Polymer particles for the intra-articular delivery of drugs to treat osteoarthritis.
Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, liposomes, and various types of particles have been explored for intra-articular drug delivery. This review will describe progress over the past several years in the development of polymer-based particles for OA treatment, as well as theirin vitro, in vivo, and clinical evaluation. Systems based on biopolymers such as polysaccharides and polypeptides, as well as synthetic polyesters, poly(ester amide)s, thermoresponsive polymers, poly(vinyl alcohol), amphiphilic polymers, and dendrimers will be described. We will discuss the role of particle size, biodegradability, and mechanical properties in the behavior of the particles in the joint, and the challenges to be addressed in future research.


Grafting Poly(Methyl Methacrylate) (PMMA) from Cork via Atom Transfer Radical Polymerization (ATRP) towards Higher Quality of Three-Dimensional (3D) Printed PMMA/Cork-g-PMMA Materials.
Cork is a unique material and its by-products are attracting an ever-growing interest for preparing new materials in an attempt to extend the outstanding properties of cork toward innovative and high value applications. Yet, the miscibility of cork particles with thermoplastic matrices is not easy due to its low density and surface properties. Here, cork is functionalized with poly(methyl methacrylate) (PMMA) via atom transfer radical polymerization (ATRP) to yield cork grafted with PMMA chains particles (cork-g-PMMA). Both the ATRP macroinitiator and the cork-g-PMMA obtained are fully characterized by Fourier-transform infrared spectroscopy (FT-IR), 13C cross-polarized magic-angle spinning solid-state nuclear magnetic resonance (13C CP/MAS solid state NMR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD) and thermogravimetric analyses (TGA). The functionalized cork particles are then blended with commercial PMMA to afford cork-g-PMMA/PMMA. To compare, cork also is mixed with PMMA and the ensuing cork/PMMA sample and its morphology, thermal, and mechanical properties are compared with those of cork-g-PMMA/PMMA and commercial PMMA. The cork surface modification via ATRP of the methyl methacrylate (MMA) yields better dispersion in the matrix. Consequently, a blend with enhanced mechanical performance, higher thermal stability, and a higher melt flow index (MFI) is obtained when compared to the blend prepared using unmodified particles. The similarity of the MFI of cork-g-PMMA/PMMA to that of PMMA suggests good printability. Indeed, a three-dimensional (3D) printed specimen is obtained confirming that grafting using ATRP is a promising route for the preparation of high quality 3D printed products.


Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers.
Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others.


PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.
Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-RAS-V12-induced senescence. Mechanistically, a PAK4 - RELB - C/EBPβ axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Ser151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPβ. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition.


Quantitative Analysis of Hydrogen in High-Hydrogen-Content Material of Magnesium Hydride via Laser-Induced Breakdown Spectroscopy.
An analytical approach that can rapidly determine a wide range of hydrogen concentration in solid-state materials has been recently demanded to contribute to the hydrogen economy. This study presents a method for estimating hydrogen concentrations ranging from 0.2 to 7.6 mass % via laser-induced breakdown spectroscopy (LIBS) in a few seconds, with an improvement in the upper limit of determination (7.6 mass %) by approximately 1.3 times compared with a previous work (5.7 mass %). This extension of the determinable concentration range was achieved by measuring the emission intensity at 656.28 nm from the sample in a helium atmosphere at 3000 Pa under focused laser irradiation and by reducing the water residues in both the sample and gas line of the LIBS system. The as-determined hydrogen concentrations in magnesium hydride (MgH2) samples agreed well with those estimated through inert gas fusion/gas chromatography. The calibration curve for LIBS analysis was acquired by measuring the emission intensity at 656.28 nm of standard Mg/MgH2 mixtures containing various hydrogen concentrations (0, 0.1, 0.2, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 7.6 mass %). Results indicated that the proposed LIBS-based method is applicable to the rapid quantitative analysis of hydrogen in hydrogen-containing material of MgH2.


Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.
Retigabine is a novel anticonvulsant with an unknown mechanism of action. It has recently been reported that retigabine modulates a potassium channel current in nerve growth factor-differentiated PC12 cells (), however, to date the molecular correlate of this current has not been identified. In the present study we have examined the effects of retigabine on recombinant human KCNQ2 and KCNQ3 potassium channels, expressed either alone or in combination in Xenopus oocytes. Application of 10 microM retigabine to oocytes expressing the KCNQ2/3 heteromeric channel shifted both the activation threshold and voltage for half-activation by approximately 20 mV in the hyperpolarizing direction, leading to an increase in current amplitude at test potentials between -80 mV and +20 mV. Retigabine also had a marked effect on KCNQ current kinetics, increasing the rate of channel activation but slowing deactivation at a given test potential. Similar effects of retigabine were observed in oocytes expressing KCNQ2 alone, suggesting that KCNQ2 may be the molecular target of retigabine. Membrane potential recordings in oocytes expressing the KCNQ2/3 heteromeric channel showed that application of retigabine leads to a concentration-dependent hyperpolarization of the oocyte, from a resting potential of -63 mV under control conditions to -85 mV in the presence of 100 microM retigabine (IC(50) = 5.2 microM). In control experiments retigabine had no effect on either resting membrane potential or endogenous oocyte membrane currents. In conclusion, we have shown that retigabine acts as a KCNQ potassium channel opener. Because the heteromeric KCNQ2/3 channel has recently been reported to underlie the M-current, it is likely that M-current modulation can explain the anticonvulsant actions of retigabine in animal models of epilepsy.


Phosphorylation of Mcm2 modulates Mcm2-7 activity and affects the cell's response to DNA damage.
The S-phase kinase, DDK controls DNA replication through phosphorylation of the replicative helicase, Mcm2-7. We show that phosphorylation of Mcm2 at S164 and S170 is not essential for viability. However, the relevance of Mcm2 phosphorylation is demonstrated by the sensitivity of a strain containing alanine at these positions (mcm2(AA)) to methyl methanesulfonate (MMS) and caffeine. Consistent with a role for Mcm2 phosphorylation in response to DNA damage, the mcm2(AA) strain accumulates more RPA foci than wild type. An allele with the phosphomimetic mutations S164E and S170E (mcm2(EE)) suppresses the MMS and caffeine sensitivity caused by deficiencies in DDK function. In vitro, phosphorylation of Mcm2 or Mcm2(EE) reduces the helicase activity of Mcm2-7 while increasing DNA binding. The reduced helicase activity likely results from the increased DNA binding since relaxing DNA binding with salt restores helicase activity. The finding that the ATP site mutant mcm2(K549R) has higher DNA binding and less ATPase than mcm2(EE), but like mcm2(AA) results in drug sensitivity, supports a model whereby a specific range of Mcm2-7 activity is required in response to MMS and caffeine. We propose that phosphorylation of Mcm2 fine-tunes the activity of Mcm2-7, which in turn modulates DNA replication in response to DNA damage.


Arthroscopic stabilization of acute initial anterior shoulder dislocation: the West Point experience.
Arthroscopic stabilization for acute initial shoulder dislocation has been the subject of thorough investigation at West Point over the past decade in an attempt to improve on the natural history of shoulder instability in our young athletic population. From January 1986 to December 1995, 127 patients were treated for acute initial shoulder dislocation at the United States Military Academy. Of the 55 patients treated nonoperatively, 47 (85%) have had recurrence of instability. Seventy-two patients were treated operatively during three separate phases in the evolution of arthroscopic management at our institution. The initial phase (1986 to 1988) of operative treatment included either arthroscopic abrasion or staple repair. The low recurrence rate (2 of 9) was promising. In the operative technique for the second phase (1988 to 1991) transglenoid sutures were used. Of the 21 patients treated in this manner, 18 (86%) had no recurrent instability at last follow-up (average, 32 months). In the third phase (1991 to 1993), patients were treated with a bioabsorbable tack and interscalene anesthesia, and in the sitting position. Thus far, 39 of the latest 42 cadetathletes with acute initial anterior shoulder dislocations have had stabilization with this bioabsorbable cannulated fixation device. The average age was 19.5 years (range, 17 to 23 years). Follow-up averaged 22 months. There were no perioperative complications. Of these 39 patients, 35 (90%) have a stable shoulder and have returned to preinjury performance status. One of 2 patients with recurrent subluxation and 1 of 2 patients with a traumatic redislocation required an open Bankart repair. In young athletes known to have high recurrence rates with nonoperative treatment, acute arthroscopic stabilization appears to be an effective minimally invasive treatment option that favorably alters the natural history of shoulder instability.


Health of the homeless in Dublin: has anything changed in the context of Ireland's economic boom?
In the context of the Irish economic boom we assessed the health, service utilisation and risk behaviour of homeless people in north Dublin city and compared findings with a 1997 study. A census of homeless adults in north Dublin city was conducted in 2005 using an adapted interviewer-administered questionnaire from the 1997 study. A total of 363 (70%) of the target population participated. Compared to 1997 the population was younger (81% versus 70% under 45 years, P < 0.01) with a higher proportion of women (39% versus 29%, P < 0.05) and long-term homeless (66% versus 44%, P < 0.001). Drug misuse superseded alcohol as the main addiction with a doubling of the proportion reporting past or current drug use (64% versus 32%, P < 0.001). The prevalence of comparable physical chronic conditions was largely unchanged while depression (51% versus 35%, P < 0.01) and anxiety (42% versus 32%, P < 0.05) had increased. There were high rates of blood-borne infections, such as HIV (6%), hepatitis B (5%) and hepatitis C (36%) in 2005 and dental problems (53%) all of which can be associated with drug use. Access to free healthcare had not increased. Similar proportions reported not having medical cards (40% versus 45% NS). Homeless people continued to have higher usage of secondary care services than the general population. This study shows a changing disease profile among the homeless population consistent with a growing drug using population. It confirms that the homeless population in Dublin in terms of health remain excluded from the benefits of an economic boom despite a government policy aimed at redressing social inclusion.


Job stress versus success factors for case management.
Job stress is all too common in the case management profession. Recognizing the signs and symptoms of stress and understanding its causes will help the nurse case manager minimize the deleterious effects of "burnout." The following article is an excerpt from the book. Nursing Case Management: A Practical Guide to Success in Managed Care. The author explores eight techniques to reduce stress and improve performance. The information can be used by the individual case manager or by supervisors and coworkers trying to help fellow case managers.


Is cisplatin a human carcinogen?
Traditionally, cisplatin has not been regarded among chemotherapeutic drugs as a carcinogenic risk to humans because it is not a classical alkylating agent. A review of recently published experimental data indicates that cisplatin is mutagenic, clastogenic, capable of inducing cell transformation, able to act as an initiator in classical mouse skin initiation/promotion experiments, and carcinogenic in laboratory animals. Notably, it causes myeloid leukemia in BD IX rats. These observations demonstrate that cisplatin should be considered a potent carcinogen in experimental settings. A review of the literature identified 65 instances of subsequent cancer in patients receiving cisplatin-based chemotherapy for an initial malignancy. The majority of second cancers were acute nonlymphocytic leukemias or myelodysplasia. In only one instance was cisplatin the sole antineoplastic drug given to patients. The routine use of cisplatin in conjunction with other known or suspected human carcinogens makes it impossible to use these anecdotal reports as a basis for assessing cisplatin's carcinogenicity in humans. Two quantitative epidemiologic studies have addressed this question: One suggested that the combination of cisplatin and doxorubicin is leukemogenic in humans, while the other implicated etoposide rather than cisplatin as the leukemogen. Formal epidemiologic studies of appropriate cohorts of cisplatin-treated patients are needed to resolve the question of its carcinogenicity in humans.


A case of primary renal angiosarcoma.
A 78-year old man was diagnosed with a left bleeding renal cyst from CT scan results. Serial CT scans revealed the left kidney mass to be increasing in size and a new lesion in the liver. Renal cell carcinoma with liver metastasis was diagnosed and a radical nephrectomy performed. The initial pathological diagnosis was a benign chronic hematoma. However, the liver mass increased in size and multiplied, while another mass emerged in the twelfth thoracic vertebra with spinal paralysis and was immediately removed. Pathological findings for that specimen showed malignancy of stromal cell origin but low atypia. The renal specimen was re-evaluated using whole cross-section analysis and immunohistochemistry, and diagnosed as a primary renal angiosarcoma. Recombinant interleukin-2 therapy was started immediately; however, the patient died of metastatic disease 13 months after the initial operation. Although contrast imaging depicted the primary lesion as a non-specific hematoma with little focal pooling, and low-grade cytological atypia was shown pathologically, the angiosarcoma was extremely aggressive.


The elephant in the room? Why spatial stigma does not receive the public health attention it deserves.
In the context of health inequalities, spatial stigma refers to the ways that areas experiencing socioeconomic inequalities become negatively portrayed and labelled in public, official and policy discourses. With respect to the body of research on social determinants of health and health inequalities, and attention accorded to this issue in policy or practice, spatial stigma remains significantly under-represented compared with other possible causal factors. We suggest three explanations contributing to this neglect. First, the lack of research into spatial stigma originates from a more limited public health focus on the symbolic meanings of places for health, compared to their physical and social dimensions. Second, lay involvement and evidence of lived experiences of health inequalities continues to be under-represented in public health decision-making. Finally, it is the case that public health organizations may also be contributing to negative area portrayals in their communications of health inequalities. There are growing examples of social action being taken by groups of residents to resist this stigma through the promotion of more positive portrayals of areas and communities. Greater public health attention to this issue as well is likely to result in health gains and aid the development of more effective health inequalities strategies.


Characterization of fiber-generated entangled photon pairs with superconducting single-photon detectors.
We demonstrate the suitability of fiber-generated entangled photon pairs for practical quantum communications in the telecom band by measuring their properties with superconducting single-photon detectors that produce negligible dark counts. The photon pairs are created in approximately 5-ps duration windows at 50 MHz rate while the detectors are operated in ungated free running mode. We obtain a coincidence to accidental-coincidence ratio >80 with raw photon-counting data, i.e., without making any post-measurement corrections. Using a previously demonstrated counter-propagating scheme we also produce polarization-entangled photon pairs at 50-MHz rate, which in coincidence detection directly yield two-photon interference with a fringe visibility >98%.


Artificial Grooming during Early Life could Boost the Activity and Human Affinity of Holstein Female Calves.
Early cow-calf separation management induced various welfare problems for dairy calves. We mimicked the maternal licking by manually brushing right after the Holstein female calves were born and during their first week of life, termed artificial grooming (AG). The behavior of these treated calves (AG, n = 17) was compared with the calves without artificial grooming (Con, n = 16) during daily behavioral observation around evening milk feeding and in the open field test (OFT) and novel human test (NHT). The number of calves ingesting starter on day six was recorded. The AG calves were observed to be more active and perform more oral behavior compared with the Con calves around evening milk feeding. In the OFT and NHT, the AG calves were again more active than the Con calves. Moreover, the AG calves tended to be less cautious and had more human interactions than the Con calves in the NHT. There tended to be a higher percentage of AG calves ingesting starter on day 6. In conclusion, artificial grooming during early life could boost the activity and the human affinity of female calves and it might advance their starter diet ingestion.


Earliest evidence of mammalian social behaviour in the basal Tertiary of Bolivia.
The vast majority of Mesozoic and early Cenozoic metatherian mammals (extinct relatives of modern marsupials) are known only from partial jaws or isolated teeth, which give insight into their probable diets and phylogenetic relationships but little else. The few skulls known are generally crushed, incomplete or both, and associated postcranial material is extremely rare. Here we report the discovery of an exceptionally large number of almost undistorted, nearly complete skulls and skeletons of a stem-metatherian, Pucadelphys andinus, in the early Palaeocene epoch of Tiupampa in Bolivia. These give an unprecedented glimpse into early metatherian morphology, evolutionary relationships and, especially, ecology. The remains of 35 individuals have been collected, with 22 of these represented by nearly complete skulls and associated postcrania. These individuals were probably buried in a single catastrophic event, and so almost certainly belong to the same population. The preservation of multiple adult, sub-adult and juvenile individuals in close proximity (<1 m(2)) is indicative of gregarious social behaviour or at least a high degree of social tolerance and frequent interaction. Such behaviour is unknown in living didelphids, which are highly solitary and have been regarded, perhaps wrongly, as the most generalized living marsupials. The Tiupampan P. andinus population also exhibits strong sexual dimorphism, which, in combination with gregariousness, suggests strong male-male competition and polygyny. Our study shows that social interactions occurred in metatherians as early as the basal Palaeocene and that solitary behaviour may not be plesiomorphic for Metatheria as a whole.


CDK control of membrane-bound organelle homeostasis.
In eukaryotes, the copy number and size of any given organelle compartment remain constant in dividing cells, underlying a tight coordination between cell division and organelle homeostasis. However, in most cases the mechanisms for this coordination remain mysterious. Here we outline a few cases where the cell cycle machinery directly impacts on organelle homeostasis, with emphasis on the control of vacuolar (lysosomal) copy number and size in budding yeast. We also discuss aspects of organelle biology that can profoundly affect certain cell cycle parameters, such as cell size.


A feasibility study of wearable activity monitors for pre-adolescent school-age children.
Understanding physical activity is key in the fight against childhood obesity. The objective of this study was to examine the feasibility of using certain wearable devices to measure physical activity among children. A qualitative study was conducted with 25 children aged 7 to 10 years to assess acceptability and compliance of wearable activity devices in this age group. During March through August 2012, children participated in a 4-week study of 3 accelerometer models and a heart rate monitor. Children were asked to use a different device each week for 7 consecutive days. Children and their parents completed structured interviews after using each device; they also completed a final exit interview. The wrist-worn Polar Active was the device most preferred by children and was associated with the highest level of compliance. Devices that are comfortable to wear, fit properly, have engaging features, and are waterproof increase feasibility and are associated with higher levels of compliance. The wrist-worn device was the most feasible for measuring physical activity among children aged 7 to 10 years. These findings will inform researchers in selecting tools for measuring children's physical activity.


Primary stability in total hip replacement: A biomechanical investigation.
In total hip replacement (THR), it is essential to achieve a primary stability to guarantee good long-term results. A novel locking screw hip (LSH)-stem, anchored to the medial cortex of the proximal femur by 5 monocortical locking screws, was developed to overcome the shortcomings of uncemented press-fit and cemented straight stems while simultaneously achieving primary stability. The aim of this study was to investigate the biomechanical competence of the LSH-stem in comparison to an uncemented press-fit stem. Six pairs of embalmed human cadaveric femora from donors aged 68 to 84 years were assigned to 2 study groups (n = 6) with equal number of right and left bones. The specimens in each group and pair were implanted with either an uncemented press-fit stem or an LSH-stem and tested biomechanically under progressively increasing cyclic axial loading until catastrophic failure. Axial construct stiffness, failure load, and cycles to failure were detected and statistically evaluated at a level of significance P = .05. Although the axial stiffness was comparable for both prosthesis types, the uncemented press-fit stem showed a significant lower stability in terms of failure load and cycles to failure in comparison to the LSH-stem, P = .04. Converting our results to percentage of bodyweight (BW) in an assumed adult patient of 80 kg shows that the LSH-stem achieves a primary stability allowing to carry average loads of up to 507% BW, whereas the uncemented press-fit stem carried average loads of up to 404% BW. We conclude that both stems achieve a primary stability strong enough to carry hip joint loads experienced in the immediate rehabilitation period after THR.


Human hematopoietic stem/progenitor cells generate CD5+ B lymphoid cells in NOD/SCID mice.
The nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenotransplantation model is increasingly utilized to study both human lymphohematopoietic stem/progenitor cells and committed cell types. Human B lymphoid cells develop and proliferate in this model. We found high numbers of CD19+CD5+ B lymphoid cells in the bone marrows and spleens of NOD/SCID mice transplanted with human CD34+ stem/progenitor cells. The CD5+ cells accounted for a particularly large percentage of the B lymphoid cells in the spleens of chimeras analyzed three months after transplantation. CD19+CD5+ cells from all the analyzed chimeras coexpressed HLA-DR, surface IgM, CD20, CD38, CD43, and CD45. However, CD19+CD5+ cells were negative for kappa light chain, CD10, CD11a, CD11b, CD15, CD21, CD22, CD23, CD25, CD34, CD35, CD44, CD62L, CD69, and CD71. Cell surface expression of the lambda light chain, surface IgD, CD9, and CD40 antigens was detected in some but not all chimeras. Thus, the CD19+CD5+ cell population detected in our study has the phenotype of previously described CD5+ B lymphoid cells in humans and other species. The origin and role of the B lymphoid cells which express CD5 cell surface glycoprotein are poorly understood. The malignant cells in B lymphoid chronic lymphocytic leukemia express CD5, and the numbers of CD5+ B lymphoid cells are elevated in several autoimmune conditions. The human-NOD/SCID chimera system may provide an in vivo model to investigate the maturation and development of this cryptic human CD5+ B lymphoid cell subpopulation.


Non-adherent culture method affects the proliferation and apoptosis of mesenchymal stem cells through inhibiting LINC00707 to promote RNF6-mediated QKI ubiquitination.
Exploration of the molecular mechanisms of mesenchymal stem cell (MSC) growth has significant clinical benefits. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in the regulation of the osteogenic differentiation of MSCs. However, the mechanism by which lncRNA affects the proliferation and apoptosis of MSCs is unclear. In this study, sequencing analysis revealed that LINC00707 was significantly decreased in non-adherent human MSCs (non-AC-hMSCs) compared to adherent human MSCs. Moreover, LINC00707 overexpression promoted non-AChMSC proliferation, cell cycle progression from the G0/G1 phase to the S phase and inhibited apoptosis, whereas LINC00707 silencing had the opposite effect. Furthermore, LINC00707 interacted directly with the quaking (QKI) protein and enhanced the E3 ubiquitin-protein ligase ring finger protein 6 (RNF6)-mediated ubiquitination of the QKI protein. Additionally, the overexpression of QKI rescued the promotive effects on proliferation and inhibitory effects on apoptosis in non-AC-hMSCs induced by the ectopic expression of LINC00707. Thus, LINC00707 contributes to the proliferation and apoptosis in non-AChMSCs by regulating the ubiquitination and degradation of the QKI protein.


The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin.
TinIV-protoporphyrin IX (Sn-protoporphyrin) potently inhibits heme degradation to bilirubin in vitro and in vivo, and it completely suppresses neonatal hyperbilirubinemia in experimental animals, including primates. It also reduces plasma bilirubin levels in certain naturally occurring or induced forms of jaundice in animals and man. We have examined in this study the fate of that fraction of heme whose degradation to bile pigment is inhibited in vivo by administration of this heme oxygenase (EC 188.8.131.52) inhibitor. In bile-duct-cannulated rats, infused exogenous heme is rapidly converted to biliary bilirubin; a small amount of the infused heme is excreted into bile as well. Sn-protoporphyrin, administered with the exogenous heme, markedly increased (3- to 4-fold) the amount of heme excreted into bile and greatly diminished biliary output of bilirubin. The increase in biliary heme output exceeded the decrease in bilirubin excretion elicited by the inhibitor metalloporphyrin. In the same experimental model, Sn-protoporphyrin substantially decreased the conversion of heme, derived from heat-damaged erythrocytes, to biliary bilirubin. This decrease in biliary bilirubin output was accounted for entirely by a prompt and marked increase in biliary excretion of unmetabolized heme. The enhanced biliary excretion of unmetabolized heme following administration of Sn-protoporphyrin is a newly defined and biologically important response associated with use of this synthetic heme analogue. The features of the action of this compound in vivo--suppression of formation of the potentially neurotoxic metabolite, bilirubin; enhancement of disposal of the untransformed substrate (heme) of the enzyme that it inhibits; and its own elimination without metabolic alteration--define some of the characteristics of a therapeutically useful chemical.


Differences in Muscle Activation and Kinematics Between Cable-Based and Selectorized Weight Training.
Signorile, JF, Rendos, NK, Heredia Vargas, HH, Alipio, TC, Regis, RC, Eltoukhy, MM, Nargund, RS, and Romero, MA. Differences in muscle activation and kinematics between cable-based and selectorized weight training. J Strength Cond Res 31(2): 313-322, 2017-Cable resistance training machines are showing resurgent popularity and allow greater number of degrees of freedom than typical selectorized equipment. Given that specific kinetic chains are used during distinct activities of daily living (ADL), cable machines may provide more effective interventions for some ADL, whereas others may be best addressed using selectorized equipment. This study examined differences in activity levels (root mean square of the EMG [rmsEMG]) of 6 major muscles (pectoralis major, PM; anterior deltoid, AD; biceps brachii, BB; rectus abdominis, RA; external obliques, EO; and triceps brachii, TB) and kinematics of multiple joints between a cable and standard selectorized machines during the biceps curl, the chest press, and the overhead press performed at 1.5 seconds per contractile stage. Fifteen individuals (9 men, 6 women; mean age ± SD, 24.33 ± 4.88 years) participated. Machine order was randomized. Significant differences favoring cable training were seen for PM and AD during biceps curl; BB, AD, and EO for chest press; and BB and EO during overhead press (p ≤ 0.05). Greater starting and ending angles were seen for the elbow and shoulder joints during selectorized biceps curl, whereas hip and knee starting and ending angles were greater for cable machine during chest and overhead presses (p < 0.0001). Greater range of motion (ROM) favoring the cable machine was also evident (p < 0.0001). These results indicate that utilization patterns of selected muscles, joint angles, and ROMs can be varied because of machine application even when similar exercises are used, and therefore, these machines can be used selectively in training programs requiring specific motor or biomechanical patterns.


An insertion mutation in the adenovirus type 12 early region 1A 13S mRNA unique region.
An adenovirus type 12 mutant, in203S, was constructed to contain an insertion of two amino acids in the early region 1A (E1A) 13S mRNA-coding region and in the E1A 12S mRNA intron. in203S could not grow in HeLa and KB cells. Virus DNA replication was scarcely detected at a low multiplicity of infection, but was detected at a high multiplicity of infection. The transcription of early genes other than E1A was not detected at 13 h after infection, but became detectable after longer incubation. The transcription of the E1A gene was also reduced to about one-fifth of the wild-type level. The mutant induced fewer foci of smaller sizes than the wild type in rat 3Y1 and secondary rat kidney cells. The induction of cellular DNA synthesis was reduced in rat 3Y1 cells infected with in203S as compared with that in wild type-infected cells. These results show that the E1A 13S mRNA-derived polypeptide of adenovirus type 12 is required for activation of early genes, cell transformation, and induction of cellular DNA synthesis.


Efficacy and Safety of Different Types of Intraocular Pressure-Lowering Surgeries in Patients with Primary Angle Closure (PAC) or PAC Glaucoma: Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.
To compare the intraocular pressure (IOP)-lowering effect of different types of surgery available in the literature using a network meta-analysis (NMA) based on a systematic review. PubMed and the Cochrane database were searched. Randomized clinical trials involving surgical interventions for high IOP for PAC (primary angle closure) or PACG (primary angle closure glaucoma) were included. Descriptive statistics and outcomes were extracted. Bayesian NMA was performed to compare the IOP-lowering effect and the change in the number of antiglaucoma drugs required between baseline and endpoint, as well as success rates. This NMA included 21 articles with 1237 eyes with PAC or PACG. Interventions were characterised as phacoemulsification (phaco), trabeculectomy, goniosynechialysis (GSL) with viscoelastic or blunt device, goniosurgery (GS) (trabeculotomy or goniotomy), micro-bypass stent (Istent®), endocyclophotocoagulation (ECPL) or various combinations of these procedures. Phaco+GSL [-1.73 (95%CrI: -3.53 to -0.13)] and phaco+GSL+GS [-3.92 (95%CrI: -6.91 to -1.31)] provided better IOP lowering effects than phaco alone. Phaco+trabeculectomy [-3.11 (95%CrI: -5.82 to -0.44)] was inferior to phaco+GSL+GS. Phaco+trabeculectomy [-0.45 (95%CrI: -0.81 to -0.13)] provided a better outcome in terms of reducing the need for antiglaucoma drug compared to phaco alone. There were no differences between the other surgeries in terms of reduction of antiglaucoma drug number and IOP lowering effect. Success rates were similar for all surgical procedures. Phaco+GSL+GS showed the most promising results for lowering IOP. Phaco+trabeculectomy resulted in a significant reduction in the number of antiglaucoma drugs compared to phaco alone.


A study of the age-related effects of lactational atrazine exposure.
A growing number of reports have demonstrated that the widely-used herbicide Atrazine (ATR) can cause injury to dopamine (DA) neurons, but the exact mechanism remains unclear. In this study, we examined the effects of lactational ATR exposure in Sprague-Dawley rats on dopaminergic neuron health later in life. Compared with control rats, rats exposed to ATR during a critical period of neural development showed decreased striatal DA content and increased rates of DA turnover. The expression of Monoamine oxidase (MAO), which is associated with DA degradation, was up-regulated, and the expression of Vesicular Monoamine Transporter 2 (VMAT2), which is associated with DA transport, was down-regulated. The expression of transcription factor Nuclear Receptor Related Factor 1 (Nurr1), which is associated with DA neuron development, was down-regulated. Increased age (6-12 months old) increased the statistical significance of the differences of the above indicators in the ATR-treated rats compared to the control rats (P<0.05). Taken together, our results indicate that ATR exposure during the critical neural development period causes a down-regulation of Nurr1, which in turn affects Nurr1 target genes, including MAO, VMAT2 and DAT, which are involved in DA degradation and transport. Reduced expression of these genes impairs the capacity for vesicular storage or reuptake of DA, causing decreased levels of striatal DA, which can ultimately lead to DA neuron injury. DA neuron injuries become more severe over time, which suggests that aging can synergistically promote the ATR-associated DA neuron injuries.


Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis.
The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236-10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793-804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers.


Does women's age matter in the SDGs era: coverage of demand for family planning satisfied with modern methods and institutional delivery in 91 low- and middle-income countries.
The Sustainable Development Goals (SDGs) include specific targets for family planning (SDG 3.7) and birth attendance (SDG 3.1.2), and require analyses disaggregated by age and other dimensions of inequality (SDG 17.18). We aimed to describe coverage with demand for family planning satisfied with modern methods (DFPSm) and institutional delivery in low- and middle-income countries across the reproductive age spectrum. We attempted to identify a typology of patterns of coverage by age and compare their distribution according to geographic regions, World Bank income groups and intervention coverage levels. We used Demographic and Health Survey and Multiple Indicator Cluster Surveys. For DFPSm, we considered the woman's age at the time of the survey, whereas for institutional delivery we considered the woman's age at birth of the child. Both age variables were categorized into seven groups of 5 year-intervals, 15-19 up to 45-49. Five distinct patterns were identified: (a) increasing coverage with age; (b) similar coverage in all age groups; (c) U-shaped; (d) inverse U-shaped; and (e) declining coverage with age. The frequency of the five patterns was examined according to UNICEF regions, World Bank income groups, and coverage at national level of the given indicator. We analyzed 91 countries. For DFPSm, the most frequent age patterns were inverse U-shaped (53%, 47 countries) and increasing coverage with age (41%, 36 countries). Inverse-U shaped patterns for DFPSm was the commonest pattern among lower-middle income countries, while low- and upper middle-income countries showed a more balanced distribution between increasing with age and U-shaped patterns. In the first and second tertiles of national coverage of DFPSm, inverse U-shaped was observed in more than half of countries. For institutional delivery, declining coverage with age was the prevailing pattern (44%, 39 countries), followed by similar coverage across age groups (39%, 35 countries). Most (79%) upper-middle income countries showed no variation by age group while most low-income countries showed declining coverage with age (71%). Large inequalities in DFPSm and institutional delivery were identified by age, varying from one intervention to the other. Policy and programmatic approaches must be tailored to national patterns, and in most cases older women and adolescents will require special attention due to lower coverage and because they are at higher risk for maternal mortality and other poor obstetrical outcomes.


Screening for biliary atresia by infant stool color card in Taiwan.
We aimed to detect biliary atresia (BA) in early infancy to prevent additional liver damage because of the delay of referral and surgical treatment and to investigate the incidence rate of BA in Taiwan. A pilot study to screen the stool color in infants for the early diagnosis of BA was undertaken from March 2002 to December 2003. We had designed an "infant stool color card" with 7 numbers of different color pictures and attached it to the child health booklet. Parents were then asked to observe their infant's stool color by using this card. The medical staff would check the number that the parents chose according to their infant's stool color at 1 month of age during the health checkup and then send the card back to the stool color card registry center. The average return rate was approximately 65.2% (78,184 infants). A total of 29 infants were diagnosed as having BA, and 26 were screened out by stool color card before 60 days of age. The sensitivity, specificity, and positive predictive value were 89.7%, 99.9%, and 28.6%, respectively. Seventeen (58.6%) infants with BA received a Kasai operation within 60-day age period. The estimated incidence of BA in screened newborns was 3.7 of 10,000. The stool color card was a simple, efficient, and applicable mass screening method for early diagnosis and management of BA. The program can also help in estimating the incidence and creating a registry of these patients.


Bilateral hydrocele. Uncommon clinical presentation of primary testicular lymphoma in the elderly.
Primary testicular lymphoma (PLT) represents 5% of testis tumors, the incidence increases in patients older than 60 years of age. Bilateral hydrocele is an unusual clinical presentation. Relapse in the central nervous system and in the contralateral testis is often observed. The US shows hypoechoic nodular lesions with a complete structural involvement of didymus and hypervascularization at Color Doppler. Orchiectomy should be performed in all cases as it is indispensable for the histopathological diagnosis and to characterize the immunophenotypic features. The most common histotype is diffuse large-B cell lymphoma. Combined biological approach and chemotherapy with rituximab and doxorubicin has radically changed the prognosis of disease. The authors report two patients of 81 and 82 years-old who referred for evaluation of massive bilateral hydrocele causing severe limitation of deambulation. Negative cytological findings for neoplastic cells in the scrotal effusion made difficult the differential diagnosis between inflammatory and malignant disease. Histopathologic findings made a diagnosis of high grade diffuse large B-cell NHL, respectively stage IV-E and stage III-E. The 82 years old patient was treated with 6 chemotherapy cycles of rituximab, cyclophosphamide, vincristine, prednisone. The exitus was dued to the umbilical hernia complications. In the 81 years old patient, cognitive deficit and severe impairment of general conditions constituted an absolute contraindication to polychemotherapy treatment. Rapid tumor progression led the patient to exitus 2 months after diagnosis. In both patients the delayed diagnosis of PLT was probably due to the reduction of welfare protection in the elderly with adverse social conditions.


[Ligamentous connections of the spinal processes].
In the cervical region the fibres of the interspinous and nuchal ligaments pass in an anterocranial direction: they act against diminishing of the cervical lordosis. In the thoracic region, longitudinal bundles of fibres connect the tops of the spinous processes; they act against an augmentation of the thoracal kyphosis. Between thoracal kyphosis and lumbal lordosis there is no exact course of the fibres of the interspinous ligts. ("thorakolumbaler Ubergangsbereich"). In the lumbar spine the fibres of the interspinous ligts., being very strong, pass in a posterocranial direction. They have the function of limitation the range of flexion ventrally and of limiting backwards-shifting of the cranial vertebra in dorsal-flexion. In the lumbosacral segment additional fibres, arising from the top of the 5th lumbar spinous process, pass in a posterocaudal direction and interlace with the thoracolumbar fascia, whose fibres form--below the 4th lumbar vertebra--a scissor-latticed structure. The supraspinous ligt. lies superficially to the thoracolumbar fascia. Its fibres pass several spinous processes. It ends caudally at the 4th lumbar spinous process.


Purification of a [3H]dihydrotetrabenazine-binding protein from bovine adrenal medulla.
A high affinity binding site for [3H]dihydrotetrabenazine is thought to be present on the monoamine transport protein from chromaffin granules. We describe a procedure for purification of this binding activity from frozen bovine adrenal tissue, and we partially characterize the purified preparation. Binding activity solubilized with sodium cholate and soybean lecithin was fractionated on wheat germ lectin-Sepharose, phenyl-Sepharose, Mono Q, and hydroxylapatite. Denaturing electrophoresis of the purified binding activity, followed by silver staining, revealed a single broad band centered at an apparent molecular weight of 85,000. This preparation bound [3H]dihydrotetrabenazine with an apparent dissociation constant of 2.7 nM and had a site density of 10 nmol/mg. Treatment of the purified protein with neuraminidase reduced the apparent molecular weight by 9000, indicating the presence of terminal sialic acids on the oligosaccharide portion of this molecule.


Immunotoxin-treated rhesus monkeys: a model for renal allograft chronic rejection.
Unlike acute and hyperacute rejection, chronic rejection (CR) still constitutes a poorly understood process. The onset is insidious, occurs in a period of months to years and, because the pathophysiology is not well understood, is untreatable. A reliable large-animal model for renal allograft CR is needed and has not been reported in the literature yet. CR biopsy changes were studied in major histocompatibility complex-mismatched renal allografts performed in nine rhesus monkeys that received CD3 T-lymphocyte depletion therapy with immunotoxin on the day of the transplantation (n=7) or 7 days before transplant (n=2). Mean graft survival time was 613.77 days. Biopsy changes of CR were identified as soon as 84 days after transplant (mean, 336 days; range, 84-896 days). Most of the experimental animals had severe interstitial fibrosis, tubular atrophy, chronic transplant glomerulopathy, and chronic vascular rejection changes at the time of necropsy. A significant positive correlation between the severity of CR and the degree of CD68+ macrophage infiltrate of renal parenchyma and the degree of anemia and serum creatinine level elevations were also observed. Our findings are similar to those seen in human renal chronic allograft nephropathy, but in contrast, our model excludes all the nonimmune factors associated with chronic allograft nephropathy, including donor disease, injury from prolonged preservation, drug toxicity, and underlying recipient disease. Immunotoxin-treated rhesus monkeys emerge as an outstanding animal model for assisting us in understanding the pathophysiology of CR.


Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.


Why, when and how to propose noninvasive ventilation in cystic fibrosis?
Cystic fibrosis (CF) lung disease is characterized by progressive airflow obstruction, due to mucus plugging and inflammation within the bronchial walls, and destruction of the lung parenchyma secondary to bronchiectasis. These alterations result in an increase of the work of breathing, leading to alveolar hypoventilation predominantly during sleep, exercise and acute respiratory exacerbations. Noninvasive positive pressure ventilation (NPPV) has been shown to unload the respiratory muscles in patients with CF, which increases alveolar ventilation and improves gas exchange. NPPV has been shown to reduce oxygen desaturation during sleep, exercise and chest physiotherapy and may facilitate the recovery of a severe hypercapnic respiratory exacerbation. Several ventilatory modes may be used in cystic fibrosis patients but the most physiological mode is pressure support. However, validated criteria to start NPPV as well as data on long term outcome, notably in terms of improved survival and quality of life, are lacking and should be assessed in the future.


Evaluation of hyaluronan and calcifications in stenotic and regurgitant aortic valves.
Hyaluronan (HA) is a major component of the interstitium and has been observed in normal heart valves. The function of HA in heart valves is unknown but contribution to biomechanical function has been proposed. The purpose of this investigation was to study the distribution of HA in relation to calcifications in diseased human aortic valves. Human aortic valves were collected at aortic valve replacement, of whom nine patients had regurgitation and 13 stenotic disease. The valves were decalcified and stained for the visualisation of HA. The specimens were macroscopically evaluated for magnitude of calcification using image analysis. The microscopic amount and distribution of HA and calcifications were semiquantitatively evaluated using histochemistry. The overall HA staining showed an inverse relationship against the magnitude of observed valve calcifications (p<0.001) and type of disease (p=0.014). Multiple-group comparison revealed regionally reduced HA staining in diffuse and heavy calcified regions inside the valve (both p<0.001) compared with normal-structured parts of the valve. HA was concentrated on the ventricular side of the valve (p=0.002). The content of HA was reduced in calcified aortic valves and had a heterogeneous distribution, potentially contributing to poor valve function. HA may also be involved in the pathophysiological process in degenerative aortic stenosis.


Detection of CTX-M-type beta-lactamase genes in fecal Escherichia coli isolates from healthy children in Bolivia and Peru.
A survey was carried out from August to November 2002 to evaluate the antimicrobial susceptibilities of fecal Escherichia coli isolates from 3,208 healthy children from four different urban areas of Latin America, two in Bolivia (Camiri and Villa Montes) and two in Peru (Yurimaguas and Moyobamba). Ceftriaxone-resistant E. coli isolates were detected in four children, one from each of the areas sampled. The isolates exhibited a multidrug-resistant phenotype, including resistance to oxyimino-cephalosporins and aztreonam, and the MICs of ceftazidime for the isolates were lower than those of cefotaxime. By PCR and sequencing, the bla(CTX-M-2) determinant was detected in three isolates and the bla(CTX-M-15) determinant was detected in one isolate (from Peru). The CTX-M-2-producing isolates belonged to three different phylogenetic groups (groups A, B2, and D), while the CTX-M-15-producing isolate belonged to phylogenetic group D. The bla(CTX-M-2) determinants were transferable to E. coli by conjugation, while conjugative transfer of the bla(CTX-M-15) determinant was not detectable. Plasmids harboring the bla(CTX-M-2) determinant exhibited similar restriction profiles, and in all of them the gene was located on a 2.2-kb PstI fragment, suggesting a genetic environment similar to that present in In35 and InS21. The findings of the present study confirm the widespread distribution of CTX-M-type beta-lactamases and underscore the role that commensal E. coli isolates could play as a potential reservoir of these clinically relevant resistance determinants. This is the first report of CTX-M-type enzymes in Bolivia and Peru and also the first report of the detection of CTX-M-15 in Latin America.


Determination of polychlorinated biphenyls in marine fish obtained from tsunami-stricken areas of Japan.
We determined the polychlorinated biphenyl (PCB) congeners in 101 marine fish obtained from tsunami-stricken areas following the Great East Japan Earthquake in 2011. In particular, to determine the degree of PCB contamination in the fish, we investigated the concentration of total PCB (∑PCB) and the proportions of 209 individual PCB congeners by high-resolution gas chromatography/high-resolution mass spectrometry. The ∑PCB concentration was 1.7-33 ng/g in fat greenling (n = 29), 0.44-25 ng/g in flounder (n = 36), and 1.6-86 ng/g in mackerel (n = 36), all values being much lower than the provisional regulatory limit in Japan. In the congener analysis, tetra-, penta-, hexa-, and hepta-chlorinated PCB congeners dominated in all samples (comprising over 86% of the ∑PCB). The proportions of the chlorinated PCB congeners were similar to the contamination patterns derived from Kanechlor in the environment, implying that the marine fish were not contaminated with fresh PCBs.


Viral infection in bone marrow transplants: is JC virus involved?
Hemorrhagic cystitis is characterized by hematuria due to inflammation of the bladder. In bone marrow transplants, this disease is linked to the infection by human polyomavirus BK, whereas the role of the human polyomavirus JC is unclear. The transcriptional control regions of both viruses contain important cellular transcription factor binding sites that undergo rearrangement process generating suitable variants that could be more active for viral replication and for the onset of hemorrhagic cystitis. In this study urine obtained from seven patients with bone marrow transplant were examined. Polyomavirus genomes were quantified by PCR and viral loads were compared. The transcriptional regions of both viruses were amplified and sequenced to determine the presence of variants. Subtypes of polyomaviruses were determined by amplification and sequencing of the viral protein 1 region. The results showed that four of seven patients were positive for BK DNA, two of seven patients had BK and JC DNA and one of seven had JC DNA. Positive samples were amplified and sequenced successively for transcriptional regions. The viral archetype was always found in both viruses. Finally, typing showed that BK virus subtype I infected patients with BK, whereas JC virus genotype IA and genotype 1B were found in patients infected with JC. The data suggest that new and different approaches are required to improve the morbidity and mortality caused by polyoma-associated hemorrhagic cystitis, since it known that BK virus is involved in the onset of hemorrhagic cystitis, whereas the role of JC virus should be investigated further.


Emerging Role of Histone Acetyltransferase in Stem Cells and Cancer.
Protein acetylation is one of the most important posttranslational modifications catalyzed by acetyltransferases and deacetylases, through the addition and removal of acetyl groups to lysine residues. Lysine acetylation can affect protein-nucleic acid or protein-protein interactions and protein localization, transport, stability, and activity. It regulates the function of a large variety of proteins, including histones, oncoproteins, tumor suppressors, and transcription factors, thus representing a crucial regulator of several biological processes with particular prominent roles in transcription and metabolism. Thus, it is unsurprising that alteration of protein acetylation is involved in human disease, including metabolic disorders and cancers. In this context, different hematological and solid tumors are characterized by deregulation of the protein acetylation pattern as a result of genetic or epigenetic changes. The imbalance between acetylation and deacetylation of histone or nonhistone proteins is also involved in the modulation of the self-renewal and differentiation ability of stem cells, including cancer stem cells. Here, we summarize a combination of in vitro and in vivo studies, undertaken on a set of acetyltransferases, and discuss the physiological and pathological roles of this class of enzymes. We also review the available data on the involvement of acetyltransferases in the regulation of stem cell renewal and differentiation in both normal and cancer cell population.


Next-generation transcriptome assembly and analysis: Impact of ploidy.
Whole genome duplications (WGD) occur widely in plants, but the effects of these events impact all branches of life. WGD events have major evolutionary impacts, often leading to major structural changes within the chromosomes and massive changes in gene expression that facilitate rapid speciation and gene diversification. Even for species that currently have diploid genomes, the impact of ancestral duplication events is still present in the genomes, especially in the context of highly similar gene families that are retained from WGD. However, the impact of these ploidies on various bioinformatics workflows has not been studied well. In this review, we overview biological significance of polyploidy in different organisms. We describe the impact of having polyploid transcriptomes on bioinformatics analyses, especially focusing on transcriptome assembly and transcript quantification. We discuss the benefits of using simulated benchmarking data when we examine the performance of various methods. We also present an example strategy to generate simulated allopolyploid transcriptomes and RNAseq datasets and how these benchmark datasets can be used to assess the performance of transcript assembly and quantification methods. Our benchmarking study shows that all transcriptome assembly methods are affected by having polyploid genomes. Quantification accuracy is also impacted by polyploidy depending on the method. These simulated datasets can be adapted for testing, such as, read mapping, variant calling, and differential expression using biologically realistic conditions.


The first study on the impact of osmolytes in whole cells of high temperature-adapted microorganisms.
The hyperthermophilic piezophile, Thermococcus barophilus displays a strong stress response characterized by the accumulation of the organic osmolyte, mannosylglycerate during growth under sub-optimal pressure conditions (0.1 MPa). Taking advantage of this known effect, the impact of osmolytes in piezophiles in an otherwise identical cellular context was investigated, by comparing T. barophilus cells grown under low or optimal pressures (40 MPa). Using neutron scattering techniques, we studied the molecular dynamics of live cells of T. barophilus at different pressures and temperatures. We show that in the presence of osmolytes, cells present a higher diffusion coefficient of hydration water and an increase of bulk water motions at a high temperature. In the absence of osmolytes, the T. barophilus cellular dynamics is more responsive to high temperature and high hydrostatic pressure. These results therefore give clear evidence for a protecting effect of osmolytes on proteins.


Mycobacterium tuberculosis Rv2536 protein implicated in specific binding to human cell lines.
The gene encoding the Mycobacterium tuberculosis Rv2536 protein is present in the Mycobacterium tuberculosis complex (as assayed by PCR) and transcribed (as determined by RT-PCR) in M. tuberculosis H37Rv, M. tuberculosis H37Ra, M. bovis BCG, and M. africanum strains. Rabbits immunized with synthetic polymer peptides from this protein produced antibodies specifically recognizing a 25-kDa band in mycobacterial sonicate. U937 and A549 cells were used in binding assays involving 20-amino-acid-long synthetic peptides covering the whole Rv2536 protein sequence. Peptide 11207 (161DVFSAVRADDSPTGEMQVAQY180) presented high specific binding to both types of cells; the binding was saturable and presented nanomolar affinity constants. Cross-linking assays revealed that this peptide specifically binds to 50 kDa U937 cell membrane and 45 kDa A549 cell membrane proteins.


Study of ketone body kinetics in children by a combined perfusion of 13C and 2H3 tracers.
Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of [3-13C]acetoacetate ([13C]AcAc) and D-(-)-beta-[4,4,4-2H3]hydroxybutyrate (beta-[2H3]OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the "single-pool" (combined enrichments) or the "two-accessible pools" models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when [13C]AcAc was the tracer, whereas the use of beta-[2H3]OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of [13C]AcAc and beta-[2H3]OHB is a convenient way to give insight into individual ketone body kinetics.


Should UNOS Status 2 patients undergo transplantation?
With recent improvements in medical and device therapy, the benefit of cardiac transplantation for UNOS Status 2 patients has been questioned. No randomized trial has been performed to compare transplantation versus contemporary medical therapy. Between January 1996 and December 2003, 203 patients were listed at our institution for heart transplantation as UNOS Status 2. We performed a retrospective review to determine outcomes in these patients. Demographics of this cohort revealed a mean age of 52 years, female sex in 28%, and ischemic etiology in 47%. Eighty-one patients (40%) had an implantable cardiac defibrillator. A total of 64 patients (32%) had to be upgraded in their UNOS status, with 9 requiring a left ventricular assist device. Of the entire group, 95 (47%) underwent transplantation at a mean time of 303 days, 45 (22%) died while waiting at a mean time of 397 days, and 24 (12%) were removed from the waiting list due to deterioration in medical condition such that transplantation was no longer an option. The remaining patients continue to wait or have been removed from consideration due to improved condition. Survival at 1- and 3-years postlisting was 94% and 87% for patients who received transplants compared to 81% and 57% for patients who did not receive transplants (P < .01). A significant number of patients listed as Status 2 are upgraded in UNOS status or die while on the waiting list. Early and midterm survival is significantly better with transplantation. Identification of variables associated with deterioration may allow for better risk stratification in the future. At this point, transplantation offers the best outcome.


The influence of classical dance training on preferred supporting leg and whole body turning bias.
A rightward turning bias has been more frequently noted during adult classical dance practice than during spontaneous rotations. Training could play a role in inducing a preferred direction. We observed the preferred direction for executing four spontaneous whole-body full turns (pirouettes), with eyes open or closed, in pre-pubertal untrained girls and classical dance students. Of untrained girls, 58% showed a leftward turning bias (LTB) and 42% a rightward turning bias (RTB), independently of vision, lateral preferences, and supporting leg. Only one dancer showed a consistent LTB while the majority showed a RTB, with a tendency to use the left leg to turn towards the right. These results suggest that the role of the vestibular and visual systems is minimal for untrained girls, and suggest a training influence for dancers. The dance students' choice of a supporting leg for turning may exploit some biomechanical properties facilitating the pirouette.


Behaviour-emotional characteristics of primary-school children rated as having language problems.
Primary-school teachers are expected to detect problems related to language function, but the teachers' evaluations may be heavily influenced by gender and classroom behaviour. To investigate the relationship between language problems (LPs) and behaviour-emotional problems as rated by primary-school teachers. All participants participated in a population-based study, the Bergen Child Study (BCS). Teachers of 9,072 children and parents of 6,234 children completed forms containing questions pertaining to language function and the strengths and difficulties questionnaire (SDQ) to screen for behaviour-emotional problems. LP was defined as a score above the 95th percentile on the sum score of five language items. Children achieving a total SDQ score above the 90th percentile were defined as high scorers, indicating a high risk for behavioural-emotional problems. Based on teacher reports, 540 children were defined as having LP, more boys (N=366) than girls. Children defined as having LP were reported to have significantly higher scores on all SDQ subscales, and a higher total difficulty score than children without language problems (NLP). More LP boys than LP girls were defined as high scorers on the SDQ, with the highest effect size on the hyperactivity-inattention subscore. The agreement between teachers and parents was moderate to low, with the highest consensus of behaviour-emotional problems in children with LP. Primary-school children defined as having LP according to their teachers are frequently characterized by behavioural-emotional problems. Further assessment is warranted for primary-school children defined as having LP by their teachers.


Multiple procedures and staging in the massive weight loss population.
Unlike traditional plastic surgery patients who present with a specific anatomical complaint, massive weight loss patients often have multiple regions of concern. No single procedure can address the whole-body deformities associated with massive weight loss. The authors sought to quantify their clinical experience to provide evidence-based analysis of procedural combination in body contouring. Patients were enrolled in an institutional review board-approved prospective clinical database over a 5-year period. Procedure categories included breast, medial thigh lift, buttock and lateral thigh lift, upper back lift, brachioplasty, and abdomen. Analysis of variance was used to analyze differences between procedure combinations. Six hundred nine massive weight loss patients underwent 661 cases involving 1070 procedures. Length of hospital stay increased with the number of procedures performed (p < 0.001). Second-stage cases (n = 60) had similar complication rates and length of hospital stay. Seroma and dehiscence were strongly correlated with the number of procedures (p < 0.001), as were tissue necrosis and infection (p = 0.02), whereas hematoma was unrelated (p = 0.25). Major complications did not increase in multiple-procedure cases. In a large experience at a high-volume center, concomitant procedures were performed safely in carefully selected patients with low major complication rates. Although aggregate minor complication rates were predictably higher than in single-procedure cases, there was no significant increase on a per-procedure basis. Multiple procedures can be combined safely in the body contouring patient, with surgical staging offering a viable alternative for patients who are unable to undergo combined procedures.


[Genetic analysis of the gastric precancer-cancer system. I. Research in different populations].
Heredity predisposition was analysed in cancer and precancer stomach diseases in distinct populations. Some phenotypic and genetic characters of the stomach "precancer--cancer" system were studied. Similarity in the degree of stomach cancer inheritance, its segregation frequency and recurrent risk was revealed for populations. However, the degree of correlation between cancer and precancer stomach disease was different in distinct populations, this being more pronounced in "cancer--gastric ulcer" system.


One year psychosocial outcome in head injury.
Psychosocial outcome at one year post-injury was examined prospectively in 466 hospitalized head-injured subjects, 124 trauma controls, and 88 friend controls. The results indicate that head injury is associated with persistent psychosocial limitations. However, the presence and extent of limitations are related to the demographics of the population injured, to other system injuries sustained in the same accident, and particularly to the severity of the head injury. More severe head injuries are associated with limitations implying greater dependence on others including poorer Glasgow Outcome Scale (GOS) ratings, dependent living, unemployment, low income, and reliance on family and social subsidy systems. Head injury severity is more closely related to more objective indices of psychosocial outcome (e.g., employment) than to self-perceived psychosocial limitations, such as measured by the Sickness Impact Profile (SIP).


Integrating Symptoms Into the Middle-Range Theory of Self-Care of Chronic Illness.
The Middle-Range Theory of Self-Care of Chronic Illness has been used widely since it was first published in 2012. With the goal of theoretical refinement in mind, we evaluated the theory to identify areas where the theory lacked clarity and could be improved. The concept of self-care monitoring was determined to be underdeveloped. We do not yet know how the process of symptom monitoring influences the symptom appraisal process. Also, the manner in which self-care monitoring and self-care management are associated was thought to need refinement. As both of these issues relate to symptoms, we decided to enrich the Middle-Range Theory with knowledge from theories about symptoms. Here, we propose a revision to the Middle-Range Theory of Self-Care of Chronic Illness where symptoms are clearly integrated with the self-care behaviors of self-care maintenance, monitoring, and management.


Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury.
In this paper the stimuli for and pattern of Schwann cell proliferation are defined under various experimental conditions. We used a tissue culture system in which fetal rat dorsal root ganglia, treated to eliminate contaminating fibroblasts (Wood, P., 1976, Brain Res. 115:361--375), appear to recapitulate many aspects of the developing peripheral nervous system. We observed that: (a) proliferation of Schwann cells on neurites is initially rapid, but, as each neurite becomes fully ensheathed, division slows considerably and is confined to the periphery of the outgrowth; (b) during the period of rapid proliferation, excision of the ganglion causes a rapid decay in the number of dividing cells; (c) excision of the ganglion from more established cultures in which there was little ongoing proliferation resulted in a small increase in labeling at the site of excision for all Schwann cells and a substantial increase in labeling for myelin-related cells with a peak labeling period at 4 d; (d) direct mechanical injury during Wallerian degeneration is mitogenic for Schwann cells; (e) a variety of potential mitogens failed to stimulate Schwann cell proliferation, and (f) replated cells have a slightly higher level of proliferation and show a small and variable response to the addition of cAMP.


Valuing lives and allocating resources: a defense of the modified youngest first principle of scarce resource distribution.
In this paper, I argue that the 'modified youngest first' principle provides a morally appropriate criterion for making decisions regarding the distribution of scarce medical resources, and that it is morally preferable to the simple 'youngest first' principle. Based on the complete lives system's goal of maximizing complete lives rather than individual life episodes, I argue that essential to the value we see in complete lives is the first person value attributed by the experiencer of that life. For a life to be 'complete' or 'incomplete,' the subject of that life must be able to understand the concept of a complete life, to have started goals and projects, and to know what it would be for that life to be complete. As the very young are not able to do this, it can reasonably be said that their characteristically human lives have not yet begun, giving those accepting a complete lives approach good reason to accept the modified youngest first principle over a simple 'youngest first' approach.


Hydroxyapatite cement to repair skull base defects: radiologic appearance.
To describe the radiologic appearance of hydroxyapatite cement (HAC), which, when mixed with liquid, forms a paste that can be contoured to osseous defects and, over time, becomes "osseointegrated" (native bone grows into the pores of the HAC and forms a strong chemical bond with the substance). Between March 1992 and June 1993, 24 adults (16 men, eight women) underwent skull base surgery that included reconstruction or closure with HAC. Fourteen patients had HAC placed in the paranasal sinuses or facial bones, and 10 had HAC placed in the mastoid cavity. HAC is homogeneously radiopaque on CT scans and plain radiographs. Large amounts (ablating a frontal sinus or mastoid air cells) are readily seen; small amounts are inconspicuous. On MR images, HAC is a signal void. Infected HAC in one patient was surrounded be enhancing soft tissue on MR images, separated from native bone by an irregular radiolucent cleft on CT scans. HAC is a valuable addition to the surgical armamentarium for the repair of skull base defects. More experience will determine the time course for normal osseointegration, as well as the typical appearance of infection.


[Hydrodynamics of dental dentinal fluid].
Dentinal fluid is very close in its physical and mechanical properties and composition to blood plasma, which makes it a potentially aggressive biological environment for modern adhesive systems. An in-depth study of the physiological processes of the functioning of tooth dentin remains relevant in order to solve problems associated with its artificial restoration. Study using computer simulation speed of movement and pressure distribution of dentinal fluid in the dentinal tubule of the tooth to assess the possibilities of their regulation. To model the distribution of flow velocity and pressure of dentinal fluid in the dentinal tubule, the finite element method (Fluent ANSYS computer program) was used. Immediately behind the spherical tip of the odontoblast, there is a rapid increase in the hydraulic diameter of the flow section of the dentinal tubule, and, accordingly, a decrease in capillary pressure, while the tip of the odontoblast creates a large local hydraulic resistance. The resulting distribution of pressure drop in the damaged dentinal tubule is consistent with the fact that fluid movement is due, to a greater extent, to the capillary effect rather than the inlet pressure into the dentinal tubule. By changing the length of the odontoblast process, it is possible to influence the parameters of the hydrodynamics of dentinal fluid in the space of the dentinal tubule.


Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes.
Centella asiatica is claimed to have a neuroprotective effect; however, its ability to protect the cerebrum against damage in diabetes has never been identified. The aims were to identify the possibility that C. asiatica ameliorates inflammation, oxidative stress, and apoptosis in the cerebrum in diabetes. C. asiatica leave aqueous extract (C. asiatica) (50, 100, and 200 mg/kg/b.w.) were given to diabetic rats for 28 days. Changes in rats' body weight, food and water intakes, and insulin and FBG levels were monitored. Following sacrificed, cerebrum was harvested and subjected for histological, biochemical, and molecular biological analyses. The results revealed treatment with C. asiatica was able to ameliorate the loss in body weight, the increase in food and water intakes, the decrease in insulin, and the increase in FBG levels in diabetic rats. Additionally, histopathological changes in the cerebrum and levels of p38, ERK, JNK, cytosolic Nrf2, Keap-1, LPO, RAGE, and AGE levels decreased; however, PI3K, AKT, IR, IRS, GLUT-1, nuclear Nrf2, Nqo-1, Ho-1, and anti-oxidative enzymes (SOD, CAT, and GPx) levels increased in diabetic rats receiving C. asiatica. Furthermore, C. asiatica treatment also caused cerebral inflammation and apoptosis to decrease as indicated by decreased inflammatory markers (cytosolic NF-κB p65, p-Ikkβ, Ikkβ, iNOS, COX-2, TNF-α, IL-6, and IL-1β), decreased pro-apoptosis markers (Casp-3, 9, and Bax), but increased anti-apoptosis marker, Bcl-2. Activity level of Na+/K+, Mg2+, and Ca2+-ATPases in the cerebrum also increased by C. asiatica treatment. Conclusions: C. asiatica treatment helps to prevent cerebral damage and maintain near normal cerebral function in diabetes.


Overexpression of a zinc-finger protein gene from rice confers tolerance to cold, dehydration, and salt stress in transgenic tobacco.
Stress perception and signal transduction leading to tolerance involve a complex interplay of different gene products. We describe here the isolation and characterization of an intronless gene (OSISAP1) from rice encoding a zinc-finger protein that is induced after different types of stresses, namely cold, desiccation, salt, submergence, and heavy metals as well as injury. The gene is also induced by stress hormone abscisic acid. Overexpression of the gene in transgenic tobacco conferred tolerance to cold, dehydration, and salt stress at the seed-germination/seedling stage as reflected by the percentage of germination/green seedlings, the fresh weight of seedlings, and their developmental pattern. Thus, OSISAP1 seems to be an important determinant of stress response in plants.


Milrinone-Associated Cardiomyopathy and Arrhythmia in Cerebral Vasospasm.
Milrinone is an inotropic and vasodilatory drug proven safe for use in treatment of cerebral vasospasm. Despite its reported safety profile, its use is not free of side effects. Milrinone-associated cardiomyopathy and arrhythmia can occur in patients with cerebral vasospasm. This is a retrospective chart review of a patient who presented with aneurysmal subarachnoid hemorrhage and developed clinical vasospasm twice over a period of 2 weeks. Sustained intravenous milrinone infusion was used in association with norepinephrine infusion during this period. The patient developed R-on-T triggered torsades de pointes and cardiogenic shock requiring resuscitation. Follow-up echocardiogram showed decreased ejection fraction from 64% to 43% consistent with cardiac remodeling. Systemic complications such as cardiotoxicity and arrhythmias with the use of intravenous milrinone can be seen particularly when used in combination with catecholamines. With increased combined milrinone and catecholamine use for the treatment of cerebral vasospasm, physicians should be aware of the potential cardiac complications of these agents. Close monitoring with daily electrocardiograms may be helpful to detect changes that suggest cardiotoxicity. If changes are noted, an echocardiogram and cardiology consultation may be warranted.


[Effect of oxygen on the fluorescence of sol-gel with ruthenium complexes].
Different Ru complexes were used in an organically modified sol-gel (ormosil) sensing film to character their quenching behaviors to oxygen. The sensing film with tris-(4,7-diphenyl-1, 10-phenanthroline) ruthenium(II) [Ru(dpp)(2+)3] as an indicator was selected because of its characteristics with high quenching efficiency, fast response time, high luminescence intensity and long-term stability. The quenching behavior of the sensing film greatly depended on the content of dimethyldimethoxysilane (DiMe-DMOS) in ormosil because DiMe-DMOS changed the polarity of sensing film. A home-made fluorescence quenching system was set up for oxygen determination based on a blue LED (lambda max = 460 nm ) as an exciting light source. Th e response time was 30 s from saturatednitrogen to oxygen in water, and 90 s from saturated oxygen to nitrogen.


Dendritic Cell-Based Immunotherapy: State of the Art and Beyond.
Dendritic cell (DC) vaccination in cancer patients aims to induce or augment an effective antitumor immune response against tumor antigens and was first explored in a clinical trial in the 1990s. More than two decades later, numerous clinical trials have been performed or are ongoing with a wide variety of DC subsets, culture protocols, and treatment regimens. The safety of DC vaccination and its ability to induce antitumor responses have clearly been established; however, although scattered patients with long-term benefit were reported, DC vaccines have not yet fulfilled their promise, perhaps mainly due to the lack of large-scale well-conducted phase II/III trials. To allow meaningful multicenter phase III trials, the production of DC vaccines should be standardized between centers which is now becoming feasible. To improve the efficacy of DC-based immunotherapy, it could be combined with other treatments.


Relation of coronary collateral circulation with epicardial fat volume in patients with stable coronary artery disease.
To investigated the relationship between epicardial fat volume (EFV) and coronary collateral circulation (CCC) in patients with stable coronary artery disease (CAD). The study population consisted of 152 consecutive patients with CAD who underwent coronary angiography and were found to have at least 95% significiant lesion in at least one major coronary artery. EFV was assessed utilizing 64-multislice computed tomography. The patients were classifield into impaired CCC group (Group 1, Rentrop grades 0-1, n = 58), or adequate CCC (Group 2, Rentrop grades 2-3, n = 94). The EFV values were significantly higher in paitients with adequate CCC than in those with impaired CCC. In multivariate logistic regression analysis, EFV (OR = 1.059; 95% CI: 1.035-1.085; P = 0.001); and presence of angina were independent predictors of adequate CCC. In receiver-operating characteristic curve analysis, the EFV value > 106.5 mL yielded an area under the curve value of 0.84, with the test sensitivity of 49.3%, and with 98.3% specifity. High EFV, and the presence of angina independently predict adequate CCC in patients with stable coronary artery disease. This association offers new diagnostic opportinities to assess collateral flow by conventional ultrasound techniques.


Trabecular bone score: perspectives of an imaging technology coming of age.
The trabecular bone score (TBS) is a new method to describe skeletal microarchitecture from the dual energy X-ray absorptiometry (DXA) image of the lumbar spine. While TBS is not a direct physical measurement of trabecular microarchitecture, it correlates with micro-computed tomography (µCT) measures of bone volume fraction, connectivity density, trabecular number, and trabecular separation, and with vertebral mechanical behavior in ex vivo studies. In human subjects, TBS has been shown to be associated with trabecular microarchitecture and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT). Cross-sectional and prospective studies, involving a large number of subjects, have both shown that TBS is associated with vertebral, femoral neck, and other types of osteoporotic fractures in postmenopausal women. Data in men, while much less extensive, show similar findings. TBS is also associated with fragility fractures in subjects with secondary causes of osteoporosis, and preliminary data suggest that TBS might improve fracture prediction when incorporated in the fracture risk assessment system known as FRAX. In this article, we review recent advances that have helped to establish this new imaging technology.


Clinical decision-making in the context of chronic illness.
This paper develops a framework to compare clinical decision making in relation to chronic and acute medical conditions. Much of the literature on patient-physician decision making has focused on acute and often life-threatening medical situations in which the patient is highly dependent upon the expertise of the physician in providing the therapeutic options. Decision making is often constrained and driven by the overwhelming impact of the acute medical problem on all aspects of the individual's life. With chronic conditions, patients are increasingly knowledgeable, not only about their medical conditions, but also about traditional, complementary, and alternative therapeutic options. They must make multiple and repetitive decisions, with variable outcomes, about how they will live with their chronic condition. Consequently, they often know more than attending treatment personnel about their own situations, including symptoms, responses to previous treatment, and lifestyle preferences. This paper compares the nature of the illness, the characteristics of the decisions themselves, the role of the patient, the decision-making relationship, and the decision-making environment in acute and chronic illnesses. The author argues for a different understanding of the decision-making relationships and processes characteristic in chronic conditions that take into account the role of trade-offs between medical regimens and lifestyle choices in shaping both the process and outcomes of clinical decision-making. The paper addresses the concerns of a range of professional providers and consumers.


Clinical response and urethral pressure profile changes after phenylpropanolamine in dogs with primary sphincter incompetence.
Based on clinical response, urethral pressure profile changes, and lack of side effects, phenylpropanolamine was effective and safe in treating dogs with primary sphincter incompetence. Primary sphincter incompetence was diagnosed in 11 female and 8 male dogs with urinary incontinence. Urodynamics of the dogs were assessed, using a combined urethral pressure profile and urethral sphincter electromyography. Male and female dogs had significantly (P less than 0.05) lower maximal urethral closure pressures, when compared with clinically normally dogs (36.91 +/- 8.20 cm of H2O vs 79.72 +/- 4.61 cm of H2O for female dogs and 48.63 +/- 8.68 cm of H2O vs 99.77 +/- 11.71 cm of H2O for male dogs). After treatment with phenylpropanolamine, there was a significant increase in maximal urethral closure pressure in both sexes to within normal range (77.73 +/- 8.70 cm of H2O in females and 92.50 +/- 14.60 cm of H2O in males). Electromyographic activity was normal before and after treatment. Urinary incontinence resolved clinically in all but 1 male and 1 female dog; however, the condition in these 2 dogs improved considerably. Minimal side effects were seen clinically. Mean arterial blood pressure was not altered by treatment. Plasma estrogen and testosterone concentrations in 8 female dogs were not different from those in continent female dogs. The incontinence in these dogs was considered a sphincter incompetence rather than estrogen responsive.


SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity.
Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell-specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2's mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.


Development and application of a high throughput natural language processing architecture to convert all clinical documents in a clinical data warehouse into standardized medical vocabularies.
Natural language processing (NLP) engines such as the clinical Text Analysis and Knowledge Extraction System are a solution for processing notes for research, but optimizing their performance for a clinical data warehouse remains a challenge. We aim to develop a high throughput NLP architecture using the clinical Text Analysis and Knowledge Extraction System and present a predictive model use case. The CDW was comprised of 1 103 038 patients across 10 years. The architecture was constructed using the Hadoop data repository for source data and 3 large-scale symmetric processing servers for NLP. Each named entity mention in a clinical document was mapped to the Unified Medical Language System concept unique identifier (CUI). The NLP architecture processed 83 867 802 clinical documents in 13.33 days and produced 37 721 886 606 CUIs across 8 standardized medical vocabularies. Performance of the architecture exceeded 500 000 documents per hour across 30 parallel instances of the clinical Text Analysis and Knowledge Extraction System including 10 instances dedicated to documents greater than 20 000 bytes. In a use-case example for predicting 30-day hospital readmission, a CUI-based model had similar discrimination to n-grams with an area under the curve receiver operating characteristic of 0.75 (95% CI, 0.74-0.76). Our health system's high throughput NLP architecture may serve as a benchmark for large-scale clinical research using a CUI-based approach.


Functionalized mesoporous silica materials for controlled drug delivery.
In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging.


[Cutting forceps. Classification (and II)].
The most common and also the simplest guideline to gain an efficient awareness about existing surgical instruments consists of, once you know their physical characteristics, establishing a relationship between every instrument and every organ or tissue, or otherwise to associate each instrument to a determined operating specialty, having a specified technique, etc. Through this method, a professional will act correctly in the majority of situations since each surgical specialty tends to opt for one unique model of cutting forceps in each instrument system both to reduce costs as to reduce the number of instruments.


[Diagnosis of rheumatoid arthritis of knee joints using magnetic resonance imaging].
A combination of clinical, X-Ray and magnetic resonance tomographic studies for 129 knee joints was made in 85 patients with rheumatoid arthritis of knee joints. MRI symptoms of rheumatoid arthritis of knee joints, including fluid accumulation in the articular cavity, degeneration of the articular cartilage, meniscus, ligaments, proliferation of the synovial membrane, destructive changes in osseous epiphysis were defined. Comparative analysis of the X-Ray and MRI imaging findings has shown that MRI has advantages structures of joints in rheumatoid arthritis.


A Novel Derivatization Reagent in the Determination of the Number of OH End Groups in Poly(ethylene glycol) by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.
The potential of a novel derivatization reagent, trifluoroacetic anhydride (TFAA), in determining the number of OH groups in poly(ethylene glycol) (PEG) was investigated by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The MALDI mass spectra of the products revealed peaks of sodiated derivative cations, whose shift by the respective increments, Δm/z: 96 × number of OH, allowed for the determination of the number of end functional groups with active hydrogens. In the present study, complete acylation of OH groups by TFAA proceeded rapidly, and only required mixing in acetonitrile solvent without purification. As a result, the number of OH end groups of PEG could be determined rapidly.