra-threshold stimuli. CAP in control sural nerves consisted of the early component (A axons: 32.73 +/- 2.91 m/s) and the late component (C axons: 0.92 +/- 0.05 m/s) with peak voltage amplitudes 4.9 +/- 1.0 mV and 0.1 +/- 0.03 mV, respectively. Anaesthesia with sodium pentobarbital had no effect on CAP latency. However, the amplitude of CAP of both A and C axons was reduced by approximately 40% and 50%, respectively. The depressant effect of pentobarbital on CAPs was statistically significant for both groups of axons (p<0.01). Non-selective sensitivity of A and C axons to pentobarbital suggests even distribution of receptors for GABA in these two populations of axons in the rat peripheral nerve.


Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies.
Monoclonal antibodies have become an important class of therapeutics in the last 30 years. Because the mechanism of action of therapeutic antibodies is intimately linked to their binding epitopes, identification of the epitope of an antibody to the antigen plays a central role during antibody drug development. The gold standard of epitope mapping, X-ray crystallography, requires a high degree of proficiency with no guarantee of success. Here, we evaluated six widely used alternative methods for epitope identification (peptide array, alanine scan, domain exchange, hydrogen-deuterium exchange, chemical cross-linking, and hydroxyl radical footprinting) in five antibody-antigen combinations (pembrolizumab+PD1, nivolumab+PD1, ipilimumab+CTLA4, tremelimumab+CTLA4, and MK-5890+CD27). The advantages and disadvantages of each technique are demonstrated by our data and practical advice on when and how to apply specific epitope mapping techniques during the drug development process is provided. Our results suggest chemical cross-linking most accurately identifies the epitope as defined by crystallography.


Long-Term Culture and Monitoring of Isolated Caenorhabditis elegans on Solid Media in Multi-Well Devices.
The nematode Caenorhabditis elegans is among the most common model systems used in aging research owing to its simple and inexpensive culture techniques, rapid reproduction cycle (~3 days), short lifespan (~3 weeks), and numerous available tools for genetic manipulation and molecular analysis. The most common approach for conducting aging studies in C. elegans, including survival analysis, involves culturing populations of tens to hundreds of animals together on solid nematode growth media (NGM) in Petri plates. While this approach gathers data on a population of animals, most protocols do not track individual animals over time. Presented here is an optimized protocol for the long-term culturing of individual animals on microfabricated polydimethylsiloxane (PDMS) devices called WorMotels. Each device allows up to 240 animals to be cultured in small wells containing NGM, with each well isolated by a copper sulfate-containing moat that prevents the animals from fleeing. Building on the original WorMotel description, this paper provides a detailed protocol for molding, preparing, and populating each device, with descriptions of common technical complications and advice for troubleshooting. Within this protocol are techniques for the consistent loading of small-volume NGM, the consistent drying of both the NGM and bacterial food, options for delivering pharmacological interventions, instructions for and practical limitations to reusing PDMS devices, and tips for minimizing desiccation, even in low-humidity environments. This technique allows the longitudinal monitoring of various physiological parameters, including stimulated activity, unstimulated activity, body size, movement geometry, healthspan, and survival, in an environment similar to the standard technique for group culture on solid media in Petri plates. This method is compatible with high-throughput data collection when used in conjunction with automated microscopy and analysis software. Finally, the limitations of this technique are discussed, as well as a comparison of this approach to a recently developed method that uses microtrays to culture isolated nematodes on solid media.


The use of PC based VR in clinical medicine: the VREPAR projects.
Virtual reality (VR) is an emerging technology that alters the way individuals interact with computers: a 3D computer-generated environment in which a person can move about and interact as if he actually was inside it. Given to the high computational power required to create virtual environments, these are usually developed on expensive high-end workstations. However, the significant advances in PC hardware that have been made over the last three years, are making PC-based VR a possible solution for clinical assessment and therapy. VREPAR - Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation - are two European Community funded projects (Telematics for health - HC 1053/HC 1055 - http://www.psicologia.net) that are trying to develop a modular PC-based virtual reality system for the medical market. The paper describes the rationale of the developed modules and the preliminary results obtained.


A genetic linkage map of the mimetic butterfly Heliconius melpomene.
Heliconius melpomene is a mimetic butterfly that exhibits great geographic variation in color pattern. We present here a genetic linkage map based on analysis of genetic markers in 73 individuals from a single F(2) family, offspring of a cross between H. m. cythera from western Ecuador and H. m. melpomene from French Guiana. A novel "three-step method" is described for the analysis of dominant markers in an F(2) cross, using outbred parental strains and taking advantage of the lack of crossing over in female Lepidoptera. This method is likely to prove useful for future mapping studies in outbred species with crossing over restricted to one sex, such as the Lepidoptera and Drosophila. The resulting linkage map has 21 linkage groups corresponding to the 21 chromosomes of H. melpomene and includes 219 AFLP markers, 23 microsatellites, 19 single-copy nuclear genes, and the color pattern switch genes Yb and Sb. The marker density is high, averaging >1/7 cM. The total map length is 1616 cM and the average chromosome length is 77 cM. The genome size of H. melpomene was estimated to be 292 Mb, giving a relationship of physical-to-map distance of 180 kb/cM. This map forms the basis for future comparative linkage analysis of color pattern evolution in Heliconius.


Oral streptococcal bacteremia in hospitalized patients: taxonomic identification and clinical characterization.
Oral streptococci have been associated with systemic diseases, including infective endocarditis and neutropenic bacteremia. We analyzed 58 recent oral streptococcal bloodstream isolates, and we obtained clinical and demographic data for source patients. The sodA gene was found to be a better target than the 16S-23S rRNA internal transcribed spacer for DNA sequence-based species identification. Together, Streptococcus mitis and Streptococcus oralis were significantly more likely than the 12 combined remaining species to be isolated from neutropenic patients.


Super-Resolution Reconstruction of CT Images Based on Multi-scale Information Fused Generative Adversarial Networks.
The popularization and widespread use of computed tomography (CT) in the field of medicine evocated public attention to the potential radiation exposure endured by patients. Reducing the radiation dose may lead to scattering noise and low resolution, which can adversely affect the radiologists' judgment. Hence, this paper introduces a new network called PANet-UP-ESRGAN (PAUP-ESRGAN), specifically designed to obtain low-dose CT (LDCT) images with high peak signal-to-noise ratio (PSNR) and high resolution (HR). The model was trained on synthetic medical image data based on a Generative Adversarial Network (GAN). A degradation modeling process was introduced to accurately represent realistic degradation complexities. To reconstruct image edge textures, a pyramidal attention model call PANet was added before the middle of the multiple residual dense blocks (MRDB) in the generator to focus on high-frequency image information. The U-Net discriminator with spectral normalization was also designed to improve its efficiency and stabilize the training dynamics. The proposed PAUP-ESRGAN model was evaluated on the abdomen and lung image datasets, which demonstrated a significant improvement in terms of robustness of model and LDCT image detail reconstruction, compared to the latest real-esrgan network. Results showed that the mean PSNR increated by 19.1%, 25.05%, and 21.25%, the mean SSIM increated by 0.4%, 0.4%, and 0.4%, and the mean NRMSE decreated by 0.25%, 0.25%, and 0.35% at 2[Formula: see text], 4[Formula: see text], and 8[Formula: see text] super-resolution scales, respectively. Experimental results demonstrate that our method outperforms the state-of-the-art super-resolution methods on restoring CT images with respect to peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and normalized root-mean-square error (NRMSE) indices.


Serious problems with the Mexican norms for the WAIS-III when assessing mental retardation in capital cases.
A Spanish-language translation of the Wechsler Adult Intelligence Scale-III (WAIS-III), normed in Mexico, is sometimes used when evaluating Spanish-speaking defendants in capital cases in order to diagnose possible mental retardation (MR). Although the manual for the Mexican test suggests use of the U.S. norms when diagnosing MR, the Mexican norms-which produce full-scale scores on average 12 points higher-are sometimes used for reasons that are similar to those used by proponents for "race-norming" in special education. Such an argument assumes, however, that the Mexican WAIS-III norms are valid. In this paper, we examined the validity of the Mexican WAIS-III norms and found six very serious problems with those norms: (1) extremely poor reliability, (2) lack of a meaningful reference population, (3) lack of score normalization, (4) exclusion of certain groups from the standardization sample, (5) use of incorrect statistics and calculations, and (6) incorrect application of the true score confidence interval method. An additional problem is the apparent absence of any social policy consensus within Mexico as to the definition and boundary parameters of MR. Taken together, these concerns lead one to the inescapable conclusion that the Mexican WAIS-III norms are not interpretable and should not be used for any high-stakes purpose, especially one as serious as whether a defendant should qualify for exemption against imposition of the death penalty.


Differential patterns of expression of three C/EBP isoforms, HNF-1, and HNF-4 after partial hepatectomy in rats.
Regenerating liver provides a system for studying the mechanisms controlling regulated proliferation of differentiated hepatocytes. A set of transcription factors termed hepatocyte nuclear factors (HNF-1, -3, -4) and CCAAT/enhancer binding protein (C/EBP) isoforms are known to regulate several genes predominantly expressed in the liver. To assess whether these factors might be involved in the hepatocyte proliferation program, we have studied the expression of the three C/EBP isoforms C/EBP alpha, C/EBP beta, and C/EBP delta and the two hepatocyte-enriched transcription factors, HNF-1 and HNF-4, in rat liver at various time points after partial hepatectomy and sham operations using transcriptional "run-on" assays and Northern blot and Western blot experiments. We report here that partial hepatectomy in rats leads to dramatic changes in the pattern of expression of some of these genes. The three C/EBP isoforms are differentially regulated in response to partial hepatectomy and are likely to play different roles in determining the proliferation/differentiation state of hepatocytes. In particular, C/EBP alpha expression is rapidly down-regulated, whereas C/EBP delta is induced. C/EBP beta expression is also increased, although an increase is also observed after sham operation. The drastic decrease in C/EBP alpha under these conditions of active DNA synthesis and rapid cell proliferation further supports the concept of a potential incompatibility between high C/EBP alpha protein levels and cell proliferation. The patterns of transcriptional rates of HNF-1 and HNF-4 during the different stages of the regenerative process are similar. However, HNF-1 steady-state mRNA and protein levels are significantly changed while HNF-4 remains virtually unaffected, indicating that post-transcriptional mechanisms are also involved in the regulation of HNF-1 gene expression.


Hospitals with higher nurse staffing had lower odds of readmissions penalties than hospitals with lower staffing.
The Affordable Care Act's Hospital Readmissions Reduction Program (HRRP) penalizes hospitals based on excess readmission rates among Medicare beneficiaries. The aim of the program is to reduce readmissions while aligning hospitals' financial incentives with payers' and patients' quality goals. Many evidence-based interventions that reduce readmissions, such as discharge preparation, care coordination, and patient education, are grounded in the fundamentals of basic nursing care. Yet inadequate staffing can hinder nurses' efforts to carry out these processes of care. We estimated the effect that nurse staffing had on the likelihood that a hospital was penalized under the HRRP. Hospitals with higher nurse staffing had 25 percent lower odds of being penalized compared to otherwise similar hospitals with lower staffing. Investment in nursing is a potential system-level intervention to reduce readmissions that policy makers and hospital administrators should consider in the new regulatory environment as they examine the quality of care delivered to US hospital patients.


Parvalbumin immunoreactivity is enhanced by brain-derived neurotrophic factor in organotypic cultures of rat retina.
The rodent retina undergoes considerable postnatal neurogenesis and phenotypic differentiation, and it is likely that diffusible neurotrophic factors contribute to this development and to the subsequent formation of functional retinal circuitry. Accordingly, perturbation of specific neurotrophin ligand-receptor interactions has provided valuable information as to the fundamental processes underlying this development. In the present studies we have built upon our previous observation that suppression of expression of trk(B), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), in the postnatal rat retina results in the alteration of a specific interneuron in the rod pathway-the parvalbumin (PV)-immunoreactive AII amacrine cell. Here, we isolated retinas from newborn rats and maintained them in organotypic culture for up to 14 days (approximating the time of eye opening, in vivo) in the presence of individual neurotrophins [BDNF or nerve growth factor (NGF)]. We then examined histological sections of cultures for PV immunoreactivity. In control cultures, only sparse PV-immunostained cells were observed. In cultures supplemented with NGF, numerous lightly immunostained somata were present in the inner nuclear layer (INL) at the border of the inner plexiform layer (IPL). Many of these cells had rudimentary dendritic arborizations in the IPL. Cultures supplemented with BDNF displayed numerous well-immunostained somata at the INL/IPL border that gave rise to elaborate dendritic arborizations that approximated the morphology of mature AII amacrine cells in vivo. These observations indicate that neurotrophins have specific effects upon the neurochemical and, perhaps, morphological differentiation of an important interneuron in a specific functional retinal circuit.


Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer.
Long QT syndrome (LQTS) has been reported in older patients with advanced non-small cell lung cancer (NSCLC) following the use of osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, there have not been analytic epidemiology studies on this topic. We aimed to compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs in older patients with advanced NSCLC. This retrospective observational study used the 2006-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included older patients with advanced NSCLC who were treated with either osimertinib or first/second-generation EGFR-TKIs during 2007-2017. Inverse probability of treatment weighting (IPTW) was used to balance the two groups with propensity scores estimated based on the patients' socioeconomic and clinical characteristics. Crude incidence rate (IR) and adjusted hazard ratio (HR) of the primary outcome, incident LQTS, were estimated. A total of 545 and 1,135 patients were included in the osimertinib and first/second-generation EGFR-TKI groups, which increased to 1,614 and 1,659, respectively, after IPTW. The osimertinib group had a higher IR of LQTS (2.62 per100 person-years, 95% CI 2.03-3.38) compared to the first/second-generation EGFR-TKI group (1.33/100 person-years, 95% CI 0.92-1.92). After adjusting for covariates, the osimertinib group had a higher risk of LQTS than the first/second-generation EGFR-TKI group, with an HR of 1.94 (95% CI 1.23-3.08). The increased LQTS risk in the osimertinib group was even higher in females, whites and patients aged ≥ 75. Given the elevated risk of LQTS associated with osimertinib user, close monitoring for cardiac rhythm irregularities of high-risk patients following initiation of EGFR-TKI is recommended.


Construction and application of dynamic protein interaction network based on time course gene expression data.
In recent years, researchers have tried to inject dynamic information into static protein interaction networks (PINs). The paper first proposes a three-sigma method to identify active time points of each protein in a cellular cycle, where three-sigma principle is used to compute an active threshold for each gene according to the characteristics of its expression curve. Then a dynamic protein interaction network (DPIN) is constructed, which includes the dynamic changes of protein interactions. To validate the efficiency of DPIN, MCL, CPM, and core attachment algorithms are applied on two different DPINs, the static PIN and the time course PIN (TC-PIN) to detect protein complexes. The performance of each algorithm on DPINs outperforms those on other networks in terms of matching with known complexes, sensitivity, specificity, f-measure, and accuracy. Furthermore, the statistics of three-sigma principle show that 23-45% proteins are active at a time point and most proteins are active in about half of cellular cycle. In addition, we find 94% essential proteins are in the group of proteins that are active at equal or great than 12 timepoints of GSE4987, which indicates the potential existence of feedback mechanisms that can stabilize the expression level of essential proteins and might provide a new insight for predicting essential proteins from dynamic protein networks.


Release of endogenous ascorbic acid preserves extracellular dopamine in the mammalian retina.
To investigate whether the inhibitory effect of nitric oxide (NO) on dopamine release from the retina is due to chemical oxidation of dopamine in the extracellular medium rather than to an inhibitory effect on dopamine release from retinal neurons. Dopamine was incubated in Krebs bicarbonate medium and its rate of chemical degradation measured by high-performance liquid chromatography (HPLC). The effects of NO donors and antioxidants on dopamine were assessed by comparing dopamine degradation in the presence and absence of drug. The effects of NO donors on the K-evoked release of [3H]dopamine were measured from isolated superfused rabbit retinas. The release of ascorbic acid from the isolated rat retina and from an eyecup preparation in anesthetized rabbits was measured by HPLC. After 10 minutes' incubation in Krebs bicarbonate medium, the dopamine concentration decreased by 20%. This decline increased to 80% in the presence of S-nitroso-N-acetyl-DL-penicillamine (SNAP) or sodium nitroprusside (SNP). The increased rate of dopamine degradation was abolished if retina was incubated in the medium and then removed before the incubation of dopamine. The protective effect of preincubation with tissue was lost in the presence of ascorbate oxidase suggesting the release of ascorbic acid. HPLC analysis confirmed a substantial release of ascorbic acid from both rabbit and rat retinas. The K-evoked release of [3H]dopamine from the rabbit retina was inhibited by SNP. NO can rapidly, oxidize dopamine in physiological medium, but in the presence of retina, sufficient endogenous antioxidants (mainly ascorbate) are released to prevent this chemical reaction. Thus, the inhibitory action of NO on dopamine release results from an action on retinal neurons. Ascorbate release in the retina may have an important physiological role in prolonging the life of dopamine, which often has to diffuse long distances from axons in the inner plexiform layer to receptors in other retinal layers.


Maternal caffeine consumption during pregnancy does not affect preimplantation development but delays early postimplantation growth in rat embryos.
Models for studying prenatal drug-induced intrauterine growth retardation (IUGR) have, without exception, measured growth-related factors in the postimplantation embryo, fetus or neonate. Therefore, it is not known whether effects of drug exposure on growth and metabolism begin early in the preimplantation embryo, or whether IUGR is exclusively a postimplantation phenomenon. The present study investigates whether caffeine, a drug known to induce a dose-dependent fetal IUGR, affects embryo development before and/or after implantation or is exclusively a fetal phenomenon. Preimplantation embryo assessment (with treatment from Days 2 to 4 of pregnancy) included glucose utilization, cell number evaluation and stage of development (morula to hatched blastocyst); whereas, postimplantation embryo assessment (treatment from Days 2 to 10, 10.5 or 11 of pregnancy) included somite number evaluation and extent of neural tube closure, as seen using scanning electron microscopy. Comparing control preimplantation embryos with those exposed to 30 and 60 mg kg(-1) caffeine did not reveal any effects of caffeine exposure, as assessed on Day 5 of gestation. However, postimplantation embryo development assessed on Day 12 of gestation revealed that caffeine exposure of 15 and 30 mg kg(-1) significantly reduced, at both dosage levels, somite number and the extent of neural tube closure. In addition, comparisons of control and experimental groups revealed that in the high-dose caffeine group the forebrain cavity was significantly enlarged and bounded by a reduced, irregularly aligned neuroepithelium. The findings suggest that IUGR is a phenomenon first identifiable during late postimplantation embryogenesis and continues in fetal life.


Salivary cortisol levels and anxiety in melanoma patients undergoing sentinel lymph node excision under local anesthesia versus general anesthesia: a prospective study.
Sentinel lymph node excision (SLNE) can be performed in tumescent local anesthesia (TLA) or general anesthesia (GA). Perioperative cortisol level changes and anxiety are common in surgical interventions and might be influenced by the type of anesthesia. In this study, we intended to determine whether the type of anesthesia impacts the patients' perioperative levels of salivary cortisol (primary outcome) and the feeling of anxiety evaluated by psychological questionnaires (secondary outcome). All melanoma patients of age undergoing SLNE at the University Hospital Essen, Germany, could be included in the study. Exclusion criteria were patients' intake of glucocorticoids or psychotropic medication during the former 6 months, pregnancy, age under 18 years, and BMI ≥ 30 as salivary cortisol levels were reported to be significantly impacted by obesity and might confound results. In total, 111 melanoma patients undergoing SLNE were included in our prospective study between May 2011 and April 2017 and could choose between TLA or GA. Salivary cortisol levels were measured three times intraoperatively, twice on the third and second preoperative day and twice on the second postoperative day. To assess anxiety, patients completed questionnaires (Hospital Anxiety and Depression Scale (HADS), State-Trait Anxiety Inventory (STAI)) perioperatively. Patients of both groups exhibited comparable baseline levels of cortisol and perioperative anxiety levels. Independent of the type of anesthesia, all patients showed significantly increasing salivary cortisol level from baseline to 30 min before surgery (T3) (TLA: t = 5.07, p < 0.001; GA: t = 3.09, p = 0.006). Post hoc independent t tests showed that the TLA group exhibited significantly higher cortisol concentrations at the beginning of surgery (T4; t = 3.29, p = 0.002) as well as 20 min after incision (T5; t = 277, p = 0.008) compared to the GA group. The type of anesthesia chosen for SLNE surgery significantly affects intraoperative cortisol levels in melanoma patients. Further studies are mandatory to evaluate the relevance of endogenous perioperative cortisol levels on the postoperative clinical course. German Clinical Trials Register DRKS00003076, registered 1 May 2011.


The effect of weather on walking behavior in older adults.
In this article, the authors examine how temperature and precipitation affect the probability that a retired American between the ages of 65 and 90 walks at least 2.5 hr/wk, using longitudinal data on walking frequency from the Consumption and Activities Mail Survey, a subpanel in the Health and Retirement Survey. Walking behavior is linked with monthly temperature and precipitation data from weather-station reports. The authors found that higher temperatures were associated with a higher probability of walking at least 2.5 hr/wk for women. In contrast, higher temperatures are associated with a lower probability of walking at least 2.5 hr/wk among men. Precipitation is not significantly associated with walking behavior for either gender.


Surgical results of mitral valve repair for congenital mitral valve stenosis in paediatric patients.
Mitral valve (MV) repairs have been performed in paediatric patients with congenital MV stenosis. However, congenital MV stenosis lesions are a heterogeneous group of lesions, and their repair remains challenging. From March 1999 to September 2014, MV repair was performed in 22 patients with congenital MV stenosis. The median age was 10.3 months (ranging from 22 days to 9.1 years), and the mean body weight was 7.9 ± 4.0 kg at the time of the operation. Multiple-level left-side heart obstructions were present in 9 (45%) patients. The main aetiology of the mitral stenosis was a supravalvular mitral ring in 8 patients, valvular stenosis in 4 patients, a parachute deformity of the papillary muscles in 4 patients and other abnormal papillary muscles in 6 patients. The mean MV pressure gradient improved from 10.4 ± 3.9 mmHg to 3.4 ± 1.7 mmHg after MV repair (n = 18, P < 0.0001). The mean follow-up duration was 6.7 ± 5.4 years. One patient died postoperatively due to septic shock. Four patients required a second operation (2 patients for mitral stenosis, 1 patient for left ventricular outflow tract obstruction and mitral stenosis and 1 patient for mitral regurgitation). Among them, 2 patients died: 1 patient died due to cardiopulmonary bypass weaning failure and another patient died due to multiple cerebral infarcts. At the last follow-up, the mean MV pressure gradient was 4.5 ± 3.1 mmHg for all patients who did not have reoperation, and moderate or greater mitral insufficiency was detected in 3 patients. At 10 years, the survival rate was 85.9 ± 7.6%, and the freedom from reoperation rate was 77.5 ± 10.1%. In the log-rank test, MV repair in the neonate was associated with mortality (P = 0.010), and presentation of mitral insufficiency was associated with reoperation (P = 0.003). MV repair in paediatric patients with congenital mitral stenosis showed acceptable results. The follow-up echocardiogram also revealed satisfactory results. Close follow-up is necessary to detect the development of postoperative mitral stenosis or regurgitation.


Predisposed to adapt? Clade-level differences in characters affecting swimming performance in damselflies.
Previous studies have shown that two or three lineages of Enallagma damselflies, which historically co-existed with fish, recently invaded and adapted to living with large dragonfly predators in fishless waters. In adapting to live with these new predators, lineages shifted behaviorally to using swimming as an evasive tactic against attacking predators, evolved morphological features that made them faster swimmers, and evolved biochemical features to increase refueling strenuous activities like swimming. However, these habitat shifts have occurred in only one of the two primary clades within the genus in North America. Here, I show that clade-level differences exist among species in the ancestral, fish-lake habitat that should make habitat shifts easier to accomplish in the clade in which they have occurred. Specifically, fish-lake species in the clade in which habitat shifts occurred have much higher propensities to swim in the laboratory, swim faster when they do swim, and have higher mass-specific activities for arginine kinase than do species in the other primary clade, in which no extant species are found in fishless waters. These results are discussed in the context of the dynamics of founder events and the potential implications for community structure.


Initiating meiosis: the case for retinoic acid.
The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible.


Relationship between dry matter digestion and metabolizable energy.
The relationship between dry matter digestion (DMD) and metabolizable energy (ME) adjusted for nitrogen balance (n) and endogenous energy losses (e) was investigated in two experiments using immature broiler chicks (i). Ingredients tested were corn, wheat, oats, and soybean meal (SBM). A bioassay utilizing 21-day-old broiler chicks was carried out for determination of MEn,e,i. These values were compared with those obtained by multiplying gross energy of the feed by dry matter digestion adjusted for excreta losses from fasted birds (DMD) using regression analysis. There was a significant (P less than .0001) correlation (4 = .96) between estimated and determined MEn,e,i values for all grains and SBM. This was improved by removal of SBM from regression analysis with a decrease in the residual standard deviation from +/- .093 to +/- .036 kcal/g.


Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia.
Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.