Surgical Technique and Outcomes of Reconstruction for Blauth Type III Thumb Hypoplasia.
Historically, amputation and pollicization has been the recommended surgical treatment for Blauth type III hypoplastic thumbs. However, due to aesthetic objections or cultural preferences, some parents seek out alternative surgical options. The present study describes a nontraditional technique that preserves and augments the hypoplastic thumb. Patient charts were retrospectively reviewed to identify patients with Blauth type III hypoplastic thumbs who underwent thumb reconstruction at our institution from 2008 to 2018. The reconstruction procedure involved toe phalanx transfer, staged tendon transfers, and lengthening as needed. Motion was assessed categorically as ability to flex, extend, or oppose the thumb. Functionality was assessed as ability to pinch and grasp with the surgical hand. Patient- or parent-reported improvement in thumb function was also recorded. Of the 13 patients, 100% could flex, extend, and oppose the thumb to some degree. Eleven patients (85%) had functional one-handed grasp, and 9 (69%) had a functional pinch. Eleven patients (85%) reported no functional limitations of the operative hand. Thirteen patients (100%) reported improvement in hand function after surgery as compared to pre-operatively. There were 2 minor complications (15%), both of which resolved after intervention. No patients experienced donor-site morbidity. Reconstruction of Blauth III thumbs is a nontraditional technique that allows for digit retention by salvaging the hypoplastic thumb. In the present study, the majority of patients had functional thumbs and all reported postoperative improvement. Overall, our results suggest that reconstruction is a viable surgical option for Blauth III hypoplastic thumbs.


Statistical issues in long-term followup studies.
The thesis of this article is that since followup studies of patients with schizophrenia have provided a rich body of informative knowledge, emphasis should now be on hypothesis testing in future studies. The consumer of research needs to have a general appreciation of statistical thinking, design, and methods to make an informed synthesis of results presented. This article presents a brief discussion of relevant statistics and statistical issues, as free of jargon as possible. Given the multivariable nature of psychiatric research, the natural focus is on multivariate statistics. A strong background in statistics is not required to understand the methods described and how and why they might be applied. Reference material for more detailed discussions is provided. It is a truism to say that the highest quality scientific work is dependent on an intimate collaboration with the expert in statistics and the expert in clinical methods, and this merits repeating only because it is so often ignored.


Cerebrospinal Fluid Penetration Rate and Efficacy of Afatinib in Patients with EGFR Mutation-positive Non-small Cell Lung Cancer with Leptomeningeal Carcinomatosis: A Multicenter Prospective Study.
Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis. Eleven patients with histologically-proven EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis were enrolled in the study between April 2014 and November 2015. They were treated with afatinib (40 mg/day), and blood and CSF levels of afatinib were analyzed on day 8. The primary endpoint was CSF penetration rate. Secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The median age of patients was 66 years. Five patients harbored an exon 19 deletion, three harbored a p.L858R point mutation, and three harbored an uncommon exon 18 mutation. The levels of afatinib in blood and CSF (mean±SD) were 233.26±195.40 nM and 3.16±1.95 nM, respectively. The CSF penetration rate was 2.45±2.91%. The ORR was 27.3% (three out of 11 patients), and two out of these three responders had uncommon EGFR mutations. The median PFS and OS were 2.0 and 3.8 months, respectively. The median CSF penetration rate of afatinib was higher than previously reported. Afatinib was effective against leptomeningeal carcinomatosis particularly in patients with NSCLC harboring uncommon EGFR mutations. The criteria for selecting a specific EGFR tyrosine kinase inhibitor for therapy of NSCLC should include its ability to penetrate CSF and its efficacy against specific mutation types.


Protection of mice against Trypanosoma cruzi by immunization with paraflagellar rod proteins requires T cell, but not B cell, function.
Previous studies have shown that immunization of mice with the paraflagellar rod proteins (PAR) of Trypanosoma cruzi induces an immune response capable of protecting mice against an otherwise lethal challenge with this parasite. Herein, we define immunologic responses that do or do not play a critical role in PAR-mediated protection. Firstly, PAR-immunized Ab-deficient (muMT) strain mice survived an otherwise lethal T. cruzi challenge, indicating that a B cell response is not required for PAR-induced immunity. However, beta2m -/- mice, which are severely deficient in MHC class I and TCR alphabeta+ CD8+ CD4- T cells, did not survive challenge infection following PAR immunization, indicating that MHC class I/CD8+ T cell function is necessary for protection induced by PAR immunization. Surprisingly, PAR-immunized mice depleted of CD4+ T cells survived a T. cruzi challenge for >84 days postinfection while maintaining a parasitemia that is generally thought to be lethal (i.e., >10(6) trypomastigotes/ml), thus associating CD4+ T cell function with the process of parasite clearance. Consistent with this association, CD4+ T cells from PAR-immunized mice released INF-gamma and stimulated T. cruzi-infected macrophages to release nitric oxide. The importance of IFN-gamma in PAR-induced protective immunity is further indicated by the observation that PAR-immunized INF-gamma knockout mice developed an extremely high parasitemia and did not survive a challenge infection. Thus, while Ab-mediated immune mechanisms are not required for protection induced by PAR immunization, T cell responses are necessary for both elimination of bloodstream parasites and survival.


A residue of the ETS domain mutated in the v-ets oncogene is essential for the DNA-binding and transactivating properties of the ETS-1 and ETS-2 proteins.
The c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that recognize purine-rich motifs. The v-ets oncogene of the avian retrovirus E26 differs from its cellular progenitor p68c-ets-1 by two amino acid substitutions (alanine 285 and isoleucine 445 in c-ets-1 both substituted by valine in v-ets, mutations A and B respectively) and its carboxy-terminal end (mutation C). The B mutation affects a well conserved residue in the carboxy-terminal 85 amino acids, ETS DNA-binding domain. To address the biological relevance of the B mutation found between v-ets and c-ets-1, we have randomly mutagenized isoleucine 445 of p68c-ets-1 by polymerase chain reaction. Using in vitro gel mobility shift assays, we show that this residue is crucial for the binding properties of c-ets-1 since the 12 mutations we have generated at this position, all diminish or even abolish the binding, to the 'optimized' Ets-1 binding site (EBS), of 35 kDa proteins corresponding to the 311 carboxy-terminal residues of c-ets-1. Among them, substitutions of isoleucine to glutamic acid, glycine or proline have the highest inhibitory effects. Similar results were obtained when the same mutations were introduced either in full-length p68c-ets-1 protein or into a carboxy-terminal polypeptide of 109 amino acids encompassing the ETS-domain which has previously been shown to display a very high binding activity as compared with the full-length protein. Consistent with the in vitro results, point mutations in p68c-ets-1 that decrease binding activity to EBS abrogate its ability to transactivate reporter plasmids carrying either the TPA Oncogene Response Unit of the Polyoma virus enhancer (TORU) or a sequence derived from the HTLV-1 LTR. Furthermore, as this isoleucine residue is rather well-conserved within the ETS gene family, we show that mutation of the corresponding isoleucine of c-ets-2 into glycine also abrogates its DNA-binding and hence, transactivating properties. Thus, the v-ets B mutation highlights the isoleucine 445 as an essential amino acid of the c-ets-1 and c-ets-2 DNA-binding domains.


Separating the effects of alcohol and expectancy on brain activation: an fMRI working memory study.
The aim of this study was to use BOLD fMRI to evaluate the effect of alcohol intoxication on neuronal activation, when controlling for expectancy. Behavioural studies have shown that both alcohol intoxication and expectancy affect cognition, mood and behaviour. However, previous neuroimaging studies have not separated the effects of alcohol intoxication from the possible confounding effects of expectancy. Forty-five healthy male participants participated in the study. A balanced placebo design with four groups was used together with a working memory paradigm. Half of the participants consumed a soft-drink before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed an alcoholic beverage), and the other half consumed an alcoholic beverage before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed a soft-drink). A blood alcohol concentration (BAC) of 0.08% was used as the alcohol intoxication level. The most conspicuous result was that alcohol intoxication decreased neuronal activation especially in the dorsal anterior cingulate cortex (dACC) and in prefrontal areas, while expectancy increased neuronal activation in the same areas. This study shows that alcohol intoxication and expectancy have opposite effects on neuronal activation. The present results could have implications for pharmacological imaging studies.


Photochemical Benzylation of White Phosphorus.
Organophosphorus compounds (OPCs) have wide application in organic synthesis, material sciences, and drug discovery. Generally, the vast majority of phosphorus atoms in OPCs are derived from white phosphorus (P4). However, the large-scale preparation of OPCs mainly proceeds through the multistep and environmentally toxic chlorine route from P4. Herein, we report the direct benzylation of P4 promoted by visible light. The cheap and readily available benzyl bromide was used as a benzylation reagent, and tetrabenzylphosphonium bromide was directly synthesized from P4. In addition, the metallaphotoredox catalysis strategy was applied to functionalize P4 for the first time, which significantly improved the application range of the substituted benzyl bromide.


Effects of moonlight exposure on plasma melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus.
Influences of light-dark (LD) cycle and moonlight exposure on plasma melatonin rhythms in the seagrass rabbitfish, Siganus canaliculatus, a lunar synchronized spawner, were determined by time-resolved fluoroimmunoassay (TR-FIA). When the fish were exposed to a natural LD (12:12) cycle, plasma melatonin levels exhibited a clear daily rhythm, with higher levels at midnight and lower levels during the day. These rhythms were not evident under either constant light (LL) or constant dark (DD) conditions. Plasma melatonin levels under LL condition were low and high under DD condition. These results indicate that plasma melatonin rhythms are driven by LD cycle in this species. When the fish were exposed to the 4 lunar phases, plasma melatonin levels around the new moon were significantly higher than during the first quarter moon and the full moon. Exposure to experimental new moon and full moon conditions caused significant increases and decreases of plasma melatonin levels, respectively. The synchronous rhythmicity of melatonin levels in the plasma support the hypothesis that the seagrass rabbitfish perceives moonlight intensity and responds with secretion of melatonin into the bloodstream.


Effects of 9,10-anthracenedione, 1,4-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-, diacetate on cell morphology and nucleic acids of friend leukemia cells.
Treatment of Friend leukemia cells for 18 hours with 9,10-anthracenedione, 1,4-bis[[(2-hydroxyethyl)amino]ethyl]amino]-, diacetate (ANT) at concentrations up to 1.0 microgram/ml induced significant changes in cell metabolism and structure. Alterations in cell nucleic acid content were detected in cells stained with acridine orange under conditions such that DNA and RNA contents could be measured simultaneously by flow cytometry. Cells treated for 18 hours with ANT at concentrations of 0.05-0.1 microgram/ml became partially blocked at the G2 phase. In addition, about 30% of the cells became polyploid and demonstrated diplochromosomes at the 8C level of mitosis. The nuclear chromatin of blocked cells had an altered structure as reflected by a change in sensitivity of DNA in situ to denaturation induced by low pH. All viable cells treated with ANT for 18 hours at concentrations of 0.4-1.0 microgram/ml were blocked in G2 phase. These cells had significantly more RNA than did untreated cells. Transmission electron microscopic observations of thin-sectioned cells suggested that this increased RNA content in ANT-treated cells was mostly due to an approximately 50% increased cell diameter and partly due to a disproportionate increase in nucleolar size. In addition, electron microscopy revealed that ANT caused increased chromatin condensation and granulation. The drug had no apparent effect on production of the endogenous Friend murine leukemia virus.


Factors associated with persistent subfoveal fluid and complete macular hole closure in the PIONEER study.
To investigate preoperative and intraoperative factors associated with persistent subfoveal fluid in surgically closed macular holes (MHs). This was a prospective consecutive case series of eyes undergoing surgical repair for full-thickness MH in the PIONEER study, a prospective intraoperative optical coherence tomography (OCT) multisurgeon single-center study. Thirty-seven eyes (36 patients) with surgically closed MH were studied. Quantitative OCT analysis was performed including intraoperative MH area, volume, ellipsoid zone to retinal pigment epithelium (EZ-RPE) height, extent of subretinal hyporeflectivity (SRHR), and the amount of postoperative subfoveal fluid. Persistent subfoveal fluid was identified in 58% of eyes at 2 weeks following surgery. The mean time to two-line improvement in visual acuity was greater in eyes with persistent subfoveal fluid (P = 0.03). Final visual acuity did not correlate with the initial presence of fluid. Two intraoperative factors following internal limiting membrane (ILM) peeling were associated with the formation of persistent subfoveal fluid: EZ-RPE height and SRHR width (P < 0.01). These were both negatively correlated with amount of postoperative subfoveal fluid (P = 0.028 and 0.04, respectively). Persistent subfoveal fluid following MH surgery is a common finding that appears to delay visual recovery but not effect final visual outcome. The incidence of persistent subfoveal fluid appears to be related to intraoperative alterations after ILM peeling in the outer retinal architecture (e.g., increased EZ-RPE height and SRHR width). This finding suggests a novel mechanism for facilitating MH closure through ILM peeling (e.g., altering photoreceptor/RPE adherence and increasing retinal mobility that allows for complete hole closure).


Effects of preconceptional and gestational exposure to Tordon 202c on fetal growth and development in CD-1 mice.
Female CD-1 mice were exposed to Tordon 202c (a picloram and 2,4-D combination herbicide) in the drinking water at concentrations of 0.21, 0.42, and 0.84% for 60 days prior to mating with untreated males. One-half of the pregnant females subsequently continued treatment throughout gestation while the remaining females were maintained on distilled water. Fetal weight, crown-rump length, placental weight, and maternal gestational weight gain were reduced in a dose-dependent manner following combined preconceptional and gestational exposure. The incidence of malformed fetuses (cleft palate, renal agenesis, hydronephrosis, unilateral testicular agenesis, and umbilical hernia) and fetuses with variants (especially incomplete ossification of the skeleton) were increased in a dose-dependent manner following combined exposure. Increased maternal mortality and decreased preconception weight gain were observed in the highest-dosage group. Relative maternal liver weight was increased in a dose-dependent manner. The results suggest that combined preconceptional and gestational exposure to Tordon 202c is required for teratogenesis and fetal growth depression. Preconceptional exposure alone is not effective in increasing the risk for embryotoxicity.


An Integrative Approach to Treat Parkinson's Disease: Ukgansan Complements L-Dopa by Ameliorating Dopaminergic Neuronal Damage and L-Dopa-Induced Dyskinesia in Mice.
Parkinson's disease (PD) is accompanied by motor impairments due to the loss of dopaminergic neurons in the nigrostriatal pathway. Levodopa (L-dopa) has been the gold standard therapy for PD since the 1960s; however, its neurotoxic features accelerate PD progression through auto-oxidation or the induction of dyskinetic movements. Ukgansan (UGS) is a well-known prescription for treating PD in traditional medicines of East Asia, and its anti-PD function has been experimentally evaluated. The present study investigated whether UGS attenuates (1) motor dysfunction and dopaminergic neuronal damage when co-treated with L-dopa and (2) L-dopa-induced dyskinesia (LID) in 6-hydroxydopamine (6-OHDA)-induced PD mice. Although L-dopa was found to reduce motor dysfunctions, it failed to decrease the dopaminergic neuronal damage and increased the expression of dopamine receptor 1 (D1R) and 2 (D2R) in the 6-OHDA-injected mouse striatum. Co-treatment with UGS resulted in normal striatal histology and ameliorated motor impairments. In addition, UGS suppressed the dyskinesia induced by chronic L-dopa treatment while restoring the dopaminergic neurons in the striatum. For the underlying mechanism, UGS reduced the overexpression of D1R-related signaling proteins, such as phosphorylated extracellular signal-regulated kinase, ΔFosB, and c-fos in the striatum. Overall, the results suggest that the effect of UGS could be complementary to L-dopa by ameliorating motor dysfunction, restoring the dopaminergic neurons, and suppressing the dyskinetic movements in PD.


Fast in situ airborne measurement of ammonia using a mid-infrared off-axis ICOS spectrometer.
A new ammonia (NH3) analyzer was developed based on off-axis integrated cavity output spectroscopy. Its feasibility was demonstrated by making tropospheric measurements in flights aboard the Department of Energy Gulfstream-1 aircraft. The ammonia analyzer consists of an optical cell, quantum-cascade laser, gas sampling system, control and data acquisition electronics, and analysis software. The NH3 mixing ratio is determined from high-resolution absorption spectra obtained by tuning the laser wavelength over the NH3 fundamental vibration band near 9.67 μm. Excellent linearity is obtained over a wide dynamic range (0-101 ppbv) with a response rate (1/e) of 2 Hz and a precision of ±90 pptv (1σ in 1 s). Two research flights were conducted over the Yakima Valley in Washington State. In the first flight, the ammonia analyzer was used to identify signatures of livestock from local dairy farms with high vertical and spatial resolution under low wind and calm atmospheric conditions. In the second flight, the analyzer captured livestock emission signals under windy conditions. Our results demonstrate that this new ammonia spectrometer is capable of providing fast, precise, and accurate in situ observations of ammonia aboard airborne platforms to advance our understanding of atmospheric compositions and aerosol formation.


The process: New methods of purification and viral safety.
From the transmission of hepatitis C virus by gammaglobulins in 1994 to the emergence of new viruses and concern over prions, intravenous immunoglobulin (IGIV) manufacturers have continued to address safety issues and respond to changing needs. New IGIV products not only provide superior antiviral safety, but also show advances in product purity and manufacturing processes. Several manufacturers have also addressed the concern over prion transmission. The sum of the processes used have collectively ensured continuous product safety. Newer products will be further differentiated by their tolerability and efficacy profiles.


Hepatic veno-occlusive disease: pathogenesis, diagnosis and treatment.
Hepatic veno-occlusive disease (VOD) is one of the most serious complications following hematopoietic stem cell transplantation (SCT) and is associated with a very high mortality in its severe form. This review outlines the pathogenesis and clinical features of VOD, with an emphasis on endothelial cell injury and risk factors. The current status and future directions of research for both prophylaxis and treatment are also discussed.


Regenerative, Highly-Sensitive, Non-Enzymatic Dopamine Sensor and Impact of Different Buffer Systems in Dopamine Sensing.
Carbon nanotube field-effect transistors are used extensively in ultra-sensitive biomolecule sensing applications. Along with high sensitivity, the possibility of regeneration is highly desired in bio-sensors. An important constituent of such bio-sensing systems is the buffer used to maintain pH and provide an ionic conducting medium, among its other properties. In this work, we demonstrate highly-sensitive regenerative dopamine sensors and the impact of varying buffer composition and type on the electrolyte gated field effect sensors. The role of the buffer system is an often ignored condition in the electrical characterization of sensors. Non-enzymatic dopamine sensors are fabricated and regenerated in hydrochloric acid (HCl) solution. The sensors are finally measured against four different buffer solutions. The impact of the nature and chemical structure of buffer molecules on the dopamine sensors is shown, and the appropriate buffer systems are demonstrated.


Phase I study of ch14.18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children's Oncology Group.
Recurrence of high-risk neuroblastoma is common despite multimodality therapy. ch14.18, a chimeric human/murine anti-G(D2) antibody, lyses neuroblastoma cells. This study determined the maximum tolerable dose (MTD) and toxicity of ch14.18 given in combination with interleukin-2 (IL-2) after high-dose chemotherapy (HDC)/stem-cell rescue (SCR). Biologic correlates including ch14.18 levels, soluble IL-2 receptor levels, and human antichimeric antibody (HACA) activity were evaluated. Patients were given ch14.18 for 4 days at 28-day intervals. Patients received IL-2 during the second and fourth courses of ch14.18 and granulocyte-macrophage colony-stimulating factor (GM-CSF) during the first, third, and fifth courses. The MTD was determined based on toxicities occurring with the second course. After the determination of the MTD, additional patients were treated to confirm the MTD and to clarify appropriate supportive care. Twenty-five patients were enrolled. The MTD of ch14.18 was determined to be 25 mg/m(2)/d for 4 days given concurrently with 4.5 x 10(6) U/m(2)/d of IL-2 for 4 days. IL-2 was also given at a dose of 3 x 10(6) U/m(2)/d for 4 days starting 1 week before ch14.18. Two patients experienced dose-limiting toxicity due to ch14.18 and IL-2. Common toxicities included pain, fever, nausea, emesis, diarrhea, urticaria, mild elevation of hepatic transaminases, capillary leak syndrome, and hypotension. No death attributable to toxicity of therapy occurred. No additional toxicity was seen when cis-retinoic acid (cis-RA) was given between courses of ch14.18. No patient treated at the MTD developed HACA. ch14.18 in combination with IL-2 was tolerable in the early post-HDC/SCR period. cis-RA can be administered safely between courses of ch14.18 and cytokines.


[Association between the alimentary factor and the immune system in migrants to the Far North].
The impact of diets different in caloric values on cellular and humoral immunity, nonspecific resistance was studied in Far North migrants. When the dietary intake of essential nutrients and vitamins was reduced, B-cell immunity and neutrophilic leukocytes were the first to react in females and males, respectively. Correlation analysis revealed significant correlations of stab neutrophils, the phagocytic number of monocytes, and B lymphocytes with the caloric value of foods.


Mefenamic acid decreases inflammation but not joint lesions in experimental osteoarthritis.
Mefenamic acid is a non-steroidal anti-inflammatory drug able to control the symptoms of osteoarthritis (OA), but its effects on protection of cartilage and bone are still unclear. This study aimed to investigate whether the control of inflammation by mefenamic acid translates into decreased joint lesions in experimental OA in rats. OA was induced by injecting 1 mg of monosodium iodoacetate (MIA) into the joints of rats. The animals were treated with mefenamic acid (50 mg/kg, daily, oral gavage) either pre-MIA injection (preventive) or post-MIA injection (therapeutic). Joint swelling and hyperalgesia were evaluated at baseline and 1, 3, 14 and 28 days after induction of OA. Intra-articular lavage and kinetics of cell migration into the synovium were measured 3 and 28 days after OA induction. Histopathological analysis, Osteoarthritis Research Society International (OARSI) score, total synovium cells count, cartilage area and levels of proteoglycans in joints were also evaluated. Mefenamic acid prevented joint oedema and hyperalgesia induced by MIA in the acute phase (3 days) of the disease. In the chronic phase (28 days), preventive and therapeutic regimens decreased the number of mononuclear cells in the joint cavity. In contrast, thickening of the synovium, bone resorption, loss of cartilage and levels of proteoglycans were unaffected by mefenamic acid when it was administered either preventively or therapeutically. Thus, mefenamic acid had anti-inflammatory effects but did not reduce the progression of OA lesions, thereby indicating that it is only effective for symptomatic control of OA.


Vortex dynamics in evolutive flows: a weakly chaotic phenomenon.
We make use of a wavelet method to extract, from experimental velocity signals obtained in an evolutive flow, the dominating velocity components generated by vortex dynamics. We characterize the resulting time series complexity by means of a joint use of data compression and of an entropy diffusion method. We assess that the time series emerging from the wavelet analysis of the vortex dynamics is a weakly chaotic process with a vanishing Kolmogorov-Sinai entropy and a power-law growth of the information content. To reproduce the Fourier spectrum of the experimental signal, we adopt a harmonic dependence on time with a fluctuating frequency, ruled by an inverse power-law distribution of random events. The complexity of these fluctuations is determined by studying the corresponding artificial sequences. We reproduce satisfactorily both spectral and complex properties of the experimental signal by locating the complexity of the fluctuating process at the border between the stationary and the nonstationary states.


Metabolic control in diabetic dogs treated with pancreatic autotransplants and insulin pumps.
Fasting metabolite and hormonal levels were studied prospectively in pancreatectomized dogs who had received grafts of their own pancreas. The results were compared with similarly diabetic animals who received exogenous insulin pumped intravenously either peripherally or portally. All animals were studied for 48-91 wk after pancreatectomy. In the autotransplanted animals, the fasting levels of glucose, lactate, pyruvate, alanine, pancreatic glucagon, insulin, gastric inhibitory peptide, and pancreatic polypeptide were all abnormal. In the peripherally infused animals, the fasting levels of glucose, pyruvate, alanine, free fatty acids, and insulin were also abnormal. In the portally infused animals, pyruvate, alanine, gastric inhibitory peptide, gastrin, and pancreatic polypeptide were abnormal. These results suggest that the portal route of insulin delivery may be necessary if fasting metabolite and hormonal levels are to approximate normal most closely whether exogenous intravenous insulin is replaced by implanted pumps or endogenous insulin is replaced by pancreatic transplants.


Comparison of the effects of 2 different doses of remifentanil infusion for sedation during in-vitro fertilization procedure.
To compare the sedation level, hemodynamic effects, patient and physician satisfactions following sedation achieved by 2 different doses of remifentanil (R) infusion with additional bolus infusions of propofol for in vitro fertilization (IVF) procedure. A double-blind prospective randomized study was implemented on 86 ASA I-II grade female patients, 18-40 years of age that underwent IVF procedure. This study was performed in the Department of Anesthesiology and Obstetrics and Gynecology, School of Medicine, Dokuz Eylul University, Izmir, Turkey between November 2006 to August 2008. Group R1 received 0.1 mcg/kg/min while Group R2 received 0.15 mcg/kg/min infusion dose remifentanil. Side effects, total doses of remifentanil and propofol administered, heart rate (HR), systolic arterial pressure and diastolic arterial pressure values have been recorded. Fertilization, cleavage, and pregnancy rates together with prognosis of pregnancies were compared. Groups did not show statistically significant differences for hemodynamic parameters of HR and MAP (p = 0.281). Comparison of the satisfaction levels of 2 groups showed that anesthesiologist satisfaction was superior in R1 (p = 0.009) whereas surgeon satisfaction was superior in R2 (p = 0.01). Both groups reported good patient satisfaction levels (p = 0.31). There were no differences between the groups in terms of fertilization, cleavage, pregnancy rates and prognosis of pregnancies (p>0.05). Both doses of remifentanil provided stable hemodynamics along with fast and uncomplicated recovery.


Case report: A rare homozygous variation in the ENPP1 gene, presenting with generalized arterial calcification of infancy in a Chinese infant.
Generalized arterial calcification of infancy (GACI) is a rare genetic disease characterized by arterial calcifications or stenoses and hypertension. GACI is caused by mutations in the ENPP1 or ABCC6 genes, and it often causes intrauterine or early infancy death. Here, we report a case of rare GACI caused by a homozygous variation in ENPP1, in a Chinese infant initially presenting with hypertension. The proband was an 8-month-old boy with in utero tricuspid valve calcification, presenting with hypertension at birth. Enhanced computed tomography revealed extensive arterial calcification. Genetic testing identified a homozygous variation in ENPP1 (c.783C > G p.Y261X), which led to the diagnosis of GACI. This mutation has been reported in only three Chinese patients, which all initially presented with hypophosphatemic rickets rather than GACI. This case enriches the clinical and genetic spectrum of ENPP1 mutations and reminds us that GACI should be considered in an infant presenting with hypertension and extensive arterial calcification, and that genetic testing should be performed.


A holistic approach to specialization.
There is a growing concern that extensive specialization in occupational therapy may so fragment the profession that it may be lost in the changes taking place in the delivery and payment of health care services. The early concepts of occupation and purposeful, developmentally appropriate activities are giving way in some settings to the use of highly specialized technologies. This article examines the trend of leaving occupational behaviors and adopting activity of a more technical nature and offers a conceptual model to preserve the traditional holistic approach to the practice of occupational therapy in today's climate of specialization. The approach is seen as important to the viability of the profession in a modern competitive health care market.


The neural basis of depth perception from motion parallax.
In addition to depth cues afforded by binocular vision, the brain processes relative motion signals to perceive depth. When an observer translates relative to their visual environment, the relative motion of objects at different distances (motion parallax) provides a powerful cue to three-dimensional scene structure. Although perception of depth based on motion parallax has been studied extensively in humans, relatively little is known regarding the neural basis of this visual capability. We review recent advances in elucidating the neural mechanisms for representing depth-sign (near versus far) from motion parallax. We examine a potential neural substrate in the middle temporal visual area for depth perception based on motion parallax, and we explore the nature of the signals that provide critical inputs for disambiguating depth-sign.This article is part of the themed issue 'Vision in our three-dimensional world'.


Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy.
Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.


A T-shaped selenenyl halide.
The title selenenyl halide complex, 3-iodo-2-phenyl-3H-3-selenaindazole, C(12)H(9)IN(2)Se, has an almost planar conformation and a nearly ideal T-shape for the Se(INC) moiety [Se-I 2.8122 (12), Se-C 1.881 (7) and Se-N2 2.051 (6) A; C-Se-N 79.6 (3), C-Se-I 96.8 (2) and N-Se-I 176.17 (17) degrees ]. This arrangement, together with the two selenium lone pairs, leads to a distorted trigonal-bipyrimidal geometry about the Se atom. Intermolecular interactions are largely limited to stacking forces.


Effect of artificial tooth material on mandibular residual ridge resorption.
In this 10-year longitudinal study we evaluated the amount of mandibular residual ridge resorption for 2 groups of subjects with complete dentures, one group with porcelain artificial teeth and the other with acrylic resin teeth. One hundred and nine patients who had undergone ridge extension procedures with skin graft and prosthetic rehabilitation with porcelain or acrylic resin teeth were investigated for mandibular bone loss. Measurements were made on serial cephalograms. There were no significant differences between the groups in terms of their baseline characteristics (age, period of edentulousness, period of observation, vertical facial morphology, sex, severity of atrophy or presence of bruxism). Similarly, there were no statistically significant differences in amount of bone loss in relation to baseline characteristics. The view that acrylic resin teeth should be preferred to prevent bone resorption of the mandibular residual ridge is not supported by these data. Further research concerning soft denture-lining material should be undertaken to elucidate the potential role of denture pressure in ridge resorption.


Ultrastructural changes in Darier's disease induced by ultraviolet irradiation.
A male patient with clinically and histopathologically verified Darier's disease and a history of deterioration after sun exposure was irradiated on uninvolved skin with 25, 50 and 75 J/cm2 of UVA once a week for five weeks. He also received 3 and 5 times his individually established MED of UVB. Since no signs of keratosis follicularis were detected one week after the last irradiation, he was then exposed to 10 times his MED with UVB, whereupon clinically characteristic lesions of keratosis follicularis developed. One week after this exposure, biopsies were taken from the UV-induced lesions and processed for light and transmission electron microscopic investigation. Light microscopy revealed suprabasal lacunae, corps ronds and grains. In the electron microscope, gaps in the basal lamina beneath the suprabasal lacunae were also observed, through which cytoplasmic processes of lymphocyte- and fibroblast-like cells and basal keratinocytes protruded. Parts of keratinocytes with disruptive cell membranes were localized in the gaps of the basal lamina. Also, multiplication of the basal lamina was frequent.


Efficacy of human papillomavirus 16/18 AS04-adjuvanted vaccine in Japanese women aged 20 to 25 years: interim analysis of a phase 2 double-blind, randomized, controlled trial.
A phase 2 double-blind, controlled, randomized multicenter study with human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is ongoing in healthy Japanese women aged 20 to 25 years. We assessed the vaccine efficacy in the event-triggered analysis. Japanese women aged 20 to 25 years were randomly assigned to receive either HPV-16/18 AS04-adjuvanted (n = 519) or hepatitis A (n = 521) vaccine at 0, 1, and 6 months. The women were assessed for virological and cytological end points associated with HPV-16/18 in cervical specimens and for the vaccine safety and immunogenicity. The mean length of follow-up for women in the primary analysis for efficacy at the time of a prespecified event-triggered interim analysis was 13.6 months after the first vaccination. Vaccine efficacy against HPV-16/18 persistent infections (6-month definition) in the according-to-protocol cohort for efficacy was 100% (99% confidence interval, 20.5-100, P = 0.0037). At 6 months after the third dose of vaccine, geometric mean titers against HPV-16 and HPV-18 were 2899.3 and 1352.2 enzyme-linked immunosorbent assay units per milliliter, respectively, that is, 97- and 60-fold higher than geometric mean titers observed after natural infection. There were no clinically meaningful differences in safety between the HPV and control group. The HPV-16/18 AS04-adjuvanted vaccine was as efficacious in Japan as in other countries and was generally safe and highly immunogenic in Japanese women.


A phase II trial of docetaxel and ifosfamide for patients with platinum-resistant or refractory non-small cell lung cancer in a salvage setting.
We conducted a phase II study of docetaxel and ifosfamide chemotherapy for patients with platinum-resistant or refractory non-small-cell lung cancer (NSCLC) to evaluate the response and toxicity profiles as a salvage treatment. Between July 2000 and July 2004, 40 patients who had previously received platinum-based regimen as the first-line or second-line therapy were enrolled in this study. The treatment consisted of a docetaxel 75 mg/m(2) intravenous infusion on day 1 and intravenous ifosfamide 3 g/m(2) with Mesna uroprotectione on day 1 through 3. This regimen was repeated every 3 weeks. One hundred thirty cycles of treatment were given, with a median of 3 cycles (range: 2 approximately 6 cycles). All the patients were evaluable for the response rate and toxicity profile. The major toxicity was myelosuppression. Grade 3 approximately 4 neutropenia occurred in 30 patients (75%) during treatment. Febrile neutropenia occurred in 16 patients (40%). Five of 40 patients (12.5%) had a partial response (95% confidence interval, 3.3 approximately 21.7%). The median time to disease progression was 2.65 months (range: 2.02 approximately 3.20 months), and the median survival was 5.24 months (range: 2.99 approximately 7.49 months). Salvage chemotherapy with docetaxel and ifosfamide showed a low efficacy and a high proportion of severe neutropenia in patients with platinum-resistant or refractory advanced NSCLC.


Physical activity of women over 60 - methodology of activity measurement.
Physical activity has a positive effect on health. The level of physical activity changes with age. Elderly people often reduce their physical activity, among other things, due to deteriorating health or the belief that it is inappropriate to indulge in sports or be physically active at old agge. On the other hand, the lack of systematic physical activity in the elderly can lead to a reduction in the body's efficiency in many health aspects. Although there are many methods of measuring human physical activity, there is no ideal tool for measuring that activity. The main aim of the study was to assess the effectiveness of the use of selected methods of measuring physical activity in the elderly, as well as to evaluate the influence of the measured activity on the nutritional status of women over 60 years of age. The study was carried out in the area of western Poland in a group of 110 generally healthy women above the age of 60, who were divided into 3 groups of intensity of undertaken physical activity (low active 30.00%, moderately active 41.82% and active 28.18%). A pedometer and a physical activity diary were used to measure physical activity. Body composition was assessed by the bioelectrical impedance method which uses a body composition analyzer. Body height and weight, lean mass of limbs and body, adipose tissue content, total water content, waist circumference to hip circumference (WHR), and BMI (Body Mass Index) were assessed. The correlation coefficient between the methods of assessing physical activity, i.e. the number of minutes/day and the number of steps/day, was 0.92 and was statistically significant at the level of p<0.001. This was assumed to be a strict correlation. Based on the physical activity diary, it was estimated that women spent an average of 92.85 minutes a day on physical activity, while the data obtained from the pedometer showed that they performed an average of 4,462 steps a day. The average age of the respondents was 67.25 years, and average BMI - 28.07 kg/m2. A close correlation was demonstrated between the applied methods for assessing physical activity shows about the appropriate selection of methods, as well as, due to their ease of use, their use to assess physical activity in the elderly.


Assembly of nitrogenase biosynthetic pathway in Saccharomyces cerevisiae by using polyprotein strategy.
Nitrogenase in some bacteria and archaea catalyzes conversion of N2 to ammonia. To reconstitute a nitrogenase biosynthetic pathway in a eukaryotic host is still a challenge, since synthesis of nitrogenase requires a large number of nif (nitrogen fixation) genes. Viral 2A peptide mediated "cleavage" of polyprotein is one of strategies for multigene co-expression. Here, we show that cleavage efficiency of NifB-2A-NifH polyprotein linked by four different 2A peptides (P2A, T2A, E2A, and F2A) in Saccharomyces cerevisiae ranges from ~50% to ~90%. The presence of a 2A tail in NifB, NifH, and NifD does not affect their activity. Western blotting shows that 9 Nif proteins (NifB, NifH, NifD, NifK, NifE, NifN, NifX, HesA, and NifV) from Paenibacillus polymyxa that are fused into two polyproteins via 2A peptides are co-expressed in S. cerevisiae. Expressed NifH from Klebsiella oxytoca NifU and NifS and P. polymyxa NifH fusion linked via 2A in S. cerevisiae exhibits Fe protein activity.


Shock experiments and numerical simulations on low energy portable electrically exploding foil accelerators.
Two low energy (1.6 and 8 kJ) portable electrically exploding foil accelerators are developed for moderately high pressure shock studies at small laboratory scale. Projectile velocities up to 4.0 km/s have been measured on Kapton flyers of thickness 125 microm and diameter 8 mm, using an in-house developed Fabry-Perot velocimeter. An asymmetric tilt of typically few milliradians has been measured in flyers using fiber optic technique. High pressure impact experiments have been carried out on tantalum, and aluminum targets up to pressures of 27 and 18 GPa, respectively. Peak particle velocities at the target-glass interface as measured by Fabry-Perot velocimeter have been found in good agreement with the reported equation of state data. A one-dimensional hydrodynamic code based on realistic models of equation of state and electrical resistivity has been developed to numerically simulate the flyer velocity profiles. The developed numerical scheme is validated against experimental and simulation data reported in literature on such systems. Numerically computed flyer velocity profiles and final flyer velocities have been found in close agreement with the previously reported experimental results with a significant improvement over reported magnetohydrodynamic simulations. Numerical modeling of low energy systems reported here predicts flyer velocity profiles higher than experimental values, indicating possibility of further improvement to achieve higher shock pressures.


Age dependence of steady state mitochondrial oxidative metabolism in the in vivo hypoxic dog brain.
Mitochondrial bioenergetics were investigated in newborn, neonatal and adult dog brains during normoxia and hypoxia. The ratio of the rate of ATP synthesis to the maximum synthesis rate (V/Vmax), phosphorylation potential, [ADP] and PCr/Pi, were used to evaluate age related mitochondrial hypoxic tolerance. These indicators were calculated from the phosphorus compounds measured by in vivo 31P MRS quantitatively using ATP as an internal reference. Indicators and substrates of mitochondrial function, V/Vmax, ADP, and Pi reached a peak value during the neonatal (3-21 days) period of development, suggesting that the oxidative metabolism of the neonate is more vulnerable to stress when compared to newborns and adults. Distinction among newborns and neonates became apparent during hypoxia. Newborns (0-2 days old) showed substantial tolerance by maintaining V/Vmax until exposure to severe hypoxia. Older neonates (3-21 days old) showed increases in V/Vmax, [Pi] and [ADP] under less than severe conditions of hypoxia. Adults exhibited low V/Vmax values even during exposure to severe hypoxia, further indicating that mitochondrial oxidative processes are more stable in adults than in newborns and neonates. This study provides evidence that newborns and adults are more capable of maintaining mitochondrial function under conditions of minimal to moderate hypoxia than 3-21 day old neonates.


Integrated Water-Level Sensor Using Thin-Film Transistor Technology.
A low-cost water-level sensor was developed utilizing a capacitive sensor design with only one thin-film transistor (TFT). The integration of the a-IGZO TFT process facilitated the complete integration of the water-level sensor on a substrate, including essential components, such as the transistor, capacitor, wires, and sensing electrode. This integration eliminates the need for a separate mounting process, resulting in a robust sensor assembly. To comprehensively assess the performance of the developed water-level sensor, rigorous evaluations were conducted using both MOSFET and TFT integration. In the case of the water-level sensor featuring a-IGZO TFT integration, a voltage output of 4.2 V was measured when the tank was empty, while a voltage output of 0.9 V was measured when the tank was full. Notably, the integrated sensor system demonstrated a higher output voltage compared with the MOSFET sensor, primarily due to the significantly reduced parasitic capacitance of the TFT. The use of a-IGZO TFT in the integrated sensor system contributes to enhanced sensitivity and accuracy. The lower parasitic capacitance inherent in TFT technology allows for improved voltage measurement precision, resulting in more reliable and precise water-level sensing capability. The development of this integrated water-level sensor holds immense potential for a wide range of applications that require a combination of cost-effectiveness, accurate monitoring, and flexibility in form factor. With its affordability, the sensor is accessible for various industries and applications.


Job satisfaction and burnout among paediatric nurses.
This study aims to determine factors of job satisfaction and burnout levels of paediatric nurses. A total of 165 nurses working in paediatric clinics completed the Minnesota job satisfaction scale and the Maslach burnout scale. Average scores of the emotional exhaustion and depersonalisation score were low, while personal accomplishment scores were high. A high level of job satisfaction, being married, increased age and a decreased number of assigned patients were significantly associated with a low level of burnout. Paediatric nurses experience burnout at significant levels. The most important variable that affected job satisfaction was income. The results of the study could guide development of strategies that might prevent or alleviate burnout of paediatric nurses.


Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Secondary α-(Trifluoromethyl)benzyl Tosylates.
A palladium-catalyzed C(sp3 )-C(sp2 ) Suzuki-Miyaura cross-coupling of aryl boronic acids and α-(trifluoromethyl)benzyl tosylates is reported. A readily available, air-stable palladium catalyst was employed to access a wide range of functionalized 1,1-diaryl-2,2,2-trifluoroethanes. Enantioenriched α-(trifluoromethyl)benzyl tosylates were found to undergo cross-coupling to give the corresponding enantioenriched cross-coupled products with an overall inversion in configuration. The crucial role of the CF3 group in promoting this transformation is demonstrated by comparison with non-fluorinated derivatives.


Congenital bilobed gallbladder with phrygian cap presenting as calculus cholecystitis.
The incidence of congenital bilobed gall bladder is 1 in 3000 to 4000. A Phrygian cap is a congenital abnormality of the gallbladder with an incidence of 4%. Preferred mode of diagnosis for Phrygian cap is cholescintigraphy and multi phase MRI, as Ultrasonography and CT are not always conclusive. The estimated prevalence of gallstone disease in India has been reported as 2% to 29%. A case of bilobed gall bladder with Phrygian cap in both the lobes and pigment gallstone in one of the lobes presenting as calculus cholecystitis is reported for its rarity and difficulty in arriving at correct preoperaive diagnosis.


Post-inflammatory hyperpigmentation: A systematic review of treatment outcomes.
Post-inflammatory hyperpigmentation is a common consequence of inflammatory dermatoses. It is more common in patients with darker skin and has significant morbidity. This systematic review summarizes treatment outcomes for post-inflammatory hyperpigmentation to help physicians better predict clinical response and improve patient outcomes. Embase, MEDLINE, PubMed databases and clinicaltrials.gov were searched in accordance with PRISMA guidelines using a combination of relevant search terms. Title, abstract and full text screening were done in duplicate. Studies were included if they met our predetermined PICOS framework criteria. Results are presented in descriptive form. In total, 41 studies representing 877 patients were included. Complete response was achieved by laser and energy-based devices in 18.1% (n = 56/309) of patients, topicals in 5.4% (n = 20/369) and combination therapies in 2.4% (n = 4/166). Partial response was achieved by combination modalities in 84.9% (n = 141/166) of patients, topicals in 72.4% (n = 267/369), laser and energy-based devices in 61.2% (n = 189/309) and peels in 33.3% (n = 5/15). Poor to no response occurred with peels in 66.7% (n = 10/15) of patients, topicals in 22.2% (n = 82/369), laser and energy-based devices in 18.1% (n = 56/309) and combination modalities in 12.7% (n = 21/166). Additionally, in 2.6% (n = 8/309) of patients treated with laser and energy-based devices, post-inflammatory hyperpigmentation worsened. Adverse events were reported in 10 patients, all while using topical treatments. In conclusion, the current treatment approaches yielded unsatisfactory rates of complete response. However, combination therapies, laser and energy-based devices and topical therapies showed high rates of partial response. Of note, the majority of post-inflammatory hyperpigmentation cases included were associated with acne, and therefore, the findings and conclusions drawn may have limited applicability to other types of post-inflammatory hyperpigmentation.


Effects of the 1991-92 El Niño on scleractinian corals of the Costa Rican central Pacific coast.
Coral communities on the central Pacific coast of Costa Rica were affected during the 1991-92 El Niño warming event. More than 57% of all observed colonies at three localities (Parque Nacional Manuel Antonio, Punta Cambutal, and Parque Marino Ballena) were bleached. Mortality during this El Niño was much lower (approximately 9%) than in previous events. Psammocora spp. accounted for approximately 66% of dead corals, while massive (Porites lobota, Pavona spp.) and branching (Pocillopora spp.) for approximately 34%. Our results suggest that the observed bleaching in P. lobata was related to zooxanthellar densities and not to changes in pigment concentrations: only chlorophyll a varied between normally pigmented and bleached colonies at one locality (Ballena). Site differences in zooxanthellar densities or their pigment concentrations, may not be the result of the bleaching event itself, because a percentage of dead corals and zooxanthellar densities of bleached colonies seems to follow a trend with the exposure to tidal regimes and currents at each site. Local oceanographic conditions can be influencing the zooxanthellar densities and their response to the warming, together with intrinsic differences between colonies as well. The impact of this event can be considered serious given the short period of time that elapsed between El Niño related mortalities and the slow reefs recovery, the mode of reproduction of reef building species, and the anthropogenic-originated disturbances which affect the coral communities and reefs of the Costa Rican central Pacific coast.


Radioprotective effects of lentil sprouts against X-ray radiation.
The present study investigated the radioprotective efficacy of lentil (Lens culinaris) sprouts against X-ray radiation-induced cellular damage. Lentil seeds were dark germinated at low temperature and the sprout extract was prepared in PBS. Free radical scavenging of extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and then the radioprotective potency of extract (0 to 1000 μg/mL) on the lymphocyte cells was determined by lactate dehydrogenases assay. Moreover, micronuclei assay was assessed using the cytokinesis-block technique. The irradiations were performed using 6 MV X-ray beam. The value of IC50 for DPPH assay was 250 μg/mL. The median lethal dose for radiation was determinate at 5.37 Gy. Pretreatment with lentil sprout extract at 1000 μg/mL reduced cytotoxicity at 6 Gy total concentration from 70% to 50%. The results of micronuclei assay indicated that cells were resistant to radiation at concentrations of 500-1000 μg/mL of exogenous lentil sprout extract. The value of median effective concentration for micronuclei assay was 500 μg/mL. The results indicated that lentil sprout extract showed actually somewhat radioprotective effect on lymphocyte cell. In addition, the obtained results suggest that extract of total lentil sprout have more antioxidant activity than radicle part.


Factors influencing outcome following limb-threatening lower limb trauma: lessons learned from the Lower Extremity Assessment Project (LEAP).
The Lower Extremity Assessment Project (LEAP) is a multicenter study of severe lower extremity trauma in the US civilian population. At 2- and 7-year follow-ups, the LEAP study found no difference in functional outcome between patients who underwent either limb salvage surgery or amputation. However, outcomes on average were poor for both groups. This study and others provide evidence of wide-ranging variations in outcome following major limb trauma, with a substantial proportion of patients experiencing long-term disability. In addition, outcomes often are more affected by the patient's economic, social, and personal resources than by the initial treatment of the injury--specifically, amputation or reconstruction and level of amputation. A conceptual framework for examining outcomes after injury may be used to identify opportunities for interventions that would improve outcomes. Because of essential differences between the civilian and military populations, the findings of the LEAP study may correlate only roughly with combat casualty outcomes.


Comparison between treadmill training with rhythmic auditory stimulation and ground walking with rhythmic auditory stimulation on gait ability in chronic stroke patients: A pilot study.
Generally, treadmill training is very effective intervention, and rhythmic auditory stimulation is designed to feedback during gait training in stroke patients. The purpose of this study was to compare the gait abilities in chronic stroke patients following either treadmill walking training with rhythmic auditory stimulation (TRAS) or over ground walking training with rhythmic auditory stimulation (ORAS). Nineteen subjects were divided into two groups: a TRAS group (9 subjects) and an ORAS group (10 subjects). Temporal and spatial gait parameters and motor recovery ability were measured before and after the training period. Gait ability was measured by the Biodex Gait trainer treadmill system, Timed up and go test (TUG), 6 meter walking distance (6MWD) and Functional gait assessment (FGA). After the training periods, the TRAS group showed a significant improvement in walking speed, step cycle, step length of the unaffected limb, coefficient of variation, 6MWD, and, FGA when compared to the ORAS group (p < 0.05). Treadmill walking training during the rhythmic auditory stimulation may be useful for rehabilitation of patients with chronic stroke.


Continuous activation of Nrf2 and its target antioxidant enzymes leads to arsenite-induced malignant transformation of human bronchial epithelial cells.
Long-term exposure to arsenite leads to human lung cancer, but the underlying mechanisms of carcinogenesis remain obscure. The transcription factor of nuclear factor-erythroid-2 p45-related factor (Nrf2)-mediated antioxidant response represents a critical cellular defense mechanism and protection against various diseases. Paradoxically, emerging data suggest that the constitutive activation of Nrf2 is associated with cancer development, progression and chemotherapy resistance. However, the role of Nrf2 in the occurrence of cancer induced by long-term arsenite exposure remains to be fully understood. By establishing transformed human bronchial epithelial (HBE) cells via chronic low-dose arsenite treatment, we showed that, in acquiring this malignant phenotype, continuous low level of ROS and sustained enhancement of Nrf2 and its target antioxidant enzyme levels were observed in the later-stage of arsenite-induced cell transformation. The downregulation of Keap1 level may be responsible for the over-activation of Nrf2 and its target enzymes. To validate these observations, Nrf2 was knocked down in arsenite-transformed HBE cells by SiRNA transfection, and the levels of Nrf2 and its target antioxidant enzymes, ROS, cell proliferation, migration, and colony formation were determined following these treatments. Results showed that blocked Nrf2 expression significantly reduced Nrf2 and its target antioxidant enzyme levels, restored ROS levels, and eventually suppressed cell proliferation, migration, and colony formation of the transformed cells. In summary, the results of the study strongly suggested that the continuous activation of Nrf2 and its target antioxidant enzymes led to the over-depletion of intracellular ROS levels, which contributed to arsenite-induced HBE cell transformation.


Interoperable and explainable machine learning models to predict morbidity and mortality in acute neurological injury in the pediatric intensive care unit: secondary analysis of the TOPICC study.
Acute neurological injury is a leading cause of permanent disability and death in the pediatric intensive care unit (PICU). No predictive model has been validated for critically ill children with acute neurological injury. We hypothesized that PICU patients with concern for acute neurological injury are at higher risk for morbidity and mortality, and advanced analytics would derive robust, explainable subgroup models. We performed a secondary subgroup analysis of the Trichotomous Outcomes in Pediatric Critical Care (TOPICC) study (2011-2013), predicting mortality and morbidity from admission physiology (lab values and vital signs in 6 h surrounding admission). We analyzed patients with suspected acute neurological injury using standard machine learning algorithms. Feature importance was analyzed using SHapley Additive exPlanations (SHAP). We created a Fast Healthcare Interoperability Resources (FHIR) application to demonstrate potential for interoperability using pragmatic data. 1,860 patients had suspected acute neurological injury at PICU admission, with higher morbidity (8.2 vs. 3.4%) and mortality (6.2 vs. 1.9%) than those without similar concern. The ensemble regressor (containing Random Forest, Gradient Boosting, and Support Vector Machine learners) produced the best model, with Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.91 [95% CI (0.88, 0.94)] and Average Precision (AP) of 0.59 [0.51, 0.69] for mortality, and decreased performance predicting simultaneous mortality and morbidity (0.83 [0.80, 0.86] and 0.59 [0.51, 0.64]); at a set specificity of 0.995, positive predictive value (PPV) was 0.79 for mortality, and 0.88 for mortality and morbidity. By comparison, for mortality, the TOPICC logistic regression had AUROC of 0.90 [0.84, 0.93], but substantially inferior AP of 0.49 [0.35, 0.56] and PPV of 0.60 at specificity 0.995. Feature importance analysis showed that pupillary non-reactivity, Glasgow Coma Scale, and temperature were the most contributory vital signs, and acidosis and coagulopathy the most important laboratory values. The FHIR application provided a simulated demonstration of real-time health record query and model deployment. PICU patients with suspected acute neurological injury have higher mortality and morbidity. Our machine learning approach independently identified previously-known causes of secondary brain injury. Advanced modeling achieves improved positive predictive value in this important population compared to published models, providing a stepping stone in the path to deploying explainable models as interoperable bedside decision-support tools.


Inhibition of hepatic 17 beta- and 3 alpha-hydroxysteroid dehydrogenases by antiinflammatory drugs and nonsteroidal estrogens.
Antiinflammatory agents and estrogens have been tested as inhibitors of two isozymes of guinea pig liver testosterone 17 beta-dehydrogenase (NADP) 188.8.131.52) and rat liver 3 alpha-hydroxysteroid dehydrogenase (EC 220.127.116.11). Antiinflammatory steroids and estradiols were highly inhibitory to 3 alpha-hydroxysteroid dehydrogenase and one isozyme of testosterone 17 beta-dehydrogenase, respectively, but nonsteroidal antiinflammatory agents and nonsteroidal estrogens such as hexestrol, dienstrol, diethylstilbestrol and zearalenone showed potent inhibitions on all the enzymes. Although the inhibitory potency of indomethacin for one isozymes of testosterone 17 beta-dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase decreased with changing pH from 9.7 to 7.0, that of the nonsteroidal estrogens for all the enzymes was little affected by pH. No additive effect in double inhibitor experiments with indomethacin and the nonsteroidal estrogens was observed, and the compounds were all competitive inhibitors with respect to steroidal substrate. The results suggest that there is a very similar region in substrate binding sites of the enzymes.


[Daily life activities following cerebrovascular infarct].
Cerebro-vascular disease is the first cause of handicap in France. Disabilities in daily life activities are due to motor, visual and cognitive impairments following a stroke. Difficulties arise while grooming, getting dressed, eating, moving around ... the WHO presents with a new classification of functioning, that has been followed by a recent law in France. The aim is to place the handicapped citizen in daily life and not just to list his/her deficiencies. Rehabilitation after stroke has to establish functional objectives early so as to include daily life goals in re-education.


The differential impact of volatile and intravenous anaesthetics on stress response in the swine.
To compare the effects of various anaesthetics on stress response in the presence and absence of surgical stimulation. Twenty-nine pigs scheduled to undergo surgical central vein catheter placement were randomly allocated to receive only sedation with ketamine-midazolam (group SHAM, n=5) or general anaesthesia with either propofol 8 mg/kg/h (group PROP, n=8), sevoflurane 1.0 MAC (group SEVO, n=8) or desflurane 1.0 MAC (group DESF, n=8). Following surgery, anaesthesia was maintained for a total period of 4 hours. Thyroid hormones, noradrenaline, cortisol, corticotrophin (ACTH), beta-endorphin, interleukin-1beta and -6 and tumor necrosis factor-alpha were determined by appropriate methodology after premedication (t0), after surgical procedure (t1) and at the end of 4h (t2). At t1 ACTH and beta-endorphin increased in all groups, thyroxin in groups SEVO, DESF and PROP, noradrenaline in group SEVO and cortisol in the SHAM and PROP groups. At t2 cortisol and ACTH levels were lower in the PROP compared to SEVO group. Serum cytokines were not significantly altered in either group. The choice of the general anaesthetic did not affect thyroid hormones levels in either the presence or absence of surgical stimulus. In the presence of surgical stimulation, sevoflurane resulted in higher noradrenaline levels and in higher activity of the ACTH-cortisol axis compared to propofol.


Circadian monitoring as an aging predictor.
The ageing process is associated with sleep and circadian rhythm (SCR) frailty, as well as greater sensitivity to chronodisruption. This is essentially due to reduced day/night contrast, decreased sensitivity to light, napping and a more sedentary lifestyle. Thus, the aim of this study is to develop an algorithm to identify a SCR phenotype as belonging to young or aged subjects. To do this, 44 young and 44 aged subjects were recruited, and their distal skin temperature (DST), activity, body position, light, environmental temperature and the integrated variable TAP rhythms were recorded under free-living conditions for five consecutive workdays. Each variable yielded an individual decision tree to differentiate between young and elderly subjects (DST, activity, position, light, environmental temperature and TAP), with agreement rates of between 76.1% (light) and 92% (TAP). These decision trees were combined into a unique decision tree that reached an agreement rate of 95.3% (4 errors out of 88, all of them around the cut-off point). Age-related SCR changes were very significant, thus allowing to discriminate accurately between young and aged people when implemented in decision trees. This is useful to identify chronodisrupted populations that could benefit from chronoenhancement strategies.


The effect of melatonin and vitamin C treatment on the experimentally induced tympanosclerosis: study in rats.
The ethiopathogenesis of tympanosclerosis has not been completely under- stood yet. Recent studies have shown that free oxygen radicals are important in the formation of tympanosclerosis. Melatonin and Vitamin C are known to be a powerful antioxidant, interacts directly with Reactive Oxygen Species and controls free radical-mediated tissue damage. To demonstrate the possible preventative effects of melatonin and Vitamin C on tympanosclerosis in rats by using histopathology and determination of total antioxidant status total antioxidant status. Standard myringotomy and standard injury were performed in the middle ear of 24 rats. The animals were divided into three groups: Group 1 received melatonin, Group 2 received vitamin C, and Group 3 received saline solution. The mean values of total antioxidant status were similar in the all study groups before the treatment period. The mean values of total antioxidant status were significantly higher in the melatonin and vitamin C groups compared to control group but vitamin C with melatonin groups were similar after the treatment period (p<0.001). Minimum and maximum wall thicknesses were lower in the melatonin and vitamin C groups compared to the control group but the differences were insignificant. Melatonin increases total antioxidant status level and might have some effect on tympanosclerosis that develops after myringotomy.


Elementary echographic estimation of cardiac output independent of the symmetry and kinetic state of the left ventricle in mitral stenosis. Potential application to the determination of the circulation of pregnancy.
An orifice equation is demonstrated which is independent of the symmetry and kinetic state of the left ventricle. The expression allows calculation of the cardiac output in conditions of mitral stenosis when the mitral valve area is known. This equation is Q = (1/21) R A T2, where Q = cardiac output in ml/min, R = heart rate, A = mitral valve area and T = diastolic filling period in sec/min. Ten patients whose gynecologic or obstetric exam suggested a diagnosis of mitral stenosis were evaluated by conventional cardiac catheterization and M-mode echocardiography. Cardiac output computed using the new equation and the Fick principle corresponded at r = 0.95, SE = 340 ml, N = 10. These results suggest that cardiac output may be conveniently estimated for serial studies by the readily measurable echographic variables of heart rate and diastolic filling period once the mitral valve area has been measured by conventional catheterization or bi-dimensional echographic methods.


Nanocrystal self-assembly with rod-rod block copolymers.
Two distinct morphologies of hexylselenophene-hexylthiophene rod-rod block copolymer films can be prepared depending on the molecular weight of the sample (see picture: left M(n) =12.9, right M(n) =3.9 kg mol(-1)). These polymers can be used to organize spherical CdSe nanocrystals (yellow) into either dispersed or aligned hierarchical structures. Scale bars: 200 nm.


Analysis of X-knife and surgery in treatment of arteriovenous malformation of brain.
The goal of treatment in arteriovenous malformation (AVM) is total obliteration of the AVM, restoration of normal cerebral function, and preservation of life and neurological function. To analyze the results of X-knife and surgery for AVM of the brain. The endpoints for success or failure were as follows: success was defined as angiographic obliteration and failure as residual lesion, requiring retreatment, or death due to hemorrhage from the AVM. From May 2002 to May 2007, 54 patients were enrolled for this study. Grade I AVM was seen in 9%, grade II in 43%, grade III in 26%, grade IV in 9%, and grade V in 13%. Thirty-eight patients were treated by microsurgical resection out of which Grade I was seen in 5 patients, Grade II was seen in 17 patients, Grade III was seen in 9 patients and Grade V was seen in 7 patients. Rest of the sixteen patients were treated by linear accelerator radiosurgery out of which Grade II was seen in 6 patients, Grade III was seen in 5 patients and Grade IV was seen in 5 patients. The follow up was in range of 3-63 months. In follow up, digital subtraction angiography/ magnetic resonance angiography (DSA/MRA) was performed 3 months after surgery and 1 year and 2 years after stereotactic radiosurgery (SRS). Among the patients treated with X-knife, 12/16 (75%) had proven angiographic obliteration. Complications were seen in 4/16 (25%) patients. Among the patients treated with microsurgical resection, 23/38 (61%) had proven angiographic obliteration. Complications (both intraoperative and postoperative) were seen in 19/38 (50%) patients. Sixty-one percent of patients were candidates for surgical resection. X-knife is a good modality of treatment for a low-grade AVM situated in eloquent areas of the brain and also for high-grade AVMs, when the surgical risk and morbidity is high.


MiR-146a-5p Expression in Peripheral CD14⁺ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.
In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14⁺ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14⁺ monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14⁺ monocytes were cultured with media containing TNF-α and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14⁺ monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14⁺ monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14⁺ monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.


[Own and Parental Predictors of Low Blood Level of High Density Lipoprotein Cholesterol in Offspring of Persons With Early Coronary Heart Disease].
to elucidate own and parental predictors of low levels of high density lipoprotein cholesterol (HDL-C) in blood of children of persons with early coronary heart disease (ECHD) (onset less or equal 55 years, men, or less or equal 60 years, women). We examined 305 families: probands with ECAD (n=289, 69.2% men), their spouses (n=213, 17.8% men) and native children of probands (n=399, 56.1% men) aged 5-38 years. Low level of HDL-C in children aged 5-17 years we defined as less or equal 25 percentile (the Lipid Research Clinics, 1981), in children aged 18-38 years - <1.03 (men) and <1.29 (women) mmol/l. Predictors of low HDL-C were selected by logistical regression with adjustment for sex and age. Low HDL-C was revealed in 48/152 (31.6%) children aged 5-17 years. Its independent predictors were own higher triglycerides (TG) and low HDL-C of spouse. Odds ratio (OR) of top (>0.94 mmol/l) vs two bottom ( less or equal 0.94 mmol/l) tertiles of TG 2.68 (95% confidence interval [CI] 1.03-6.94; =0.043); low HDL-C of spouse 2.33 (95% CI 1.03-5.26; =0.041). Low HDL-C was revealed in 91/247 (36.8%) offsprings aged 18-38 years. Its independent predictors were higher waist circumferences (WC, OR top [>85 cm] vs bottom [ less or equal 73 cm] tertile 5.43, 95% CI 2.39-12.3; =0.000) and TG (OR 1.45, 95% CI 1.01-2.09; =0.047) of these children, atherogenic dyslipidemia of proband (OR 2.44, 95% CI 1.34-4.44; =0.0036); metabolic syndrome (OR 4.14, 95% CI 1.96-8.75; =0.0002) and lower heart rate (OR top [>72 bpm] vs two bottom [ less or equal 72 bpm] tertiles 0.41, 95% CI 0.17-0.97; =0.043) of consort-parent. In this group of different age children with parental ECHD independent predictors of low HDL-C were mostly own (TG) and parental metabolic factors.


Analysis of focused laser differential interferometry.
A computational method for predicting the output of a focused laser differential interferometer (FLDI) given an arbitrary density field is presented. The method is verified against analytical predictions and experimental data. The FLDI simulation software is applied to the problem of measuring Mack-mode wave packets in a hypervelocity boundary layer on a 5° half-angle cone. The software is shown to complement experiments by providing the necessary information to allow quantitative density fluctuation magnitudes to be extracted from experimental measurements.


The neural substrate of spatial memory stabilization depends on the distribution of the training sessions.
SignificanceDistributed training has long been known to lead to more robust memory formation as compared to massed training. Using the water maze, a well-established task for assessing memory in laboratory rodents, we found that distributed and massed training differentially engage the dorsolateral and dorsomedial striatum, and optogenetic priming of dorsolateral striatum can artificially increase the robustness of massed training to the level of distributed training. Overall, our findings demonstrate that spatial memory consolidation engages different neural substrates depending on the training regimen, identifying a therapeutic avenue for memory enhancement.


Protein-nucleoside contacts in the interaction between the replication terminator protein of Bacillus subtilis and the DNA terminator.
The interaction between the DNA replication terminator, IRI, of Bacillus subtilis and its cognate replication terminator protein (RTP) has been examined by the technique of missing nucleoside interference (MNI). IRI contains two adjacent binding sites (A and B) for RTP dimers. The B site is proximal to the replication fork arrest site. The present results have shown that nucleoside contacts with RTP in the two sites are very different. There are more extensive contacts of nucleosides in both strands of the B site with RTP compared with the A site. The data also strongly suggest that filling by RTP of the B site occurs first and is needed for subsequent co-operative filling of an overlapping A site. The A site alone binds RTP poorly. The findings are consistent with interaction occurring between RTP dimers bound to adjacent sites of IRI, which would explain why RTP bound to the B site alone cannot cause replication fork arrest.


[Heterogeneity of the chemical element composition of the human myocardium after sudden cardiac death].
The content of Si, Fe, S, Ca, Cl in different heart compartments was studied in the autopsy material of human myocardium obtained after sudden cardiac death preceded by emotional stress. Damage of the element content was detected both within the myocardium of one chamber and the whole heart. Zones of high intracellular Ca content were found in the myocardium of the left ventricle and right atrium. Their location coincided with the area of ultrastructural alterations, which were earlier characterized as calcium damage of the myocardium. The same sites were characterized by high Cl content. The size of the areas was determined by roentgenologic mapping. S and Fe content was also different in different heart compartments.


Phospholemman modulates the gating of cardiac L-type calcium channels.
Ca(2+) entry through L-type calcium channels (Ca(V)1.2) is critical in shaping the cardiac action potential and initiating cardiac contraction. Modulation of Ca(V)1.2 channel gating directly affects myocyte excitability and cardiac function. We have found that phospholemman (PLM), a member of the FXYD family and regulator of cardiac ion transport, coimmunoprecipitates with Ca(V)1.2 channels from guinea pig myocytes, which suggests PLM is an endogenous modulator. Cotransfection of PLM in HEK293 cells slowed Ca(V)1.2 current activation at voltages near the threshold for activation, slowed deactivation after long and strong depolarizing steps, enhanced the rate and magnitude of voltage-dependent inactivation (VDI), and slowed recovery from inactivation. However, Ca(2+)-dependent inactivation was not affected. Consistent with slower channel closing, PLM significantly increased Ca(2+) influx via Ca(V)1.2 channels during the repolarization phase of a human cardiac action potential waveform. Our results support PLM as an endogenous regulator of Ca(V)1.2 channel gating. The enhanced VDI induced by PLM may help protect the heart under conditions such as ischemia or tachycardia where the channels are depolarized for prolonged periods of time and could induce Ca(2+) overload. The time and voltage-dependent slowed deactivation could represent a gating shift that helps maintain Ca(2+) influx during the cardiac action potential waveform plateau phase.


Effect of reversible inactivation of locus ceruleus on spatial reference and working memory.
The locus coeruleus (LC) is the largest source of norepinephrine (NE) in the prefrontal cortex and the hippocampus, influencing the cognitive functions of these areas. All previous studies have studied the role of the LC-NE system on learning and memory using the irreversible lesion technique, employing either electrocoagulation or excitotoxins. However, the reversible functional inactivation of LC by means of stereotaxic local microinjection of lidocaine could measure the phases of memory processing (acquisition, consolidation and retention) without any interference with the other cognitive functions of the same structure either during earlier or later phases of the same process. The aim of this study is to investigate LC involvement in spatial reference and working memory by inducing bilateral pre-training, post-training and pre-retrieval lidocaine functional inactivation using the Morris water maze task. The reversible inactivation of LC was applied at different stages of spatial memory formation: (1) immediately before the training sessions to determine the effects on acquisition of the both reference and working memory; (2) immediately after the training session to evaluate effects on both spatial memory consolidation and retention of working memory; and (3) immediately before the 24 h retention session to analyze the effects on the retrieval process of reference memory. Our results indicate that the bilateral reversible inactivation of LC significantly impaired the acquisition of reference and working memory, while it had no effect on consolidation and/or retention of such memories in the Morris water maze (MWM) task. Therefore, the noradrenergic system of the LC may play a more important role in acquisition than in consolidation and retrieval of spatial memory in wistar rats.


Some problems of research exploring sex differences in sport-related concussions: a narrative review.
This narrative review scrutinizes research exploring sex-based differences in experiences of sport-related concussion. The article argues that the limitations of epidemiological studies identifying the greater incidence and severity of concussion among females require that these findings are read with caution. It secondly argues that the dominant explanations for these data are based on and extend historical tendencies to "other" female participation in sport and construct male experiences as the "norm". Finally, the article critiques policy recommendations related to these research findings, arguing that they are likely to embed rather than challenge sex inequality in sport, and that they are both impractical and unethical. While this commentary builds on a broader body of work advocating greater sex/gender equality in sports science research, the prominence of social concerns about concussions in sport makes the broader implications of the focus on sex and sport-related concussion particularly problematic and thus in need of redress.


Modeling developmental plasticity after perinatal stroke: defining central therapeutic targets in cerebral palsy.
Perinatal stroke is presented as the ideal human model of developmental neuroplasticity. The precise timing, mechanisms, and locations of specific perinatal stroke diseases provide common examples of well defined, focal, perinatal brain injuries. Motor disability (hemiparetic cerebral palsy) constitutes the primary adverse outcome and the focus of models explaining how motor systems develop in health and after early injury. Combining basic science animal work with human applied technology (functional magnetic resonance imaging, diffusion tensor imaging, and transcranial magnetic stimulation), a model of plastic motor development after perinatal stroke is presented. Potential central therapeutic targets are revealed. The means to measure and modulate these targets, including evidence-based rehabilitation therapies and noninvasive brain stimulation, are suggested. Implications for clinical trials and future directions are discussed.


Patient waiting time in the outpatient clinic at a central surgical hospital of Vietnam: Implications for resource allocation.
Background: Patient waiting time is considered as a crucial parameter in the assessment of healthcare quality and patients' satisfaction towards healthcare services. Data concerning this has remained limited in Vietnam. Thus, this study aims to assess patient waiting time in the outpatient clinic in Viet Duc Hospital (Hanoi, Vietnam) in order to enable stakeholders to inform evidence-based interventions to improve the quality of healthcare services. Methods: A cross-sectional study was conducted from June 2014 to June 2015 in the outpatient clinic at Viet Duc Hospital. Waiting time stratified by years (2014 and 2015), months of the year, weekdays, and hours of the day were extracted from Hospital Management software and carefully calculated. Stata 12.0 was employed to analyze data, including the average time (M± SD), frequencies and percentage (%). Results: There was a total of 137,881 patients involved in the study. The average waiting time from registration to preliminary diagnosis in 2014 was 50.41 minutes, and in 2015 was 42.05 minutes. A longer waiting time was recorded in the morning and in those having health insurance. Conclusions: Our results provided evidence that despite the decrease of waiting time from 2014 to 2015, waiting time was much higher among patients having health insurance compared to their counterparts. The findings suggest that human resources promotion and distribution should be emphasized in outpatient clinics and health insurance-related administrative procedures should be simplified.


Dynamic MRI of solitary pulmonary nodules: comparison of enhancement patterns of malignant and benign small peripheral lung lesions.
The purpose of this study was to compare the dynamic contrast-enhanced MRI enhancement characteristics of malignant and benign solitary pulmonary nodules. The characteristics of 202 solitary pulmonary nodules (diameter, 1-3 cm; 144 cases of primary lung cancer, 31 cases of focal organizing pneumonia, 15 tuberculomas, 12 hamartomas) were reviewed retrospectively. In all cases dynamic MR images were obtained before and 1, 2, 3, 4, 5, 6, and 8 minutes after bolus injection of gadopentetate dimeglumine. Maximum enhancement ratio, time at maximum enhancement ratio, slope of time-enhancement ratio curves, and washout ratio were assessed. Statistical analyses were performed with the Kruskal-Wallis test with Bonferroni correction, chi-square test, and receiver operating characteristic curves. For 122 (85%) of 144 primary lung cancers, time at maximum enhancement ratio was 4 minutes or less. For all tuberculomas and hamartomas, time at maximum enhancement ratio was greater than 4 minutes or gradual enhancement occurred without a peak time (p < 0.0001). Lung cancers had different maximum enhancement ratios and slopes than benign lesions (all p < 0.005). With 110% or lower maximum enhancement ratio as a cutoff value, the positive predictive value for malignancy was 92%; sensitivity, 63%; and specificity, 74%. With 13.5%/min or greater slope as a cutoff value, sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 94%, 96%, 99%, and 74%, respectively. Dynamic contrast-enhanced MRI is helpful in differentiating benign from malignant solitary pulmonary nodules. Absence of significant enhancement is a strong predictor that a lesion is benign.


Differentially Expressed Conserved Plant Vegetative Phase-Change-Related microRNAs in Mature and Rejuvenated Silver Birch In Vitro Propagated Tissues.
In plants, phase change from the juvenile stage to maturity involves physiological and anatomical changes, which are initiated and controlled by evolutionary highly conserved microRNAs. This process is of particular significance for the in vitro propagation of woody plant species, as individuals or tissues that have undergone the transition to vegetative maturity are recalcitrant to propagation. Conserved miRNAs differentially expressed between juvenile (including rejuvenated) and mature silver birch tissues were identified using high-throughput sequencing of small RNA libraries. Expression of some miR156 isoforms was high in juvenile tissues and has been previously reported to regulate phase transitions in a range of species. Additional miRNAs, such as miR394 and miR396, that were previously reported to be highly expressed in juvenile woody plant tissues were also differentially expressed in this study. However, expression of miR172, previously reported to be highly expressed in mature tissues, was low in all sample types in this study. The obtained results will provide insight for further investigation of the molecular mechanisms regulating vegetative phase change in silver birch and other perennial woody plant species, by analysing a wider range of genotypes, tissue types and maturation stages. This knowledge can potentially assist in identification of rejuvenated material at an earlier stage than currently possible, increasing the efficiency of silver birch in vitro propagation.


Sex-Biased Population Admixture Mediated Subsistence Strategy Transition of Heishuiguo People in Han Dynasty Hexi Corridor.
The Hexi Corridor was an important arena for culture exchange and human migration between ancient China and Central and Western Asia. During the Han Dynasty (202 BCE-220 CE), subsistence strategy along the corridor shifted from pastoralism to a mixed pastoralist-agriculturalist economy. Yet the drivers of this transition remain poorly understood. In this study, we analyze the Y-chromosome and mtDNA of 31 Han Dynasty individuals from the Heishuiguo site, located in the center of the Hexi Corridor. A high-resolution analysis of 485 Y-SNPs and mitogenomes was performed, with the Heishuiguo population classified into Early Han and Late Han groups. It is revealed that (1) when dissecting genetic lineages, the Yellow River Basin origin haplogroups (i.e., Oα-M117, Oβ-F46, Oγ-IMS-JST002611, and O2-P164+, M134-) reached relatively high frequencies for the paternal gene pools, while haplogroups of north East Asian origin (e.g., D4 and D5) dominated on the maternal side; (2) in interpopulation comparison using PCA and Fst heatmap, the Heishuiguo population shifted from Southern-Northern Han cline to Northern-Northwestern Han/Hui cline with time, indicating genetic admixture between Yellow River immigrants and natives. By comparison, in maternal mtDNA views, the Heishuiguo population was closely clustered with certain Mongolic-speaking and Northwestern Han populations and exhibited genetic continuity through the Han Dynasty, which suggests that Heishuiguo females originated from local or neighboring regions. Therefore, a sex-biased admixture pattern is observed in the Heishuiguo population. Additionally, genetic contour maps also reveal the same male-dominated migration from the East to Hexi Corridor during the Han Dynasty. This is also consistent with historical records, especially excavated bamboo slips. Combining historical records, archeological findings, stable isotope analysis, and paleoenvironmental studies, our uniparental genetic investigation on the Heishuiguo population reveals how male-dominated migration accompanied with lifestyle adjustments brought by these eastern groups may be the main factor affecting the subsistence strategy transition along the Han Dynasty Hexi Corridor.


Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure.
Cigarette smoking and pulmonary emphysema are strongly associated with abdominal aortic aneurysms (AAAs), but the biologic mechanisms linking these conditions are undefined. To determine if exposure to cigarette smoke influences formation and growth of experimental AAAs, 129/SvEv mice were acclimated to daily cigarette smoke exposure for 2 weeks followed by transient elastase perfusion of the abdominal aorta to induce aneurysmal degeneration. Smoking was continued for intervals of either 2 or 12 weeks (8 mice per group). Nonsmoking 129/SvEv controls (n = 29) underwent elastase perfusion and followup evaluation at the same time intervals. In all animals, abdominal aortic diameter (AD) was measured to determine interval increases in AD (Delta AD), with AAAs defined as a Delta AD > 100%. Preperfusion and immediate postperfusion ADs were not significantly different between experimental groups. Aneurysmal dilatation was present 2 weeks after elastase perfusion in both smoking mice and nonsmoking controls, with no significant difference in final AD (mean +/- SEM: smoking, 1.23 +/- 0.11 mm versus nonsmoking, 1.22 +/- 0.05 mm). There were also no differences in the overall extent of aortic dilatation (Delta AD smoking, 136 +/- 24% versus nonsmoking, 138 +/- 10%), or the incidence of AAAs (smoking, 75% versus nonsmoking, 79%). Although all animals had developed AAAs by 12 weeks after elastase perfusion, the overall extent of aortic dilatation was 50% greater in smoking mice compared with nonsmoking controls (Delta AD smoking, 204 +/- 23% versus nonsmoking, 135 +/- 17%; p < 0.05). Short-term exposure to cigarette smoke did not alter initial development of experimental AAAs, but chronic smoke exposure was associated with a substantial increase in the late progression of aneurysmal dilatation. This novel combination of in vivo experimental models offers a new approach to investigate mechanisms by which cigarette smoking promotes aneurysmal degeneration.


Theileria parva: detection of genomic polymorphisms by polymerase chain reaction amplification of DNA using arbitrary primers.
Genomic DNA fingerprints were generated from Theileria parva piroplasm DNA by polymerase chain reaction amplification using arbitrary decamers as primers. Four of 12 primers tested generated amplified fragments which were polymorphic between different T. parva stocks or clones. Hybridization of radiolabeled total amplification products to Southern blots of T. parva piroplasm and uninfected bovine DNA confirmed that none of the amplified fragments were derived from any contaminating bovine DNA which may have been present in small quantities. Polymorphic DNA fragments were reproducibly amplified from independent DNA preparations made from cloned parasites. Individual amplified DNA fragments were gel purified and shown to hybridize to size-polymorphic EcoRI fragments in T. parva genomic DNA. Hybridization of individual amplified fragments to total fingerprints, generated using the same arbitrary primer, demonstrated that a single primer detected at least three independent genomic polymorphisms in T. parva DNA.