Bilayer conformation of fusion peptide of influenza virus hemagglutinin: a molecular dynamics simulation study.
Unraveling the conformation of membrane-bound viral fusion peptides is essential for understanding how those peptides destabilize the bilayer topology of lipids that is important for virus-cell membrane fusion. Here, molecular dynamics (MD) simulations were performed to investigate the conformation of the 20 amino acids long fusion peptide of influenza hemagglutinin of strain X31 bound to a dimyristoyl phosphatidylcholine (DMPC) bilayer. The simulations revealed that the peptide adopts a kinked conformation, in agreement with the NMR structures of a related peptide in detergent micelles. The peptide is located at the amphipathic interface between the headgroups and hydrocarbon chains of the lipid by an energetically favorable arrangement: The hydrophobic side chains of the peptides are embedded into the hydrophobic region and the hydrophilic side chains are in the headgroup region. The N-terminus of the peptide is localized close to the amphipathic interface. The molecular dynamics simulations also revealed that the peptide affects the surrounding bilayer structure. The average hydrophobic thickness of the lipid phase close to the N-terminus is reduced in comparison with the average hydrophobic thickness of a pure dimyristoyl phosphatidylcholine bilayer.


Genetics of postoperative complications following thoracic surgery.
The field of complex trait-gene interaction research has expanded exponentially in recent years, and new insights into the ways patients respond to surgical stimuli have arisen from this body of work. From a physiological systems perspective, thoracic surgical procedures (thoracotomy in particular) represent a massive input stimulus, and it is, therefore, not surprising that approximately 30% of these patients experience an adverse postoperative event. The best risk prediction models have typically explained about 60% to 70% of the risk, leaving a large residual component unaccounted for. It is quite possible that there is a genetic (heritable) component to this residual risk. This article explores some of the concepts underlying gene-disease interactions, the preliminary work that has been done to date in this area, and finally discusses some of the more important methodological issues involved in complex trait association study design.


Understanding colorectal cancer patient follow-up: a qualitative interview study.
There are increasing numbers of patients who have been treated for colorectal cancer (CRC) who struggle with ongoing physical and psychological symptoms. 'Cancer survivor' is often used to describe these patients but this terminology remains controversial. This study sought to understand the follow-up experience of CRC patients in the UK and identify the terminology they prefer following diagnosis and treatment. Purposeful sampling of patients from specialist CRC follow-up clinics was performed until data saturation was achieved. Two 1:1 semi-structured qualitative interviews were performed for each participant. Data were analysed thematically. Seventeen participants, median age = 62, 53% male were interviewed. Several themes were identified. Of note, fear of cancer recurrence dominates patients' agendas at follow-up appointments. There are also clinical and administrative barriers to discussing symptoms including being embarrassed, feeling that their symptoms were not relevant or not having enough time to discuss issues. However, there are several methods which may improve this, such as through the use of video consultations and questionnaires. In addition, patients identified inadequate holistic support despite significant psychological and social distress. Our data suggest that labelling a diverse group of patients as 'cancer survivors' can be problematic. It is important that clinicians systematically screen patients for symptoms that are known to occur following treatment. Clinicians and patients should have routine access to pathways and programmes that can support patients in navigating their life after cancer therapy.


SARS-CoV-2 RNA polymerase as target for antiviral therapy.
A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.


Generation of hydroxyl radicals and singlet oxygen during oxidation of rhododendrol and rhododendrol-catechol.
The generation of hydroxyl radicals and singlet oxygen during the oxidation of 4-(4-hydroxyphenyl)-2-butanol (rhododendrol) and 4-(3,4-dihydroxyphenyl)-2-butanol (rhododendrol-catechol) with mushroom tyrosinase in a phosphate buffer (pH 7.4) was examined as the model for the reactive oxygen species generation via the two rhododendrol compounds in melanocytes. The reaction was performed in the presence of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin trap reagents for hydroxyl radical or 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP), an acceptor of singlet oxygen, and their electron spin resonances were measured. An increase in the electron spin resonances signal attributable to the adduct of DMPO reacting with the hydroxyl radical and that of 4-oxo-TEMP reacting with singlet oxygen was observed during the tyrosinase-catalyzed oxidation of rhododendrol and rhododendrol-catechol, indicating the generation of hydroxyl radical and singlet oxygen. Moreover, hydroxyl radical generation was also observed in the autoxidation of rhododendrol-catechol. We show that generation of intermediates during tyrosinase-catalyzed oxidation of rhododendrol enhances oxidative stress in melanocytes.


Therapeutic efficacy of endoscopic retrograde cholangiopancreatography among pregnant women with severe acute biliary pancreatitis.
To explore the feasibility of endoscopic retrograde cholangiopancreatography (ERCP) in pregnant women with severe acute biliary pancreatitis. In total, 24 pregnant patients with severe acute biliary pancreatitis were enrolled in our study between January 2003 and January 2008. Emergency ERCP and endoscopic nasobiliary drainage (ENBD) without fluoroscopy were performed successfully in all 24 patients within 12-72 hours of admission. Once stabilized, 15 patients in late pregnancy underwent a second ERCP with fluoroscopy to remove common bile duct (CBD) stones after pregnancy termination. Nine patients in early or mid-pregnancy continued gestating and underwent endoscopic retrograde biliary drainage (ERBD) with a second ERCP without fluoroscopy, and their stents and CBD stones were removed during a third ERCP with fluoroscopy 1 week after parturition. Among the mothers, all 24 patients were cured, and none of them died. The CBD stones in all 24 patients were completely removed with a two-step ERCP, and no serious post-ERCP complications occurred, although 2 patients had mild hemorrhage in the final ERCP to remove CBD stones. No recurrent pancreatitis or cholangitis occurred in patients who underwent ERBD. Among the infants, all survived without developmental problems or abnormality. Twenty infants were born at term; four infants were born prematurely at 35-37 weeks of gestation without developmental problems or complications. Emergency ERCP and ENBD without fluoroscopy in pregnant women with severe acute biliary pancreatitis are feasible and safe for both mothers and infants. It is also appropriate to remove CBD stones with two-step ERCP in pregnant women according to the stage of pregnancy.


Validity of measures of neurological status used for predicting functional independence in adults after a cerebrovascular accident: a systematic review protocol.
Are the measures of neurologic status that are used in adults who have had a cerebrovascular accident valid in predicting functional independence?More specifically, the objective of this review is to assess the predictive validity of functional independence of the National Institutes of Health Stroke Scale and the Canadian Neurological Scale.


On-line analysis of avermectin fermentation cell growth kinetics in an industrial pilot plant.
Experimental data are presented which show that on-line calculation of oxygen uptake rate can be used to estimate the cell concentration of Streptomyces avermitilis during the active growth phase of this fermentation. Moreover, by dividing the oxygen uptake rate by the total oxygen consumed, an on-line estimate of specific growth rate of this culture can be generated. A theoretical basis is provided for this model. Use of a mass spectrometer for vent gas analysis coupled with computer data acquisition has made this information both very accurate and readily available. Examples are given which illustrate the kinetics of the avermectin fermentation as well as the effect of a temperature shift on the specific growth rate.


S-amlodipine--the 2007 clinical review.
S-amlodipine is the only vaso-active enantiomer of amlodipine. This article reviews the published data in nearly 5000 patients. Randomised controlled trials of S-amlodipine at half the dose of racemate in the treatment of hypertension, have shown it to be as effective as racemic amlodipine. The postmarketing surveillance studies (n = 4089) of S-amlodipine confirmed its antihypertensive efficacy and showed that the incidence of peripheral oedema is negligible with S-amlodipine compared to racemic amlodipine. Further, the patients with peripheral oedema who were switched over from racemic amlodipine to S-amlodipine resolved their oedema associated with the racemate, while sustaining the blood pressure control. Subgroup analyses showed S-amlodipine to be effective and safe in elderly hypertensives and isolated systolic hypertension patients. A clinical study in normotensive angina patients confirmed the anti-anginal efficacy of S-amlodipine at half the dose of racemate. Fixed-dose combinations of S-amlodipine with atenolol and S-amlodipine with hydrochlorothiazide have been shown to be effective and well tolerated in clinical practice. In the light of its efficacy and favourable tolerability profile, S-amlodipine used alone or in combination with other antihypertensive or anti-anginal drugs, is a valuable treatment option in the management of hypertension and angina.


[Venezuelan consensus guidelines on the use of magnetic resonance in diagnosis and follow up of patients with multiple sclerosis].
The clinical use of magnetic resonance (MR) in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Several groups around the world have developed consensus guidelines about the role of MR in MS at diagnosis and during follow up. However, in some regions is difficult to extrapolate the recommendations. To provide recommendations for the implementation of MR in MS patients at diagnosis and follow up in Venezuela. A group of experts from Venezuela that included neurologists and radiologists, by using the online surveys methodology as well as face to face meetings developed the intended consensus for the use of MR during the diagnosis and follow up of MS patients in Venezuela. Seventeen recommendations were established based on published evidence and the expert opinion. Recommendations focused on the role of conventional MR techniques and brain atrophy measurement in MS patients both at diagnosis and during follow-up. The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Venezuela.


Comparative Toxicological Effects of Biologically and Chemically Synthesized Copper Oxide Nanoparticles on Mice.
Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal's organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice. Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally. TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm-1 and 425 cm-1 in biologically synthesized NPs and between 858 cm-1 and 524 cm-1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs. This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.


Association Between Arterial Oxygen Saturation and Lung Ultrasound B-Lines After Competitive Deep Breath-Hold Diving.
Breath-hold diving (freediving) is an underwater sport that is associated with elevated hydrostatic pressure, which has a compressive effect on the lungs that can lead to the development of pulmonary edema. Pulmonary edema reduces oxygen uptake and thereby the recovery from the hypoxia developed during freediving, and increases the risk of hypoxic syncope. We aimed to examine the efficacy of SpO2, via pulse-oximetry, as a tool to detect pulmonary edema by comparing it to lung ultrasound B-line measurements after deep diving. SpO2 and B-lines were collected in 40 freedivers participating in an international deep freediving competition. SpO2 was measured within 17 ± 6 min and lung B-lines using ultrasound within 44 ± 15 min after surfacing. A specific symptoms questionnaire was used during SpO2 measurements. We found a negative correlation between B-line score and minimum SpO2 (r s = -0.491; p = 0.002) and mean SpO2 (r s = -0.335; p = 0.046). B-line scores were positively correlated with depth (r s = 0.408; p = 0.013), confirming that extra-vascular lung water is increased with deeper dives. Compared to dives that were asymptomatic, symptomatic dives had a 27% greater B-line score, and both a lower mean and minimum SpO2 (all p < 0.05). Indeed, a minimum SpO2 ≤ 95% after a deep dive has a positive predictive value of 29% and a negative predictive value of 100% regarding symptoms. We concluded that elevated B-line scores are associated with reduced SpO2 after dives, suggesting that SpO2 via pulse oximetry could be a useful screening tool to detect increased extra-vascular lung water. The practical application is not to diagnose pulmonary edema based on SpO2 - as pulse oximetry is inexact - rather, to utilize it as a tool to determine which divers require further evaluation before returning to deep freediving.


Pharmacist's role in management of hypertensive patients in an ambulatory care clinic.
A program involving a pharmacist in the management of ambulatory hypertensive patients is discussed. A hypertension monitoring protocol was developed by a physician and a pharmacist. The protocol provided for initial patient assessment and treatment by the physician, counseling and education of the patient by the pharmacist, patient follow-up by the pharmacist every one to two months and follow-up by the physician every four to six months. In the first four months of the program, 28 of 75 newly diagnosed hypertensive patients were referred by the physician to the pharmacist for follow-up.


Incorporating Multiple Perspectives Into the Development of an Electronic Survivorship Platform for Head and Neck Cancer.
To improve the care of survivors of head and neck cancer, we developed the Head and Neck Survivorship Tool: Assessment and Recommendations (HN-STAR). HN-STAR is an electronic platform that incorporates patient-reported outcomes into a clinical decision support tool for use at a survivorship visit. Selections in the clinical decision support tool automatically populate a survivorship care plan (SCP). We aimed to refine HN-STAR by eliciting and incorporating feedback on its ease of use and usefulness. Human-computer interaction (HCI) experts reviewed HN-STAR using think-aloud testing and the Nielsen Heuristic Checklist. Nurse practitioners (NPs) thought aloud while reviewing the clinical decision support tool and SCP and responded to an interview. Survivors used HN-STAR as part of a routine visit and were interviewed afterward. We analyzed themes from the feedback. We described how we addressed each theme to improve the usability of HN-STAR. Five HCI experts, 10 NPs, and 10 cancer survivors provided complementary usability insight that we categorized into themes of improvements. For ease of use, themes included technical design considerations to enhance user interface, ease of completion of a self-assessment, streamlining text, disruption of the clinic visit, and threshold for symptoms to appear on the SCP. The theme addressing usefulness was efficiency and comprehensiveness of the clinic visit. For each theme, we report revisions to HN-STAR in response to the feedback. HCI experts provided key technical design insights into HN-STAR, whereas NPs and survivors provided usability feedback and clinical perspectives. We incorporated the feedback into the preparation for additional testing of HN-STAR. This method can inform and improve the ease of use and usefulness of the survivorship applications.


Rostrocaudal localization of cardiovascular responses induced by intrathecal administration of apomorphine in conscious, freely moving rats.
In conscious freely moving rats, administration of apomorphine (179 nmol), a dopamine receptor agonist, into the intrathecal (i.t.) space decreased mean aortic blood pressure (MBP) and heart rate (HR). Both the magnitude and the time of appearance of the response varied according to the spinal level of administration. The largest and immediately appearing effect was observed after the injection at the upper thoracic site, whereas the magnitude of the responses was smaller with an immediate or slightly delayed (0.5-1.5 min) onset at lower thoracic and midcervical levels. More caudal responses appeared to be due to spreading of the drug along the spinal axis (onset in 1-2 min after administration). Behavioral responses (stereotyped movements) were observed within 2-3 min after administration and were nearly the same whatever the site of administration. These results corroborate, as do those provided by i.t. injections of tritiated apomorphine, the spinal origin of cardiovascular effects of i.t. apomorphine. Furthermore, spinal transection at the T5-T7 level did not change the magnitude and duration of decreases in MBP and HR elicited by i.t. apomorphine injected at the T2-T4 level. Moreover, this procedure enhanced responses to i.t. administration at the T9-T10 level. In conclusion, these results favor the existence of a spinal site of action for the cardiovascular effects of apomorphine. Furthermore, they indicate that spinal transection is accompanied by development of a hypersensitive phenomenon (of a mechanism to be determined).


Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.
Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones. In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18 degrees C) and warm (30 degrees C) ambient temperatures in a temperature and humidity-controlled laboratory. Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2x2 design [i.e., two sessions at 30 degrees C and two at 18 degrees C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion. MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA. Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.


Clinical response of two brush-applied peroxide whitening systems.
A randomized, examiner-blind parallel design study was conducted to evaluate the clinical efficacy and tolerability of two brush-applied, peroxide-based tooth whiteners. A total of 38 subjects were randomized to Colgate Simply White, an 18% carbamide peroxide paint-on liquid in an applicator bottle, or Crest Night Effects, a 19% sodium percarbonate system in unit dose sachets that dries to form an adherent film. Treatment was for 14 days. The 18% carbamide peroxide gel was applied twice daily, while the 19% sodium percarbonate film was applied for overnight use. Subjects were evaluated at baseline, and again after 7 and 14 days of treatment using digital images to assess tooth color, and oral examinations to establish safety. Whitening efficacy was determined by evaluating the reduction in tooth yellowness (delta b*), increase in tooth brightness (delta L*), reduction in tooth redness (delta a*) and overall tooth color change relative to pure white (delta W*). After 14 days, the mean change in yellowness (delta b*) was -1.43 +/- 0.20 for the 19% sodium percarbonate film, and -0.44 +/- 0.06 for the 18% carbamide peroxide gel. Mean change in brightness (delta L*) was 1.13 +/- 0.13 and 0.55 +/- 0.13 in the film and gel groups, respectively. Between-group comparisons showed highly significant (p < or = 0.003) whitening for the 19% sodium percarbonate film compared to the 18% carbamide peroxide gel for all 14-day color measurements (delta b*, delta L*, delta a* or delta W). Both products were well-tolerated, with no subjects discontinuing treatment early due to a causal adverse event. In a direct clinical comparison of two brush-applied products over 14 days, Crest Night Effects provided significant and meaningful improvement in tooth color, representing more than double the whitening measured for the Colgate Simply White.


Caenorhabditis elegans prom-1 is required for meiotic prophase progression and homologous chromosome pairing.
A novel gene, prom-1, was isolated in a screen for Caenorhabditis elegans mutants with increased apoptosis in the germline. prom-1 encodes an F-box protein with limited homology to the putative human tumor suppressor FBXO47. Mutations in the prom-1 locus cause a strong reduction in bivalent formation, which results in increased embryonic lethality and a Him phenotype. Furthermore, retarded and asynchronous nuclear reorganization as well as reduced homologous synapsis occur during meiotic prophase. Accumulation of recombination protein RAD-51 in meiotic nuclei suggests disturbed repair of double-stranded DNA breaks. Nuclei in prom-1 mutant gonads timely complete mitotic proliferation and premeiotic replication, but they undergo prolonged delay upon meiotic entry. We, therefore, propose that prom-1 regulates the timely progression through meiotic prophase I and that in its absence the recognition of homologous chromosomes is strongly impaired.


Relationships between disk displacement, joint effusion, and degenerative changes of the TMJ in TMD patients based on MRI findings.
This study was performed to investigate the relationships between disk displacement, joint effusion, and degenerative changes in patients with temporomandibular disorders using MRI. Randomly selected MRIs of 508 temporomandibular joints of 254 patients (92 males and 162 females, mean age was 30.5±12.0 years) were reviewed retrospectively. Seventy-eight percent (198 out of 254) of the patients complained of joint pain. Compared with joints with a normal disk position, the joints with anterior disk displacement with reduction showed a 2.01 odds ratio (P<0.01) of degenerative changes and a 2.85 odds ratio (P<0.001) of joint effusions. The joints with anterior disk displacement without reduction showed a 4.43 odds ratio (P<0.001) of degenerative changes and a 4.61 odds ratio (P<0.001) of joint effusions. These results clearly show that the risk of degenerative changes and joint effusions increase with displacement of the disk position in patients with temporomandibular disorders. Although all disk displacement situations do not progress to painful joints and/or degenerative joint diseases, the possibility of an increased risk of progression by a breakdown in the balance between a patient's adaptive capacity and functional loading of the TMJ should be assessed in each and every patient through comprehensive evaluation of various contributing factors.


The regional turnover of cartilage collagen matrix in late-stage human knee osteoarthritis.
Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage. Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks duration. Deuterium oxide (D2O) was administered orally by weekly boluses at 70% D2O, initially 150 ml followed by three boluses of 50 ml. Cartilage from the medial tibia plateau was sampled centrally, under the meniscus, and from osteophytes and treated enzymatically with hyaluronidase and trypsin. Samples were analysed for deuterium incorporation in alanine using mass spectrometry and for gene expression by real-time reverse transcriptase polymerase chain reaction. Twenty participants completed the study: mean (SD) age 64 ± 9.1 years, 45% female, BMI 29.5 ± 4.8 kg/m2. Enzymatically treated cartilage from central and submeniscal regions showed similar enrichments at 0.063% APE, while osteophytes showed significantly greater enrichment at 0.072% APE (95% confidence interval of difference) [0.004-0.015]). Fractional synthesis rates were similar for central 0.027%/day and submeniscal cartilage 0.022%/day but 10-fold higher in osteophytes 0.22%/day [0.098-0.363]. When compared to central cartilage, submeniscal cartilage had increased gene expression of MMP-3 and decreased lubricin expression. Untreated cartilage had higher turnover (enrichments at 0.073% APE) than enzymatically treated cartilage (0.063% APE). In OA, despite regional differences in gene expression, the turnover of the articular cartilage matrix across the entire joint surface is very limited, but higher turnover was observed in osteophyte cartilage.


[Osteosynthesis of intracapsular femoral neck fractures].
To evaluate outcomes of internal fixation of intracapsular femoral neck fractures. Between the beginning of 1998 and end of 2002 the authors performed internal fixation of intracapsular fracture of the femoral neck in 47 patients (21 women, 26 men). The average age of patients was 56 years, range, 17 to 86 years (men 54.5 years, women 58.2 years). Forty patients (18 women, 22 men) went through the follow-up at the minimal interval of 1 year after the surgery. Their average age was 56 years. The remaining 7 patients were lost to follow-up. In 21 patients the case was Garden 1 and 2 fractures, in 19 patients Garden 3 and 4 displaced fractures. Internal fixation by three lag screws was performed in 16 cases, fixation by DHS with antirotational screw in 24 cases. The fracture healed in 70% of cases, non-union occurred 3times and avascular necrosis developed 9times. Garden 1 and 2 fractures were associated with 14.3% and Garden 3 and 4 fractures with 47.4% of complications. Of fractures treated by lag screws, 71% of cases healed, while in those treated by DHS the percentage was 69%. Both duration of surgery and x-ray exposure was in lag screws by 50% longer than in DHS. In terms of the development of avascular necrosis, the study did not prove any advantage of a shorter interval between the injury and surgery. However, development of avascular necrosis was influenced also by other factors and therefore the significance of urgent surgery within 6 hours after injury should not be questioned. Garden 3 and 4 displaced fractures have a worse prospect than Garden 1 and 2 fractures. Duration of surgery and x-ray exposure in DHS is shorter than in lag cancellous screws with the same percentage of good results. Of great importance is an exact reduction of the fracture in both projections, a correct position of implants and evacuation of intracapsular haematoma as a prevention of avascular necrosis of the femoral head.


A full dimensional investigation of infrared spectroscopy of the RbCs dimer using the multi-configuration time-dependent Hartree method.
The geometry and infrared absorption spectrum of (RbCs)2 have been studied by full dimensional quantum dynamics simulations. For this purpose, the potential energy and dipole moment surfaces are generated by means of a cluster expansion with all two and three mode correlations, and fitted to analytical expressions with negligible deviations. Accordingly, the ground state (RbCs)2 has a diamond geometry with D(2h) symmetry. The infrared spectrum with frequencies up to 120 cm(-1), exhibits rich details of the fundamentals, overtones, and combination bands; the highest fundamental frequency of (RbCs)2 is only 40.26 cm(-1). The present study unravels important details of the interactions between the widely investigated ultracold RbCs molecules.


[When patient and therapist disagree--discrepancies in evaluation of change].
The following study concerns the interaction of different measures for therapeutic change. 1377 inpatients of a psychosomatic hospital were examined. Measures for change were the subjective global rating of the inpatient, the subjective global rating the psychotherapist, and the Symptom-Check-List SCL-90-R. To get additional information for possible predictive variables for discrepant judgements, also personality questionnaires and sociodemographic variables were considered. Results demonstrated only medium correlations between subjective ratings for change of the patient and the psychotherapist, although the same categories were used (R = 0.44). The correlations to measures of change of the self-rating-scales are even lower. Therefore we conclude that these measures focus to different information, because the common part of variance is low. Discrepancies between the judgement of therapists and patients can be found after all when the patient makes a negative rating. Predictive variables for discrepancies of the judgements for change of the psychotherapists and patients are: age, sex, phobic anxiety and bodily complaints. While younger patients tend to make better judgements than their therapists we find the contrary for elder patients. Women tend to make better judgements than their psychotherapists. We find also discrepancies in patients with multiple syndromes, when phobic anxiety and bodily complaints exist and are perhaps not adequately concerned in the psychotherapy.


Repartition of oil miscible and water soluble UV filters in an applied sunscreen film determined by confocal Raman microspectroscopy.
Photoprotection provided by topical sunscreens is expressed by the sun protection factor (SPF) which depends primarily on the UV filters contained in the product and the applied sunscreen amount. Recently, the vehicle was shown to significantly impact film thickness distribution of an applied sunscreen and sunscreen efficacy. In the present work, repartition of the UV filters within the sunscreen film upon application is investigated for its role to affect sun protection efficacy. The spatial repartition of an oil-miscible and a water-soluble UV filter within the sunscreen film was studied using confocal Raman microspectroscopy. Epidermis of pig ear skin was used as substrate for application of three different sunscreen formulations, an oil-in-water emulsion, a water-in-oil emulsion, and a clear lipo-alcoholic spray (CAS) and SPF in vitro was measured. Considerable differences in the repartition of the UV filters upon application and evaporation of volatile ingredients were found between the tested formulations. A nearly continuous phase of lipid-miscible UV filter was formed only for the WO formulation with dispersed aggregates of water-soluble UV filter. OW emulsion and CAS exhibited interspersed patches of the two UV filters, whereas the segregated UV filter domains of the latter formulation were by comparison of a much larger scale and spanned the entire thickness of the sunscreen film. CAS therefore differed markedly from the other two formulations with respect to filter repartition. This difference should be reflected in SPF when the absorption spectra of the employed UV filters are not the same. Confocal Raman microspectroscopy was shown to be a powerful technique for studying this mechanism of sun protection performance of sunscreens.


Assessing the relationship between terrorist attacks against ingroup or outgroup members and public support for terrorism.
Terrorist groups rely on constituency support for their long-term survival. Here, we examined the extent to which terrorists' own activities are related with public opinion on terrorism. Specifically, we assessed whether more frequent and more costly terrorist attacks against the ingroup are associated with war weariness or retaliatory sentiments, thus, either weaker or stronger approval of terrorism. We further investigated if more frequent and costly attacks that target an outgroup predict higher levels of justification of terrorism. Lastly, we identified the timeframe during which domestic and outgroup terrorist attacks correlate with (lower or higher) public support. The analyses focused on Jordan (ingroup) and Israel (outgroup), over an 8-year period (2004-2011), drawing on data from the Pew Global Attitudes Survey and the Global Terrorism Database. Results showed that support for terrorism in Jordan decreased in 2005 and, again, in 2008. The frequency of terrorist attacks and fatality/injury rates in Jordan did not vary significantly during the study period. The number of attacks and fatalities/people injured in Israel, however, changed between 2004 and 2011. Cross-correlations of the time-series further demonstrated that the number of attacks and fatalities/people injured in Jordan was not related with the level of public approval of terrorism in the country. Importantly, and in line with the literature, the casualty rate in Israel was positively associated with support for terrorism in Jordan, in the next year. That is, there is evidence that more/less costly terrorist attacks on an outgroup can predict stronger/weaker public support for the tactic relatively quickly. Those findings provide insights for counter-terrorism measures.


Preterm meconium-stained amniotic fluid is an ominous sign for the development of chorioamnionitis and for in utero cord compression.
Meconium-stained amniotic fluid (MSAF) is rarely observed in preterm pregnancies, and its clinical significance is undetermined. We evaluated the correlation between MSAF and obstetrical and perinatal complications prior to 34 weeks' gestation. Pregnancies complicated with MSAF between 24 and 34 weeks of gestation were compared with same gestational age-matched controls. The variables measured were: obstetrical complications: clinical chorioamnionitis, Intrahepatic Cohlestasis of Pregnancy - ICP, Intra Uterine Growth Restriction - IUGR, preeclampsia, gestational diabetes; nonobstetrical complications; and perinatal complications: cord around neck/body, Apgar <7 at 5 min, cord pH, Neonatal Intensive Care Unit - NICU admission, complications during NICU hospitalization, and composite outcome. Higher incidence of clinical chorioamnionitis (15% versus 4.3%; p = 0.041) and higher incidence of cord around the neck/body were found in the MSAF group in comparison with the clear AF group (27.4% versus 18.4%; p = 0.04). No significant differences between the study's groups were found in nonobstetrical complications or other perinatal complications investigated in our study. MSAF in preterm pregnancy is an ominous sign for the occurrence of chorioamnionitis and for in utero cord compression. Therefore, MSAF in preterm pregnancies should be considered as a non-reassuring sign.


Intravenous administration of epoetin in haemodialysis patients.
Recombinant human erythropoietin (epoetin, rHuEPO) can be administered to haemodialysis patients intravenously or subcutaneously. Although the intravenous route is the originally approved and used route of administration, subcutaneous administration has been quite common throughout Europe since the introduction of prefilled syringes. The intravenous route has been shown to be as effective as the subcutaneous route, but patients should have adequate iron stores. In addition, intravenous administration is patient-friendly and results in fewer injections, less pain and bruising, and a minimised risk of immunogenicity. Furthermore, intravenous administration of epoetin is convenient for the nurse and is commonly used in Germany, Belgium and the USA. The purpose of this paper is to illustrate the very easy, practical ways of administering epoetin in prefilled syringes during dialysis at machine level, based on the authors' experiences in Belgium and Germany.


Service-learning across an accelerated curriculum.
In support of the community-based education philosophy, nursing faculty at a small health careers college in the midwestern United States incorporated a service-learning experience involving Sudanese refugee families and Latino community members into its accelerated community-based nursing program (ACE) curriculum. The purpose of the service-learning experience is to allow students the opportunity develop relationships through which they may gain an understanding of unique needs within a community. This article describes the development and benefits of the service-learning experience across the ACE curriculum. Through reflection, students broaden and deepen their understanding about the health of individuals in the community and acquire a more sophisticated understanding of risk


Comparison Between Wrist-Worn and Waist-Worn Accelerometry.
To use the most recent ActiGraph model (GT9X) to compare counts per minute (CPM) estimates between wrist-worn and waist-worn attachment sites. Participants completed 2 conditions (laboratory [N = 13] and free-living conditions [N = 9]), in which during both of these conditions they wore 2 ActiGraph GT9X accelerometers on their nondominant wrist (side-by-side) and 2 ActiGraph GT9X accelerometers on their right hip in line with the midaxillary line (side-by-side). During the laboratory visit, participants completed 5 treadmill-based trials all lasting 5 min: walk at 3 mph, 3.5 mph, 4 mph, and a jog at 6 mph and 6.5 mph. During the free-living setting, participants wore the monitors for 8 hours. Paired t test, Pearson correlation and Bland-Altman analyses were employed to evaluate agreement of CPM between the attachment sites. Across all intensity levels and setting (laboratory and free-living), CPM were statistically significantly and substantively different between waist- and wrist-mounted accelerometry. Attachment site drastically influences CPM. As such, extreme caution should be exercised when comparing CPM estimates among studies employing different attachment site methodologies, particularly waist versus wrist.


Students' perceptions of the Script Concordance Test and its impact on their learning behavior: a mixed methods study.
The Script Concordance Test (SCT) is increasingly used in postgraduate and undergraduate education as a method of summative clinical assessment. It has been shown to have high validity and reliability but there is little evidence of its use in veterinary education as assessment for learning. This study investigates some students' perceptions of the SCT and its effects on their approaches to learning. Final-year undergraduates of the School of Veterinary Medicine and Science (SVMS) at the University of Nottingham participated in a mixed-methods study after completing three formative SCT assessments. A qualitative, thematic analysis was produced from transcripts of three focus group discussions. The quantitative study was a survey based on the analyses of the qualitative study. Out of 50 students who registered for the study, 18 participated in the focus groups and 28 completed the survey. Clinical experience was regarded as the most useful source of information for answering the SCT. The students also indicated that recall of facts was perceived as useful for multiple-choice questions but least useful for the SCT. Themes identified in the qualitative study related to reliability, acceptability, educational impact, and validity of the SCT. The evidence from this study shows that the SCT has high face validity among veterinary students. They reported that it encouraged them to reflect upon their clinical experience, to participate in discussions of case material, and to adopt a deeper approach to clinical learning. These findings strongly suggest that the SCT is potentially a valuable method for assessing clinical reasoning and enhancing student learning.


High-speed information reconciliation with syndrome-based early termination for continuous-variable quantum key distribution.
Information reconciliation (IR) is an indispensable component in the post-processing stage of continuous-variable quantum key distribution (CV-QKD), which adopts error-correcting codes to address the asymmetry of secret keys. Currently, low-density parity-check (LDPC) decoding in IR is a post-processing bottleneck in high-speed CV-QKD systems since the upper bound on secret key rate is higher than the information throughput delivered by decoder. In this paper, we study the relationship between the syndrome variation pattern (SVP) in iterative decoding and reconciliation frame error rate. An early termination scheme based on SVP is proposed and applied to multidimensional reconciliation, which can increase information throughput by adaptively adjusting the iteration number of iterative decoding to real-time decoding status. Furthermore, we show that only the resulting syndrome of the highest-rate code part in Raptor-like LDPC codes needs to be calculated to verify whether the reconciliation is successful by studying the convergency of resulting syndrome, which can save a large fraction of computational resources for syndrome calculation. Simulation results show that information throughput of the proposed scheme can be improved by 617.1% compared to the existing scheme when the IR efficiency reaches 97.09%. The proposed scheme points out a new direction for breaking the post-processing bottleneck in high-speed CV-QKD systems.


"There's so much to be done": a qualitative study to elucidate research priorities in childhood-onset systemic lupus erythematosus.
There is a pressing need for high-quality, comprehensive research to describe the natural history, best treatments, access to care and disparities in care for patients with childhood-onset SLE (cSLE). Building on a previously published survey study of cSLE clinicians and researchers to describe research priorities in cSLE, the primary objective of this study was to conduct expert interviews to define high-priority areas for cSLE research. Individuals with identified multidisciplinary expertise in cSLE were recruited worldwide using purposive sampling technique. Experts participated in open-ended, semistructured qualitative interviews. Interviews were designed to elicit expert perspectives on research priorities, optimal research approaches, and factors that facilitate and hinder advancing cSLE research. Interviews were digitally recorded, transcribed and de-identified for analysis. Analysis for underlying themes of cSLE expert perspectives was performed using a constant comparative approach. Twenty-nine experts with diverse clinical and research backgrounds participated. Themes emerged within five domains: (1) expanding disease knowledge; (2) investigator collaboration; (3) partnering with patients and families; (4) improving care to optimise research; and (5) overcoming investigator barriers. Choosing a singular area of focus was difficult; experts identified many competing priorities. Despite the numerous priorities that emerged, experts described several existing and potential opportunities for advancing cSLE research. In addition to the priorities identified by cSLE experts in this study, the opportunities for advancing cSLE research and care that were proposed should be used as a foundation for creation of a cSLE research agenda for both research and funding allocation.


Selectivity Control in the Direct CO Esterification over Pd@UiO-66: The Pd Location Matters.
The selectivity control of Pd nanoparticles (NPs) in the direct CO esterification with methyl nitrite toward dimethyl oxalate (DMO) or dimethyl carbonate (DMC) remains a grand challenge. Herein, Pd NPs are incorporated into isoreticular metal-organic frameworks (MOFs), namely UiO-66-X (X=-H, -NO2 , -NH2 ), affording Pd@UiO-66-X, which unexpectedly exhibit high selectivity (up to 99 %) to DMC and regulated activity in the direct CO esterification. In sharp contrast, the Pd NPs supported on the MOF, yielding Pd/UiO-66, displays high selectivity (89 %) to DMO as always reported with Pd NPs. Both experimental and DFT calculation results prove that the Pd location relative to UiO-66 gives rise to discriminated microenvironment of different amounts of interface between Zr-oxo clusters and Pd NPs in Pd@UiO-66 and Pd/UiO-66, resulting in their distinctly different selectivity. This is an unprecedented finding on the production of DMC by Pd NPs, which was previously achieved by Pd(II) only, in the direct CO esterification.


Precision medicine for the diagnosis and treatment of carbapenem-resistant Enterobacterales: time to think from a different perspective.
Carbapenem-resistant Enterobacterales (CRE) represent a global public health problem. Precision medicine (PM) is a multicomponent medical approach that should be used to individualize the management of patients infected with CRE. Here, we differentiate carbapenem-producing CRE (CP-CRE) from non-CP-CRE and the importance of this distinction in clinical practice. The current phenotypic CRE-case definition and its implications are also discussed. Additionally, we summarize data regarding phenotypic and molecular diagnostic tools and available antibiotics. In order to review the most relevant data, a comprehensive literature search of peer-reviewed articles in PubMed and abstracts presented at high-impact conferences was performed. PM in CRE infections entails a multi-step process that includes applying the current phenotypic definition, utilization of the right phenotypic or molecular testing methods, and thorough evaluation of risk factors, source of infection, and comorbidities. A powerful armamentarium is available to treat CRE infections, including recently approved agents. Randomized controlled trials targeting specific pathogens instead of site of infections may be appropriate to fill in the current gaps. In light of the diverse enzymology behind CP-CRE, PM should be employed to provide the best therapy based on the underlying resistance mechanism.


A cross comparison between Ayurvedic etiology of Major Depressive Disorder and bidirectional effect of gut dysregulation.
Ayurveda, an Indian medical science has been practiced for thousands of years. What makes Ayurveda relevant today is its subtle understanding of the environment and its focus on the generation of good health through one's own lifestyle choices. The digestive system has long been an area of critical importance within the Ayurvedic system and is only now being acknowledged by modern science as a key component in the regulation of physical and mental well-being. The gut microbiome and enteric nervous system are two particular areas in which the onset of psychiatric disorders, such as depression, have been associated. There are some striking similarities between this biomedical understanding of the gastrointestinal system and the Ayurvedic perspective of disease development. Major Depressive Disorder (MDD) is becoming increasingly linked with gut dysregulation in contemporary literature and is a pathology explored within both the Ayurvedic and Western systems of medicine. This literature review seeks to draw parallels between these two areas of study and highlight the importance of the digestive system when diagnosing and treating MDD.


The use of natural products to target cancer stem cells.
The cancer stem cell hypothesis has been used to explain many cancer complications resulting in poor patient outcomes including induced drug resistance, metastases to distant organs, and tumor recurrence. While the validity of the cancer stem cell model continues to be the cause of much scientific debate, a number of putative cancer stem cell markers have been identified making studies concerning the targeting of cancer stem cells possible. In this review, a number of identifying properties of cancer stem cells have been outlined including properties contributing to the drug resistance and metastatic potential commonly observed in supposed cancer stem cells. Due to cancer stem cells' numerous survival mechanisms, the diversity of cancer stem cell markers between cancer types and tissues, and the prevalence of cancer stem cell markers among healthy stem and somatic cells, it is likely that currently utilized treatments will continue to fail to eradicate cancer stem cells. The successful treatment of cancer stem cells will rely upon the development of anti-neoplastic drugs capable of influencing many cellular mechanisms simultaneously in order to prevent the survival of this evasive subpopulation. Natural compounds represent a historically rich source of novel, biologically active compounds which are able to interact with a large number of cellular targets while limiting the painful side-effects commonly associated with cancer treatment. A brief review of select natural products that have been demonstrated to diminish the clinically devastating properties of cancer stem cells or to induce cancer stem cell death is also presented.


Multiple giant cell tumors in a patient with Gulf War syndrome.
"Persian Gulf syndrome" refers to a group of clinical findings found in military personnel who served in the Persian Gulf War. The most commonly reported symptoms include chronic fatigue, headache, and neurologic disorders. Recently, new information has linked Whipple's disease and Ki-1 anaplastic large cell lymphoma to this syndrome. Presented here is an unusual case of multiple giant cell tumors of the hand in a patient with documented Persian Gulf syndrome. The epidemiologic significance between these two entities is unclear, because this is a single reported case. However, the practical message is clear. Physicians must meticulously evaluate patients who are veterans of the Persian Gulf conflict to further our understanding and confirm the existence of this syndrome.


Simultaneous immunoassay analysis of plasma IL-6 and TNF-α on a microchip.
Sandwich enzyme-linked immunosorbant assay (ELISA) using a 96-well plate is frequently employed for clinical diagnosis, but is time-and sample-consuming. To overcome these drawbacks, we performed a sandwich ELISA on a microchip. The microchip was made of cyclic olefin copolymer with 4 straight microchannels. For the construction of the sandwich ELISA for interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α), we used a piezoelectric inkjet printing system for the deposition and fixation of the 1st anti-IL-6 antibody or 1st anti-TNF-α antibody on the surface of the each microchannel. After the infusion of 2 µl of sample to the microchannel and a 20 min incubation, 2 µl of biotinylated 2nd antibody for either antigen was infused and a 10 min incubation. Then 2 µl of avidin-horseradish peroxidase was infused; and after a 5 min incubation, the substrate for peroxidase was infused, and the luminescence intensity was measured. Calibration curves were obtained between the concentration and luminescence intensity over the range of 0 to 32 pg/ml (IL-6: R(2) = 0.9994, TNF-α: R(2) = 0.9977), and the detection limit for each protein was 0.28 pg/ml and 0.46 pg/ml, respectively. Blood IL-6 and TNF-α concentrations of 5 subjects estimated from the microchip data were compared with results obtained by the conventional method, good correlations were observed between the methods according to linear regression analysis (IL-6: R(2) = 0.9954, TNF-α: R(2) = 0.9928). The reproducibility of the presented assay for the determination of the blood IL-6 and TNF-α concentration was comparable to that obtained with the 96-well plate. Simultaneous detection of blood IL-6 and TNF-α was possible by the deposition and fixation of each 1st antibody on the surface of a separate microchannel. This assay enabled us to determine simultaneously blood IL-6 and TNF-α with accuracy, satisfactory sensitivity, time saving ability, and low consumption of sample and reagents, and will be applicable to clinic diagnosis.


Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough.
Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T H 1 and T H 2 cells. We sought to determine whether levels of T H 1/T H 2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease. The T H 1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell alpha chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T H 2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3 + and CCR5 + (T H 1) and CCR4 + and CCR3 + (T H 2) chemokine receptors were determined in BALF by flow cytometry. Pulmonary CCR4 + CD4 + cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4 + CD4 + cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV 1 . In contrast, CXCR3 + CD8 + cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3 + CD8 + cells correlated with levels of ITAC and IFN-gamma. Pulmonary CCR4 + CD4 + and CXCR3 + CD8 + cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.


Radical Cationic Pathway for the Decay of Ionized Glyme Molecules in Liquid Solution.
Chemical stability of primary radical cations (RCs) generated in irradiated matter determines substantially the radiation resistance of organic materials. Transformations of the RCs of the glyme molecules, R(-O-CH2-CH2-)nO-R (R = CH3, n = 1-4) has been studied on the nanosecond time scale by measuring the magnetic field effects in the recombination fluorescence from irradiated liquid solutions of the glymes. In all cases, the RCs observed were different from that expected for the primary ones and revealed very similar hyperfine couplings independent of the poly(ethylene oxide) chain length and of the substitution of terminal methyl groups by C2H5 or CH2CH2Cl, as has been shown with diglyme as an example. Quantum chemical analysis of possible chemical transformations for the monoglyme RC as a model system allowed us to discover the reaction pathway yielding the methyl vinyl ether RC. The pathway involves intramolecular proton transfer followed by C-O bond cleavage. Only one (-O-CH2-CH2-O-) fragment is involved in this transformation, which is nearly barrierless due to the catalytic effect of adjacent glyme molecules. The rapid formation of the methyl vinyl ether RC in the irradiated monoglyme was confirmed by the numerical simulation of the experimental curves of the time-resolved magnetic field effect. These findings suggest that the R'-O-CH═CH2(•+) formation is a typical decay pathway for the primary RCs in irradiated liquid glymes.


Data Sharing and Data Registries in Physical Medicine and Rehabilitation.
The field of physical medicine & rehabilitation (PM&R), along with all the disciplines it encompasses, has evolved rapidly in the past 50 years. The number of controlled trials, systematic reviews, and meta-analyses in PM&R increased 5-fold from 1998 to 2013. In recent years, professional, private, and governmental institutions have identified the need to track function and functional status across providers and settings of care and on a larger scale. Because function and functional status are key aspects of PM&R, access to and sharing of reliable data will have an important impact on clinical practice. We reviewed the current landscape of PM&R databases and data repositories, the clinical applicability and practice implications of data sharing, and challenges and future directions. We included articles that (1) addressed any aspect of function, disability, or participation; (2) focused on recovery or maintenance of any function; and (3) used data repositories or research databases. We identified 398 articles that cited 244 data sources. The data sources included 66 data repositories and 179 research databases. We categorized the data sources based on their purposes and uses, geographic distribution, and other characteristics. This study collates the range of databases, data repositories, and data-sharing mechanisms that have been used in PM&R internationally. In recent years, these data sources have provided significant information for the field, especially at the population-health level. Implications and future directions for data sources also are discussed.


Intergenerational stability of the myotonic dystrophy protomutation.
The amplification of the CTG trinucleotide repeat in myotonic dystrophy (DM) correlates with increasingly severe phenotypes. We designate its minimal amplification the 'protomutation' since it is the mutation itself at an early stage of intergenerational evolution and is associated with very mild clinical signs. From the study of 536 DM mutation carriers (from 158 affected families), a total of 60 DM-parent/DM-offspring pairings were identified in which the parent had the protomutation. We found a strong correlation between the protomutation length and the amplification observed in the next generation. We also observed the stable transmission of the protomutation through successive generations. This stability may explain the maintenance in the population of this autosomal dominant disease despite the low reproductive fitness of severe DM phenotypes.


A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better?
Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).


Computational analysis of an aortic valve jet with Lagrangian coherent structures.
Important progress has been achieved in recent years in simulating the fluid-structure interaction around cardiac valves. An important step in making these computational tools useful to clinical practice is the development of postprocessing techniques to extract clinically relevant information from these simulations. This work focuses on flow through the aortic valve and illustrates how the computation of Lagrangian coherent structures can be used to improve insight into the transport mechanics of the flow downstream of the valve, toward the goal of aiding clinical decision making and the understanding of pathophysiology.


Ultra-high speed digital micro-mirror device based ptychographic iterative engine method.
To reduce the long data acquisition time of the common mechanical scanning based Ptychographic Iterative Engine (PIE) technique, the digital micro-mirror device (DMD) is used to form the fast scanning illumination on the sample. Since the transverse mechanical scanning in the common PIE is replaced by the on/off switching of the micro-mirrors, the data acquisition time can be reduced from more than 15 minutes to less than 20 seconds for recording 12 × 10 diffraction patterns to cover the same field of 147.08 mm2. Furthermore, since the precision of DMD fabricated with the optical lithography is always higher than 10 nm (1 μm for the mechanical translation stage), the time consuming position-error-correction procedure is not required in the iterative reconstruction. These two improvements fundamentally speed up both the data acquisition and the reconstruction procedures in PIE, and relax its requirements on the stability of the imaging system, therefore remarkably improve its applicability for many practices. It is demonstrated experimentally with both USAF resolution target and biological sample that, the spatial resolution of 5.52 μm and the field of view of 147.08 mm2 can be reached with the DMD based PIE method. In a word, by using the DMD to replace the translation stage, we can effectively overcome the main shortcomings of common PIE related to the mechanical scanning, while keeping its advantages on both the high resolution and large field of view.


Optimization of the Small Glycan Presentation for Binding a Tumor-Associated Antibody: Application to the Construction of an Ultrasensitive Glycan Biosensor.
The main aim of the study was to optimize the interfacial presentation of a small antigen-a Tn antigen (N-acetylgalactosamine)-for binding to its analyte anti-Tn antibody. Three different methods for the interfacial display of a small glycan are compared here, including two methods based on the immobilization of the Tn antigen on a mixed self-assembled monolayer (SAM) (2D biosensor) and the third one utilizing a layer of a human serum albumin (HSA) for the immobilization of a glycan forming a 3D interface. Results showed that the 3D interface with the immobilized Tn antigen is the most effective bioreceptive surface for binding its analyte. The 3D impedimetric glycan biosensor exhibited a limit of detection of 1.4 aM, a wide linear range (6 orders of magnitude), and high assay reproducibility with an average relative standard deviation of 4%. The buildup of an interface was optimized using various techniques with the visualization of the glycans on the biosensor surface by atomic force microscopy. The study showed that the 3D biosensor is not only the most sensitive compared to other two biosensor platforms but that the Tn antigen on the 3D biosensor surface is more accessible for antibody binding with better kinetics of binding (t50% = 137 s, t50% = the time needed to attain 50% of a steady-state signal) compared to the 2D biosensor configuration with t50% = 354 s. The 3D glycan biosensor was finally applied for the analysis of a human serum sample spiked with an analyte.


Dopamine and insulin interact to modulate in vitro glucose transport in rat adipocytes.
The in vitro effects of dopamine (DA) and insulin on -14C glucose oxidation (transport) in isolated rat adipocytes was studied. Low to intermediate concentrations of DA combined with low concentrations of insulin tended to stimulate glucose transport whilst high concentrations of DA combined with high concentrations of insulin produced inhibition of insulin stimulated glucose transport. The effect of DA on glucose transport was mediated via beta-adrenergic receptors, since propranolol, but not haloperidol or phentolamine, antagonised these effects of dopamine. These effects of dopamine on glucose transport may be relevant to the pathophysiology of Parkinson's disease and other neuropsychiatric conditions in which abnormalities of dopaminergic functions are thought to be of major pathogenic importance.


The effects of co-ordinating postures with shoulder and elbow flexion angles on maximum grip strength and upper-limb muscle activity in standing and sitting postures.
Eighteen co-ordination postures with shoulder flexion angles (0°, 45° and 90°) and elbow flexion angles (0°, 45° and 90°) in standing and sitting positions were evaluated to identify the effects of co-ordination postures on maximum grip strength and muscle activities of the upper limb in this study. Thirty-nine subjects were recruited and their maximum grip strengths were measured. According to the analysis of grip strength, grip strength was shown to be stronger in a standing posture (297.4 N) than in a sitting posture (274.6 N). In addition, grip strength (293.8 N) at 90° shoulder flexion angle was significantly higher than that at 0° and 45° shoulder angles. There was no statistically significant difference in grip strength from the effects of elbow angles in this study. The results of muscle activities for all muscle groups showed a similar trend with the results of grip strength associated with shoulder angles.


Performance assessment of bio-inspired systems: flow sensing MEMS hairs.
Despite vigorous growth in biomimetic design, the performance of man-made devices relative to their natural templates is still seldom quantified, a procedure which would however significantly increase the rigour of the biomimetic approach. We applied the ubiquitous engineering concept of a figure of merit (FoM) to MEMS flow sensors inspired by cricket filiform hairs. A well known mechanical model of a hair is refined and tailored to this task. Five criteria of varying importance in the biological and engineering fields are computed: responsivity, power transfer, power efficiency, response time and detection threshold. We selected the metrics response time and detection threshold for building the FoM to capture the performance in a single number. Crickets outperform actual MEMS on all criteria for a large range of flow frequencies. Our approach enables us to propose several improvements for MEMS hair-sensor design.


Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies.
Ebola virus (EBOV) is considered one of the most aggressive infectious agents and is capable of causing death in humans and nonhuman primates (NHPs) within days of exposure. Recent strategies have succeeded in preventing acquisition of infection in NHPs after treatment; however, these strategies are only successful when administered before or minutes after infection. The present work shows that a combination of three neutralizing monoclonal antibodies (mAbs) directed against the Ebola envelope glycoprotein (GP) resulted in complete survival (four of four cynomolgus macaques) with no apparent side effects when three doses were administered 3 days apart beginning at 24 hours after a lethal challenge with EBOV. The same treatment initiated 48 hours after lethal challenge with EBOV resulted in two of four cynomolgus macaques fully recovering. The survivors demonstrated an EBOV-GP-specific humoral and cell-mediated immune response. These data highlight the important role of antibodies to control EBOV replication in vivo, and support the use of mAbs against a severe filovirus infection.


The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury.
Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.


Hybrid Cubature Kalman filtering for identifying nonlinear models from sampled recording: Estimation of neuronal dynamics.
Kalman filtering methods have long been regarded as efficient adaptive Bayesian techniques for estimating hidden states in models of linear dynamical systems under Gaussian uncertainty. Recent advents of the Cubature Kalman filter (CKF) have extended this efficient estimation property to nonlinear systems, and also to hybrid nonlinear problems where by the processes are continuous and the observations are discrete (continuous-discrete CD-CKF). Employing CKF techniques, therefore, carries high promise for modeling many biological phenomena where the underlying processes exhibit inherently nonlinear, continuous, and noisy dynamics and the associated measurements are uncertain and time-sampled. This paper investigates the performance of cubature filtering (CKF and CD-CKF) in two flagship problems arising in the field of neuroscience upon relating brain functionality to aggregate neurophysiological recordings: (i) estimation of the firing dynamics and the neural circuit model parameters from electric potentials (EP) observations, and (ii) estimation of the hemodynamic model parameters and the underlying neural drive from BOLD (fMRI) signals. First, in simulated neural circuit models, estimation accuracy was investigated under varying levels of observation noise (SNR), process noise structures, and observation sampling intervals (dt). When compared to the CKF, the CD-CKF consistently exhibited better accuracy for a given SNR, sharp accuracy increase with higher SNR, and persistent error reduction with smaller dt. Remarkably, CD-CKF accuracy shows only a mild deterioration for non-Gaussian process noise, specifically with Poisson noise, a commonly assumed form of background fluctuations in neuronal systems. Second, in simulated hemodynamic models, parametric estimates were consistently improved under CD-CKF. Critically, time-localization of the underlying neural drive, a determinant factor in fMRI-based functional connectivity studies, was significantly more accurate under CD-CKF. In conclusion, and with the CKF recently benchmarked against other advanced Bayesian techniques, the CD-CKF framework could provide significant gains in robustness and accuracy when estimating a variety of biological phenomena models where the underlying process dynamics unfold at time scales faster than those seen in collected measurements.


Prefabrication of vascularized porous three-dimensional scaffold induced from rhVEGF(165): a preliminary study in rats.
Several shortcomings have limited the routine use of autogenous vascularized bone graft. The present study investigates the prefabrication of vascularized scaffold with the desired shape and microarchitecture combined with recombinant human vascular endothelial growth factor 165 (rhVEGF(165)) to mimic autogenous vascularized bone graft. Eighty-five porous calcium phosphate cement scaffolds constructed by rapid prototyping technology were divided into four groups: group A [rhVEGF(165)-fibrin sealant (FS) scaffold], group B (hVEGF(165) scaffold), group C (FS scaffold), and group D (scaffold alone). The release of rhVEGF(165) from the scaffolds was examined in vitro. The vessel density, relative functionalized vessels, vessel diameter and relative vessel area were also measured. The sustained release of hVEGF(165) lasted 14 days in the absence of plasmin and 12 days in the presence of plasmin in group A and 10 days in group B. There was no statistical difference between groups A and B at 2 or 4 weeks in terms of vessel density, relative functionalized vessels, vessel diameter, and relative vessel area, as between groups C and D. However, the above parameters were greater in groups A and B than groups C and D. The scaffolds with the desired shape and microarchitecture combined with rhVEGF(165) could shorten the time needed for the construction of prefabricated vascularized grafts and accelerate the maturation of the vessels.


Mesenteric vein thrombosis after surgery and radiotherapy for pancreatic carcinoma. A case report.
A case is reported of a 54-year-old female patient undergoing the resection of a pancreatic carcinoma with intraoperative radiation therapy (10 Gy) on the tumor bed and subsequent external beam radiotherapy (50 Gy). After surgery the patient presented chronic diarrhea resistant to oral pancreatic enzymes. Twenty-five months postoperatively, mesenteric vein thrombosis was diagnosed after an episode of melena and was treated with conservative therapy. At five-year follow-up the patient had no evidence of neoplastic disease and bowel movements had increased. On imaging examinations, the presence of venous collaterals and cavernous appearance of the portal trunk were documented.


Exact finite-size corrections of the free energy for the square lattice dimer model under different boundary conditions.
We express the partition functions of the dimer model on finite square lattices under five different boundary conditions (free, cylindrical, toroidal, Möbius strip, and Klein bottle) obtained by others (Kasteleyn, Temperley and Fisher, McCoy and Wu, Brankov and Priezzhev, and Lu and Wu) in terms of the partition functions with twisted boundary conditions Z(alpha, beta) with (alpha, beta)=(1/2,0), (0,1/2) and (1/2,1/2). Based on such expressions, we then extend the algorithm of Ivashkevich, Izmailian, and Hu [J. Phys. A 35, 5543 (2002)] to derive the exact asymptotic expansion of the logarithm of the partition function for all boundary conditions mentioned above. We find that the aspect-ratio dependence of finite-size corrections is sensitive to boundary conditions and the parity of the number of lattice sites along the lattice axis. We have also established several groups of identities relating dimer partition functions for the different boundary conditions.


Kinetic hindrance during the surface oxidation of Cu(100)-c(10x2)-Ag.
The influence of c(10x2)-Ag superstructure on the oxidation kinetics and oxygen adsorption-induced nanostructures on Cu(100) has been investigated as a function of O(2) exposure at 373 K by employing scanning tunneling microscopy and x-ray photoelectron spectroscopy. The oxygen adsorption-induced segregation of Cu through the Ag overlayer is found to trigger agglomeration of Ag and subsequent formation of ordered oval-shaped nanosize metallic Ag islands separated by Cu(100)-(2 radical2x radical2)R45 degrees -O surface phase. As oxygen exposure is further increased, all Ag is eventually covered by oxidized Cu. The presence of Ag delays the completion of the fully reconstructed (2 radical2x radical2)R45 degrees -O surface and the nucleation and growth of Cu(2)O islands by limiting Cu diffusion toward the surface. Once Cu(2)O grows into the bulk deeper than buried Ag, the oxidation kinetics follow that of the unalloyed clean Cu(100) surface. Similar kinds of Cu-O nanostructures are found on both clean Cu(100) and Cu(100)-c(10x2)-Ag surfaces. Details of the morphology of the Ag structures and kinetic control of the surface oxidation mechanism on Cu(100)-c(10x2)-Ag are discussed.


Patient Perception of Speech Outcomes: The Relationship Between Clinical Measures and Self-Perception of Speech Function Following Surgical Treatment for Oral Cancer.
Treatment for oral cancer can result in speech impairments that can have varying impacts on patient quality of life. This study explored the relationship between clinical measures of speech impairment and the perception that patients had of this change in the early stage of recovery. This was a quasi-experimental 1-group pre-post study design carried out on 10 patients with surgical intervention for oral cancer. Two clinical measures (word intelligibility and consonant phoneme error) and 2 patient-perception measures (Speech Handicap Index total score and Speech Handicap Index patient criteria score) were collected at preoperative and 1-month postoperative appointments. Qualitative analysis revealed discordance between clinical and patient-perceived measures in 4 of 10 patients. Change in consonant phoneme error and change in word intelligibility were significantly correlated (r = .827). Furthermore, on average, statistically significant relationships were not found between clinical and patient-perceived measures or between the 2 patient-perception measures. Discordance between clinical and patient-perceived measures was observed in almost half of the sample, indicating that clinical tests did not fully explain the extent of impairment perceived by patients. Speech outcomes should focus on both types of measures, and patient perception outcomes should be carefully considered when recommending speech therapy.


Rnf2 knockdown reduces cell viability and promotes cell cycle arrest in gastric cancer cells.
Rnf2 is a fundamental component of the polycomb repressive complex 1and acts as the really interesting new gene finger E3 ligase, which is responsible for histone 2A modification. Previous studies have shown that the ring finger protein 2 (Rnf2) is overexpressed in various types of tumor and has a close association with tumor development. However, few studies have been carried out into the expression and biological function of Rnf2 in gastric cancer cells. The present study measured the expression of Rnf2 in gastric cancer cells and normal epithelial gastric cells. The results demonstrate that Rnf2 is upregulated in gastric cancer cells. In addition, the knockdown of Rnf2 inhibited the cell viability and induced increased G1 phase followed by a substantial reduction of the G2/M phase. The expression levels of p21 and p27 were also significantly elevated by the knockdown of Rnf2. These results provide evidence of the oncogenic function of Rnf2 in gastric cancer, possibly through an inhibition of cellular proliferation and a delay of the G2/M phase. Therefore, Rnf2 may be a novel target for the prognosis and therapy of gastric cancer.


Platycodon grandiflorum roots: A comprehensive study on odor/aroma and chemical properties during roasting.
Platycodon is a ubiquitous plant widely grown in Asia. This study investigated changes in odor/aroma associated sensory attributes and chemical properties in Platycodon grandiflorum roots upon roasting. Amino acid analysis, electronic tongue analysis, chemical property analysis, volatile compound analysis, GC-olfactometry-assisted sensory attributes, and electronic nose analysis were performed. In results, amino acid profiles showed diverse patterns. Electronic tongue analysis somewhat corresponded to the free amino acid profiles. Total phenolic content, antioxidant capacity, and browning intensity significantly increased up to 4 min and slightly decreased afterward. Various pyrazines relevant to roasted odor such as 3-ethyl-2, 5-dimethyl-pyrazine, and 2, 6-dimethyl-pyrazine were generated by roasting. In electronic nose analysis, positive odor parameter significantly increased and potential unpleasant odorants significantly decreased over time. This is believed to be the first study demonstrating overall insight on odor/aroma and chemical characteristics and utilizing objective sensory measures on roasted Platycodon grandiflorum roots for food applications. PRACTICAL APPLICATIONS: This study will be utilized (a) to researchers and food companies who are interested in medicinal foods (b) to individuals and food industry that search for changes in sensory characteristics and chemical changes of foods induced by roasting, and (c) to farmers and crop producers who look for utilization and applications of Platycodon grandiflorum roots as food sources and ingredients.


Detection methods of the drug-addiction and alcoholism treatment programme of the Spanish National Railway Company (RENFE).
Social problems in enterprises need to be approached by all groups involved in order to achieve a satisfactory result. With regard to Occupational Health and, specifically, drug-addiction, the groups concerned are Occupational Health Services, Trade Unionists and Managers. To analyse the involvement of the social groups (Occupational Health Service, Management and Trade Unions) in relation to the detection of workers suffering from drug-addiction and/or alcoholism. During the first eight years of implementation (1990-1997) of the Drug-Addiction and Alcoholism Treatment Programme of the Spanish National Railway Company (RENFE), a total of 477 workers consuming alcohol and drugs were detected and treated under the Programme (1.1% prevalence), 465 men (97.5%) and 12 women (2.5%), with an average age of 39.8 years. The subjects were detected by occupational physicians (55.4%), occupational psychologists (2.9%), managers (11.3%), trade unionists (19.5%), via self-referral (9.4%) and by other means (1.5%). The results demonstrate the efficiency and the profitability to the company of prevention and treatment interventions and the need for the coordination of managers, trade unions and occupational health services.


[Long-term hemodynamic compromise in internal carotid artery dissection: quantitative blood volume flow evaluation using 2D Cine phase-contrast MR imaging].
To use the magnetic resonance (MR) phase-contrast technique as a non-invasive method to determine blood volume flow in internal carotid artery (ICA) dissection, which has variable initial volume flow reduction and long term hemodynamic compromise. ICA dissection can lead to partial or complete recanalization or persistent occlusion, and strong clinical motivation exists for reliable assessment of the blood flow, in particular blood volume flow, in the carotid artery circulation after ICA dissection. Blood volume flow in the carotid artery circulation was quantified in 28 patients with unilateral ICA dissection and 20 age-matched normal controls. Blood volume flow was measured in the ICAs and the common carotid arteries (CCAs) using 2D cine phase-contrast MR imaging. Final measurements were performed until after at least 6 months the hemodynamic compromise showed no changes by ultrasound and MRA. In long term follow up, 11/28 patients demonstrated remaining vessel occlusion, 10/28 partial and 7/28 complete recanalizations. Patients with ICA occlusion showed a significant contralateral volume flow increase (mean 56 %, p < 0.001) in comparison to normal controls. Patients with partial recanalization demonstrated volume flow rates between 24 ml/min and 188 ml/min in the dissected ICA and a less but significant (p < 0.001) increase in the contralateral volume flow. In patients with complete recanalization, normal volume flow conditions were found for both ICAs and CCAs. In ICA dissection, quantitative volume flow determination using 2D cine phase-contrast MR imaging is helpful in the initial assessment and long term follow-up of hemodynamic compromise. ICA dissection demonstrated a partial or complete recanalization in nearly (2/3) of the investigated patients and a persisting vessel occlusion in little more than (1/3). Compensatory contralateral increase in volume flow was found.


The development of a measure of correlates of child sexual abuse: the Traumatic Sexualization Survey.
The present research developed an instrument which assesses cognitive and behavioral factors purportedly associated with child sexual abuse histories. Finkelhor and Browne's construct of traumatic sexualization served as a guide for item selection. The study resulted in a 38-item reliable measure consisting of four subscales: Avoidance and Fear of Sexual and Physical Intimacy, Thoughts About Sex, Role of Sex in Relationships, and Attraction/Interest and Sexuality. Construct validity was established using a variety of self-report instruments associated with the dimensions of traumatic sexualization. Sexually abused women scored higher than nonabused women on three TSS factors. Physically abused women differed from nonabused women on only one factor. Sexually abused women did not score significantly higher than physically abused women on any factors.


Hydroxyurea-induced hemolytic anemia in a patient with essential thrombocythemia.
Hydroxyurea (HU) has been used in patients with essential thrombocythemia (ET) to reduce the frequency and severity of thrombotic complications of the disease. It acts by causing bone marrow depression, resulting in a decrease in platelet and leukocyte counts and in anemia with megaloblastosis. Herein we report a case of an 80-year-old man with ET who developed severe hemolytic anemia requiring multiple packed RBC transfusions while being treated with HU. The hemolysis persisted until discontinuation of the drug. This case suggests hemolysis as a potential side effect of HU and raises the clinical concern that not all HU-induced anemia is secondary to erythropoiesis depression. With the increasing use of HU in the management of ET, hemoglobinopathy, and other diseases, the importance of monitoring for hemolysis must be further emphasized in these patients.


Prevention of respiratory infections with alpha- and gamma-herpesviruses in weanling foals by using a modified live intra-nasal equine influenza vaccine.
This study aimed to determine if the administration of a modified live equine influenza virus vaccine (FluAvert) to foals would positively impact their health and reduce colonization of their upper airways with equine herpesviruses (EHV) during the weaning period. A single dose of FluAvert was given to 20 healthy foals 7 days prior to being weaned; 20 healthy foals served as unvaccinated controls. Nasal secretions and blood were collected before vaccination, the day of weaning, and weekly thereafter for 3 weeks. Nasal secretions were tested by quantitative polymerase chain reaction (qPCR) for EHV-1, -2, -4 and -5. Whole blood was analyzed for a complete blood cell count and fibrinogen concentration. Physical assessments were made daily. The use of FluAvert was associated with a better clinical outcome. However, the equine influenza virus (EIV) vaccine did not influence selected hematological parameters and kinetics of herpesviruses. The clinical benefit observed in vaccinates may explain the perception that the EIV vaccine induces cross-protection against respiratory agents.


Student loan burden and its impact on career decisions in dermatology.
Dermatology departments in the United States face difficulties in recruiting dermatologists to academic positions, raising concerns for the future of dermatology education and research. This preliminary study aimed to explore the impact of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program can be used as a recruitment tool for academic positions in dermatology. Results from this electronic survey, which was distributed to dermatology residents and attending physicians, revealed that debt burden may influence career decisions in dermatology. Dermatologists may not be fully educated on loan repayment options. With increased awareness, the PSLF can potentially be used as a recruitment tool for academic positions in dermatology.


Development of allocentric spatial recall from new viewpoints in virtual reality.
Using landmarks and other scene features to recall locations from new viewpoints is a critical skill in spatial cognition. In an immersive virtual reality task, we asked children 3.5-4.5 years old to remember the location of a target using various cues. On some trials they could use information from their own self-motion. On some trials they could use a view match. In the very hardest kind of trial, they were 'teleported' to a new viewpoint and could only use an allocentric spatial representation. This approach provides a strict test for allocentric coding (without either a matching viewpoint or self-motion information) while avoiding additional task demands in previous studies (it does not require them to deal with a small table-top environment or to manage stronger cue conflicts). Both the younger and older groups were able to point back at the target location better than chance when they could use view matching and/or self-motion, but allocentric recall was only seen in the older group (4.0-4.5). In addition, we only obtained evidence for a specific kind of allocentric recall in the older group: they tracked one major axis of the space significantly above chance, r(158) = .28, but not the other, r(158) = -.01. We conclude that there is a major qualitative change in coding for spatial recall around the fourth birthday, potentially followed by further development towards fully flexible recall from new viewpoints.


A detailed and validated three dimensional dynamic model of the patellofemoral joint.
A detailed 3D anatomical model of the patellofemoral joint was developed to study the tracking, force, contact and stability characteristics of the joint. The quadriceps was considered to include six components represented by 15 force vectors. The patellar tendon was modeled using four bundles of viscoelastic tensile elements. Each of the lateral and medial retinaculum was modeled by a three-bundle nonlinear spring. The femur and patella were considered as rigid bodies with their articular cartilage layers represented by an isotropic viscoelastic material. The geometrical and tracking data needed for model simulation, as well as validation of its results, were obtained from an in vivo experiment, involving MR imaging of a normal knee while performing isometric leg press against a constant 140 N force. The model was formulated within the framework of a rigid body spring model and solved using forth-order Runge-Kutta, for knee flexion angles between zero and 50 degrees. Results indicated a good agreement between the model predictions for patellar tracking and the experimental results with RMS deviations of about 2 mm for translations (less than 0.7 mm for patellar mediolateral shift), and 4 degrees for rotations (less than 3 degrees for patellar tilt). The contact pattern predicted by the model was also consistent with the results of the experiment and the literature. The joint contact force increased linearly with progressive knee flexion from 80 N to 210 N. The medial retinaculum experienced a peak force of 18 N at full extension that decreased with knee flexion and disappeared entirely at 20 degrees flexion. Analysis of the patellar time response to the quadriceps contraction suggested that the muscle activation most affected the patellar shift and tilt. These results are consistent with the recent observations in the literature concerning the significance of retinaculum and quadriceps in the patellar stability.


Contribution of SPECT to imaging of gastrointestinal adenocarcinoma with 111In-labeled anti-CEA monoclonal antibody.
Fourteen patients with suspected adenocarcinoma of the gastrointestinal tract received 1 mg of 111In-labeled anticarcinoembryonic antigen monoclonal antibody type ZCE025 combined with 40 mg unlabeled antibody of the same type. Planar and single-photon emission CT (SPECT) imaging studies were performed 3 days after infusion and, when possible, 7 days after infusion. Scan findings were correlated with the findings at surgery when possible. Tumor was detected by day-3 planar imaging in eight of 13 patients in whom tumor was documented histopathologically. Day-3 SPECT allowed demonstration of tumor in 11 of these 13 patients. In another patient whose scan was negative, no residual tumor was found at surgery. SPECT was particularly helpful in identifying small and midline tumors. In two cases, localization on SPECT helped identify the tumor mass on CT. Two primary tumors weighing less than 5 g could not be detected on either planar or SPECT scans. Histologically positive, normal-sized lymph nodes were not seen by planar imaging or SPECT. SPECT increased the detection rate over that achieved with planar imaging, helped to better localize scan abnormalities, and afforded more useful comparison between the monoclonal antibody study and CT.