Czech dysplasia metatarsal type: another type II collagen disorder.
Czech dysplasia metatarsal type is an autosomal-dominant disorder characterized by an early-onset, progressive spondyloarthropathy with normal stature. Shortness of third and/or fourth toes is a frequently observed clinical feature. Similarities between individuals with this dysplasia and patients with an R275C mutation in the COL2A1 gene, prompted us to analyze the COL2A1 gene in the original families reported with Czech dysplasia. Targeted sequencing of exon 13 of the COL2A1 gene was performed, followed by sequencing of the remaining exons in case the R275C mutation was not identified. We identified the R275C substitution in two of the original patients reported with Czech dysplasia and three additional patients. All affected individuals had a similar phenotype characterized by normal height, spondyloarthropathy, short postaxial toes and absence of ocular and orofacial anomalies. The R275C mutation was excluded in a third patient reported with Czech dysplasia. However, the identification of the Y1391C mutation in this patient with disproportionate short stature made the diagnosis of spondyloperipheral dysplasia (SPD) more probable. The Y1391C mutation is located in the C-propeptide of the procollagen chain and has been reported before in a patient with the Torrance type of lethal platyspondylic skeletal dysplasia (PLSD-T). Our observation of the same Y1391C mutation in an additional unrelated patient with SPD further supports the evidence that PLSD-T and SPD represent a phenotypic continuum. The R275C mutation in the COL2A1 gene causes a specific type II collagen disorder that was recently delineated as Czech dysplasia.


Indiana Palliative Excellence in Alzheimer's Care Efforts (IN-PEACE): Protocol for a randomized controlled trial in persons with advanced dementia.
Dementia affects 6.5 million persons in the U.S., a number which is expected to double by 2060. More than half of persons with dementia die at home, creating an enormous burden for both patients and caregivers. However, there is a paucity of research on community-based palliative care interventions for advanced dementia. The Indiana Palliative Excellence in Alzheimer's Care Efforts (IN-PEACE) study is a randomized trial to test the effectiveness of a collaborative predominantly telehealth home-based intervention for persons with advanced dementia residing in the community and their primary, informal caregivers. The primary aim is to determine if this palliative care focused supportive intervention is superior to usual care in reducing neuropsychiatric symptoms of dementia. Secondarily, intervention effects on other patient symptoms (e.g., pain), caregiver distress and depression, and emergency department (ED)/hospitalization events are examined. The study population consists of participant pairs comprising a person with dementia and their primary, informal caregiver. The person with dementia must be ≥65 years old, with a clinical diagnosis of moderate to severe dementia. A total of 201 demographically and socioeconomically diverse participant pairs have been randomized to the IN-PEACE care coordination intervention (n = 99) or usual care (n = 102). Outcome assessments are conducted at baseline, and quarterly for up to 2 years (3, 6, 9, 12, 15, 18, 21, and 24 months). IN-PEACE results will inform care for the large number of individuals with advanced dementia residing in the community and enable informal caregivers to provide effective home-based care. clinicaltrials.gov Identifier: NCT03773757.


An unusual presentation of penetrating bladder injury with vesicocutaneous fistula: a case report.
Blunt trauma to the urinary bladder is common with penetrating injury being a rare occasion. Most common entry pint for penetrating injuries includes buttock, abdomen and perineum with thigh being rare. There are a number of complications that may develop as a result of penetrating injury with vesicocutanous fistula being a rare occurrence that usually presents with typical sign and symptoms. We present a rare case of penetrating bladder injury through medial upper thigh as an entry point that had complicated into vesicocutaneous fistula with atypical presentation of long-standing pus discharge that had been managed by incision and drainage several times with no success. MRI demonstrated a presence of fistula tract and a foreign body (piece of wood) in-situ confirmed the diagnosis. Fistulas are a rare complication of bladder injuries and can cause negative impact on the quality of life of patients. Delayed urinary tract fistulations and secondary thigh abscesses are uncommon therefore a high index of suspicion is needed for early diagnosis. This case emphasizes the importance of radiological tests in aiding the diagnosis and ultimately proper management.


Hairy root induction and Farnesiferol B production of endemic medicinal plant Ferula pseudalliacea.
The effects of medium, gibberellic acid (GA3) and stratification treatments on the seed germination of Ferula pseudalliacea were evaluated. Filter paper medium, 500 micro molar GA3 and 8 week chilling treatment were resulted in significantly more seed germination than others. F. pseudalliacea was also transformed by Agrobacterium rhizogenes. Explants from young leaves, stems, cotyledon, and embryo were inoculated with A. rhizogenes strains ATCC 15834, 1724, A4, LB9402 and Ar318. Hairy roots were induced only from 10 to 12-days embryo explants using strains ATCC 15824 and 1724. Although, the transformation efficiency of ATCC 15834 (4%) strain was higher than 1724 (2%). Maximum hairy root transformation frequency (25%) was obtained in infection time of 10 min compared to that of 20 (20%) and 30 (5%) min. In addition, the transformation rate was significantly higher at the inoculation time of 72 h (29%) compared to that of 48 h (22%) and 24 h (6%). Transgenic hairy root lines were confirmed by PCR amplification of rolB gene. Hairy root lines were produced higher biomass in half B5 medium compared to that of half MS medium. Hairy roots lines from the strain ATCC 15834 produced more hairy root numbers and fresh and dried biomass compared to that of the strain 1724. Analyses of transgenic hairy root and natural roots extracts using HPLC showed that all the hairy root lines produced farnesiferol B.


Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine.
Chronic morphine administration induced ultrastructural alterations in neurons of the facial nucleus and increased the incidence of cell death after axotomy. These findings may correlate with the significant depression of neuronal metabolism known to occur after opiate treatment.


The protective effect of the active components of ERPC on diabetic peripheral neuropathy in rats.
Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes. The aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved. After diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence. cERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats. cERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.


Dose-dependent effects of higher methionine levels on the transcriptome and metabolome of transgenic Arabidopsis seeds.
Higher methionine levels in transgenic Arabidopsis seeds trigger the accumulation of stress-related transcripts and primary metabolites. These responses depend on the levels of methionine within seeds. Methionine, a sulfur-containing amino acid, is a key metabolite in plant cells. To reveal the regulatory role of the Arabidopsis thaliana CYSTATHIONINE γ-SYNTHASE (AtCGS), methionine main regulatory enzyme, in the synthesis of methionine in seeds, we generated transgenic RNAi seeds with targeted repression of AtCGS during late developmental stages of seeds. Unexpectedly, these seeds accumulated 2.5-fold more methionine than wild-type seeds. To study the nature of these seeds, transcriptomic and primary metabolite profiling were employed using Affymetrix ATH1 microarray and gas chromatography-mass spectrometry analyses, respectively. The results were compared to transgenic Arabidopsis seeds expressing a feedback-insensitive form of AtCGS (named SSE-AtD-CGS) that were previously showed to accumulate up to sixfold more soluble methionine than wild-type seeds. Statistical assessments showed that the nature of transcriptomic and metabolic changes that occurred in RNAi::AtCGS seeds were relatively similar, but to lesser extents, to those previously reported for SSE-AtD-CGS seeds, and linked to the induction of global transcriptomic and metabolic responses associated with stronger desiccation stress. As transgenic seeds obtained by both manipulations exhibited higher, but different methionine levels, the data strongly suggest that these changes depend on the absolute amounts of methionine within seeds and much less to the expression level of AtCGS.


Biochemical properties of cytochrome c nitrated by peroxynitrite.
Nitration of tyrosine residues is taken as evidence for intracellular formation of peroxynitrite. Cytochrome c (cyt c) can be nitrated by peroxynitrite and nitrated cyt c has been observed in cells and tissues under stress conditions. Here we studied the biochemical properties of nitrated cyt c in order to understand its potential roles in nitrative stress. Nitration of cyt c resulted in disruption of the heme-methionine bond and rapid binding to cyanide. Equilibrium unfolding by guanidine hydrochloride showed that cyt c was slightly destabilized upon nitration but the unfolding transition of nitrated cyt c was highly cooperative indicating that the overall folding was largely preserved. Nitrated cyt c could not be reduced by superoxide and did not support electron transfer between ascorbate and cyt c oxidase. Nitration of cyt c resulted in a tremendous increase in peroxidase activity so that nitrated cyt c rapidly oxidized dihydrodichlorofluorescein even in the presence of a high concentration of glutathione. Enhanced peroxidase activity of nitrated cyt c was responsible for H2O2-induced oxidation of phospholipid membranes and H2O2/NO2--mediated nitration of other proteins. These results suggest that nitration of cyt c by peroxynitrite may exacerbate oxidative damage to mitochondrial proteins and membranes.


Intrinsically elastic polymer ferroelectric by precise slight cross-linking.
Ferroelectrics are an integral component of the modern world and are of importance in electrics, electronics, and biomedicine. However, their usage in emerging wearable electronics is limited by inelastic deformation. We developed intrinsically elastic ferroelectrics by combining ferroelectric response and elastic resilience into one material by slight cross-linking of plastic ferroelectric polymers. The precise slight cross-linking can realize the complex balance between crystallinity and resilience. Thus, we obtained an elastic ferroelectric with a stable ferroelectric response under mechanical deformation up to 70% strain. This elastic ferroelectric exerts potentials in applications related to wearable electronics, such as elastic ferroelectric sensors, information storage, and energy transduction.


Prenatal ultrasound may predict fetal response to therapy in non-hydropic fetuses with supraventricular tachycardia.
To study the fetal response to prenatal therapy in non-hydropic fetuses with supraventricular tachycardia (SVT) as a function of fetal haemodynamic status at presentation. Retrospective study. Between 1990 and 2000, 40 non-hydropic fetuses presented with SVT. Twenty-eight had reciprocating SVT and 12 had atrial flutter. Ten fetuses had significant tricuspid valve regurgitation. All fetuses were treated prenatally. The main outcome measurement was fetal response to therapy as assessed by the rate of prenatal SVT reduction and by the mean time interval to sinus rhythm restoration. The mean gestational age at presentation was 29 +/- 4.9 weeks. Overall, there were 39 live births and 1 intrauterine death. Reduction of SVT was achieved prenatally in 32 cases (80%). Among the 30 cases without tricuspid regurgitation, prenatal conversion to sinus rhythm was achieved in 27 cases (90%) with a mean time interval of 7 days. Among the 10 fetuses presenting with tricuspid regurgitation, the rate of prenatal conversion was significantly lower (5/10) and the mean time interval to conversion was significantly longer (24 days; p = 0.04, Mann-Whitney test). In the subgroup treated by digoxin as first-line therapy (n = 32), the interval to sinus rhythm restoration was also significantly higher in the presence of tricuspid regurgitation, with a slightly but not significantly lower reduction rate. The response to prenatal therapy may be poorer in cases presenting with tricuspid regurgitation.


The CT scan and subtraction angiography in chemodectomas.
The value of subtraction angiography and CT scanning in the diagnosis of chemodectomas are illustrated by two cases, a glomus jugulare tumour which exhibited true malignant behaviour, and a carotid body tumour. The characteristic early arterial blush of a chemodectoma, which can be obscured by bone, is clearly seen following subtraction techniques revealing tumours as small as 0.5 cm. The chemodectoma appeared as an isodense tumour on the CT scan with uniform contrast enhancement and well-defined margins. The appearances, however, are not diagnostic of a chemodectoma and may be simulated by other tumours.


Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
The objective of this analysis was to evaluate the clinical factors influencing survival outcomes in patients with localized (clinical group I-III), FOXO1 fusion-positive rhabdomyosarcoma (RMS). Patients with confirmed FOXO1 fusion-positive RMS who were enrolled on 3 completed clinical trials for localized RMS were included in the analytic cohort. Outcomes were analyzed using the Kaplan-Meier method to estimate event-free survival (EFS) and overall survival (OS), and the curves were compared using the log-rank test. A Cox proportional hazards regression model was used to perform multivariate analysis of prognostic factors that were significant in the univariate analysis. The estimated 4-year EFS and OS of 269 patients with localized, FOXO1 fusion-positive RMS was 53% (95% CI, 47%-59%) and 69% (95% CI, 63%-74%), respectively. Univariate analysis revealed that several known favorable clinical characteristics, including age at diagnosis between 1 and 9 years, complete surgical resection, tumor size ≤5 cm, favorable tumor site, absence of lymph node involvement, confinement to the anatomic site of origin, and PAX7-FOXO1 fusion, were associated with improved outcomes. Multivariate analysis identified older age (≥10 years) and large tumor size (>5 cm) as independent, adverse prognostic factors for EFS within this population, and patients who had both adverse features experienced substantially inferior outcomes. Patients with localized, FOXO1 fusion-positive RMS can be further risk stratified based on clinical features at diagnosis, and older patients with large primary tumors have the poorest prognosis.


Ruxolitinib altered IFN-β induced necroptosis of human dental pulp stem cells during osteoblast differentiation.
This study aimed to evaluate the role of ruxolitinib in the interferon beta (IFN-β) mediated osteoblast differentiation using human dental pulp stem cells (hDPSCs). hDPSCs from five deciduous teeth of healthy patients were stimulated by adding human recombinant IFN-β protein (1 or 2 ng/ml) to the osteogenic differentiation induction medium. Substrate formation was determined using Alizarin Red staining, calcium concentration, and osteoblast marker expression levels. Ruxolitinib was used to inhibit the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Apoptosis was detected using terminal deoxynucleotidyl nick-end labeling (TUNEL) staining, and necroptosis was detected using propidium iodide staining and phosphorylated mixed lineage kinase domain-like protein (pMLKL) expression. In the IFN-β-treated group, substrate formation was inhibited by a reduction in alkaline phosphatase (ALP) expression in a concentration-dependent manner. Although the proliferation potency was unchanged between the IFN-β-treated and control groups, the cell number was significantly reduced in the experimental group. TUNEL-positive cell number was not significantly different; however, the protein level of necroptosis markers, interleukin-6 (IL-6) and pMLKL were significantly increased in the substrate formation. Cell number and ALP expression level were improved in the group administered ruxolitinib, a JAK-STAT inhibitor. Additionally, ruxolitinib significantly suppressed IL-6 and pMLKL levels. Ruxolitinib interfered with the IFN-β-mediated necroptosis and osteogenic differentiation via the JAK-STAT pathway.


Biochemical and cytologic characteristics of pleural effusions secondary to pulmonary embolism.
To characterize the biochemical and cytologic constituents of pleural effusions secondary to pulmonary embolism. A descriptive clinical study. A community teaching hospital with 750 beds, which acts as a tertiary referral center for several subspecialties. Patients with pleural effusions secondary to pulmonary embolism who underwent diagnostic thoracentesis during the last 7 years were retrospectively studied. Pleural fluid mesothelial hyperplasia was revised and compared with that found in patients with pleural effusions of different origin. Pleural effusions from all 60 patients with pulmonary embolism were exudates, and in 40 patients (67%) contained erythrocyte counts > 10,000/microL. A bloody appearance was not related to the use of anticoagulant therapy before thoracentesis. Polymorphonuclear leukocytes were predominant in 36 patients (60%); in 11 patients (18%), a proportion of eosinophils > 10% was found. Mesothelial hyperplasia was significantly higher in patients with pulmonary embolism than in patients in the control group (p < 0.01). In the absence of trauma, a bloody or eosinophilic effusion with a marked mesothelial hyperplasia should prompt a workup to rule out embolism. The finding of transudative pleural fluid chemistries in these patients should not be assumed to be secondary to embolism before ruling out other causes of transudative effusion.


Serum lipid pattern unifies following renal transplantation in children.
Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls ( n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children.


Deamination of methylamine by semicarbazide-sensitive amine oxidase in human umbilical artery and rat aorta.
The deamination of methylamine (MA) by amine oxidase enzymes has been studied and compared with that of benzylamine (BZ) in homogenates of rat aorta and human umbilical artery by means of a radiochemical assay to estimate the radiolabelled deaminated metabolites produced, and also a spectrophotometric assay to measure H2O2 formation during the metabolism of these substrates. The effects of various inhibitors used in these assays suggest that a semicarbazide-sensitive amine oxidase (SSAO) is predominantly if not wholly responsible for the deamination of both MA and BZ in these tissues. MA was found to have a relatively higher apparent Km (102 microM in aorta; 779 microM in umbilical artery) than BZ (6.8 microM in aorta; 207 microM in umbilical artery) for metabolism by SSAO in these tissues. However, these large differences between species in the apparent Km values for each amine indicate that the biochemical properties of SSAO in human and rat vasculature are not identical. SSAO in human umbilical artery was particularly active towards MA, with a Vmax which was approximately 70% greater than that for BZ as substrate, whereas in rat aorta the Vmax for MA was around 60% of that for BZ. MA is known to occur endogenously in man and other species, and the possibility that it may be a physiological substrate in vivo for SSAO is discussed.


A Novel Technique for Total En bloc Spondylectomy of the Fifth Lumbar Tumor Through Posterior-Only Approach.
A retrospective study. To describe a new surgical technique for total en bloc spondylectomy (TES) of the fifth lumbar (L5) tumor and evaluate the efficacy and safety of this new technique. TES has been considered an optimal treatment for tumor, including certain spinal tumors, but it requires a combined posterior-anterior approach, which is often complicated by a long operation time, considerable blood loss and severe trauma. Seven patients with primary or solitary metastatic tumors of L5 were treated with this new technique in our center between March 2014 and November 2017. The critical points were fabrication of the iliac graft, dissection, resection, and reconstruction. Other parameters including surgical time, blood loss, complications, pre- and postoperative neurological function, tumor control, and overall survival (OS) were presented and analyzed. All the included patients received one stage TES. The mean surgical time was 365.7 minutes with an average blood loss of 2514.3 mL. No serious perioperative complication was observed or reported during the mean follow-up period of 27.4 months. Wound disruption occurred in one patient and numbness of the left lower limb in another, but both recovered rapidly after appropriate management. Adventitial avulsion of the abdominal aorta occurred during dissection in one patient. Two patients died during the follow-up period due to advanced malignancy. One patient was alive but developed a newly diagnosed thoracolumbar tumor in 40 months. The other four patients recovered well without evidence of disease. All patients were able to walk independently 3 to 4 weeks after operation, with satisfied fusion of the iliac grafts in a mean period of 6.7 months after operation. No evidence of internal fixation failure occurred. This new technique offers satisfactory surgical exposure, total en bloc spondylectomy, reliable reconstruction, and good tumor control for certain L5 tumors through the posterior-only approach. 4.


Co-existence of a giant splenic hemangioma and multiple hepatic hemangiomas and the potential association with the use of oral contraceptives: a case report.
Hepatic and splenic hemangiomas are common benign tumors that mainly affect female patients. Giant splenic hemangiomas are extremely rare, especially when correlated with multiple hepatic hemangiomas. Pathogenetic mechanisms between hemangiomas and oral contraceptives, as well as therapeutic approaches, are analyzed in this case report, in particular for the management of synchronous splenic and hepatic hemangiomas. We report here a 42-year-old woman with a giant splenic hemangioma, multiple hepatic hemangiomas and a history of oral estrogen intake for many years. At first it was difficult to determine the organ from which the giant hemangioma originated. Angiography proved extremely helpful in tracing its origin in the spleen. Hematomas in the giant hemangioma posed a significant threat of rupture and catastrophic hemorrhage. We left the small hepatic hemangiomas in place, and removed the spleen along with the giant splenic hemangioma. Diagnostic pitfalls in the determination of the origin of this giant hemangioma, attribution of its origin to the spleen angiographically, the unusual co-existence of the giant splenic hemangioma with multiple hepatic ones, and the potential threat of rupture of the giant hemangioma are some of the highlights of this case report. Estrogen administration represents a pathogenic factor that has been associated with hemangiomas in solid organs of the abdominal cavity. The therapeutic dilemma between resection and embolization of giant hemangiomas is another point of discussion in this case report. Splenectomy for the giant splenic hemangioma eliminates the risk of rupture and malignant degeneration, whereas observation for the small hepatic ones (<4 cm) was the preferable therapeutic strategy in our patient.


Crossvalidation of two heart rate-based equations for predicting VO2max in white and black men.
The purpose of this investigation was to crossvalidate 2 equations that use the ratio of maximal heart rate (HRmax) to resting HR (HRrest) for predicting maximal oxygen consumption (VO2max) in white and black men. One hundred and nine white (n = 51) and black (n = 58) men completed a maximal exercise test on a treadmill to determine VO2max. The HRrest and HRmax were used to predict VO2max via the HRindex and HRratio equations. Validity statistics were done to compare the criterion versus predicted VO2max values across the entire cohort and within each race separately. For the entire group, VO2max was significantly overestimated with the HRindex equation, but the HRratio equation yielded no significant difference compared with the criterion. In addition, there were no significant differences shown between VO2max and either HR-based prediction equation for the white subgroup. However, both equations significantly overestimated VO2max in the black group. Furthermore, large standard error of estimates (ranging from 6.92 to 7.90 ml·kg(-1)·min(-1)), total errors (ranging from 8.30 to 8.62 ml·kg(-1)·min(-1)), and limits of agreement (ranging from upper limits of 16.65 to lower limits of -18.25 ml·kg(-1)·min(-1)) were revealed when comparing the predicted to criterion VO2max for both the groups. Considering the results of this investigation, the HRratio and HRindex methods appear to crossvalidate and prove useful for estimating the mean VO2max in white men as a group but not for an age-matched group of black men. However, because of inflated values for error, caution should be exercised when using these methods to predict individual VO2max.


Dispositional pessimism is related to reduced respiratory sinus arrhythmia reactivity to a psychosocial stressor.
The associations among dispositional optimism/pessimism, baseline RSA and RSA reactivity were investigated in the current study. Physiological data were collected from 102 young adults during baseline, social stress task (i.e., a public speaking task) and recovery periods in the laboratory. Dispositional optimism and pessimism were assessed using the revised Life Orientation Test. Results showed that higher dispositional pessimism is significantly related to lower levels of RSA reactivity to the social stress task. Finding highlight that individuals with higher levels of pessimism may be at elevated risk for physiological maladjustment.


The Effect of Normal Saline Injection Volumes on the Optic Nerve Sheath Diameter during Thoracic Epidural Analgesia.
Saline or local anesthetic injection into the epidural space increases intracranial pressure (ICP), at least transiently. Measurement of the optic nerve sheath diameter (ONSD) using ocular ultrasonography is one of the noninvasive methods for ICP assessment. The purpose of this study is to investigate the effects of the different volume on the ONSD and cerebral oxygen saturation (rSO2) during thoracic epidural saline injection under awake conditions. Prospective randomized, controlled trial. An interventional pain management practice in South Korea. This study included 71 patients receiving thoracic epidural catheterization for pain management, following upper abdominal or thoracic surgery. Following successful epidural space confirmation, patients were randomly allocated to receive 5 mL (5 mL group), 10 mL (10 mL group), and 20 mL (20 mL group) of epidural normal saline. Transorbital sonography was performed to measure the ONSD. This was measured at 3 mm posterior to the optic nerve head. An rSO2 was measured using cerebral oximeter sensors. All 3 groups showed significant increases of ONSD from 10 minutes to 40 minutes as compared to baseline (before procedure). Among the 3 groups, the 20 mL group demonstrated the most significantly increased ONSD, as compared to the 5 mL and 10 mL groups. At the 20 minute and 40 minute time points, the ONSD showed a volume-dependent increase (P = 0.0005, P = 0.014). All 3 groups showed the rSO2 to be distributed between 60~70% without any statistical difference. We could not determine the returning point of the normalized ONSD value. Twenty milliliters of normal saline epidural injection resulted in a significant increase of ONSD, as compared to the 5 mL and 10 mL groups. Our results also indicate that an increase of ONSD occurs in accordance with the injected volume of normal saline.


Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?
It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls). While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.


Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy: effect of nimesulide.
Thiamine deficiency (TD) in both humans and experimental animals results in severe mitochondrial dysfunction and leads to selective neuronal cell death in diencephalic and cerebellar structures. We have investigated cyclooxygenase-2 (COX-2) expression in vulnerable (medial thalamus, inferior colliculus) and spared (frontal cortex) regions of rats with thiamine deficiency. Expression of COX-2 mRNA was selectively increased (twofold, p < 0.001) in vulnerable regions at symptomatic stages of encephalopathy (14 days) of TD compared to pair-fed controls or presymptomatic (days 12) rats. Induction of COX-2 expression was accompanied by a significant increase (two- to threefold, p < 0.001) in prostanglandin E2 (PGE2) synthesis in vulnerable regions at symptomatic stages of TD. COX-2 immunolabeling revealed a neuronal localization and COX-2 immunoreactive neurons were significantly increased at symptomatic stages of encephalopathy. Administration of nimesulide, a highly specific COX-2 inhibitor, significantly reduced PGE-2 levels in vulnerable regions but, rather than being neuroprotective, precipitated encephalopathy and exacerbated neuronal cell death due to TD. These findings suggest that newly synthesized prostanoids exert a neuroprotective role in TD.


Brain network architecture constrains age-related cortical thinning.
Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including "hotspots" of pronounced age effects in sensorimotor areas. Regional age-related differences were strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.


Applicability of an in-house extraction protocol in a Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system for the identification of Streptococcus agalactiae from broth-enriched vaginal/rectal swab specimens.
Early laboratory identification of group B Streptococcus (GBS, Streptococcus agalactiae) in the birth canal of pregnant women is critical for prompt administration of antimicrobial therapy and may further reduce the mortality rate due to GBS neonatal infection. A total of 164 vaginal/rectal swab specimens collected from pregnant women at 35-37 weeks of gestation were screened for GBS vaginal colonization. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, Bruker Biotyper, Bruker Daltonik GmbH, Bremen, Germany) system was used to detect GBS from Carrot broth and LIM broth enrichment using an in-house extraction protocol. The results were compared to those by conventional broth-enriched culture/identification methods as the gold standard. BD MAX™ GBS assay (Becton Dickinson, Sparks, MD, USA) was also performed for Carrot broth-enriched specimen. Discordant results were investigated using the GeneXpert® GBS PCR assay (Cepheid Inc., Sunnyvale, CA, USA). Using the extraction protocol, 33 (20.1%) of the 164 specimens were positive in Carrot broth, and 19 (11.6%) were positive in LIM broth. Using the culture protocol, 38 (23.2%) samples in Carrot broth and 35 (21.3%) in LIM broth were positive. The sensitivity, specificity, and positive and negative predictive values using the extraction protocol in Carrot broth and LIM broth compared to the gold standard conventional culture/identification method were 86.8% and 50.0%, 100% and 100%, 100% and 100%, and 96.2% and 86.9%, respectively. The extraction protocol with MALDI-TOF MS from Carrot broth-enriched samples provides a more rapid turnaround time, lower cost, and acceptable sensitivity and specificity to correctly identify pathogens when compared to conventional culture/identification methods.


[Sorbitol and xylitol in post-operative infusion therapy (author's transl)].
The effect of a 24-hour continuous infusion of sorbitol in the recommended maximum dosage of 0.25 g . kg-1 . h-1 or of xylitol in the recommended maximum dosage of 0.125 g . kg-1 . h-1 on metabolic parameters was investigated in seven healthy adult men. The results demonstrate the continued applicability for longer than the recommended time as well as the acceptability of continuous infusion of polyols used clinically with combined solutions.


A simple atraumatic clamp technique without a stabilizer in off-pump CABG: how to do it.
A method of stabilization of the heart and the coronary artery during the construction of the distal anastomosis in coronary artery procedures without cardiopulmonary bypass is described. The technique exposes and immobilizes the coronary artery, allowing a precise anastomosis on the beating heart. In addition, it is simple, safe, and inexpensive.


Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency.
Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/- hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C>A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic aciduria with prominence of the C12 dicarboxylic (dodecanedioic) acid. This C12 dicarboxylic aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic acids by mitochondria after their initial shortening by beta-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric acid was detected in all three patients, a finding previously observed only in glutaric aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.


Effects of pH on weak and positive control mutagens in the Ames Salmonella plate assay.
The effects of pH on the mutagenic activity of several chemicals were evaluated in the standard Ames Salmonella typhimurium plate-incorporation assay. The pH of the base agar was varied between 6.0 and 8.0. The positive control compounds routinely used in this laboratory, 2-aminoanthracene, 4-nitro-o-phenylenediamine, sodium azide and nitrofurantoin, showed increasing mutagenic activity as the pH was decreased to 6.0. However, the activity of two weakly mutagenic cosmetic ingredients, 2,2',4,4'-tetrahydroxybenzophenone and trans-4-phenyl-3-buten-2-one, was completely eliminated at pH levels near 6.0. It is concluded that plates poured with agar with pH levels below 7.0 can result in strong responses for the positive control chemicals but give negative results for some mutagens.


The Mangled Extremity Severity Score Fails to be a Good Predictor for Secondary Limb Amputation After Trauma with Vascular Injury in Central Europe.
The Mangled Extremity Severity Score (MESS) was constructed as an objective quantification criterion for limb trauma. A MESS of or greater than 7 was proposed as a cut-off point for primary limb amputation. Opinions concerning the predictive value of the MESS vary broadly in the literature. The aim of this study was to evaluate the applicability of the MESS in a contemporary civilian Central European cohort. All patients treated for extremity injuries with arterial reconstruction at two centres between January 2005 and December 2014 were assessed. The MESS and the amputation rate were determined. Seventy-one patients met the inclusion criteria and could be evaluated for trauma mechanism and injury patterns. The mean MESS was 4.97 (CI 4.4-5.6). Seventy-three per cent of all patients (52/71) had a MESS < 7 and 27% (19/71) of ≥7. Eight patients (11%) underwent secondary amputation. Patients with a MESS ≥ 7 showed a higher, but statistically not significant secondary amputation rate (21.1%; 4/19) than those with a MESS < 7 (7.7%; 4/52; p = 0.20). The area under the ROC curve was 0.57 (95% CI 0.41; 0.73). Based on these results, the MESS appears to be an inappropriate predictor for amputation in civilian settings in Central Europe possibly due to therapeutic advances in the treatment of orthopaedic, vascular, neurologic and soft-tissue traumas.


Bonding of amalgam to tooth structure: tensile adhesion and microleakage tests.
Amalgam can be bonded to etched enamel by a thin coat of Panavia resin cement with a resulting mean bond strength of 1404 psi to enamel and 469 psi to dentin as tested in tension. Less microleakage was observed in resin-bonded amalgam restorations than in Copal varnish-lined or unlined restorations. The technique could be used clinically with possible implications for cavity design, fracture resistance of restored teeth, and recurrent caries. These properties as well as the variables affecting bond strength need further exploration.


Tumor-augmenting Effect of Histone Methyltransferase WHSC1 on Colorectal Cancer Via Epigenetic Upregulation of TACC3 and PI3K/Akt Activation.
Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone methyltransferase which is frequently expressed in an aberrant manner in tumors, but its specific roles and targets in colorectal cancer (CRC) remain unclear. Expression of WHSC1 in CRC tissues and cells was examined by RT-qPCR, immunohistochemistry and immunoblot assays. WHSC1 was knocked down in CRC cells to examine its effect on cell proliferation, invasiveness, migration, epithelial-mesenchymal transition (EMT) activity and apoptosis. The binding between WHSC1 and transforming acidic coiled-coil containing protein 3 (TACC3) was predicted using bioinformatics systems and subsequently validated. In addition, altered expression of TACC3 was introduced into CRC cells to perform functional assays. Stably transfected cells were injected into nude mice to induce xenograft tumors. WHSC1 was highly expressed in CRC tumor tissues and cells with a positive correlation with TACC3 concentration. Specific downregulation of WHSC1 in two CRC cell lines blocked cell proliferation, invasiveness, EMT and migration activity and promoted cell apoptosis. WHSC1 triggers H3K36me2 modification at the level of the TACC3 promoter to induce TACC3 activation. TACC3 suppression similarly blocked the malignant activity of CRC cells, whereas TACC3 restoration in cells counteracted the cancer-suppressive functions of WHSC1 silencing. TACC3 levels were correlated with increased phosphorylation of the PI3K/Akt signaling pathway in cells. Likewise, WHSC1 suppression blocked tumor growth in nude mice. The results of this study revealed TACC3 as a target of WHSC1 in CRC that is positively correlated with PI3K/Akt pathway activation and tumor development.


Carcinogenic-potential ecological risk assessment of soils and wheat in the eastern region of Konya (Turkey).
The drainage channel where the wastewater of Konya city center is discharged, the solid waste storage center, the soils surrounding the industrial area, the potential accumulation of toxic elements (PTE) accumulated in the wheat grown in these soils, and their effects on human health were examined. Between 1977 and 2010, the water in the drainage channel was used for a variety of crops, mainly wheat grown in the nearby agricultural areas until the commissioning of the wastewater treatment plant. Industrial facilities, solid waste landfills, and military firing areas are actively used and are thought to be important factors in heavy metal accumulation in soils. In addition, the investigation area is on the sediments of the deposits stored in the large Konya Lake depending on the geological structure around Konya and caused geogenic heavy metal accumulation as a result of the separation and transportation of ophiolitic, magmatic, metamorphic, and sedimentary rocks in the region. In the research, PTE accumulation was determined in the samples of N1 (Pb, As, and Hg), N9 (Cd, As), and N10 (Cd and As) and N8 (Pb) in wheat. The carcinogenic risk factor of Ni, Al, Mn, and Cr elements in the territory of the region has been found as "medium" for children and adults. It has been determined that the potential source of toxic elements does not only depend on anthropogenic events but also occurs as a result of geological events.


Pharmacological effects of lysozyme on COPD and bronchial asthma with sputum: A randomized, placebo-controlled, small cohort, cross-over study.
Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL). Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated. This study was a placebo-controlled, double-blind, randomized, cross-over design. Twenty-four patients with COPD and twenty-four patients with BA were enrolled. LYS or placebo was administered for 28 days in each treatment period, with a 28-day washout between the first and second treatment periods. The results of spirometry, impulse oscillometry system (IOS) examination, fractional exhaled nitric oxide (FeNO) measurement, as well as the changes in the subjective symptoms, were evaluated after the treatment period. On spirometry, airway function (FEV1) improved in patients with COPD after administration of LYS (LYS vs placebo: 0.08 L vs 0.029 L, p = 0.030). Similar trends were also found in %FEV1 in COPD patients. On IOS examination, resistance of the respiratory system at 5 Hz levels was significantly improved only in patients with COPD (LYS vs placebo: -0.455 cm H2O/L/s vs 0.095 cmH2O/L/s, p = 0.012). Similar trends were found in terms of the resistance of the respiratory system at 20 Hz, and of the reactance area. In the COPD assessment test, subjective symptoms also significantly improved in patients with COPD during the LYS treatment period (improvement rates-LYS vs. placebo: 69.6% vs. 39.1%; p = 0.022). A similar effect of LYS was not seen in BA patients. LYS, a mucolytic agent, has capability to improve the function of peripheral airways in patients with COPD, which leads to improvements of the patients' symptoms and QOL.


Long-term prognosis on recurrence of seizures among children with epilepsy after drug withdrawal-elimination.
The long-term prognosis of 110 children after withdrawal-elimination of the drugs on the basis of our rigid criteria was analyzed. The 12 cases (10.9%) of 110 patients experienced recurrences, which occurred between three months to three years after drug elimination, but there were no recurrences later than three years to 10 years after drug elimination. The asymmetry in the EEG during the first two to three years after drug elimination appeared in 6.4% and seizure discharge appeared in 17.1%. But no asymmetry nor seizure discharge was found in EEG later than three years after drug elimination.


In vitro gastro-small intestinal digestion of conventional and mildly processed pea protein ingredients.
We report on the effect of processing, particularly heating, on the digestion dynamics of pea proteins using the standardised semi-dynamic in vitro digestion method. Fractions with native proteins were obtained by mild aqueous fractionation of pea flour. A commercial pea protein isolate was chosen as a benchmark. Heating dispersions of pea flour and mild protein fractions reduced the trypsin inhibitory activity to levels similar to that of the protein isolate. Protein-rich and non-soluble protein fractions were up to 18% better hydrolysed after being thermally denatured, particularly for proteins emptied later in the gastric phase. The degree of hydrolysis throughout the digestion was similar for these heated fractions and the conventional isolate. Further heating of the protein isolate reduced its digestibility as much as 9%. Protein solubility enhances the digestibility of native proteins, while heating aggregates the proteins, which ultimately reduces the achieved extent of hydrolysis from gastro-small intestinal enzymes.


Association of tumor necrosis factor-α (TNF-α) promoter polymorphisms with overweight/obesity in a Korean population.
Obesity is characterized by the activation of an inflammatory process leading to an increase in proinflammatory cytokines and adipokines. This study was designed to investigate the genetic association between tumor necrosis factor-α (TNF-α) polymorphisms and the risk of obesity in the Korean population. Three single nucleotide polymorphisms [G-238A (rs361525), C-857T (rs1799724), and C-863A (rs1800630)] in the promoter region of TNF-α gene were analyzed in 123 control [body mass index (BMI) between 18 and 23] and 208 overweight/obese (BMI ≥ 23) subjects. The mean values of BMI in the control and overweight/obese groups were 21.1 ± 1.4 and 25.4 ± 1.8, respectively. Of the three SNPs, G-238A presented a significant association with overweight/obesity in the codominant model; the frequency of the G/G genotype in the overweight/obese group was 9.3% higher than that in the control group (P = 0.0046). When control and overweight/obesity subjects were combined together and analyzed, the level of high-density lipoprotein (HDL) was significantly higher in the C-857T C/C type SNP (P < 0.05). The results of this study suggest that the G allele of G-238A in TNF-α gene may be a risk factor for overweight/obesity in the Korean population and that the C allele of C-857T may be an protective factor in relation to the HDL level in the general Korean population.


The complications of Dupuytren's contracture surgery.
To determine the complication rate of a modified Skoog's technique in the surgical treatment of Dupuytren's contracture. A retrospective analysis was performed on 253 patients who had surgery by 1 surgeon using 1 technique with a mean follow-up period of 3.6 years. We studied the complication rate of the modified Skoog's procedure, relating it to a grading system for disease severity. A separate prospective long-term study was performed with an unselected cohort in which disease recurrence producing contracture was investigated prospectively in a group of 75 patients. Complications occurred in 46 patients. Thirty-five patients had 1 complication and 11 patients had more than 1 complication. Intraoperative complications included 6 patients with nerve injury and 1 patient with an arterial injury. Early postoperative complications before wound healing included 5 patients with digital hematoma, 24 patients with wound infection, 6 patients with sympathetic dystrophy, and 6 patients with skin slough. Late postoperative complications included 3 patients with scar contraction and 2 patients with carpal tunnel syndrome. There were 3 non-hand-related complications: 1 urinary retention, 1 left ventricular failure, and 1 myocardial infarction. Recurrence of Dupuytren's disease occurred in 23 of 75 patients after a mean follow-up period of 9.4 years. The complication rate increased with the severity of disease particularly if the proximal interphalangeal joint contracture was 60 degrees or more. There was no difference in the complication rate for patients who had surgery for primary or recurrent disease.


Deletion 3p: the only chromosome loss in a primary renal cell carcinoma.
The cytogenetic findings obtained by G- and C-banding in short-term culture from a primary renal cell carcinoma are reported. This tumor is characterized by loss of the short arm of chromosome #3 and t(Y;3). The aberration of chromosome #3 in renal cell carcinomas is discussed.


A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors.
Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.


Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma.
Knowledge of lymph node metastasis (LNM) status is crucial to determine whether patients with superficial esophageal squamous cell carcinoma (ESCC) can be cured with endoscopic resection alone, without the need for additional esophagectomy. The present study aimed to identify predictive factors and develop a prediction model for LNM in patients with superficial ESCC. Clinicopathologic data from 501 patients with superficial ESCC treated with radical esophagectomy were reviewed. Stepwise logistic regression analysis determined the predictors of LNM. Using these predictors, a nomogram for predicting the risk of LNM was constructed and internally validated using a bootstrap resampling method. LNM rates of tumors invading the lamina propria, muscularis mucosa, and SM1 layers were 3.7%, 15.5%, and 40.7%, respectively. Deep tumor invasion depth, moderately or poorly differentiated histology, and lymphovascular invasion were independent predictors of LNM. ESCC with muscularis mucosa and SM1 invasion had odds ratios of 3.635 and 11.834, respectively, compared with that for ESCC confined to the lamina propria. Large tumor size (>2.0 cm) and presence of tumor budding showed borderline significance for LNM prediction. These five variables were incorporated into a nomogram. A constructed nomogram showed good calibration and good discrimination with an area under the receiver-operating characteristic curve (area under the curve [AUC]) of 0.812. After bootstrapping, AUC was 0.811. We developed a nomogram that can facilitate individualized prediction of risk of LNM in patients with superficial ESCC. This model can aid in decision-making for the need for additional esophagectomy after endoscopic resection for superficial ESCC.


Characterization of two glucuronic acid-containing glycosphingolipids in larvae of the green-bottle fly, Lucilia caesar.
Two glucuronic acid-containing glycosphingolipids were purified from larvae of the green-bottle fly, Lucilia caesar by DEAE-Sephadex and Iatrobeads column chromatography. Structures of these acidic glycolipids, glycolipids X and Y, were elucidated by means of sugar analysis, permethylation, enzymatic hydrolysis, negative-ion fast atom bombardment mass spectrometry, and NMR studies. Glycolipid X was determined to have the following structure: GlcA beta 1-3Gal beta 1-3GalNAc alpha 1-4 GalNAc beta 1-4 GlcNAc beta 1-3Man beta 1-4Glc beta 1-1 ceramide. The other acidic glycolipid, glycolipid Y contains a phosphoethanolamine residue linked through the 6-hydroxy group of the N-acetyl-glucosamine unit of glycolipid X. The ceramide moieties were composed of saturated fatty acids (16:0-22:0) and tetradeca- and hexadeca-4-sphingenines. Based on the structural similarity of the ceramide moieties it appears likely that glycolipid X is an intermediate from which glycolipid Y is synthesized by addition of a phosphoethanolamine residue.


Improving access to essential tests for infectious diseases.
Recently, WHO published the first ever Essential Diagnostics List (EDL), which includes 113 tests, including tests for HIV, TB, malaria, hepatitis B and C, human papillomavirus (HPV) and syphilis. The EDL is a welcome first step in ensuring that diagnostics are a key part of all health systems. The impact of the list, however, will depend greatly on how countries adopt and implement the EDL.


Dental health status of third grade children and their families within the context of a community's dental health care system.
Utilizing structure, process, and outcomes as conceptual dimensions of appraisal of quality, data were analyzed to present an evaluation of the quality of a community's dental health care system as reflected in a population subgroups' dental health status. Data were collected from 838 Caucasian third-graders and their parents through interviews, mail questionnaires, and dental screening examinations. Indicators of structure were: status of community water fluoridation in the study community, dentist to population ratio, and dental care resources in the public sector available to eligible residents. Process indicators of quality were: 1) screening, case finding, examinations, and quality of restorations as measures of provider behaviors, and 2) complaints, compliance, conditioned behaviors, level of dental health knowledge, and utilization of dental services as measures of client behaviors. Outcomes, subjected to analysis included indices indicative of dental disease experience. Variables operationally defined as indicators of the subgroup's dental health status were subjected to a descriptive analysis and were then crosstabulated with the socioeconomic status of the child's family to identify socioeconomic differences in the process of obtaining care and in dental health outcomes. Findings indicate which elements in a community's prevailing dental health care system function well and which would need alteration to maximize dental health for the subgroup.


The effects of chloride ions on electrodiffusion in the membrane of a leaky epithelium. Studies of intact tissue by microelectrodes.
The electrodiffusive permeability for Cl-, its dependence on low extracellular Cl--concentrations and the interaction between the movements of Cl- and K+ were investigated in the ventricular membrane of epithelial cells from the choroid plexus of Necturus maculosus. Cells were probed with ion-selective microelectrodes sensitive to Cl-, K+ and H+. The initial effects of abrupt changes in the Cl--concentration (Cl-v) and/or the K+-concentration (K+v) of the ventricular solution were investigated. The effect of changing the membrane potential by changing K+v was twofold: It caused an electrodiffusive flux of Cl- via a permeability of 1.3 X 10(-6) cm s-1. This permeability together with the K+-permeability of the ventricular membrane (24 X 10(-6) cm s-1) determined the membrane potential in the given steady state within a few mV. The other effect of the depolarization was an increase in the intracellular concentration of HCO-3 which in turn caused an influx of Cl- via electroneutral Cl-/HCO-3 exchange. The Cl--permeability was reduced by more than 60% and the neutral exchange by more than 90% by furosemide. The effect of decreases in Clv was a tenfold increase of the electrodiffusive Cl--permeability of the ventricular membrane to 12.2 X 10(-6) cm s-1 and also a tenfold increase in the permeability to K+. This activation was reduced by two thirds by furosemide, and by depolarizations of the cell by high K+v. In the given steady state the HCO-3/Cl- exchanger at the ventricular membrane transports at a rate of 300 pmol cm-2 s-1 and moves Cl- into the cell and HCO-3 into the ventricular solution. Thus the epithelium alkalinizes the cerebrospinal fluid at a rate which is about three times faster than the net transport rate of Na+.


Laryngotracheal separation using skin flap formation: a novel surgical procedure.
Laryngotracheal separation is often performed to prevent intractable aspiration for children with severe mental and physical disabilities. However, tracheo-innominate artery fistula after surgery can occur as a severe complication and cause fatal hemorrhage. We have therefore developed a novel procedure to prevent tracheo-innominate artery fistula. Surgery was performed by making an H-shaped incision and creating skin flaps. The trachea was not raised anteriorly and the skin flaps were sutured to the trachea. We performed this procedure on nine patients, and no major complications occurred in any case. This procedure can be expected to reduce the occurrence of tracheo-innominate artery fistula.


The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells.
The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as "outside-in" signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death.


Sequence redesign and the assembly mechanism of the oxytocin/bovine neurophysin I biosynthetic precursor.
The structural organization of neurohypophysial hormone biosynthetic precursors and the interdependence between intramolecular folding and precursor self-association were examined using sequence-engineered mutants of the semisynthetic oxytocin/bovine neurophysin precursor (pros-OT/BNPI). In [N alpha 1-Ac,N epsilon 30,71-diacetimidyl, Ala2,des-His106] Pro-Ot/BNPI or [N alpha 1-Ac,Ala2]pros-OT/BNPI), two structural elements (Tyr2 and free alpha-amino group) were eliminated which were predicted to be critical for intramolecular conformation by stabilizing contact between hormone and neurophysin domains. This mutant was used to test the dependence of precursor self-association on intramolecular conformation. In the second mutant precursor, [N alpha 30,71-diacetimidyl,D-Pro7,D-Leu8,des-His106]p ro-OT/BNPI (or [D-Pro7,D-Leu8]pros-OT/BNPI), the stereochemistry at L-Pro7-L-Leu8 was changed to test the extent to which precursor conformation depends on ordered structure in the processing/spacer sequence which connects the interacting hormone and neurophysin I domains. Intramolecular conformation was characterized for the precursor and mutants by analytical affinity chromatography on immobilized hormone analog Met-Tyr-Phe and by circular dichroism. Data obtained by both methods showed that, while pros-OT/BNPI is folded, with hormone domain occupying the hormone-binding site of the neurophysin domain, the alpha-acetyl-Ala2 mutant is not so organized intramolecularly. When pros-OT/BNPI and the alpha-acetyl-Ala2 mutant were eluted on immobilized BNPII to measure self-association propensity, the native-like precursor was found to bind with 12-15-fold higher affinity than the assembly mutant. Thus, while pros-OT/BNPI assumes a molecular structure containing a high-affinity self-association surface induced by intramolecular hormone domain-neurophysin domain interaction, [N alpha 1-Ac,Ala2]pros-OT/BNPI does not. The results with the alpha-acetyl-Ala2 mutant show that intramolecular domain-domain interaction is the obligatory "trigger" which induces the high-affinity precursor self-association that likely drives precursor to aggregated forms in the concentrated intragranular environment that exists in peptide hormone-synthesizing cells. In contrast, affinity chromatographic and circular dichroism properties of the D-Pro7,D-Leu8 mutant show that this intramolecular trigger is dependent, but only weakly, on the conformation of the peptide sequence between domains, as judged by native-like interaction properties below 40 degrees C but lowered stability to elevated temperature.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term effect of the superior vena cava-pulmonary artery anastomosis on pulmonary blood flow.
The long-term effects of the superior vena cava-pulmonary artery anastomosis were evaluated in 15 patients a mean of 8.5 years postoperatively. There were eight patients with tricuspid atresia and seven with other complex anomalies. Ten patients underwent 133xenon ventilation scans and 99mtechnetium perfusion scans in the upright and suprine positions. Perfusion scans showed decreased perfusion of the right upper lobe which improved in the supine position. Shunt flow, measured by thermodilution in nine patients, was a mean of 1.7 L. per minute per square meter, with a mean superior vena caval pressure of 8 mm. Hg and a resistance of 3.0 units. Right and left pulmonary venous saturations were 94 and 96 percent, respectively, showing little intrapulmonary shunting. Venous collaterals were the major cause for shunt failure. Six patients underwent a left Blalock-Taussig shunt and division of venous collaterals a mean of 6 years after the Glenn shunt and are all doing well. The superior vena cava-pulmonary artery anastomosis did not result in progressive pulmonary deterioration in the patients studied. The staged treatment of tricuspid atresia by the Glenn shunt followed by a systemic-pulmonary artery shunt and ligation of venous collaterals gives prolonged effective palliation.


Vibrating glass stylets: tools for precise microsurgery on cuticular structures.
Precisely localized lesions in cuticular structures of insects can be produced by fine glass rods, vibrating transversally at frequencies above 100 kHz. The oscillating edge of the glass rod scrapes off the chitinous material at minimal elastic deformation during treatment. The achieved roughness height is in the 0.1 micron range. The method is most fruitfully applied to insect sensilla. Studies of central projections of sensory nerves (degeneration; cobalt staining) profit from the new chance of eliminating selected single sensilla in close vicinity to others which are to remain intact. This can barely be achieved with conventional fine scissors.


Sleep EEG provides evidence that cortical changes persist into late adolescence.
To examine developmental changes in the human sleep electroencephalogram (EEG) during late adolescence. A 4-bed sleep laboratory. Fourteen adolescents (5 boys) were studied at ages 15 or 16 (initial) and again at ages 17 to 19 (follow-up). N/A. All-night polysomnography was recorded at each assessment and scored according to the criteria of Rechtschaffen and Kales. A 27% decline in duration of slow wave sleep, and a 22% increase of stage 2 sleep was observed from the initial to the follow-up session. All-night spectral analysis of 2 central and 2 occipital leads revealed a significant decline of NREM and REM sleep EEG power with increasing age across frequencies in both states. Time-frequency analysis revealed that the decline in power was consistent across the night for all bands except the delta band. The decreases in power were most pronounced over the left central (C3/A2) and right occipital (O2/A1) derivations. Using longitudinal data, we show that the developmental changes to the sleeping EEG that begin in early adolescence continue into late adolescence. As with early adolescents, we observed hemispheric asymmetry in the decline of sleep EEG power. This decline was state and frequency nonspecific, suggesting that it may be due to the pruning of synapses known to occur during adolescence.


Locating QTLs controlling several adult root traits in an elite Chinese hybrid rice.
This study aimed to elucidate the genetics of the adult root system in elite Chinese hybrid rice. Several adult root traits in a recombinant inbred line (RIL) population of Xieyou 9308 and two backcross F1 (BCF1) populations derived from the RILs were phenotyped under hydroponic culture at heading stage for quantitative trait locus (QTL) mapping and other statistical analysis. There a total of eight QTLs detected for the root traits. Among of them, a pleiotropic QTL was repeatedly flanked by RM180 and RM5436 on the short arm of chromosome 7 for multiple traits across RILs and its BCF1 populations, accounting for 6.88% to 25.26% of the phenotypic variances. Only additive/dominant QTLs were detected for the root traits. These results can serve as a foundation for facilitating future cloning and molecular breeding.


Development and implementation of health care transition resources for youth with autism spectrum disorders within a primary care medical home.
As adolescents become adults, they typically change from seeing a pediatric health care provider to seeing a health care provider who specializes in working with adults. Adolescents with autism spectrum disorder may have more difficulty finding an adult health care provider who is trained to address the varied needs and medical and mental health issues that often are seen with autism spectrum disorder. Without careful planning for transition to adult health care, patients may continue to be seen by pediatric providers who may not be familiar with adult health needs. This quality improvement project focused on improving transition to adult health care by creating varied supports for the patient, family, and the health care team and putting them into action within a pediatric medical practice that serves over 250 adolescent and young adult patients with autism spectrum disorder. Before the supports were put into place, patients and families received limited and inconsistent communication to help them with transition. While the supports helped increase the amount and quality of help patients and families received, medical providers skipped or put off transition discussion in approximately half of well visits for targeted patients. Challenges in implementing the transition process included finding time to discuss transition-related issues with patients/families, preference of medical providers to have social workers discuss transition, and difficulty identifying adult health care providers for patients. This suggests more work is needed to both train and partner with patients, families, and health staff to promote smooth and positive health transitions.


Endogenous arginase 2 as a potential biomarker for PEGylated arginase 1 treatment in xenograft models of squamous cell lung carcinoma.
Depletion of arginine induced by PEGylated arginase 1 (ARG1) (BCT-100) has shown anticancer effects in arginine auxotrophic cancers that lack argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). High levels of endogenous arginase 2 (ARG2) have been previously reported in human lung cancers. Although a high-ARG2 level neither causes immunosuppression nor affects disease progression, it may theoretically affect the efficacy of PEGylated ARG1 treatment. ARG2 was shown to be highly expressed in H520 squamous cell lung carcinoma (lung SCC) xenografts but undetectable in SK-MES-1 and SW900 lung SCC xenografts. We propose that high-endogenous expression of ARG2 could impede the anti-tumor effect of PEGylated ARG1 in lung SCC. The in vivo effect of PEGylated ARG1 was investigated using three xenograft models of lung SCC. PEGylated ARG1 (60 mg/kg) suppressed tumor growth in SK-MES-1 and SW900 but not H520 xenografts. ASS1 was expressed in SK-MES-1 and SW900 xenografts while OTC expression remained low in all xenografts. A high-endogenous ARG2 level was detected only in H520 xenografts. Serum arginine level was decreased significantly by PEGylated ARG1 in all xenografts. Nonetheless intratumoral arginine level was decreased by PEGylated ARG1 in SK-MES-1 and SW900, not H520 xenografts. In SK-MES-1 xenografts, PEGylated ARG1 treatment induced G1 arrest, downregulation of Ki67 and Mcl-1 and activation of apoptosis. In SW900 xenografts, upregulation of Bim and activation of apoptosis were observed upon PEGylated ARG1 treatment. Silencing of ARG2 re-sensitized the H520 xenografts to PEGylated ARG1 treatment, partially mediated through arginine depletion via G1 arrest and apoptosis. PEGylated ARG1 treatment (BCT-100) was effective in lung SCC xenografts with low-endogenous levels of ASS1/OTC and ARG2. High-endogenous ARG2 expression may cause resistance to PEGylated ARG1 treatment in lung SCC xenografts. ARG2 may serve as a third predictive biomarker in PEGylated ARG1 treatment in lung SCC.


Macrophage Imaging of Cerebral Aneurysms with Ferumoxytol: an Exploratory Study in an Animal Model and in Patients.
The purpose of this study is to assess the validity and feasibility of macrophage imaging using an ultrasmall superparamagnetic iron oxide nanoparticle, ferumoxytol, in the cerebral aneurysmal wall in an animal model and in humans. Engulfment of ferumoxytol by primary culture of macrophages and RAW264.7 cells was assessed. Uptake of ferumoxytol was evaluated histologically in a cerebral aneurysmal model in rats. In an exploratory clinical study of magnetic resonance macrophage imaging, 17 unruptured aneurysms in 17 patients were imaged using thin-slice gapless magnetic resonance images of 2D-gradient-recalled echo (2D-GRE) and 3D-T1-fast-spin echo sequences on day 0 and of the same sequences with infusion of ferumoxytol 24 hours after the first imaging. Pre- and postinfusion images were evaluated independently by 2 medical doctors. Engulfment of ferumoxytol was confirmed in vitro, but the amount of ferumoxytol uptake was independent of the activation state or the differentiation state. Ferumoxytol uptake in CD68-positive cells was observed in the cerebral arterial walls of 4 out of 15 (26.7%) experimentally induced aneurysms in rats. In a clinical study, 17 aneurysms were enrolled and 2 aneurysms were not assessed because of incomplete images. Eleven aneurysms without oral intake of recent anti-inflammatory agents of the remaining 15 aneurysms showed ferumoxytol uptake on 2D-GRE subtraction images, and the size of the aneurysms was significantly related to positive images. Ferumoxytol uptake was confirmed in cultured macrophages and in the cerebral aneurysmal wall in rats. Thin-slice gapless magnetic resonance imaging with ferumoxytol in human cerebral aneurysmal walls may reflect macrophages in the cerebral aneurysmal wall, but its application to small-sized lesions may be restricted.


A working plan to understand and control financial pressures.
As financial changes affect hospitals and nursing budgets, nurse executives must know how to anticipate financial results and make aggressive decisions based upon the financial ramifications.


The monoethylglycinexylidide test for grading of liver cirrhosis.
Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration. To determine the optimal sampling time for MEGX determination. A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score). Only the MEGX fractional formation rate (kf) and formation delay (tau) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 +/- 0.03 vs. 0.32 +/- 0.10 min-1 (mean +/- s.d.); tau = 7.7 +/- 2.0 vs. 3.9 +/- 2.9 min-1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method. The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.


Boosting charge transfer via molybdenum doping and electric-field effect in bismuth tungstate: Density function theory calculation and potential applications.
Regulating internal electronic structure of photocatalysts via elements doping holds huge potential in tuning efficient charge transfer and boosting high-performance. Herein, molybdenum embedded bismuth tungstate (Bi2WO6) is employed to explore the electronic structures and various performances via the assistance of experimental verification and density function theory (DFT) simulation. The band structures and Mo ions doping behaviors of Bi2MoxW1-xO6 are systematically measured. Doping can induce the distortion of intrinsic electric density and internal electric-field, resulted in efficient charge transfer of Bi2Mo0.4W0.6O6. It exhibits much efficient photocatalytic activities under visible-light irradiation, also manifests huge potential as an anode material in lithium-ion batteries (LIBs) which is rarely reported before. This work may provide insights in the development of bismuth-based semiconductors in energy related applications.


Adolescent rat social play: Amygdalar proteomic and transcriptomic data.
This data article contains the proteomic and transcriptomic data of the amygdala of adolescent rats involved in social play compared to non-behavioural animals. Social play was performed on male Sprague Dawley rats on postnatal day 38 and protein and gene expression in the amygdala was determined following behavioural testing. The protein expression was measured by analysing trypsin digested protein samples using a LTQ Orbitrap Velos mass spectrometer equipped with an Advion nanomate ESI source. The obtained tandem mass spectra were extracted by Thermo Proteome Discoverer 1.3 and the data were displayed with Scaffold v 4.5.1. The transcriptomic data were generated by llumina HiSeq 4000 system. Cuffdiff (v2.2.1) program was used to calculate RNA-seq based gene expression levels. For further interpretation of data presented in this article, please see the research article 'Proteomic and Transcriptional Profiling of Rat Amygdala Following Social Play' (Alugubelly et al. 2019).


Selective internal radiation therapy for liver malignancies.
Selective internal radiation therapy (SIRT) is a non-ablative technique for the treatment of liver primaries and metastases, with the intention of reducing tumour bulk. This study aimed to determine optimal patient selection, and elucidate its role as a downsizing modality. Data were collected retrospectively on patients who underwent SIRT between 2011 and 2014. The procedure was performed percutaneously by an expert radiologist. Response was analysed in two categories, based on radiological (CT/MRI according to Response Evaluation Criteria In Solid Tumours (RECIST)) and biological (α-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, chromogranin A) parameters. Forty-four patients were included. Liver metastases from colorectal cancer (22 patients) and hepatocellular carcinoma (HCC) (9) were the most common pathologies. Radiological response data were collected from 31 patients. A reduction in sum of diameters (SOD) was observed in patients with HCC (median -24.1 (95 per cent c.i. -43.4 to -3.8) per cent) and neuroendocrine tumours (-30.0 (-45.6 to -7.7) per cent), whereas a slight increase in SOD was seen in patients with colorectal cancer (4.9 (-10.6 to 55.3) per cent). Biological response was assessed in 17 patients, with a reduction in 12, a mixed response in two and no improvement in three. Six- and 12-month overall survival rates were 71 and 41 per cent respectively. There was no difference in overall survival between the RECIST response groups (median survival 375, 290 and 214 days for patients with a partial response, stable disease and progressive disease respectively; P = 0.130), or according to primary pathology (P = 0.063). Seven patients underwent liver resection with variable responses after SIRT. SIRT may be used to downsize tumours and may be used as a bridge to surgery in patients with tumours deemed borderline for resection.


Differential survival of γδT cells, αβT cells and NK cells upon engagement of NKG2D by NKG2DL-expressing leukemic cells.
Herein, we show that γδT, CD8(+) αβT lymphocytes and natural killer (NK) cells display a different sensitivity to survival signals delivered via NKG2D surface receptor. All the three effector cell populations activate Akt1/PKBalpha through the engagement of this molecule. Upon binding to leukemic cells expressing NKG2D ligands (NKG2DL), including chronic lymphocytic leukemias treated with transretinoic acid, most γδT (>60%) and half CD8(+) αβT cells (about 50%) received a survival signal, at variance with the majority of NK cells (>80%) that underwent apoptosis by day 5. Interestingly, oligomerization of NKG2D in γδT or CD8(+) αβT cells, led to a significant rise in nuclear/cytoplasmic ratio of both NF-kBp52 and RelB, the two NF-kB subunits mainly involved in the transcription of antiapoptotic proteins of the Bcl family. Indeed, the ratio between the antiapoptotic protein Bcl-2 or Bcl-x(L) and the proapoptotic protein Bax raised in γδT or CD8(+) αβT cells following NKG2D engagement by specific monoclonal antibodies or by NKG2DL expressing leukemic cells. Conversely, nuclear translocation of NF-kBp52 or RelB did not increase, nor the Bcl-2/Bax or the Bcl-x(L) /Bax ratios changed significantly, in NK cells upon oligomerizaton of NKG2D. Of note, transcripts for α5 importin, responsible for nuclear translocation of NF-kBp52/Rel B heterodimer, are significantly higher in γδT and CD8(+) αβT cells than in NK cells. These biochemical data may explain, at least in part, why γδT and CD8(+) αβT cells are cytolytic effector cells more resistant to target-induced apoptosis than NK cells.


Should a Patient with Severe Left Ventricular Dysfunction, Congestive Heart Failure, and Right Bundle Branch Block QRS Receive Cardiac Resynchronization Therapy?
Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure and mechanical dyssynchrony. Patients with left bundle branch block and QRS greater than or equal to 150 milliseconds derive the greatest clinical response. Patients with right bundle branch block (RBBB) may not derive the same benefit. The reasons for this disparity are unclear, but may relate to differences in biventricular activation sequence and timing in the presence of left versus RBBB. This article provides a comprehensive review of current understanding of the clinical effectiveness of CRT in patients with left ventricular dysfunction and RBBB.


Proposed identification of physiological classification and theoretical mechanisms of yogāsanas.
Yoga in the theoretical and practical form is now accepted all over the world, by the researchers as well as by the general population. Yogāsana or Yogic postures are one of the main foundations of practical yoga. Mechanisms of Mediation and Prānāyāma has already been established. In this article, the author is for the first time proposing physiological classification of Yogāsana i.e. (a) Stretch (b) Contraction (c). Neuromuscular Coordination (d) Sense Reduction (e) Spine Brain Activation. In support of this physiological classification author has proposed five hypothetical theories i.e. (i) Stretch Relaxation Awareness (ii) Contraction Relaxation Awareness (iii) Ballastic Contraction Relaxation Awareness (iv) Sensory Motor Function Awareness and (v) Vital Energy Flow Awareness to understand the underlying mechanisms of Yogāsana practice and to explain its benefits.


Glutamic acid decarboxylase autoantibody prevalence and association with HLA genotype in patients with younger-onset type 1 diabetes and proliferative diabetic retinopathy.
To investigate the relationship of HLA status and autoantibodies to glutamic acid decarboxylase (GAD) in proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity and genetic markers in retinopathy. Retrospective, nonrandomized, comparative study. Patients who had suffered from type 1 diabetes for >10 years and who had been first diagnosed as diabetic under 30 years of age were studied. They were classified into 3 groups: 20 patients with diabetes and PDR (PDR group), 22 patients who had diabetes and severe nonproliferative diabetic retinopathy (SNPDR group), and 25 patients who had diabetes with no diabetic retinopathy (non-DR group). Blood was collected, and the relationship between HLA status and GAD autoantibody positivity in diabetic retinopathy was investigated in a cross-sectional study. Human leukocyte antigen status and GAD autoantibody positivity. The highest positive rate of GAD autoantibody was 56.0% in the non-DR group, followed by the SNPDR group (40.1%) and the PDR group (15.0%). The frequencies of the HLA-DQ4 and -DR4/-DQ4 haplotypes were significantly higher in the PDR group (75.0% and 65%, respectively) than in the SNPDR group (40.9% and 31.8%) or the non-DR group (40.0% and 28.0%) (P = 0.035 and P = 0.026, respectively). The prevalence of GAD antibodies was lower in patients with the HLA-DR4 and HLA-DQ4 alleles and -DR4/-DQ4 haplotype frequencies in the PDR group (P = 0.018, P = 0.0088, and P = 0.0031, respectively). We found that the existence of GAD antibodies is inversely related and HLA status is directly related to the stage or severity of retinopathy.


AZGP1 mRNA levels in normal human lung tissue correlate with lung cancer disease status.
Evidence in animal models has suggested an association between susceptibility to lung tumorigenesis and gene-expression profiles in normal lung. Here, we compared RNA pools from normal lung tissue of lung adenocarcinoma patients (cases) or non-lung cancer patients (controls) by hybridization of whole-human genome expression arrays. Principal component analysis identified a gene-expression signature of 85 genes that distinguishes cases from controls as well as smokers from nonsmokers. Elevated mRNA levels of one of these genes, AZGP1, were significantly associated with disease status. These results support the hypothesis that differences in the gene-expression levels of the normal tissue may be predictive of genetic predisposition to lung cancer in humans.


Response of pulmonary vein potentials to premature stimulation.
Pulmonary vein potentials reflect depolarization of muscle fascicles within the myocardial sleeves that surround the pulmonary veins. The response of pulmonary vein potentials to premature stimulation has not been described. In 31 patients with paroxysmal atrial fibrillation referred for segmental isolation of the pulmonary veins, programmed stimulation with a single atrial extrastimulus was performed from the coronary sinus. Bipolar and unipolar electrograms were recorded with a decapolar Lasso catheter positioned sequentially within the left superior, left inferior, and right superior pulmonary veins, near the ostium. Premature stimulation often resulted in greater separation of the atrial and pulmonary vein potentials recorded within the pulmonary veins, fractionation of the pulmonary vein potentials, a change in the circumferential activation sequence of the pulmonary vein potentials, and dropout of pulmonary vein potentials. In response to premature stimulation, the muscle fascicles within the myocardial sleeves that surround the pulmonary veins display a greater degree of decremental conduction than do the myocardial fibers in the adjacent left atrium, and they display heterogeneity in conduction properties and refractoriness. Discrimination of pulmonary vein potentials from atrial electrograms is facilitated by premature stimulation.


Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: I. Implantation rate and fetal development.
Pregnant CD1 mice were exposed or sham-exposed from day 0 to day 17 of gestation to a 50 Hz sinusoidal magnetic field at 20 mT (rms). Preimplantation and postimplantation survival were assessed and fetuses examined for the presence of gross external, internal, and skeletal abnormalities. There were no statistically significant field-dependent effects on preimplantation or postimplantation survival, sex ratio, or the incidence of fetuses with internal or skeletal abnormalities. Magnetic field exposure was, however, associated with longer and heavier fetuses at term, with fewer external abnormalities. The results lend no support to suggestions of increased rates of spontaneous abortion or congenital malformation following prenatal exposure to power frequency magnetic fields.


Toxicokinetics of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rats: UPLC-ESI-MS/MS method development for the simultaneous determination of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rat plasma, urine, feces, and 11 various tissues collected from a toxicokinetic study.
The aim of this study was to explore the toxicokinetics of diisobutyl-phthalate (DiBP) and its major metabolite, monoisobutyl-phthalate (MiBP), by developing a UPLC-ESI-MS/MS method for simultaneously measuring DiBP and MiBP in rat plasma, urine, feces, and 11 different tissues. For the experiment, 0.1% (v/v) aqueous formic acid and acetonitrile mobile phase by gradient elution at a flow rate of 0.3 mL/min, equipped with a KINETEX core-shell C18-column (50 × 2.1 mm, 1.7 μm), was used to completely separate analytes. The mass transitions were m/z 279.1 → 149.0 for DiBP, 221.0 → 77.0 for MiBP, and 283.2 → 153.0 for DiBP-d4 as an internal standard. The developed assay had lower limits of quantification of 0.01 ng/mL for DiBP and 0.1 ng/mL for MiBP at all biological matrices. Toxicokinetics of DiBP were characterized by extensive distribution, short half-life, and high clearance. DiBP was rapidly metabolized to MiBP, with MiBP levels consistently exceeding the DiBP levels. Distribution of MiBP to tissues was considerable. The developed analytical method satisfied international criteria and was successfully applied to toxicokinetic studies after oral and intravenous administration of DiBP to rats. Findings of this study may be useful for evaluating the external exposure and toxic potential of DiBP and its metabolite in risk assessment.


Pharmacokinetics of calcium-entry blockers.
Effective use of drugs in therapy depends not only on clinical acumen but also on the availability of relevant pharmacokinetic and pharmacodynamic data. Such information assists in development of safe dosing regimens, prediction of abnormal handling of drugs in states of disease and disorder and anticipation of drug interactions. For the calcium-entry blocking agents now available in the United States (verapamil, nifedipine and diltiazem), these data appeared well after clinical patterns of use evolved. Nonetheless, their relevance continues to be demonstrated by the dependence of each agent on intact liver blood flow and function for normal rates of elimination; by the nonlinear kinetic characteristics for verapamil and diltiazem (and probably for nifedipine, as well) and the derivative implications for decreased dosing frequency requirements; and by observations now appearing on the relation between plasma drug levels and drug effects, both therapeutic and toxic. Such data are discussed herein, with emphasis on those aspects that impact on the clinical use of the calcium-entry antagonists.


Radiation enhances the invasive potential of primary glioblastoma cells via activation of the Rho signaling pathway.
Glioblastoma multiforme (GBM) is among the most treatment-refractory of all human tumors. Radiation is effective at prolonging survival of GBM patients; however, the vast majority of GBM patients demonstrate progression at or near the site of original treatment. We have identified primary GBM cell lines that demonstrate increased invasive potential upon radiation exposure. As this represents a novel mechanism by which radiation-treated GBMs can fail therapy, we further investigated the identity of downstream signaling molecules that enhance the invasive phenotype of irradiated GBMs. Matrigel matrices were used to compare the extent of invasion of irradiated vs. non-irradiated GBM cell lines UN3 and GM2. The in vitro invasive potential of these irradiated cells were characterized in the presence of both pharmacologic and dominant negative inhibitors of extracellular matrix and cell signaling molecules including MMP, uPA, IGFR, EGFR, PI-3K, AKT, and Rho kinase. The effect of radiation on the expression of these signaling molecules was determined with Western blot assays. Ultimately, the in vitro tumor invasion results were confirmed using an in vivo 9L GBM model in rats. Using the primary GBM cell lines UN3 and GM2, we found that radiation enhances the invasive potential of these cells via activation of EGFR and IGFR1. Our findings suggest that activation of Rho signaling via PI-3K is required for radiation-induced invasion, although not required for invasion under physiologic conditions. This report clearly demonstrates that radiation-mediated invasion is fundamentally distinct from invasion under normal cellular physiology and identifies potential therapeutic targets to overcome this phenomenon.


Laminin interactions with head and neck cancer cells under low fluid shear conditions lead to integrin activation and binding.
Lymphatic metastasis of cancer cells involves movement from the primary tumor site to the lymph node, where the cells must be able to productively lodge and grow. It is there that tumor cells encounter cellular and non-cellular constituent elements that make up the lymph node parenchyma. Our work shows that head and neck squamous cell carcinoma (HNSCC) cell lines are able to bind to laminin, fibronectin, vitronectin, and hyaluronic acid, which are extracellular matrix elements within the lymph node parenchyma. HNSCC cell lines bound to laminin under lymphodynamic low shear stress (0.07 dynes/cm(2)), consistent with lymph flow via β1 integrins, including α2β1, α3β1, and α6β1. Binding occurred in the presence of shear stress and not in the absence of flow. Additionally, tumor cell binding to laminin under flow did result in calcium signaling. Our data indicate a novel role for β1 integrin-mediated binding of HNSCC cells to laminin under conditions of lymphodynamic flow that results in intracellular calcium signaling within the cancer cell.