Bilateral, Simultaneous, Acute Angle Closure Glaucoma in Pseudophakia Induced by Chlorthalidone.
Purpose. To report two persons with acute, bilateral, and simultaneous angle closure glaucoma in pseudophakia secondary to uveal effusions induced by administration of chlorthalidone. Methods. Results. Bilateral shallow anterior chambers and high intraocular pressure with decline in visual acuity were reported in two patients within days of intake of chlorthalidone for systemic hypertension. Gonioscopy confirmed appositional angle closure while choroidal detachment and ciliochoroidal detachment were revealed on ultrasonographic studies. Discontinuing chlorthalidone and institution of aqueous suppressants to reduce IOP and cycloplegics reversed angle closure and glaucoma. Conclusions. Reports of angle closure glaucoma in pseudophakic eyes induced by idiosyncratic reaction to chlorthalidone confirms that osmotic changes in the crystalline lens has no role in the pathogenesis of drug induced glaucoma and reaffirms that glaucoma is secondary to ciliochoroidal detachment and ciliary body rotation and edema.


Fractures of the femoral neck in patients between the ages of twelve and forty-nine years.
Femoral neck fractures in young adults have a poor prognosis because the incidence of non-union and aseptic necrosis is high. We reviewed the results in twenty-seven consecutive patients with a femoral neck fracture who were younger than fifty years and who were treated with a standard protocol at Harborview Medical Center from 1975 to 1981. There were twenty-two male and five female patients, and they ranged in age from twelve to forty-nine years (mean, 32.4 years). Twenty patients were involved in high-velocity trauma and twelve of them had significant injuries to other organ systems. One of the remaining seven patients had sustained the fracture while running, and in the other six the fracture was associated with a metabolic disorder. Eight patients had a Garden Stage-II fracture; twelve, Stage-III; and seven, Stage-IV. The fractures were fixed with multiple 6.5-millimeter cancellous screws after adequate closed reduction, which was usually performed within eight hours after injury. All of the fractures united and there were no wound infections. Aseptic necrosis of the femoral head developed in five patients (20 per cent), three of whom had symptoms at the time of writing and will require surgical revision of the hip.


Effects of PHA-665752 and Cetuximab Combination Treatment on In Vitro and Murine Xenograft Growth of Human Colorectal Cancer Cells with KRAS or BRAF Mutations.
It remains unknown whether blockade of c-Met signaling and epidermal growth factor receptor signaling is effective in suppressing the growth of human colorectal cancer (CRC) cells. In this study, we investigated the effects of the c-Met inhibitor PHA-665752 alone and in combination with cetuximab on the growth of human CRC cells in vitro and in mouse xenografts. Human CRC cell lines (Caco2, HCT-116, and HT-29) and mice bearing HCT-116 xenografts were treated with cetuximab in the absence or presence of PHA-665752. Cell viability and apoptosis were examined using the MTT and TUNEL assays, respectively. Vimentin was measured by immunohistochemistry as a marker for epithelial-to-mesenchymal transition. Western blotting was used to determine signaling protein expression levels. The MTT assay showed that the growth of Caco2, HCT-116, and HT-29 cells was inhibited by PHA-665752 in a dose-dependent manner, but only Caco2 cell growth was suppressed by cetuximab. Combination treatment with PHA-665752 and cetuximab inhibited the proliferation of Caco2 cells and RAS mutant CRC cell lines. However, relative to the PHA-665752-alone treatment group, HT-29 cells with a BRAF mutation showed no noticeable effect. The mean tumor volume in mice treated with cetuximab in combination with PHA-665752 was significantly smaller than that in the mice treated with only cetuximab (P = 0.033) or PHA-665752 (P < 0.01). Similarly, the expression of vimentin in the mice treated with PHA-665752 in combination with cetuximab was significantly lower than that in the mice treated with cetuximab or PHA-665752 alone (P < 0.05 in each case). TUNEL assays revealed that treatment with PHA-665752 in combination with cetuximab markedly increased CRC cell apoptosis. Western blotting analysis of signaling protein expression showed that PHA- 665752 inhibited Met phosphorylation (P < 0.05). In addition, treatment with cetuximab alone or in combination with PHA-665752 effectively inhibited EGFR phosphorylation (P < 0.05). Combination treatment with PHA-665752 and cetuximab suppressed in vitro and in vivo CRC cell growth more than treatment with either agent alone did.


Reductions in Children's Blood Lead Levels from a Drinking-Water Intervention in Madagascar, Sub-Saharan Africa.
One in three children globally is estimated to have blood lead levels (BLL) at or above the BLL reference value of 5 μg/dL with increased burden falling on low- and middle-income countries (LMIC). Within developed countries, aqueous lead is the predominant exposure route. However, aqueous lead exposure is rarely examined in the LMIC, leaving a gap in the literature that ignores a potentially significant route of exposure. Furthermore, limited lead-based remediation efforts around consumer products have been examined. This study investigates the importance of lead exposure from the water supply through a case study in Toamasina, Madagascar. The project measured aqueous lead and BLL of children pre- and postremediation efforts (i.e., removal of leaded pump components in hand pumps) to verify the impact of aqueous lead exposure within this community. Removal of the leaded pump components (i.e., piston and foot valves) and replacement with nonleaded components decreased aqueous lead levels below the World Health Organization provisional guideline of 10 μg/L in all but 4% of pumps tested. Measured BLL concentrations indicated a statistically significant decrease in BLL from pre- to postremediation. Furthermore, the remediation resulted in a decrease in BLL for 87% of children with the greatest changes in BLL observed for children with the highest preremediation concentrations. These findings point to a need for greater consideration of lead in drinking and cooking waters as an important exposure route in LMIC.


Atomic Layer Deposition Al2O3 Coatings Significantly Improve Thermal, Chemical, and Mechanical Stability of Anodic TiO2 Nanotube Layers.
We report on a very significant enhancement of the thermal, chemical, and mechanical stability of self-organized TiO2 nanotubes layers, provided by thin Al2O3 coatings of different thicknesses prepared by atomic layer deposition (ALD). TiO2 nanotube layers coated with Al2O3 coatings exhibit significantly improved thermal stability as illustrated by the preservation of the nanotubular structure upon annealing treatment at high temperatures (870 °C). In addition, a high anatase content is preserved in the nanotube layers against expectation of the total rutile conversion at such a high temperature. Hardness of the resulting nanotube layers is investigated by nanoindentation measurements and shows strongly improved values compared to uncoated counterparts. Finally, it is demonstrated that Al2O3 coatings guarantee unprecedented chemical stability of TiO2 nanotube layers in harsh environments of concentrated H3PO4 solutions.


Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review.
A comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81) and externally (0.49-0.87). Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.


[Transurethral electrovaporization of the prostate: results in the course of five years].
The most common surgical intervention for lower urinary tract symptoms due to benign prostatic enlargement has been transurethral resection of the prostate (TURP). Transurethral electrovaporization of the prostate (TUVP) is a recent modification of TURP and has been used in Central Hospital Akureyri from 1997. The purpose of this study was to evaluate the safety, complications, efficacy and clinical indications in patients undergoing TUVP with benign prostatic enlargement in five years period. 36 patients underwent TUVP in the period January 1997 to March 2002. Prospective registration was performed during the first 4-8 weeks after operation. The author evaluated all patients before the intervention. Conventional surgical instruments for transurethral surgery were used with a roller electrode instead of a loop and in half of the patients some tissue was removed with a loop. The average age was 77.2 years (56-94) and average hospital stay was 5.3 days (2-14). 24 (58.4%) patients had urinary retention before the operation and average operation time was 27.6 minutes (15-42). No operative or in-hospital mortality was in this study or during the first 30 days and all patients were discharged. No one required transfusion or re-intervention within 30 days from operation. Three (8.3%) patients got complications within 30 days and one underwent bladder neck incision during the follow-up period. 32 (89%) were discharged without urinary catheter and 33 (91.7%) were satisfied with the result of the operation. TUVP is a safe, efficacious and technically feasible operation for patients with benign prostatic enlargement. Despite limited material, the clinical outcome and complications rate were comparable to larger series.


Regio- and Diastereoselective Access to 4-Imidazolidinones via an Aza-Mannich Initiated Cyclization of Sulfamate-Derived Cyclic Imines with α-Halo Hydroxamates.
An efficient regio- and diastereoselective cyclization of sulfamate-derived cyclic imines with unsubstituted or monosubstituted α-halo hydroxamates is developed under mild conditions. This reaction proceeds smoothly under transition-metal-free conditions via a domino aza-Mannich addition/intramolecular nucleophilic substitution sequence, providing a convenient route to access 2-monosubstituted and 2,5-disubstituted 4-imidazolidinones. Notably, the products were obtained with single trans-isomers in moderate to excellent yields.


Nitric oxide activates buccal motor patterns in Lymnaea stagnalis.
The mollusc, Lymnaea stagnalis, has been used as a model to study the mechanisms of nitric oxide (NO)-dependent processes in the CNS. Putative NO-containing neurones in Lymnaea are localized in the buccal ganglia, predominantly in areas where sensory neurones known to regulate feeding are found. The NO-generating substance, S-nitrosocysteine (S-NC, 5 x 10(-5)-10(-3 M) activates feeding movements of the buccal mass and modulates the activity of buccal motoneurones. An inhibitor of NO synthase, NG-methyl-L-arginine (10(-4) M) decreases the frequency of background buccal movements and has opposite effects to S-NC on the buccal motoneurones. We suggest that NO is a messenger in the CNS of Lymnaea and may be involved in coordination of feeding motor patterns.


Sarcoid-like reaction mimicking vaginal cancer recurrence.
A sarcoid-like reaction is a development of non-caseating granuloma in patients with underlying malignancy and represents a false positive finding on positron emission tomography/computed tomography (PET/CT). A sarcoid-like reaction is a benign condition; therefore, differentiating a sarcoid-like reaction from cancer recurrence is necessary. Only uterine and ovarian cancer related cases have been reported in the gynecological field and to the best of our knowledge, this is the first case of a sarcoid-like reaction in vaginal cancer. A 59-year-old vaginal cancer patient received concurrent chemoradiotherapy and achieved complete remission. Recurrence of vaginal cancer was suspected because of the elevation of serum squamous cell carcinoma antigen level. PET/CT revealed abnormal uptake at the bilateral mediastinal and hilar lymph nodes. A non-caseating granuloma was detected from the biopsy of the swollen lymph nodes. No evidence of cancer recurrence was observed. A sarcoid-like reaction should be considered when evaluating PET/CT in cancer patients to prevent unnecessary treatments.


Effects of Fatigue on Balance in Individuals With Parkinson Disease: Influence of Medication and Brain-Derived Neurotrophic Factor Genotype.
Because falls can have deleterious consequences, it is important to understand the influence of fatigue and medications on balance in persons with Parkinson disease (PD). Thus, the purpose of this study was to investigate the effects of fatigue on balance in individuals with PD. Because brain-derived neurotrophic factor (BDNF) has been shown to be related to motor performance, we also explored its role. A total of 27 individuals (age = 65.4 ± 8.1 years; males = 14, females = 13) with neurologist-diagnosed PD with 13 genotyped for BDNF as Val66Val, 11 as Val66Met, 2 as Met66Met (1 refused). Participants were tested both on and off medication, 1 week apart. On both days, they completed a pre- and posttest separated by a fatiguing condition. Factorial analyses of variance were performed for the following balance domains: (1) anticipatory postural responses; (2) adaptive postural responses; (3) dynamic balance; (4) sensory orientation; and (5) gait kinematics. For BDNF, t-tests were conducted comparing genotype for the pre-post difference scores in both the on and off medication states. There were no interactions between time (pre- and postintervention) and medication for any of the domains (Ps ≥ 0.187). Participants with BDNF Met alleles were not significantly different from Val66Val participants in balance (Ps ≥ 0.111) and response to a fatiguing condition (Ps ≥ 0.070). Fatigue does not appear to have a detrimental effect on balance, and there was not a differential effect of medication in individuals with PD. These results also indicate that participants with a BDNF Met allele did not have a greater decay in function after a fatiguing condition.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A196).


Systematic review of the impact of osteoarthritis on health outcomes for comorbid disease in older people.
A systematic review was undertaken examining the impact of comorbid osteoarthritis on health outcomes for people aged 50 years or older with cardiovascular disease, diabetes or obesity. The protocol is registered in PROSPERO (CRD42015023417). Relevant electronic databases and grey literature were systematically searched for studies published in English between January 2005 and December 2016. Two reviewers independently screened studies for selection using predetermined inclusion and exclusion criteria, and independently completed methodological quality review. Data was extracted at study level by one reviewer and independently checked by a second reviewer, using a standardized form. The results across studies were qualitatively synthesized with outcomes described and summarized. Of 1456 articles, we identified 15 relevant studies, with nine good to high quality studies describing significant negative impact of osteoarthritis on outcomes for cardiovascular diseases. There were too few studies focussing on diabetes and obesity to make conclusions in regard to these diseases. This review provides evidence that osteoarthritis should not be overlooked when impacts of chronic disease on health outcomes and related health service use are considered. There is a clear need for more studies that consider the impacts of osteoarthritis on comorbid disease, especially those that consider the impact of osteoarthritis beyond the morbidity impacts. The management of comorbid osteoarthritis should be addressed for those with cardiovascular disease, and treatment choices considered given this association.


An electrophysiological comparison of recollection for emotional words using an exclusion recognition paradigm.
The positive-going shift of event-related potential (ERP) components that occur when recognizing emotional words has been thought to be due to valence effects on either recollection or familiarity. This study investigated the independent contributions of recollection and familiarity on recognition of emotional words in order to examine which is thus responsible for the greater magnitude of ERP components seen in response to recognition of emotional, as opposed to neutral words. ERPs were measured while participants completed an exclusion recognition task. In the test phase, participants were required to respond "old" only to target items, which were included in one of two lists that were presented in the study phase. They were also asked to respond "new" to distracters and non-target items that were in the other previously presented list. "Old" responses to targets and non-targets were contrasted with an ERP analysis. Results suggested that the late positivity reflected recollection. The magnitude of this positivity, elicited around the left parietal area, was greater for negative stimuli compared to neutral and positive stimuli. The findings of the present study suggested that enhanced recollection of negative words may contribute to increased magnitudes of components such as the LPC. The emotional valence of words may have separate behavioral and electrophysiological effects on recollection and familiarity.


Enhancing rigour in the validation of patient reported outcome measures (PROMs): bridging linguistic and psychometric testing.
A strong consensus exists for a systematic approach to linguistic validation of patient reported outcome measures (PROMs) and discrete methods for assessing their psychometric properties. Despite the need for robust evidence of the appropriateness of measures, transition from linguistic to psychometric validation is poorly documented or evidenced. This paper demonstrates the importance of linking linguistic and psychometric testing through a purposeful stage which bridges the gap between translation and large-scale validation. Evidence is drawn from a study to develop a Welsh language version of the Beck Depression Inventory-II (BDI-II) and investigate its psychometric properties. The BDI-II was translated into Welsh then administered to Welsh-speaking university students (n = 115) and patients with depression (n = 37) concurrent with the English BDI-II, and alongside other established depression and quality of life measures. A Welsh version of the BDI-II was produced that, on administration, showed conceptual equivalence with the original measure; high internal consistency reliability (Cronbach's alpha = 0.90; 0.96); item homogeneity; adequate correlation with the English BDI-II (r = 0.96; 0.94) and additional measures; and a two-factor structure with one overriding dimension. Nevertheless, in the student sample, the Welsh version showed a significantly lower overall mean than the English (p = 0.002); and significant differences in six mean item scores. This prompted a review and refinement of the translated measure. Exploring potential sources of bias in translated measures represents a critical step in the translation-validation process, which until now has been largely underutilised. This paper offers important findings that inform advanced methods of cross-cultural validation of PROMs.


Nomograms for clinically localized prostate cancer. Part II: radiation therapy.
Prostate cancer can be effectively treated with either external beam radiation techniques or with brachytherapy. This study was designed to address the methodology that is used to assess outcome data in the current radiation literature and to evaluate available nomograms that can be used to predict outcomes. A literature search was performed and 12 articles reviewed. Risk stratification was the most frequently used methodology to analyze data. This method encompasses disease-specific variables: the pretreatment prostate-specific antigen (PSA) value and the Gleason score are classified by using cut points into low, intermediate, and high-risk groups. Another methodology uses nomograms to predict outcome. The nomogram uses continuous values of each variable so that the outcome probability for a specific set of parameters is quite specific. The advantage of nomogram analysis over risk stratification analysis is presented. In conclusion, only 3 reports were identified in the radiation literature that used a nomogram to predict outcome. One of the nomograms is proprietary and difficult to interpret. The other 2 nomograms, 1 for 3-dimensional radiation and the other for brachytherapy, have been incorporated into hand-held devices that can be used at consultation with the patient to discuss outcome probabilities to assist in treatment decisions.


Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study.
Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015-Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614.


Subdiffusion in the nonlinear Schrödinger equation with disorder.
The nonlinear Schrödinger equation in the presence of disorder is considered. The dynamics of an initially localized wave packet is studied. A subdiffusive spreading of the wave packet is explained in the framework of a continuous time random walk. A probabilistic description of subdiffusion is suggested, and a transport exponent of subdiffusion is obtained to be 2/5.


Detection of methicillin-resistant staphylococci.
Susceptibility tests commonly used in the clinical laboratory for detection of methicillin-resistant strains of staphylococci are discussed. The biochemical and genetic basis of methicillin resistance, including heterogeneous expression of resistance, is summarized. The conditions that can affect results of disk diffusion, broth dilution, and agar screen tests and sensitivity and specificity of these tests are reviewed. DNA detection methodologies, which, with their greater accuracy, may replace susceptibility testing, also are discussed.


Glomus tumor of the anterior urethra: A rare case report and review of the literature.
Glomus tumors are rare and benign neoplasms, which normally originate from peripheral soft tissue. To date, reported cases of glomus tumor occurring in genitourinary tract, particularly in the urethra, are exceedingly rare. The present study presented a rare case of glomus tumor of the anterior urethra in a 42 year-old male, his main complaints were a history of anterior urethra pain for 3 years, and a palpable and tender mass in the urethra for 2 weeks. Urethrocystoscopy examination and the resection of the urethral mass were performed. Pathological and immunohistochemical examination revealed that the mass was a benign glomus tumor. The patient remained in good condition by 6 month follow-up, and revealed no problems or recurrence following surgery. This is the first case, to the best of our knowledge, to present a glomus tumor occurring in a male's urethra and the present report provided a supplementary review for the previous cases and the literature.


Evaluation Criteria and Surgical Technique for Transoral Access to the Thyroid Gland: Experimental Study.
Background: The development of endoscopic techniques motivated surgeons to search for alternative and more cosmetic approaches for thyroid and parathyroid surgery. Several variations of transoral access to the anterior neck areas were applied in recent years. One of them is a premandibular access proposed by Nakajo et al, it is performed through the oral vestibule by creating the working space by means of the lifting method. Materials and methods: Nineteen unfixed human cadavers were used to develop the endoscopic access to the thyroid gland and surgical techniques of its resection. The Nakajo access was modified by altering the spatial location of the working instruments, resulting in practically no impact on the cosmetic outcome but providing a more comfortable operation for the thyroid gland. We determined evaluation criteria of the cadaver model before initiation of the experimental trial. Parameters that influence on alteration of these criteria were registered. Results: Of the 19 operated objects, the first 7 were used to practice the access technique from the incision in the oral vestibule to the thyroid gland in order to evaluate the possibility of endoscopic dissection of the important anatomical. The next 12 surgeries were carried out by manipulating the thyroid gland in the settings maximally close to real. Access implied good cosmetic results, less surgical traumatic due to a smaller area of detachment of the musculocutaneous flap. Conclusions: The achieved results show feasibility of introducing the described modification of transoral thyroidectomy into clinical practice.


Design and simulation of a near-infrared enhanced Si-based SPAD for an automotive LiDAR.
A near-infrared (NIR)-enhanced single-photon avalanche diode (SPAD) with a retrograded NM/XP junction for an automotive LiDAR was designed based on CSMC 0.18 µm BCD technology. A 3 µm depth NM/XP junction embedded in a lightly doped deep p-well (DP) improves the absorption efficiency in the NIR regime; the photo-generated electrons generated in the depletion region are efficiently collected into the central multiplication region by a drift process, and then the impact ionization is triggered by the strong field, resulting in a high photon detection efficiency (PDE). Additionally, the deep NM/XP junction and the buried layer effectively isolate the dark noise originating from the interface and the substrate. The SPAD was initially simulated by numerical calculation, and then was evaluated with active quench/reset electronics in a circuit simulator. The results revealed that the SPAD with an active area of 314µm 2 achieves a PDE of 16.2% at 905 nm and a dark count rate (DCR) of 1.46H z/µm 2, with an excess bias of 5 V at room temperature. The designed SPAD is well suited for the low-cost, miniaturized automotive LiDAR.


Contrast-enhanced harmonic ultrasonography of medial iliac lymph nodes in healthy dogs.
Herein, we describe the normal contrast-enhanced harmonic, color, and power Doppler ultrasonographic characteristics of the medial iliac lymph nodes in healthy dogs. Contrast-enhanced harmonic ultrasonography of the medial iliac lymph nodes was performed on 14 healthy dogs after intravenous administration of the lipoprotein-bound inert gas-filled microbubble contrast media Definity. Time-pixel intensity curves were generated for 1-min postinjection. Quantification of these curves was performed using Philips QLab software. Non-contrast-enhanced power and color Doppler examinations were performed in each node to assess vascular patterns subjectively. Normal lymph nodes exhibited a mean contrast wash-in phase beginning at 6.3 s from the time of injection with mean peak pixel intensity at 12.1s. Angioarchitecture was best visualized with contrast-enhanced harmonic ultrasound compared with power and color Doppler. Normal lymph nodes in dogs have a central artery with a centrifugal and uniform branching pattern. Contrast-enhanced harmonic ultrasonography is a noninvasive examination that demonstrates improved visibility of the intranodal architecture of healthy medial iliac lymph nodes in dogs compared with conventional, non-contrast-enhanced Doppler methods that may have future clinical applications.


Thyroid hormone regulation of RC3, a brain-specific gene encoding a protein kinase-C substrate.
RC3 is a brain-specific mRNA expressed in discrete neuronal groups of the forebrain that encodes a 78-amino acid protein, also called neurogranin, a calmodulin-binding, protein kinase-C substrate. Expression of RC3 mRNA was studied in normal and hypothyroid animals during the first month of life. Hypothyroid rats were produced by administration of methyl-mercapto-imidazol to the pregnant dams and subsequent surgical thyroidectomy on postnatal day 5 of the neonates. As studied by slot-blotting of total cerebrum poly(A)+ RNA, RC3 mRNA accumulates in normal brain from the fifth to seventh postnatal day, reaching maximal levels around days 10-12. RC3 mRNA accumulation in hypothyroid animals was blunted, and the maximal levels attained were about 30-50% of normal values. The effect of hypothyroidism on steady state mRNA levels was also observed by Northern blotting of RNA from cerebral cortex and striatum. As studied by immunoblotting using a polyclonal antibody, hypothyroidism also led to clear decreases in the amount of the RC3 protein in extracts from cerebral cortex, striatum, and hippocampus. A single administration of 10 micrograms T4 to hypothyroid rats on postnatal day 12 led to a steady increase in striatal RC3 mRNA from levels that were about 40% of normal to about 70% of normal at 16 h and 115% of normal at 48 h. In contrast to the effect on RC3, hypothyroidism did not affect developmental expression of the mRNA encoding GAP-43, another brain protein kinase-C substrate of axonal localization. RC3 is, thus, one of the few known neuronal genes whose expression is influenced by thyroid hormone in the brain. Thyroid hormone is required for an appropriate level of expression, not for the developmentally programmed timing of expression of the RC3 gene.


Management of spontaneous abortion in family practices and hospitals.
We performed two retrospective chart surveys, the first of 200 consecutive hospital emergency visits for spontaneous abortion and the second in 33 family physicians' offices examining 245 patients with spontaneous abortions. This study determined the rate of surgical management of spontaneous abortions within family practices and hospitals, as well as the rate of referrals and complications. In the retrospective chart surveys, the information collected included the number of spontaneous abortions, dilation and curettages (D&Cs), referrals, and complications. Of the women presenting to the hospitals, 92.5% had D&Cs, while 51% of the women presenting to family physicians had D&Cs. Of the women presenting to the hospitals, 99.5% were referred to gynecologists, compared with 41% of the family practice patients. Hemorrhage occurred in 4.6% of the hospital patients and 2% of the family practice patients. Infection occurred in 6% of the hospital patients and .8% of the family practice patients. Patients with spontaneous abortions who saw their family physicians were more likely to be managed conservatively than those seen in the hospitals. There was no increase in complications in the conservatively managed patients.


Modeling of electrochemical double layers in thermodynamic non-equilibrium.
We consider the contact between an electrolyte and a solid electrode. At first we formulate a thermodynamic consistent model that resolves boundary layers at interfaces. The model includes charge transport, diffusion, chemical reactions, viscosity, elasticity and polarization under isothermal conditions. There is a coupling between these phenomena that particularly involves the local pressure in the electrolyte. Therefore the momentum balance is of major importance for the correct description of the boundary layers. The width of the boundary layers is typically very small compared to the macroscopic dimensions of the system. In the second step we thus apply the method of asymptotic analysis to derive a simpler reduced bulk model that already incorporates the electrochemical properties of the double layers into a set of new boundary conditions. With the reduced model, we analyze the double layer capacitance for a metal-electrolyte interface.


Cardiovascular autonomic function in patients with relapsing remitting multiple sclerosis: a new surrogate marker of disease evolution?
Twenty patients with active relapsing remitting multiple sclerosis (MS) were examined annually for 2 years with a set of autonomic function tests (AFT) consisting of heart rate variability during deep breathing (IE), standing-up, and ratios of Valsalva manoeuvre (VR). Disease characteristics, including T2-weighted magnetic resonance imaging (MRI) of the brain and the expanded disability status scale (EDSS) score were documented each year within 1 week of the AFT. The EDSS score, MRI load lesion and VR did not change significantly over the follow-up period. The IE and initial heart-rate on standing during the first 30 s (DeltaHRMAX) showed significant worsening during follow-up. No relationship was found between deterioration of AFT and EDSS score, number of exacerbations, duration of disease, gender, age, size and number of lesions on MRI. We conclude that patients with active relapsing remitting MS show progression of autonomic dysfunction over a relatively short time. Therefore, in the absence of changes in clinical disability or brain MRI lesion load, AFT might be useful as a sensitive surrogate outcome measure for demonstrating subclinical change in MS.


[Combining Different Aerobic/Anoxic Durations with Zoned Sludge Discharge to Optimize Short-cut Nitrification Denitrifying Phosphorus Removal Granules in Domestic Sewage].
In this study, domestic sewage was used to inoculate mature short-cut nitrification denitrifying phosphorus removal particles, which were cultivated and matured under artificial water. The operation of the short-cut nitrification denitrifying phosphorus removal system was optimized using different aerobic/anoxic durations combined with zoned sludge discharge. The results showed that regulating the aerobic/anoxic duration, in combination with zoned sludge discharge, can realize the stable operation of the system. In the later stable period, the effluent COD concentration was below 50 mg·L-1, the effluent TN concentration was below 15 mg·L-1, the TN removal rate reached about 83% and remained stable, the effluent P concentration was below 0.5 mg·L-1, and the average P removal rate was 93.72%. At the same time, zoned sludge discharge (70% top sludge and 30% bottom sludge) can be used to screen out microorganisms, maintain good nitrosation and phosphorus removal performance, limit the particle size distribution, and ensure the growth advantages of AOB and DPAOs. Increases in the anoxic duration improved the growth rate of anoxic heterotrophic bacteria, causing them to secrete more EPS and ensuring granular sludge improvements and continued stability.


Vasoinhibin Suppresses the Neurotrophic Effects of VEGF and NGF in Newborn Rat Primary Sensory Neurons.
Studies on the biological actions of vasoinhibins have focused mainly on endothelial cells. However, there is incipient knowledge about how vasoinhibins affect the nervous system, even if the target cells and mechanisms of action involved in these effects are unknown. In order to determine if neurons are direct targets of vasoinhibins, we examined cellular outcomes and the intracellular pathways involved in the neuronal actions of vasoinhibins using newborn rat dorsal root ganglion (DRG) neurons as a model system. Vascular endothelial growth factor (VEGF) or nerve growth factor (NGF) treatment for 48 h resulted in neurite outgrowth stimulation in both DRG cultured explants and isolated primary sensory neurons. Interestingly, a recombinant vasoinhibin containing the first 123 amino acids of human prolactin antagonized the VEGF- and NGF-induced stimulation of neurite outgrowth. Vasoinhibin significantly reduced the density of neurites in DRG explants and obliterated neuritogenesis in isolated DRG neurons in primary culture, supporting a direct neuronal effect of vasoinhibin. In cultures of isolated DRG cells, virtually all β3-tubulin-labeled cells express TrkA, and the majority of these cells also express VEGFR2. Short-term VEGF or NGF treatment of DRG explants resulted in increased ERK1/2 and AKT phosphorylation, whereas incubation of DRG with the combination of either VEGF or NGF together with vasoinhibin resulted in blunted VEGF- or NGF-induced phosphorylation of both ERK1/2 and AKT. Our results show that primary sensory neurons are direct targets of vasoinhibin, and suggest that vasoinhibin inhibition of neurite outgrowth involves the disruption of ERK and AKT phosphorylation cascades.


The relationship between early drinking contexts of women "coming out" as lesbian and current alcohol use.
Several decades of research show that lesbians are at risk for hazardous drinking. Compared with heterosexual women, lesbians are less likely to abstain from drinking, less likely to decrease their alcohol consumption as they age, and more likely to report alcohol-related problems. Stress associated with lesbian identity and reliance on lesbian or gay bars for socialization and support are frequently posited--but largely untested--explanations for lesbians' heightened risk. Results from general population studies indicate that patterns of alcohol use established early in the life-course or during life transitions influence later alcohol use and alcohol-related problems. Further, heavy-drinking peers, availability of alcohol, and drinking in particular social contexts--such as at bars and parties--are believed to contribute to heavier drinking and to alcohol-related problems. To better understand lesbians' risks for hazardous drinking, we examined relationships between retrospective accounts of drinking patterns and drinking contexts in the early stages of lesbian identity development and current drinking outcomes in a large sample of adult lesbians. Findings suggest that early drinking patterns and drinking contexts influence later alcohol use and have important implications for risk reduction and prevention among lesbians.


Effect of Light of Different Spectral Compositions on Pro/Antioxidant Status, Content of Some Pigments and Secondary Metabolites and Expression of Related Genes in Scots Pine.
The aim of this study was to investigate the effect of light quality (white fluorescent light, WFL, containing UV components), red light (RL, 660 nm), blue light (BL, 450 nm), and white LED light (WL, 450 + 580 nm) on the components of the cellular antioxidant system in Pinus sylvestris L. in needles, roots, and hypocotyls, focusing on the accumulation of key secondary metabolites and the expression of related genes. The qualitative and quantitative composition of carotenoids; the content of the main photosynthetic pigments, phenolic compounds, flavonoids (catechins, proanthocyanidins, anthocyanins), ascorbate, and glutathione; the activity of the main antioxidant enzymes; the content of hydrogen peroxide; and the intensity of lipid peroxidation (MDA and 4-HNE contents) were determined. RL resulted in an increase in the content of hydrogen peroxide and 4-HNE, as well as the total fraction of flavonoids in the needles. It also enhanced the expression of several PR (pathogen-related) genes compared to BL and WL. WFL increased the content of phenols, including flavonoids, and enhanced the overall activity of low-molecular antioxidants in needles and hypocotyls. BL increased the content of ascorbate and glutathione, including reduced glutathione, in the needles and simultaneously decreased the activity of peroxidases. Thus, by modifying the light quality, it is possible to regulate the accumulation of secondary metabolites in pine roots and needles, thereby influencing their resistance to various biotic and abiotic stressors.


Neuronal scaling in the olfactory system of bats.
Comparative studies are a common way to address large-scale questions in sensory biology. For studies that investigate olfactory abilities, the most commonly used metric is olfactory bulb size. However, recent work has called into question the broad-scale use of olfactory bulb size. In this paper, we use three neuroanatomical measures with a more mechanistic link to olfactory function (number of olfactory sensory neurons (OSNs), number of mitral cells (MCs), and number of glomeruli) to ask how species with different diets may differ with respect to olfactory ability. We use phyllostomid bats as our study system because behavioral and physiological work has shown that fruit- and nectar-feeding phyllostomids rely on odors for detecting, localizing, and assessing potential foods, while insect-eating species do not. Therefore, we predicted that fruit- and nectar-feeding bats would have larger numbers of these three neuroanatomical measures than insect-eating species. In general, our results supported the predictions. We found that fruit-eaters had greater numbers of OSNs and glomeruli than insect-eaters, but we found no difference between groups in number of MCs. We also examined the allometric relationship between the three neuroanatomical variables and olfactory bulb volume, and we found isometry in all cases. These findings lend support to the notion that neuroanatomical measures can offer valuable insights into comparative olfactory abilities, and suggest that the size of the olfactory bulb may be an informative parameter to use at the whole-organism level.


Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks.
Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV), which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV) protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV.


A kinetic analysis of hybridoma growth and metabolism in continuous suspension culture on serum-free medium.
The steady-state metabolic parameters for a murine hybridoma cell line have been determined in continuous suspension culture over a wide range of dilution rates. Long-term adaption occurred over seven months in culture and resulted in lower glucose consumption rates, reduced lactate production, higher cell viability, and, consequently, growth rates more nearly matching the dilution rate. Antibody production rates decreased over the first two months and then remained stable for at least 75 days. The antibody production rate was not found to be growth associated. Steadystate amino acid uptake rates are presented for a wide range of growth rates.


Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence.
A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis.


Pancreatic T/histiocyte-rich large B-cell lymphoma: A case report and review of literature.
Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal malignant lymphoma. The most common histological subtype of PPL is diffuse large B cell lymphoma (DLBCL). In rare cases, PPL can also present as follicular lymphoma, small lymphocytic lymphoma, and T cell lymphoma either of non-Hodgkin's lymphoma or of Hodgkin's lymphoma. T-cell/histiocyte-rich large B-cell lymphoma (T/HRBCL) is an uncommon morphologic variant of DLBCL with aggressive clinical course, it is predominantly a nodal disease, but extranodal sites such as bone marrow, liver, and spleen can be involved. Pancreatic involvement of T/HRBCL was not presented before. Herein, we report a 48-year-old male who was hospitalized with complaints of jaundice, dark brown urine, pale stools, and nausea. The radiological evaluation revealed a pancreatic head mass and, following operative biopsy, the tumor was diagnosed as T/HRBCL. The patient achieved remission after six cycles of CHOP chemotherapy. Therefore, T/HRBCL can be treated similarly to the stage-matched DLBCL and both of them get equivalent outcomes after chemotherapy.


Managing congenitally missing lateral incisors. Part III: single-tooth implants.
Three treatment options exist for the replacement of congenitally missing lateral incisors. They include canine substitution, a tooth-supported restoration, and a single-tooth implant. Selecting the appropriate treatment option depends on the malocclusion, anterior relationship, specific space requirements, and condition of the adjacent teeth. The ideal treatment is the most conservative option that satisfies individual esthetic and functional requirements. Today, the single-tooth implant has become one of the most common treatment alternatives for the replacement of missing teeth. This article closely examines the many interdisciplinary issues that arise when treatment planning the placement of single-tooth implants in patients with congenitally missing lateral incisors. The specific criteria that must be evaluated illustrate the importance of an interdisciplinary treatment approach to achieve optimal esthetics and long-term predictability. This is the final article of a three-part series discussing the three treatment alternatives for replacing congenitally missing lateral incisors. When treatment planning single-tooth implants to replace congenitally missing lateral incisors, an interdisciplinary approach is necessary to provide the most predictable treatment outcome.


Human glucosamine-6-phosphate isomerase, a homologue of hamster oscillin, does not appear to be involved in Ca2+ release in mammalian oocytes.
Injections of cytosolic preparations from mammalian sperm into oocytes have been shown to trigger calcium [Ca2+]i oscillations and initiate activation of development. Recently, a protein isolated from hamster sperm has been suggested to be involved in the generation of these oscillations and it was named "oscillin." The human homologue of hamster oscillin is glucosamine 6-phosphate isomerase (GPI, EC no. 184.108.40.206), an enzyme so far described to be involved in hexose phosphate metabolism. To assess the role of GPI on Ca2+ signaling, a human recombinant protein was generated in a prokaryotic system and injected into fura-2-dextran-loaded metaphase II (MII) mouse oocytes. Injection of recombinant GPI failed to induce Ca2+ responses in 12/12 injected MII oocytes despite the fact that the recombinant GPI was active as assessed by an enzymatic assay. Injection of buffer (0/6 oocytes) or fructose-6-phosphate, a product of GPI enzymatic reaction (0/5 oocytes), also failed to initiate Ca2+ responses. Conversely, injections of sperm cytosolic factor induced [Ca2+]i oscillations in all 17/17 oocytes. In addition, injection of recombinant GPI or GPI mRNA failed to induce parthenogenetic activation (0/30 oocytes). Immunofluorescence studies using an anti-GPI polyclonal antibody (GK) resulted in localization of GPI to the sperm's equatorial region. Incubation of the GK antibody with sperm extracts failed to block the [Ca2+]i responses induced by these extracts. Moreover, near complete depletion of GPI from sperm fractions by immunoprecipitation did not impair the ability of these fractions to induce [Ca2+]i oscillations. In summary, our results support the role of a sperm cytosolic component(s) in the generation of [Ca2+]i oscillations during mammalian fertilization, although a protein other than GPI/oscillin is likely to be the active calcium releasing factor.


Comprehensive evaluation method of stope stability and its application in deep metal mine.
The problem of high stress conditions is a critical challenge for mining activity in deep metal mines, and the difficulty and economic cost of maintaining stope stability also increases. In order to ensure stope stability in the mining process, it is necessary to evaluate stope stability for a more stable stope structure. However, there are many kinds of methods for rock stability assessment, and most of them are based on empirical and analytical methods, which lead to uncertain results. In this paper, a comprehensive evaluation method including factors of stope stability, self-stabilization time, maximum safety span, and support measure is determined, which is more likely to provide a comprehensive result. Finally, it was verified by the field application in Jiaojia Gold Mine. Results show that it can accurately evaluate the stope stability from different aspects compared with the traditional single evaluation method, and it leads to a more comprehensive and reliable result.


Baseline characteristics and outcomes of children with cancer in the English-speaking Caribbean: A multinational retrospective cohort.
English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5.7 years (interquartile range 2.9-10.6 years). One hundred thirty (35.4%) patients were diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with solid tumors. A relative paucity of children with brain tumors was seen (N = 58, 15.8%). Two-year event-free survival (EFS) for the cohort was 48.5% ± 3.2%; 2-year overall survival (OS) was 55.1% ± 3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumor (WT) experienced better 2-year EFS (62.1% ± 6.4% and 66.7% ± 10.1%), while dismal outcomes were seen in children with acute myeloid leukemia (AML; 22.7 ± 9.6%), rhabdomyosarcoma (21.0% ± 17.0%), and medulloblastoma (21.4% ± 17.8%). Of 108 deaths with known cause, 58 (53.7%) were attributed to disease and 50 (46.3%) to treatment complications. Death within 60 days of diagnosis was relatively common in acute leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators adversely impacted outcome in ALL, including higher age, higher white blood cell count, and T-cell lineage. ESC childhood cancer outcomes are significantly inferior to high-income country outcomes. Based on these data, interventions for improving supportive care and modifying treatment protocols are under way. Continued data collection will allow evaluation of interventions and ensure maximal outcome improvements.


Graphene Jet Nanomotors in Remote Controllable Self-Propulsion Swimmers in Pure Water.
A remote controllable working graphite nanostructured swimmer based on a graphene jet nanomotor has been demonstrated for the first time. Graphite particles with pyramidal-like morphologies were fabricated by the creation of suitable defects in wide high-purity graphite flakes followed by a severe sonication. The particles were able to be self-exfoliated in water after Na intercalation between the graphene constituents. The self-exfoliation resulted in jet ejection of graphene flakes from the end of the swimmers (with speeds as high as ∼7000 m/s), producing a driving force (at least ∼0.7 L (pN) where L (μm) is swimmer size) and consequently the motion of the swimmer (with average speed of ∼17-40 μm/s). The jet ejection of the graphene flakes was assigned to the explosion of H2 nanobubbles produced between the Na intercalated flakes. The direction of motion of the swimmers equipped with TiO2 nanoparticles (NPs) can be controlled by applying a magnetic field in the presence of UV irradiation (higher UV intensity, lower radius of rotation). In fact, the negative surface charge of the graphene flakes of the swimmers increased by UV irradiation due to transferring the photoexcited electrons of TiO2 NPs into the flakes. Because of higher production of H2 nanobubbles under UV irradiation, the speed of swimmers exposed to UV light significantly increased. In contrast, UV irradiation with various intensities could not affect total distance traversed by the self-exfoliated swimmers having the same initial sizes. These confirmed the mass ejection mechanism for motion of the swimmers. The self-exfoliation of swimmers (and so their motion) occurred only in water (and not, e.g., in organic solutions). Such swimmers promise the design of remote controllable nanovehicles with the capability of initiating and/or improving their operations in response to environmental changes in order to realize broad ranges of versatile and fantastic nanotechnology-based applications.


[Comparison of long-term dental treatment effects of children treated under general anesthesia and passive restraint].
Objective: To compare the long-term dental treatment effects, oral health habits and oral-health-related qualities of life of children treated under general anesthesia (GA) and passive restraint (PR), respectively. Methods: Twenty seven 2 to 4-year-old children treated under GA and thirty four children treated under PR were recruited in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology. Up to 2 years after the treatment, a follow up assessment was conducted. The data of general information, dental plaque level and the unplanned treatments were recorded and analyzed. The questionnaire of oral health habits and early childhood oral health impact scale (ECOHIS) for each child was also completed and analyzed. The survival rate and median survival time of the deciduous teeth were calculated. Multivariate analysis was performed by using Cox proportional hazard model. Results: Twenty-five children under GA and 32 under PR were finally included, with a total of 1 098 deciduous teeth. The postoperative dental plaque indicesin both GA and PR groups had significantly improved than that of before the treatments (P=0.019, P<0.001). The oral health habits had also improved, and the improvement in PR group was more obvious than that in GA group. Totally 128 teeth (27.0%) appeared unplanned treatments in GA group and 232 teeth (37.2%) in PR group during the follow-ups. The new caries and recurrent caries in PR group were significantly more than that in GA group (P<0.001, P=0.012). No significant differences were found between the two groups in restoration failure, secondary caries and endodontic diseases (P=0.129, P=0.822, P=0.642). However, the time of occurrence of endodontic disease and secondary caries in GA group were significantly longer than that in PR group (P<0.01, P<0.001). The median survival time of teeth in GA group was 1 018 days comparing to 944 days in PR group. The difference was statistically significant (P<0.05). The survival rate was associated with such factors as decayed-missing-filled tooth (dmft), anterior or posterior teeth, feeding frequency, brushing habits and behavior management techniques. Conclusions: The long-term dental treatment effects of children treated under GA was significantly better than that of PR group. Continuous reinforcement of proper dietary and oral hygiene habits might help in maintaining the long-term treatment effect.


Roy markham: pioneer in plant pathology.
I first met Roy Markham in September 1945, when I came to Cambridge after four years in the New Zealand army to begin research for the PhD in plant virology. As far as the University was concerned Dr. K. M. Smith was my supervisor, but I very rapidly came under Roy's influence, and he was my de facto supervisor for three years. I came back to his group for four full years from 1952 to 1956 and later made several short visits to his laboratory both in Cambridge and, after the shift, in Norwich. Thus, I knew him well for a significant portion of his working life. Roy made a number of seminal contributions to plant virology and thus to plant pathology. However, he was in no sense a plant pathologist himself. His formal training was in biochemistry, and he learned a great deal in the physical sciences on his own account. In the main thrust of his research, he was really one of the pioneers in that branch of science now known as molecular biology.


Age-related alterations and senescence of mesenchymal stromal cells: Implications for regenerative treatments of bones and joints.
The most common clinical manifestations of age-related musculoskeletal degeneration are osteoarthritis and osteoporosis, and these represent an enormous burden on modern society. Mesenchymal stromal cells (MSCs) have pivotal roles in musculoskeletal tissue development. In adult organisms, MSCs retain their ability to regenerate tissues following bone fractures, articular cartilage injuries, and other traumatic injuries of connective tissue. However, their remarkable regenerative ability appears to be impaired through aging, and in particular in age-related diseases of bones and joints. Here, we review age-related alterations of MSCs in musculoskeletal tissues, and address the underlying mechanisms of aging and senescence of MSCs. Furthermore, we focus on the properties of MSCs in osteoarthritis and osteoporosis, and how their changes contribute to onset and progression of these disorders. Finally, we consider current treatments that exploit the enormous potential of MSCs for tissue regeneration, as well as for innovative cell-free extracellular-vesicle-based and anti-aging treatment approaches.


Interaction between stray electrostatic fields and a charged free-falling test mass.
We present an experimental analysis of force noise caused by stray electrostatic fields acting on a charged test mass inside a conducting enclosure, a key problem for precise gravitational experiments. Measurement of the average field that couples to the test mass charge, and its fluctuations, is performed with two independent torsion pendulum techniques, including direct measurement of the forces caused by a change in electrostatic charge. We analyze the problem with an improved electrostatic model that, coupled with the experimental data, also indicates how to correctly measure and null the stray field that interacts with the test mass charge. Our measurements allow a conservative upper limit on acceleration noise, of 2 (fm/s2)/Hz(1/2) for frequencies above 0.1 mHz, for the interaction between stray fields and charge in the LISA gravitational wave mission.


Microbial Identification Using rRNA Operon Region: Database and Tool for Metataxonomics with Long-Read Sequence.
Recent development of long-read sequencing platforms has enabled researchers to explore bacterial community structure through analysis of full-length 16S rRNA gene (∼1,500 bp) or 16S-ITS-23S rRNA operon region (∼4,300 bp), resulting in higher taxonomic resolution than short-read sequencing platforms. Despite the potential of long-read sequencing in metagenomics, resources and protocols for this technology are scarce. Here, we describe MIrROR, the database and analysis tool for metataxonomics using the bacterial 16S-ITS-23S rRNA operon region. We collected 16S-ITS-23S rRNA operon sequences extracted from bacterial genomes from NCBI GenBank and performed curation. A total of 97,781 16S-ITS-23S rRNA operon sequences covering 9,485 species from 43,653 genomes were obtained. For user convenience, we provide an analysis tool based on a mapping strategy that can be used for taxonomic profiling with MIrROR database. To benchmark MIrROR, we compared performance against publicly available databases and tool with mock communities and simulated data sets. Our platform showed promising results in terms of the number of species covered and the accuracy of classification. To encourage active 16S-ITS-23S rRNA operon analysis in the field, BLAST function and taxonomic profiling results with 16S-ITS-23S rRNA operon studies, which have been reported as BioProject on NCBI are provided. MIrROR (http://mirror.egnome.co.kr/) will be a useful platform for researchers who want to perform high-resolution metagenome analysis with a cost-effective sequencer such as MinION from Oxford Nanopore Technologies. IMPORTANCE Metabarcoding is a powerful tool to investigate community diversity in an economic and efficient way by amplifying a specific gene marker region. With the advancement of long-read sequencing technologies, the field of metabarcoding has entered a new phase. The technologies have brought a need for development in several areas, including new markers that long-read can cover, database for the markers, tools that reflect long-read characteristics, and compatibility with downstream analysis tools. By constructing MIrROR, we met the need for a database and tools for the 16S-ITS-23S rRNA operon region, which has recently been shown to have sufficient resolution at the species level. Bacterial community analysis using the 16S-ITS-23S rRNA operon region with MIrROR will provide new insights from various research fields.


The Role of Telomerase and Telomeres in Interstitial Lung Diseases: From Molecules to Clinical Implications.
Telomeres are distal chromosome regions associated with specific protein complexes that protect the chromosome against degradation and aberrations. Telomere maintenance capacity is an essential indication of healthy cell populations, and telomere damage is observed in processes such as malignant transformation, apoptosis, or cell senescence. At a cellular level, telomere damage may result from genotoxic stress, decreased activity of telomerase enzyme complex, dysfunction of shelterin proteins, or changes in expression of telomere-associated RNA such as TERRA. Clinical evidence suggests that mutation of telomerase genes (Tert/Terc) are associated with increased risk of congenital as well as age-related diseases (e.g., pneumonitis, idiopathic pulmonary fibrosis (IPF), dyskeratosis congenita, emphysema, nonspecific interstitial pneumonia, etc.). Thus, telomere length and maintenance can serve as an important prognostic factor as well as a potential target for new strategies of treatment for interstitial lung diseases (ILDs) and associated pulmonary pathologies.


Effect of ethanol shock pretreatment on the tolerance of Cronobacter sakazakii BCRC 13988 exposed to subsequent lethal stresses.
Cronobacter spp., formerly Enterobacter sakazakii, are human pathogens. They are the etiological agent of life-threating bacterial infections in infants. In this study, the survival behavior of C. sakazakii Bioresources Collection and Research Center (BCRC) 13988 in the presence of various ethanol concentrations was first examined. Besides, the test organism was subjected to treatment with 5% ethanol for 60 min (ethanol shock). The effect of ethanol shock on the resistance of C. sakazakii to lethal stresses, including high ethanol concentration (15%), low temperature (4°C and -20°C), high temperature (51°C) and high acidity (pH 3.3), was investigated. Results revealed that 4-5% ethanol is the maximum concentration that will allow C. sakazakii BCRC 13988 to grow in trypticase soy broth (TSB). Etthanol at 6% and 7% or more, respectively, exerted bacteriostatic and bactericidal effects, respectively, on the test organism. Although ethanol shock did not affect the resistance of C. sakazakii to a refrigerated temperature (4°C), the ethanol-shocked C. sakazakii survived better under other lethal stress conditions. After 50 min of exposure to 15% ethanol, the ethanol-shocked C. sakazakii showed a survival percentage of 16.11%, which was a 6400-fold increase over the control cells (<0.01%). On the other hand, the ethanol-shocked C. sakazakii exhibited a 45-fold higher survival after 120-min exposure to 51°C. At the end of the 7-day storage at -20°C, the ethanol-shocked cells exhibited a survival percentage of 0.25% which was significantly (p<0.05) higher than that (less than 0.01%) of the control. Additionally, the ethanol-shocked cells showed a survival percentage of 13.80% compared to only 1.60% noted with the control cells after exposure to pH 3.3 for 60 min.


A long-term evaluation of erythema and pigmentation induced by ultraviolet radiations of different wavelengths.
The long-term reactions of human skin by different ultraviolet (UV)-wavebands were not reported. This study was to investigate a time course of erythema and pigmentation induced by UVA-1, broadband UVA (BBUVA), narrowband UVB (NBUVB) and broadband UVB (BBUVB). Ten volunteers participated in this study for 6 months. Four skin areas, from the back of each subject, were irradiated with two minimal erythema dose (MED) of four different UV wavelengths corresponding to UVA-1, BBUVA, NBUVB and BBUVB. For both UVA-1 and BBUVA, erythema and pigmentation were most pronounced immediately and 1 h after exposure. Erythema rapidly diminished but pigmentation persisted throughout the study. For both NBUVB and BBUVB, test areas reacted with erythema of maximum intensity at 1 and 2 days, respectively. A maximum tanning was reached at 3-6 days for NBUVB and 4-7 days for BBUVB, and the return toward the original point was at 1 and 3 months, respectively. Two MED of UVA produced far prolonged erythema and pigmentation than UVB. For UVA, UVA-1 and BBUVA showed similar intensity and time course of skin reaction. For UVB, erythema and pigmentation produced by NBUVB were milder in intensity and shorter in a time course than those by BBUVB.


Modulation of Core Turbulent Density Fluctuations by Large-Scale Neoclassical Tearing Mode Islands in the DIII-D Tokamak.
We report the first observation of localized modulation of turbulent density fluctuations n[over ˜] (via beam emission spectroscopy) by neoclassical tearing modes (NTMs) in the core of the DIII-D tokamak. NTMs are important as they often lead to severe degradation of plasma confinement and disruptions in high-confinement fusion experiments. Magnetic islands associated with NTMs significantly modify the profiles and turbulence drives. In this experiment n[over ˜] was found to be modulated by 14% across the island. Gyrokinetic simulations suggest that n[over ˜] could be dominantly driven by the ion temperature gradient instability.


Metabolic imbalance in a Saccharomyces cerevisiae mutant unable to grow on fermentable hexoses.
A mutant of Saccharomyces cerevisiae unable to grow on fermentable hexoses has been studied. The mutant grew normally on galactose or maltose. It was also able to grow on a medium containing glucose or fructose with a 25-fold excess of D-xylose. Assay of the glycolytic enzymes in vitro did not show differences between the parental and the mutant strains. Upon addition of fructose, metabolites up to triose phosphates accumulated and the ATP dropped to low levels. It is proposed that an imbalance between the initial and final segments of glycolysis that depletes the cell of ATP produces the observed phenotype.


Clinical pathways for inborn errors of metabolism: warranted and feasible.
Inborn errors of metabolism (IEMs) are known for their low prevalence and multidisciplinary care mostly founded on expert opinion. Clinical pathways are multidisciplinary tools to organise care which provide a clear route to the best care and improve communication. In 2010 the Dutch Society for Children and Adults with an Inborn Error of Metabolism (VKS) initiated development of clinical pathways for inborn errors of metabolism. In this letter to the editor we describe why it is warranted to develop clinical pathways for IEMs and shortly discuss the process of development for these pathways in the Netherlands.


Management of hyperglycemia in diabetic patients with hematologic malignancies during dexamethasone therapy.
To compare the response to different insulin regimens for management of hyperglycemia in diabetic patients with hematologic malignancies who are receiving dexamethasone. A retrospective analysis was conducted to determine whether a basal bolus insulin (BBI) regimen with detemir and aspart is superior to a sliding scale regular insulin (SSI) regimen for management of hyperglycemia in hospitalized diabetic patients receiving dexamethasone. Forty patients with hematologic malignancies were treated with intravenous (8 to 12 mg/day) or oral (40 mg/day) dexamethasone for 3 days. The average blood glucose (BG) level was 301 ± 57 mg/dL in the SSI group (n = 28) and 219 ± 51 mg/dL in the BBI group (n = 12) (P <.001). The BBI regimen resulted in an average BG reduction of 52 ± 82 mg/dL throughout the course of dexamethasone therapy, while the SSI regimen produced an increase in the mean daily BG level of 128 ± 77 mg/dL (P <.001). On the last day of dexamethasone administration, the insulin requirement was 49 ± 29 units/day in the SSI group and 122 ± 39 units/day in the BBI group (P <.001). Three patients in the SSI group developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy. No hypoglycemia was observed in either group. The length of stay and infection rates were similar between groups. Basal and bolus insulin regimen is an effective and safe approach for managing dexamethasone-induced hyperglycemia in hospitalized patients with hematologic malignancies.


A new species of the genus Entomogonus Solier, 1848 (Coleoptera: Tenebrionidae) from Eastern Anatolia.
A new species Entomogonus (Delonurops) doguanatolicus Nabozhenko, sp. n. (Coleoptera: Tenebrionidae) is described from Diyarbakır (Turkey). It differs from all members of the subgenus Delonurops Reitter, 1922 in the flattened lateral sides of pronotum. The newly described species is similar to E. clavimanus Reitter, 1903, E. makovskyi Nabozhenko et Tichý, 2011 and E. bialookii Nabozhenko et Tichý, 2011 from which it also differs by a more robust body, structure of pro- and mesotibiae, pro- and mesotarsi and elytral apex. A key to species (based on males) of the subgenus Delonurops of Eastern Anatolia is given.


Influence of age and sex on bone mineral density in dialysis patients.
In the present study, we evaluated bone mineral density (BMD) in relation to the age and sex of dialysis patients. The study was performed in 30 patients divided into two groups according to age (older group: 12 patients older than 65 years; younger group: 18 patients 65 years of age or younger) and according to sex (18 women, 12 men). We used dual-energy X-ray absorptiometry to examine BMD in the femoral neck (N) and lumbar spine (L2-L4). We simultaneously evaluated parathyroid hormone, calcium-phosphate balance, blood pH, markers of inflammation and nutrition status, and measurements of body composition by bioimpedance analysis. We found significant differences for BMD measured in N (older group: 0. 709 +/- 0.111 g/cm2; younger group: 0.884 +/- 0.130 g/cm2), T-score [older group: -2.64 (range: -4.06 to -0.17); younger group: -0.88 (range: -3.25 to 2.37)], and BMD as a percentage of peak bone density [older group: 68.0% (54.2%-97.0%); younger group: 89.5% (range; 61.4%-135.0%)]. The older patients also had lower serum albumin and higher serum ferritin. After adjustment of the results by sex, the older group also showed lower serum Ca and lean body mass and higher serum glucose. Grouping of the patients by sex revealed significant differences in BMD when results were adjusted for age: men had a higher BMD in N (0.85 +/- 0.16 g/cm2) than women did (0. 79 +/- 0.14 g/cm2). We conclude that older age, which is more frequently associated with protein malnutrition, inflammation, and glucose abnormalities than is younger age, is also the important factor influencing BMD loss in dialysis patients.


Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors.
Hematopoietic stem cell and solid organ transplant recipients diagnosed with biopsy-confirmed posttransplant lymphoproliferative disorder (PTLD) at our institution from 1989 to 2010 were identified. Patient-, transplant- and disease-related characteristics, prognostic factors and outcome were collected and analyzed. One hundred and forty biopsy-proven cases of PTLD were included. Overall incidence in the transplant population was 2.12%, with heart transplant recipients carrying the highest risk. Most PTLDs were monomorphic (82%), with diffuse large B-cell lymphoma being the most frequent subtype. The majority of cases (70.7%) occurred > 1 year posttransplant, and 66% were Epstein-Barr virus positive. Following initial therapy the overall response rate was 68.5%. Three-year relapse-free and overall survivals were 59% and 49%, respectively. At last follow-up, 44% of the patients were alive. Multivariable analysis identified several classical lymphoma-specific poor prognostic factors for the different outcome measures. The value of the International Prognostic Index was confirmed in our analysis.


Interaction of MDIMP with the Voltage-Gated Calcium Channels.
Amino acid-derived isoindolines are synthetic compounds that were created with the idea of investigating their biological actions. The amino acid moiety was included on the grounds that it may help to avoid toxic effects. Recently, the isoindoline MDIMP was shown to inhibit both cardiac excitation-contraction coupling and voltage-dependent calcium channels. Here, we revealed that MDIMP binds preferentially to low-voltage-activated (LVA) channels. Using a holding potential of -90 mV, the following IC50 values were found (in micromolars): >1000 (CaV2.3), 957 (CaV1.3), 656 (CaV1.2), 219 (CaV3.2), and 132 (CaV3.1). Moreover, the isoindoline also promoted both accelerated inactivation kinetics of high-voltage-activated Ca2+ channels and a modest upregulation of CaV1.3 and CaV2.3. Additional data indicate that although MDIMP binds to the closed state of the channels, it has more preference for the inactivated one. Concerning CaV3.1, the compound did not alter the shape of the instantaneous current-voltage curve, and substituting one or two residues in the selectivity filter drastically increased the IC50 value, suggesting that MDIMP binds to the extracellular side of the pore. However, an outward current failed in removing the inhibition, which implies an alternative mechanism may be involved. The enantiomer (R)-MDIMP [methyl (R)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate], on the other hand, was synthesized and evaluated, but it did not improve the affinity to LVA channels. Implications of these findings are discussed in terms of the possible underlying mechanisms and pharmacological relevance. SIGNIFICANCE STATEMENT: We have studied the regulation of voltage-gated calcium channels by MDIMP, which disrupts excitation-contraction coupling in cardiac myocytes. The latter effect is more potent in atrial than ventricular myocytes, and this could be explained by our results showing that MDIMP preferentially blocks low-voltage-activated channels. Our data also provide mechanistic insights about the blockade and suggest that MDIMP is a promising member of the family of Ca2+ channel blockers, with possible application to the inhibition of subthreshold membrane depolarizations.


Evaluating a potential technique with local optical flow vectors for automatic organ-at-risk (OAR) intrusion detection and avoidance during radiotherapy.
Various techniques of deep inspiration breath hold (DIBH) have been used to mitigate the likelihood and risk of exposing the heart, an organ-at-risk (OAR) for unintended radiation during left breast radiotherapy. However, issues of reproducibility of these techniques warrant further investigation into the feasibility of detecting the intrusion of an OAR into the treatment field during intra-fractional treatment delivery. The increase of high-dose, low-fraction radiotherapy treatments makes it important to immediately adapt treatment once an OAR is detected in the treatment field. This proof-of-concept implementation includes an algorithm that detects and tracks the motion at the edges of a treatment field and a control algorithm that adapts the treatment aperture according to the motion detected. In accordance to the AAPM Task-Group (TG-132) report, image registration techniques should be verified with virtual and physical phantoms prior to clinical application. Since most OARs move as a result of respiration-induced motion, we have used a lung phantom to generate images of a generic OAR intruding into a treatment field with known velocity. The phantom was programmed to move with sinusoidal and lung patient tumor motion patterns and the accuracy of intrusion tracking and MLC adaptation were benchmarked with the ground truth-programmed motion of the OAR. The motions were recorded with an electronic portal imaging device (EPID). An optimal cluster size of 9 × 9 motion vectors was found to provide the smallest average absolute position error of 0.3 mm. A strong linear correlation between the adapted MLC leaves and the actual OAR position was observed. The algorithm had a mean position tracking error of -0.4 ± 0.3 mm and a precision of 1.1 mm. It is possible to adapt MLC leaves based on the motion detected at the edges of the irradiated field, and it would be feasible to shield an unplanned intrusion of an OAR into the treatment field.


Sulfated archaeal glycolipid archaeosomes as a safe and effective vaccine adjuvant for induction of cell-mediated immunity.
Archaeosomes are liposomal vesicles composed of ether glycerolipids unique to the domain of Archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high stability and possess strong adjuvant and immunostimulatory properties making them an attractive vaccine delivery vehicle. Traditionally comprised of total polar lipids (TPL) or semi-synthetic phospho-glycerolipids of ether-linked isoprenoid phytanyl cores with varied glycol- and amino-head groups, archaeosomes can induce robust and long-lasting humoral and cell-mediated immune responses against antigenic cargo and provide protection in murine models of infectious disease and cancer. However, traditional TPL archaeosome formulations are relatively complex comprising several lipid species. Semi-synthetic archaeosomes tested previously contain a combination of several phospho-glycolipids (negative and neutral charged) to produce a stable, uniform-sized liposome formulation. Moreover, they involve many synthetic steps to arrive at the final desired glycolipid composition. Herein, we present a novel adjuvant formulation comprising a sulfated saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA). SLA individually or mixed with uncharged glyolipid (lactosylarchaeol, LA) constituted efficacious carrier vesicles for entrapped antigens (ovalbumin or melanoma associated tyrosinase-related protein 2 [TRP-2]) and induction of strong cell-mediated responses in mice and protection against subsequent B16 melanoma tumor challenge. Thus, semi-synthetic sulfated glycolipid archaeosomes represent a new class of adjuvants that will potentially ease manufacturing and scale-up, while retaining immunostimulatory activity.


Comparison of the neuronal differentiation abilities of bone marrow‑derived and adipose tissue‑derived mesenchymal stem cells.
Bone marrow‑derived mesenchymal stem cells (BMSCs) and adipose tissue‑derived mesenchymal stem cells (ADSCs) are able to differentiate into neuron‑like cells when exposed to small molecule compounds, however the specific differences in their neuronal differentiation abilities remain to be fully elucidated. The present study aimed to compare the neuronal differentiation abilities of BMSCs and ADSCs. BMSCs and ADSCs from the same Sprague Dawley rats were isolated and cultured for use. The proliferation capacity was revealed using a cell counting method. Following BMSCs and ADSCs induction by four types of small‑molecular compounds, the expression of various neuronal markers and the secretion of several neurotrophic factors were detected by immunofluorescence, western blotting, reverse transcription‑quantitative polymerase chain reaction and ELISA. It was demonstrated that the ADSCs exhibited an increased proliferation capacity compared with BMSCs, according to cumulative population doubling analyses. Following a 7‑day neuronal induction period, BMSCs and ADSCs exhibited a neuron‑like morphology, and were termed neuronal induced (NI)‑BMSCs and NI‑ADSCs. They expressed neuronal markers including β‑tubulin III, microtubule associated protein 2 and choline acetyltransferase. The number of NI‑BMSCs that positively expressed the neuronal markers was significantly decreased compared with NI‑ADSCs, and the expression and secretion of the neurotrophic factors nerve growth factor and 3'‑nucleotidase in NI‑BMSCs were additionally decreased compared with NI‑ADSCs. The findings of the present study indicated that the neuronal differentiation abilities and neurotrophic factor secretion abilities of ADSCs were increased compared with BMSCs. ADSCs may therefore act as efficient candidates in cell transplantation therapy for diseases and injuries of the nervous system.


Modulators of Sphingosine-1-phosphate Pathway Biology: Recent Advances of Sphingosine-1-phosphate Receptor 1 (S1P1) Agonists and Future Perspectives.
The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the various proteins involved in the interconversion of the ligands, or targeting the receptors that respond to the ligands. The focus of this article is on the most advanced of the sphingosine-related therapeutics, agonists of sphingosine-1-phosphate receptor 1 (S1P1). The diverse structural classes of S1P1 agonists will be discussed and the status of compounds of clinical relevance will be detailed. An examination of how potential safety concerns are being navigated with compounds currently under clinical evaluation is followed by a discussion of the novel methods being explored to identify next-generation S1P1 agonists with improved safety profiles. Finally, therapeutic opportunities for sphingosine-related targets outside of S1P1 are touched upon.


Molecular Dynamic Studies of Interferon and Innate Immunity Resistance in MERS CoV Non-Structural Protein 3.
The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate MERS CoV Non-Structural Protein 3 (NSP3) specific proteins that resist host innate immunity. MERS CoV papain-like protease (Plpro) was more conformationally flexible than Severe Acute Respiratory Syndrome CoV (SARS) CoV Plpro. This flexibility was evident in either the free form or when bound with ubiquitin. There were marked changes in the root-mean-square deviation (RMSD) in the ubiquitin like domain (Ubl) and the fingers subdomain of the catalytic domain of Plpro. An interesting feature is the dynamic change in Ubl, which shows a rigid conformation in the free form of Plpro but is fully flexible upon the binding of ubiquitin. This increased flexibility could be important for the downstream effects of the interaction with other proteins and the inhibition of the innate immunity. Four major residues involved in deubiquitination, L106, P163, R168 and F265, were conserved in all MERS CoVs and differed from other Beta CoVs. These conserved CoV residues were associated with lower deubiquitinating activity and render MERS CoV Plpro with less potent deubiquitinating potential. The number of residues and total interactions with ubiquitin were lower for the MERS CoV Plpro than for the SARS CoV. These factors contribute to the lower deubiquitinating actions of MERS CoV NSP3 and its subsequently lower interaction with the host immune system.


Trial of vaginal delivery for twins - is it safe? a single center experience.
This study assessed our hospital protocol of vaginal delivery for twins and evaluated whether trial of vaginal delivery (unless contraindicated) was as safe as elective cesarean. Risk factors leading to failed trial of labor (TOL) were characterized to improve our ability to advise patients and select cases for TOL. This retrospective, cohort study included women >32 weeks gestation, with twin A in cephalic presentation and no contraindications for vaginal delivery. Controls were women with twin pregnancy and planned cesarean delivery (PCD). Maternal and neonatal morbidity between TOL and PCD were compared. TOL group was subcategorized by vaginal or cesarean delivery to characterize pre-labor risk factors for failed TOL. Of the 411 twins, 215 had TOL and 196 had PCD. Among TOL, 196/215 (91%) delivered vaginally. TOL was more likely to have spontaneous pregnancy, pregnancy complications and tended to deliver earlier. More TOL had postpartum hemorrhage (p < .05), although transfusion rates in each group were similar. Neonatal outcomes between groups did not differ. Induction and gestational age at delivery were risk factors for failed TOL. The results support the contemporary practice of TOL for twins at term when the first is in cephalic presentation with no other contraindications.


The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome.
Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/- 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels < 200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fasting TG values and postprandial TG peak values showed bimodal frequency distributions. Statistical analysis of fasting TG discriminated two groups: a low fasting TG group with normally distributed values < 150 mg/dl (mean +/- SEM: 79.5 +/- 2.7 mg/dl; n = 104) and a high fasting TG group > 150 mg/dl (194.5 +/- 7.2 mg/dl; n = 13). Likewise, two groups could be differentiated according to their maximal postprandial TG response (TG max) to the lipid load: (1) normal responders with TG max < 260 mg/dl (mean +/- SEM: 123 +/- 4.8 mg/dl; n = 96) and (2) high responders with TG max > 260 mg/dl (272.5 +/- 20.5 mg/dl; n = 17). Fasting TG and TG max were highly correlated (r = 0.745; p < 0.0001). However, 9 of 17 (53%) high responders had fasting TG < 150 mg/dl, which means that the prediction of high response is only 47.0% based on fasting TG values. Fasting insulin levels were significantly higher in high responders than in normal responders, whereas they did not differ between the low and high fasting TG group. In conclusion, the bimodal frequency distribution of TG max after a lipid load permitted the differentiation of two groups, normal responders and high responders, with higher fasting insulin levels, which might indicate a link to the metabolic syndrome.


Characteristics and clinical managements of chronic skin ulcers based on traditional chinese medicine.
Chronic skin ulcer (CSU), including diabetic ulcers, venous ulcers, radiation ulcers, and pressure ulcers, remains a great challenge in the clinic. CSU seriously affects the quality of life of patients and requires long-term dedicated care, causing immense socioeconomic costs. CSU can cause the loss of the integrity of large portions of the skin, even leading to morbidity and mortality. Chinese doctors have used traditional Chinese medicine (TCM) for the treatment of CSU for many years and have accumulated much experience in clinical practice by combining systemic regulation and tropical treatment of CSU. Here, we discuss the classification and pathogenic process of CSU and strategies of TCM for the intervention of CSU, according to the theories of TCM. Particularly, we describe the potential intervenient strategies of the "qing-hua-bu" protocol with dynamic and combinational TCM therapies for different syndromes of CSU.


A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.
Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells.


Nefazodone: single versus twice daily dose.
This pilot study involved six men with major depression treated with nefazodone dosed either twice/day or once/day at bedtime. Depression was rated before nefazodone therapy and at 4 weeks by the self-report version of the Hamilton Depression Rating Scale. A simple 10-cm visual analog side effect scale for daytime drowsiness was completed at the latter time. Dosages of nefazodone were at least 400 mg/day. The results suggest that nefazodone given once/day at bedtime may be as effective as the currently accepted twice/day regimen, with less daytime drowsiness.


Harmonic generation in solids with direct fiber laser pumping.
High harmonic generation in solids presents the possibility for bringing attosecond techniques to semiconductors and a simple source for frequency comb spectroscopy in the vacuum ultraviolet. We generate up to the seventh harmonic of a Tm fiber laser by focusing in silicon or zinc oxide. The harmonics are strong and stable, with no indication of material damage. Calculations show the potential for generating nineteenth harmonic photons at 12 eV photons of energy.


The potential impact of using donations after cardiac death on the liver transplantation program and waiting list in the state of Sao Paulo, Brazil.
Liver transplantation was first performed at the University of Sao Paulo School of Medicine in 1968. Since then, the patient waiting list for liver transplantation has increased at a rate of 150 new cases per month. Liver transplantation itself rose 1.84-fold (from 160 to 295) from 1988 to 2004. However, the number of patients on the liver waiting list jumped 2.71-fold (from 553 to 1500). Consequently, the number of deaths on the liver waiting list moved to a higher level, from 321 to 671, increasing 2.09-fold. We have applied a mathematical model to analyze the potential impact of using a donation after cardiac death (DCD) policy on our liver transplantation program and on the waiting list. Five thousand one hundred people died because of accidents and other violent causes in our state in 2004; of these, only 295 were donors of liver grafts that were transplanted. The model assumed that 5% of these grafts would have been DCD. We found a relative reduction of 27% in the size of the liver transplantation waiting list if DCD had been used by assuming that 248 additional liver transplants would have been performed annually. In conclusion, the use of DCD in our transplantation program would reduce the pressure on our liver transplantation waiting list, reducing it by at least 27%. On the basis of this model, the projected number of averted deaths is about 41,487 in the next 20 years.


Influence of different boost techniques on radiation dose to the left anterior descending coronary artery.
The purpose of this study is to compare the dosimetry of electron beam (EB) plans and three-dimensional helical tomotherapy (3DHT) plans for the patients with left-sided breast cancer, who underwent breast conserving surgery. We selected total of 15 patients based on the location of tumor, as following subsite: subareolar, upper outer, upper inner, lower lateral, and lower medial quadrants. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clip plus 1 cm margin. The conformity index (CI), homogeneity index (HI), quality of coverage (QC) and dose-volume parameters for the CTV, and organ at risk (OAR) were calculated. The following treatment techniques were assessed: single conformal EB plans; 3DHT plans with directional block of left anterior descending artery (LAD); and 3DHT plans with complete block of LAD. 3DHT plans, regardless of type of LAD block, showed significantly better CI, HI, and QC for the CTVs, compared with the EB plans. However, 3DHT plans showed increase in the V1Gy at skin, left lung, and left breast. In terms of LAD, 3DHT plans with complete block of LAD showed extremely low dose, while dose increase in other OARs were observed, when compared with other plans. EB plans showed the worst conformity at upper outer quadrants of tumor bed site. 3DHT plans offer more favorable dose distributions to LAD, as well as improved target coverage in comparison with EB plans.


Effect of a magnetic field on intersubband polaritons in a quantum well: strong to weak coupling conversion.
We investigate theoretically the effect of a magnetic field on intersubband polaritons in an asymmetric quantum well placed inside an optical resonator. It is demonstrated that the field-induced diamagnetic shift of electron subbands in the well increases the broadening of optical lines corresponding to intersubband electron transitions. As a consequence, the magnetic field can switch the polariton system from the regime of strong light-matter coupling to the regime of a weak one. This effect paves a way for the effective control of polaritonic devices with a magnetic field.