'The time it takes…' How doctors spend their time admitting a patient during the acute medical take.
Patient safety depends on adequate staffing but the number of doctors required for safe staffing for medical emergencies is not known. We measured the duration of the admission process for patients seen by medical teams in emergency departments (EDs) and acute medical units. History taking and examination by a core medical trainee took 22 minutes for a patient referred from the ED and 21 minutes for a patient referred from primary care. A complete admission clerking with prescription and ordering of investigations ranged from a mean of 15 minutes for a consultant in acute medicine to a mean of 55 minutes for a foundation year 1 trainee. The duration of post-take ward rounds also showed significant variability.Our data can be used to model staffing patterns if combined with information about admission numbers and local set up.


Characteristics of two broad spectrum antibiotics produced by Mycoplasma sp. RP III.
Two extracellular antibiotics produced by Mycoplasma sp. RP III growing in serum-containing media have been purified by solvent extraction and ion-exchange chromatography. Factor I inhibits Gram-positive and Gram-negative bacteria in vitro and a crude preparation protected mice from Pseudomonas and Straphylococcus infections; it is of low cytotoxicity. Factor II, a lipid, inhibits Gram-positive and Gram-negative bacteria, Candida species, and is as cytotoxic as the actinomycins.


Beyond step counts: Including wear time in prosthesis use assessment for lower-limb amputation.
The purpose of this study was to test a novel activity monitor that tracks the time a prosthesis is worn, and the nature of the ambulatory activity conducted with the prosthesis. These capabilities allow prosthesis users' wear and accommodation practices (e.g., temporary doffing) to be monitored, and the intensity of their activities to be assessed. A portable limb-socket motion sensing system was used to monitor doffs, walk bouts (≥5 steps), low locomotion (2-4 steps), stationary positions, and weight shifts in a group of transtibial prosthesis users. The relationship between doff time and active motion time was investigated, and durations of low and high intensity active motions were compared. For the 14 participants tested, the median prosthesis day duration ranged from 12.8-18.8 h. Eleven participants typically doffed five or fewer times per day, and three participants typically doffed 10 or more times per day. Nine participants demonstrated a positive correlation between daily doff duration and active motion duration. Six participants spent more time in weight shifts than walk bouts, while eight participants spent more time in walk bouts than weight shifts. Capturing don time and temporary doffs and distinguishing weight shifts from walks may provide insight relevant to patient care. Longer-term monitoring studies should be conducted, and the clinical utility of the data evaluated.


Conditional deletion of the retinoblastoma (Rb) gene in ovarian granulosa cells leads to premature ovarian failure.
The retinoblastoma protein (RB) regulates cell proliferation and survival by binding to the E2F family of transcription factors. Recent studies suggest that RB also regulates differentiation in a variety of cell types, including myocytes, neurons, adipocytes, and chondrocytes. Rb mutations have been found in ovarian cancer; however, the role of RB in normal and abnormal ovarian function remains unclear. To test the hypothesis that loss of Rb induces ovarian tumorigenesis, we generated an ovarian granulosa cell conditional knockout of Rb (Rb cKO) using the Cre/lox recombination system. Rb cKO females showed 100% survival and no ovarian tumor formation through 9 months of age, but they developed progressive infertility. Prepubertal Rb cKO females showed increased ovulation rates compared with controls, correlating with increased follicle recruitment, higher Fshr and Kitl mRNA levels, and lower anti-Müllerian hormone levels. In contrast, the ovulation rate of 6-wk-old females was similar to that of controls. Morphometric analysis of Rb cKO ovaries from 6-wk-old and older females showed increased follicular atresia and apoptosis. Rb cKO ovaries and preantral follicles had abnormal levels of known direct and indirect target genes of RB, including Rbl2/p130, E2f1, Ccne2, Myc, Fos, and Tgfb2. In addition, preantral follicles showed increased expression of the granulosa cell differentiation marker Inha, decreased levels of Foxl2 and Cyp19a1 aromatase, and abnormal expression of the nuclear receptors Nr5a1, Nr5a2, and Nr0b1. Taken together, our results suggest that RB is required for the temporal-specific pattern of expression of key genes involved in follicular development.


Single-Collision Statistics Reveal a Global Mechanism Driven by Sample History for Contact Electrification in Granular Media.
Models for same-material contact electrification in granular media often rely on a local charge-driving parameter whose spatial variations lead to a stochastic origin for charge exchange. Measuring the charge transfer from individual granular spheres after contacts with substrates of the same material, we find instead a "global" charging behavior, coherent over the sample's whole surface. Cleaning and baking samples fully resets charging magnitude and direction, which indicates the underlying global parameter is not intrinsic to the material, but acquired from its history. Charging behavior is randomly and irreversibly affected by changes in relative humidity, hinting at a mechanism where adsorbates, in particular, water, are fundamental to the charge-transfer process.


Photophysical properties of metal ion functionalized NaY zeolite.
A series of luminescent ion exchanged zeolite are synthesized by introducing various ions into NaY zeolite. Monometal ion (Eu(3+), Tb(3+), Ce(3+), Y(3+), Zn(2+), Cd(2+), Cu(2+)) exchanged zeolite, rare-earth ion (Eu(3+), Tb(3+), Ce(3+)) exchanged zeolite modified with Y(3+) and rare-earth ion (Eu(3+), Tb(3+), Ce(3+)) exchanged zeolite modified with Zn(2+) are discussed here. The resulting materials are characterized by Fourier transform infrared spectrum radiometer (FTIR), XRD, scanning electronic microscope (SEM), PLE, PL and luminescence lifetime measurements. The photoluminescence spectrum of NaY indicates that emission band of host matrix exhibits a blueshift of about 70 nm after monometal ion exchange process. The results show that transition metal ion exchanged zeolites possess a similar emission band due to dominant host luminescence. A variety of luminescence phenomenon of rare-earth ion broadens the application of zeolite as a luminescent host. The Eu(3+) ion exchanged zeolite shows white light luminescence with a great application value and Ce(3+) exchanged zeolite steadily exhibits its characteristic luminescence in ultraviolet region no matter in monometal ion exchanged zeolite or bimetal ions exchanged zeolite.


Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.
Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.


Horizontal equity in utilisation of care and fairness of health financing: a comparison of micro-health insurance and user fees in Rwanda.
This paper uses two methods to compare the impact of health care payments under insurance and user fees. Concentration indices for insured and uninsured groups are computed following the indirect standardisation method to evaluate horizontal inequity in utilisation of basic health care services. The minimum standard approach analyses the extent to which out-of-pocket health spending contributed to increased poverty. The analysis uses cross-sectional household survey data collected in Rwanda in 2000 in the context of the introduction of community-based health insurance. Results indicate that health spending had a small impact on the socio-economic situation of uninsured and insured households; however, this is at the expense of horizontal inequity in utilisation of care for user-fee paying individuals who reported significantly lower visit rates than the insured.


Lacrimal sac identification for dacryocystorhinostomy: the role of sodium hyaluronate.
Sodium hyaluronate in a 1% solution (Healon) mixed with a few drops of 2% fluorescein has been found to be useful in exposing the lumen of the lacrimal sac at the time of dacryocystorhinostomy (DCR) surgery. Injection of the solution into the sac facilitates proper opening and allows accurate identification of the edges of the sac flaps. This technique is especially valuable when the sac is small or when previous DCR surgery was unsuccessful.


Impact of illness and variables associated with functional impairment in Chinese patients with psoriatic arthritis.
To assess the impact of disease and functional outcomes in Chinese patients with psoriatic arthritis (PsA) and to identify variables associated with poor functional outcomes. A cross sectional study performed in 80 consecutive patients with PsA from a single center. Functional outcomes were assessed by the Health Assessment Questionnaire (HAQ) and the Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical variables included social-demographic characteristics and clinical features. Linear regression analyses were performed to identify variables associated with functional impairment. Thirty-six men and 44 women with mean (+/-SD) age and duration of arthritis of 48.6 (+/-13.0) and 10.2 (+/-6.9) years were studied. One-third reported PsA related unemployment and change in job nature. Another third experienced a reduction of income due to PsA. The median (IQR) HAQ and BASFI were 0.44 (1.09) and 2.1 (4.38). These functional scores correlated highly with each other and with the patient's perception of health, but correlated only moderately or poorly with other disease activity variables. Multivariate analysis identified higher damaged joint count, poorer patients' perception of health, poor socioeconomic factor and higher CRP as factors associated with higher HAQ. Higher back pain score; higher CRP, higher damaged joint count and poor socioeconomic factor were associated with BASFI. PsA in Chinese subjects has had significant social-economic impact. Joint damage was found to be associated with functional impairment.


A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma.
This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dose to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30cm(3) of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30cm(3) of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.


The simplicity complex: exploring simplified health messages in a complex world.
A challenge in individual and public health at the start of the 21st century is to effectively communicate health and science information about disease and complex emergencies. The low health literacy of millions of adults in the USA has been referred to as a 'silent killer'. A popular approach to improving health communication and health promotion to low health literate consumers has been to simplify the language of health information. The expected result has been that individuals and groups will better understand information and will then make informed decisions about their health and behaviors. This expectation has grown to include the belief that the public will be better prepared to take appropriate action in complex natural and man-made emergencies. Demonstrating the efficacy of this approach remains, in large part, uninvestigated. And it is becoming more evident that health literacy itself is complex and multifaceted. This article applies linguistic and sociolinguistic models in order to better articulate the role of simplification in health communication and health promotion. Focusing on two models from sociolinguistics-pragmatics and text theory-the article discusses their usefulness in rethinking message simplification. The discussion proposes that a richer, more theory-based understanding of text structures and functions, along with other powerful constructs, including cultural appropriateness, relevancy and context, are needed to close the gaps between health messages, health messengers and patients/the public. The article concludes by making recommendations for future study to empirically test the strengths and limitations of these models and constructs.


Lateral Thoracic Artery Pseudoaneurysm as a Result of Penetrating Chest Trauma.
Pseudoaneurysms are potentially fatal complications of vascular trauma; however, they are rarely seen as the sole complication of penetrating injury. We present a case of a pseudoaneurysm with an associated arteriovenous fistula of the left lateral thoracic artery as a result of direct trauma from a knife stab. The patient presented only with a painful, swollen left pectoralis muscle. Upon diagnosis, he was taken to the interventional radiology suite and treated successfully with fluoroscopic guided coil embolization. Cases such as these are infrequent and should encourage more aggressive use of contrast enhanced computed tomography imaging for soft tissue injury, as a missed traumatic pseudoaneurysm may result in life-threatening hemorrhage.


New molecular packing in a crystal of pseudoazurin from Alcaligenes faecalis: a double-helical arrangement of blue copper.
Pseudoazurin from the denitrifying bacterium Alcaligenes faecalis (AfPAz) is a blue copper protein and functions as an electron donor to copper-containing nitrite reductase (CuNIR). Conventionally, AfPAz has been crystallized using highly concentrated ammonium sulfate as a precipitant. Here, a needle-like crystal of AfPAz grown in a solution containing a macromolecular precipitant, polyethylene glycol 8000 (PEG 8000), is reported. The crystal belonged to space group P61, with unit-cell parameters a = b = 68.7, c = 94.2 Å. The structure has been determined and refined at 2.6 Å resolution. The asymmetric unit contained two AfPAz molecules contacting each other on negatively charged surfaces. The molecular packing of the crystal showed a right-handed double-helical arrangement of AfPAz molecules and hence of blue copper sites. This structure provides insight into the excluded-volume effect of PEG and the manner of assembly of AfPAz.


Evaluation of activated carbon fiber supported nanoscale zero-valent iron for chromium (VI) removal from groundwater in a permeable reactive column.
An activated carbon fiber supported nanoscale zero-valent iron (ACF-nZVI) composite for Cr(VI) removal from groundwater was synthesized according to the liquid phase reduction method. The techniques of N2 adsorption/desorption, FESEM, EDX, XRD and XPS were used to characterize the ACF-nZVI composite and the interaction between the ACF-nZVI composite and Cr(VI) ions. Batch experiments were conducted to evaluate the effects of several factors, including the amount of nZVI on activated carbon fiber (ACF), pH value, initial Cr(VI) concentration, and co-existing ions on Cr(VI) removal. The results indicate that presence of ACF can inhibit the aggregation of nanoscale zero-valent iron (nZVI) particles and increase its reactivity, and the Cr(VI) removal efficiency increases with increasing amounts of nZVI on ACF and a decrease in the initial Cr(VI) concentration. In acidic conditions, almost 100% of Cr(VI) in solution can be removed after 60 min of reaction, and the removal efficiency decreases with increasing initial pH values. The Cr(VI) removal is also dependent on the co-existing ions. Reusability experiments on ACF-nZVI demonstrate that the ACF-nZVI composite can keep a high reactivity after five successive reduction cycles. The removal mechanisms are proposed as a two-step interaction including the physical adsorption of Cr(VI) on the surface or inner layers of the ACF-nZVI composite and the subsequent reduction of Cr(VI) to Cr(III) by nZVI.


High alcohol consumption and the risk of renal damage: a systematic review and meta-analysis.
The risk of renal damage in patients with high alcohol consumption is controversial. The objective of this meta-analysis was to evaluate the associations between high alcohol consumption and progression of kidney damage including chronic kidney disease (CKD), end-stage renal disease (ESRD) and proteinuria. A literature search was performed using MEDLINE, EMBASE and Cochrane Databases from inception through August 2014 to identify studies investigating the association between high alcohol consumption and CKD, ESRD or proteinuria. Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of CKD, ESRD or proteinuria in patients consuming high amount of alcohol versus those who did not consume alcohol were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Twenty studies with 292 431 patients were included in our analysis to assess the associations between high alcohol consumption and progression of kidney damage. The pooled RRs of CKD, proteinuria and ESRD in patients with high alcohol consumption were 0.83 (95% CI: 0.71-0.98), 0.85 (95% CI: 0.62-1.17) and 1.00 (95% CI: 0.55-1.82), respectively. Post hoc analysis assessing the sex-specific association between high alcohol consumption and CKD demonstrated pooled RRs of 0.72 (95% CI: 0.57-0.90) in males and 0.78 (95% CI: 0.58-1.03) in females. Our study demonstrates an inverse association between high alcohol consumption and risk for developing CKD in males. There is no significant association between high alcohol consumption and the risk for developing proteinuria or ESRD.


17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.
Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.


Pressure injections of fluid in the nanoliter range via micropipettes.
The relationship between pressure, ejection duration and volume ejected was experimentally determined in vitro for micropipettes with different external tip diameters. The relationship between ejection duration and ejected volume is linear in the steady state (i.e. with ejection durations of 1 s or longer) and at sufficiently high pressures (above about 100 kPa) and for pipettes with a sufficiently high hydrodynamic conductance (larger than 1 pl s-1 kPa-1 at 230 kPa). In this range, flows were found with low Reynolds numbers (smaller than 10), which is consistent with laminar flows. For all but the largest micropipettes, the relationship between pressure and ejected volume is alinear: the pipettes' apparent hydrodynamic conductances increase with increasing pressure. Micropipettes with apparent hydrodynamic conductances between 0.04 and 1400 pl s-1 kPa-1 (at 230 kPa) were tested. Duration-pressure combinations could be defined where the duration-volume relationship was either linear or monotonic. such duration-pressure combinations were different for pipettes with different apparent hydrodynamic conductances. A quick method is described to measure the pipette's apparent hydrodynamic conductance at the pressure used, corrected for the fluid's viscosity. Measurement of this conductance permits predictable injections of known volumes of fluid in the range of 100 pl to 1 microliter with a precision of 10-20%.


The role of serum antibodies in the protection against rotavirus disease: an overview.
A critical observation in understanding immunity to rotavirus is that children infected with wild virus or vaccinated with oral live vaccines develop a humoral immune response and are protected against severe disease upon reinfection. Nevertheless, much controversy exists as to whether these serum antibodies are directly involved in protection or merely reflect recent infection, leaving the protective role to mucosal or cell-mediated immunity or to other as-yet-undefined mechanisms. We have reviewed data from a variety of studies in humans, including challenge experiments in adult volunteers, longitudinal studies of rotavirus infection in young children, and clinical trials of animal and animal-human reassortant rotavirus vaccines in infants. These data suggest that serum antibodies, if present at critical levels, are either protective themselves or are an important and powerful correlate of protection against rotavirus disease, even though other host effectors may play an important role as well.


A degree-day concept for estimating degradation time under field conditions.
Development of degradation rate information for crop protection products in soil is typically a time consuming and costly process. Therefore, development of methodology that would allow extrapolation of limited degradation information to wider field conditions in a predictive fashion would be desirable. This study presents an approach that uses a modified heat unit model to estimate organic compound degradation time using limited datasets. The model requires daily soil or air temperature and volumetric water content. Predictions based on the model for three different compounds in five different field studies were within 80% of measured values based on soil analysis. Results from this research indicate that the model was able to predict compound half-life values across all sites with r2 = 0.99.


[Periarthritis scapulohumeralis].
Periarthritis scapulohumeralis, also known as frozen shoulder, is a common disease in which the patient has a painful and restricted range of active and passive shoulder motion involving capsular contraction with no identifiable cause. Pathogenesis is thought to be a progression of inflammation and fibrosis of the capsule. Appropriate physical examination and radiologic studies can help in differentiating this condition from rotator cuff tear and other diseases. The natural progression of a frozen shoulder includes three phases (freezing, frozen and thawing) over a duration of 1 to 3.5 years and resolves spontaneously. Conservative treatment includes physical therapy and medication for pain relief but arthroscopic capsular release is sometimes performed in refractory cases.


Methylene blue blocks cGMP production and disrupts directed migration of microglia to nerve lesions in the leech CNS.
Migration and accumulation of microglial cells at sites of injury are important for nerve repair. Recent studies on the leech central nervous system (CNS), in which synapse regeneration is successful, have shown that nitric oxide (NO) generated immediately after injury by endothelial nitric oxide synthase (eNOS) stops migrating microglia at the lesion. The present study obtained results indicating that NO may act earlier, on microglia migration, and aimed to determine mechanisms underlying NO's effects. Injury induced cGMP immunoreactivity at the lesion in a pattern similar to that of eNOS activity, immunoreactivity, and microglial cell accumulation, which were all focused there. The soluble guanylate cyclase (sGC) inhibitor methylene blue (MB) at 60 microM abolished cGMP immunoreactivity at lesions and blocked microglial cell migration and accumulation without interfering with axon conduction. Time-lapse video microscopy of microglia in living nerve cords showed MB did not reduce cell movement but reduced directed movement, with significantly more cells moving away from the lesion or reversing direction and fewer cells moving toward the lesion. The results indicate a new role for NO, directing the microglial cell migration as well as stopping it, and show that NO's action may be mediated by cGMP.


High-level secretion of native recombinant human calreticulin in yeast.
Calreticulin (CRT) resides in the endoplasmic reticulum (ER) and functions to chaperone proteins, ensuring proper folding, and intracellular Ca(2+) homeostasis. Emerging evidence shows that CRT is a multifunctional protein with significant roles in physiological and pathological processes with presence both inside and outside of the ER, including the cell surface and extracellular space. These recent findings suggest the possible use of this ER chaperone in development of new therapeutic pharmaceuticals. Our study was focused on human CRT production in two yeast species, Saccharomyces cerevisiae and Pichia pastoris. Expression of a full-length human CRT precursor including its native signal sequence resulted in high-level secretion of mature recombinant protein into the culture medium by both S. cerevisiae and P. pastoris. To ensure the structural and functional quality of the yeast-derived CRTs, we compared yeast-secreted human recombinant CRT with native CRT isolated from human placenta. In ESI-MS (electrospray ionization mass spectrometry), both native and recombinant full-length CRT showed an identical molecular weight (mass) of 46,466 Da and were monomeric by non-denaturing PAGE. Moreover, limited trypsin digestion yielded identical fragment patterns of calcium-binding recombinant and native CRT suggesting that the yeast-derived CRT was correctly folded. Furthermore, both native and recombinant CRT induced cellular proliferation (MTS assay) and migration of human dermal fibroblasts (in vitro wound healing assay) with the same specific activities (peak responses at 1-10 ng/ml) indicating that the functional integrity of yeast-derived CRT was completely preserved. Simple one-step purification of CRT from shake-flask cultures resulted in highly pure recombinant CRT protein with yields reaching 75 % of total secreted protein and with production levels of 60 and 200 mg/l from S. cerevisiae and P. pastoris, respectively. Finally, cultivation of P. pastoris in a bioreactor yielded CRT secretion titer to exceed 1.5 g/l of culture medium. Yeasts are able to correctly process and secrete large amounts of mature recombinant human CRT equally and fully biologically active as native human CRT. This allows efficient production of high-quality CRT protein in grams per liter scale.


Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice.
Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d x 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal body weight loss. Tetramine 10 and hexamine 18 were the most efficient among the five analogues in arresting tumor growth. Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss. It was further assessed at a weekly administration regimen of (q1w x 4) in two cycles with a four-week break between the cycles. At this dosing schedule, 10 again efficiently arrested tumor growth with negligible effect on animal body weight. Tetramine 10 also arrested the growth of large tumors (ca. 2000 mm(3)) treated 66 days postimplantation. Studies on the metabolism of 10 showed that it accumulates in tumor within 6 h after the end of administration and reached a maximum level 72 h after cessation of dosing. Intracellular concentrations of 10 in liver and kidney were much smaller when compared to those in the tumor when measured 72 h after cessation of dosing. In liver and kidney, the deethyl metabolites of 10 accumulated over a 96 h period after cessation of dosing.


Primary obstructive megaureter with ruptured kidney.
A 17-year-old boy presented to the emergency department for severe left flank pain and gross hematuria 1 hour after playing basketball without significant collision. Laboratory tests showed normal renal function and massive hematuria. Abdominal computed tomography scan disclosed a primary megaureter with ruptured kidney. We successfully treated him with ureteral stenting followed by endoscopic ureterotomy and ureteroneocystostomy.


[Effect of early acupuncture intervention on post-stroke depression: a randomized controlled trial].
To observe the effects of conventional drug therapy combined with acupuncture and conventional drug therapy on the morbidity of post-stroke depression and recovery of neurological function in patients with acute stroke, and provide new ideas for prevention and treatment of post-stroke depression. Sixty patients were randomly divided into an observation group and a control group, 30 cases in each one.Conventional drug therapy was given in the control group;on the basis of conventional drug therapy,acupuncture was applied at Baihui (GV 20), Sishencong (EX-HN1), Neiguan (PC 6), Hegu (LI 4), Taixi (KI 3), etc. The treatment was given once every day, 6 times a week for 4 weeks in the two groups. The 24 Hamilton depression rating scale (HAMD), modified Edinburgh-Scandinavian stroke scale (MESSS) scores were recored before treatment, after 1 week of treatment, and after 4 weeks of treatment in the two groups,and the morbidity of post-stroke depression was compared between the two groups. After 1 week of treatment, the HAMD scale scores of the two groups were higher than those before treatment (both P<0.05), and the MESSS scores were lower than those before treatment in the two groups (both P<0.05). After 4 weeks of treatment, the HAMD scale scores in the observation group were lower than that before treatment (P<0.05), and significantly better than that in the control group (P<0.01), but there was no significant difference in the control group before and after treatment (P>0.05). The MESSS scores were lower than those after 1 week of treatment in the two groups (both P<0.05), and the score in the observation group was significantly lower than that in the control group (P<0.01). After 4 weeks of treatment, the morbidity of post-stroke depression in the observation group was 23.3% (7/30), which was lower than 66.7% (20/30) in the control group (P<0.05). Early acupuncture intervention on stroke patients can not only promote the recovery of neurological function, but also reduce the morbidity of post-stroke depression effectively.


Spatial reorientation decline in aging: the combination of geometry and landmarks.
The study is focused on the assessment of reorientation skills in a sample of community-dwelling elderly people, manipulating landmarks and geometric (layout) information. A neuropsychological assessment was administered to 286 elderly participants, divided into six groups (healthy controls, HC; four subgroups of participants with mild cognitive impairment, MCI; participants with probable dementia, Prob_D) and tested with the Virtual Reorientation Test (VReoT). VReoT manipulated different spatial cues: geometry and landmarks (proximal and distal). Compared with HC, participants with MCI and Prob_D showed to be impaired in tasks involving geometry, landmarks and a combination of them. Both single and multiple domain impairment in MCI had an impact on reorientation performance. Moreover, VReoT was marginally able to discriminate between amnesic and non-amnesic MCI. The occurrence of getting lost events seemed to be associated to learning of geometric information. The associative strength between landmark and target plays an important role in affecting spatial orientation performance of cognitively impaired participants. Geometry significantly supports landmark information and becomes helpful with the increase of cognitive impairment which is linked to a decrement in landmark encoding. VReoT seems to represent a reliable evaluation supplement for spatial orientation deficits in prodromal stages of dementia.


Forty-year trends in cardiovascular risk factors in Finland.
Finland has experienced remarkable changes in population levels of coronary heart disease risk factors and mortality over the past decades. The National FINRISK studies have monitored risk factors in major non-communicable diseases from 1972 to 2012. The 40-year changes in those risk factors are presented. Study population included participants aged 30-59 years in the series on independent random population samples. Data were collected in 5-year intervals in 1972-2012. FINRISK studies so far comprised 53 589 men and women who participated in a health examination, gave a venous blood sample and filled in questionnaires. Serum total cholesterol, systolic and diastolic blood pressure, and body mass index (BMI) were measured using standardized protocol, and smoking status was recorded. Total serum cholesterol decreased remarkably until 2007, but after that has increased. Systolic blood pressure has continued to decline over time since 1972, while decrease in diastolic blood pressure has levelled off during the last 10 years. Smoking prevalence has markedly decreased. BMI has increased in the population, but most significantly in the earlier survey years, not the past 10 years. After three decades of favourable development, the population risk factor levels showed some increase in total cholesterol and diastolic blood pressure. This emphasizes the need for continued efforts towards national disease prevention and health promotion.


Cancer Microenvironment and Endoplasmic Reticulum Stress Response.
Different stressful conditions such as hypoxia, nutrient deprivation, pH changes, or reduced vascularization, potentially able to act as growth-limiting factors for tumor cells, activate the unfolded protein response (UPR). UPR is therefore involved in tumor growth and adaptation to severe environments and is generally cytoprotective in cancer. The present review describes the molecular mechanisms underlying UPR and able to promote survival and proliferation in cancer. The critical role of UPR activation in tumor growth promotion is discussed in detail for a few paradigmatic tumors such as prostate cancer and melanoma.


A comparison of clonogenic and radionuclide uptake assays for determining the radiation response of human small-cell lung cancer xenografts and cell lines.
Previous work has suggested that a radionuclide (3HTdR) uptake assay can provide a measure of drug and radiation sensitivity comparable with that given by the clonogenic assay. We have now extended this work to examine the radiation response of human small-cell lung cancer xenografts and cell lines with a wide range of plating efficiencies. Preliminary experiments using cultured cells indicated that irradiation of a single-cell suspension following disaggregation generally produced similar response data to those obtained when cultures were irradiated in situ and subsequently disaggregated. The response of eight cell lines to a single dose of 2 Gy was measured using both radionuclide uptake and clonogenic assays. There was no correlation between the two sets of data. Agreement between the radiation-response curves obtained using 3HTdR uptake and clonogenic assays was better for high plating efficiency xenografts (NCI-H69, COR-L51) than for low plating efficiency xenografts (COR-L24, COR-L31). Radionuclide uptake indicated very shallow response curves for the low plating efficiency lines. Altering the time of radionuclide addition from the standard Day 4 to other times between Day 2 and Day 6 did not greatly change the indications of radioresponsiveness provided by the assay. Growth-curve experiments for line COR-L24 showed that cell numbers at Day 4 after irradiation with 1.5 Gy or 3 Gy were very similar to those in unirradiated cultures. For NCI-H69, however, the cell numbers were very different for the different radiation doses. It appears that a high proportion of cells in lines such as COR-L24 take many days to show radiation damage as measured by reduced 3HTdR uptake.


Opportunities to Reduce Diabetes Risk in Women of Reproductive Age: Assessment and Treatment of Prediabetes within a Large Integrated Delivery System.
Preventing diabetes before pregnancy may be important to improve maternal and infant outcomes. Although the preconception period is a crucial time to focus on chronic disease prevention, little is known about preventive services for reproductive-aged women at risk of developing diabetes. Using electronic health record data from patients at Kaiser Permanente Northern California, we identified 21,965 nonpregnant women aged 18 to 44 with incident prediabetes (PDM; fasting plasma glucose [FPG] = 100-125 or glycated hemoglobin A1c = 5.7%-6.4%) between 2007 and 2010. We looked for evidence of a "clinical response" to PDM in the 6 months after laboratory testing, defined as retesting of blood glucose levels, referral or attendance to health education, diagnosis of PDM, metformin initiation, or a clinical note of discussion of PDM. Multilevel models were used to examine the relationship between patient characteristics and clinical response, and to assess provider-level variation. Fewer than one-half of women had a documented clinical response to the PDM-range laboratory result. Women with higher FPG values and body mass indexes were more likely to have a PDM diagnosis (FPG 120-125 vs. 100-119: OR, 1.96; 95% CI, 1.78-2.17; body mass index, 30-34 kg/m2 vs. <25 kg/m2: OR, 1.30; 95% CI, 1.13-1.48) and have 'PDM' recorded in the notes (FPG 120-125 vs. 100-119: OR, 1.15; 95% CI, 1.06-1.26; body mass index: 30-34 kg/m2 vs. <25 kg/m2: OR, 1.58; 95% CI, 1.44-1.74). Provider-level variation was modest, except for metformin initiation (intraclass correlation coefficient, 0.8; p < .01). Low clinical response to PDM among women of reproductive age suggests there are missed opportunities for diabetes prevention among this vulnerable population.


Psychosocial developmental trajectory of adolescents with inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a chronic, debilitating disorder occurring in young patients in the most productive period of their lives. Little is known about the effect on the developmental trajectory of adolescents growing up with IBD. The purpose of this study was to assess the psychosocial developmental trajectory ("course of life") and sociodemographic outcomes in adolescents with IBD compared with peers from the general population. A total of 62 adolescents (response rate 74%, boys 51.6%, mean age 18.6 years) completed the course of life questionnaire. Patients with IBD achieved fewer milestones on the domains of autonomy and social and psychosexual development compared with their healthy peers. They went less frequently on holidays without adults, had fewer jobs during secondary school, were less frequently going out to a bar/disco during secondary school, and were older when falling in love for the first time. After secondary school, patients with IBD were more often unemployed. Negative consequences in terms of psychosocial development are prevalent in adolescents with IBD. Physicians should be attentive to these consequences and provide additional support if necessary. During transition to adult clinic, these topics are of major importance and should be an integral component of the comprehensive care of chronically ill adolescents and young adults.


Association of Geometric Characteristics of Knee Anatomy (Alpha Angle and Intercondylar Notch Type) With Noncontact ACL Injury.
The femoral intercondylar notch type and the alpha angle (the angle between the femoral notch roof and the long axis of the femur) are easily measured in clinical settings; however, their associations with anterior cruciate ligament (ACL) injury remain unclear. The purpose was to determine if the alpha angle and the femoral notch type are associated with noncontact ACL injury univariately and in combination with previously identified knee geometric risk factors. We hypothesized that the alpha angle and the femoral notch type are associated with noncontact ACL injury and that the association differs between men and women. Case control study; Level of evidence, 3. The alpha angle and the femoral notch type were measured via 3T magnetic resonance imaging (MRI) acquired from 61 women and 25 men with a first-time noncontact ACL injury. Each injured patient was matched with a control participant based on age, sex, and participation on the same sports team. A conditional logistic regression was used to assess univariate associations with ACL injury as well as multivariate associations using MRI-based risk factors of knee geometry identified in previous analyses: femoral intercondylar notch width at the anterior outlet, femoral intercondylar notch anteromedial ridge thickness, volume of the ACL, tibial plateau lateral compartment subchondral bone slope, lateral compartment middle articular cartilage slope, lateral compartment meniscus-cartilage height, lateral compartment meniscus-bone angle, and medial tibial spine volume. For female athletes, the alpha angle (odds ratio, [OR], 1.82 per 1-degree increase; P = .001), the tibial lateral compartment articular cartilage slope (OR, 1.25 per 1-degree increase in the posterior-inferior directed slope; P = .022), and the femoral notch anteromedial ridge thickness (OR, 3.36 per 1-mm increase; P = .027) were independently associated with ACL disruption. For men, no other variables entered the models after the alpha angle was inputted as the first step (OR, 2.19 per 1-degree increase; P = .010). For women, ACL injury was most strongly associated with increased alpha angle, increased tibial plateau slope, and increased femoral notch ridge thickness. For men, increased alpha angle was the most significant factor associated with ACL injury. The mechanism of injury might be associated with a combination of impingement of the ACL against the bone and increased ligament loading.


Mechanism Investigations on Water Gas Shift Reaction over Cu(111), Cu(100), and Cu(211) Surfaces.
Cu-based catalysts are commonly applied in low-temperature water gas shift (WGS) reactions, owing to their low cost and high catalytic activity. The influence of different Cu surfaces on catalytic activity and mechanism over the WGS reaction remains unclear. In this work, the effect of different structures of surfaces on the WGS mechanism is studied using density functional theory (DFT). Three surface terminations (Cu(100), Cu(111), and Cu(211)) of Cu are considered, and the coordination number (CN) of the active Cu site is in the range from 7 to 9. The most stable surface is Cu(211). Then, d-band center values are calculated, which decrease in the following sequence: Cu(211) > Cu(100) > Cu(111). This shows that d-band center values decrease with increasing coordination number. The increase in the centers of the d-band leads to an increase in the adsorption strength of CO and H2O adsorbates, which is in line with the theory of the d-band center. In addition, the further calculated mechanism for WGS reaction over three different Cu surfaces illustrates that the carboxyl path is the most favorable mechanism, and the rate-determining step is H2O dissociation. Cu(211) shows excellent WGS catalytic performance, better than the Cu(100) and Cu(111) surfaces. This work provides theoretical insights into the rational design of highly active Cu-based catalysts toward WGS reaction.


CDK6 is essential for mesenchymal stem cell proliferation and adipocyte differentiation.
Background: Overweight or obesity poses a significant risk of many obesity-related metabolic diseases. Among all the potential new therapies, stem cell-based treatments hold great promise for treating many obesity-related metabolic diseases. However, the mechanisms regulating adipocyte stem cells/progenitors (precursors) are unknown. The aim of this study is to investigate if CDK6 is required for mesenchymal stem cell proliferation and adipocyte differentiation. Methods: Cyclin-dependent kinase 6 (Cdk6) mouse models together with stem cells derived from stromal vascular fraction (SVF) or mouse embryonic fibroblasts (MEFs) of Cdk6 mutant mice were used to determine if CDK6 is required for mesenchymal stem cell proliferation and adipocyte differentiation. Results: We found that mice with a kinase inactive CDK6 mutants (K43M) had fewer precursor residents in the SVF of adult white adipose tissue (WAT). Stem cells from the SVF or MEFs of K43M mice had defects in proliferation and differentiation into the functional fat cells. In contrast, mice with a constitutively active kinase CDK6 mutant (R31C) had the opposite traits. Ablation of RUNX1 in both mature and precursor K43M cells, reversed the phenotypes. Conclusion: These results represent a novel role of CDK6 in regulating precursor numbers, proliferation, and differentiation, suggesting a potential pharmacological intervention for using CDK6 inhibitors in the treatment of obesity-related metabolic diseases.


Evaluation of cats as the source of endemic sporotrichosis in Peru.
Although contact with domestic cats has been shown to be a risk factor for sporotrichosis in endemic areas, systematic evaluation of apparently unaffected cats as possible reservoirs for infection has not been explored. The goals of this study were to identify the following aspects of sporotrichosis in the endemic area of Abancay, Peru: (i) the overall prevalence of sporotrichosis in the cat population, (ii) the most common site where the fungus can be isolated from these cats, and (iii) whether cats without identifiable skin lesions may be carriers of the fungus in the oral mucosa, nasal mucosa, or nails. One household cat in each of 85 neighborhoods within the endemic area of Abancay, Peru was randomly selected. Oral and nasal swabs, as well as nail clippings were taken from 84 of the cats. In addition, samples from skin lesions that were suspected to be due to sporotrichosis were collected from cats or members of families that owned the pets. Cultures inoculated with two nasal swabs and one set of nail clippings from two different cats yielded Sporothrix schenckii, the identity of which were confirmed by rDNA sequencing. The overall prevalence of Sporothrix schenckii colonization was 2.38% (95% CI 0.41-9.14) in this cat population. None of the skin lesion samples from the cats and only one such sample from a family member were positive for Sporothrix schenckii in culture. These results suggest a role for domestic cats as a possible reservoir for sporotrichosis infection in Abancay.


Anti-HBs response to standard hepatitis B vaccination in children and adolescents with diabetes mellitus.
Patients with type 1 diabetes mellitus are expected to respond poorly to hepatitis B (HB) vaccination. In this study we tested this hypothesis for the standard vaccination schedule. Ninety-nine patients (age 10.8 +/- 3.5 years) were vaccinated against HB (10 pg/dose at 0, 1, and 6 months) using a vaccine containing no pre-S2 antigen (Engerix Bs). The sero-conversion and -protection rates after the completion of three doses, the relation of anti-HBs titers to clinical parameters, and comparison with those of healthy counterparts (51 children, aged 9.7 +/- 4.4 years) were analyzed. The vaccine used was pre-S2 antigen containing (Genhevac B) in 23 and Engerix B in 28; both types yielded a similar response. The geometric mean of the anti-HBs titer was 322.9 vs 1476.8 IU/l (non-significant), sero-convertion rate 96.9% vs 100%, and seroprotection rate 93.9% vs 99% in the diabetic and control groups, respectively. In the diabetic group, there was no correlation between anti-HBs titer and clinical characteristics except for age. We concluded that the standard vaccination schedule is less effective but still effective enough in children and adolescents with type 1 diabetes mellitus.


Collaboration of national organizations and the legislative means to advance pulmonary rehabilitation.
Getting involved in the public policy process empowers health care professionals to help ensure the preservation of patient rights. An organization must form strong relationships with legislators using simple yet occasionally unconventional strategies. Too few patients currently have access to rehabilitative services. Passing national legislation promoting patient access to pulmonary rehabilitation will have a great impact by enabling more and more patients to take advantage of pulmonary rehabilitation programs because they are fully reimbursed.


Genome Sequence of a Tomato-Infecting Tomato Mosaic Virus Isolate from Zimbabwe.
A tomato-infecting tomato mosaic virus (ToMV) isolate was detected in Zimbabwe using lateral flow kits and double-antibody sandwich enzyme-linked immunosorbent assay. Next-generation sequencing and de novo assembly were subsequently performed to determine its genome sequence. The ToMV genome of the Zimbabwe isolate is the second to be reported in Africa.


Cardiac pacemaker leads--a radiographic perspective.
To comment on the adequacy of positioning of single- or dual-chambered pacemaker leads requires some knowledge of the type of electrode used. Earlier leads relied upon force transmitted along the body of the lead to the electrode-myocardial interface to maintain positioning. These relatively large stiff leads were placed almost exclusively near the apex of the right ventricle to prevent dislodgement. More recent leads incorporate mechanical fixation devices to maintain position, commonly either tined or screw-in electrodes (or variations of these) representing passive and active fixation mechanisms respectively. The tines are not radiopaque; the screw-in devices are metallic. Such newer electrodes permit the use of smaller, more flexible leads, reduce the necessity for precise positioning, and reduce the frequency of lead dislodgement.


Management of Symmetrical Peripheral Gangrene.
Symmetrical peripheral gangrene (SPG) is a rare, debilitating disease that deserves more widespread concern among the medical fraternities. The objective of this review is to outline the etiology, pathology findings, and management practices of SPG. About 18%-40% mortality rate was reported, and survivors have high frequency of multiple limb amputations. SPG is the hallmark of disseminated intravascular coagulation (DIC). The main pathogenesis theory, to date, is microthrombosis associated with disturbed procoagulant-anticoagulant balance. The treatment of SPG is largely anecdotal and theoretically involves heparin-based anticoagulation and substitution of natural anticoagulants. Early recognition, prompt management of DIC, and underlying conditions may halt the progression of the disease. The multicenter randomized controlled trial should be set up to formulate the proper treatment guidelines.


Intravenous administration of tirofiban versus loading dose of oral clopidogrel for preventing thromboembolism in stent-assisted coiling of intracranial aneurysms.
Background Thromboembolic complications after stenting of intracranial aneurysms may be affected by antiplatelet administration. Aims This retrospective study aimed to assess the safety of intravenous tirofiban versus loading dose of oral clopidogrel for preventing thromboembolism in stent-assisted coiling of intracranial aneurysms. Methods From January 2006 to December 2013, 281 patients with cerebral aneurysms were treated with stent-coiling using two antiplatelet strategies in comparison: the initial strategy (a loading dose of ≥300 mg clopidogrel followed by dual antiplatelet, clopidogrel group) and the modified strategy (intravenous administration of tirofiban 8 µg/kg over 3 min followed by a maintenance dose of 0.1 µg/kg/min for 24 h, tirofiban group). The end points were rates of perioperative thromboembolic events and intracranial hemorrhages. Results Thromboembolic events were observed more often in the clopidogrel group (13/120 aneurysms, 10.83%) than the tirofiban group (6/178 aneurysms, 3.37%; P = 0.010), with no increase in the rate of intracranial hemorrhages ( P = 0.164). In the ruptured subgroups, thromboembolic events were significantly fewer in the tirofiban subgroup (5/128, 3.91%) compared with the clopidogrel subgroup (7/53, 13.21%; P = 0.043) with no increase in the rate of hemorrhage ( P = 0.360). Conclusions Intravenous administration of tirofiban is safe in intracranial aneurysms treated with stent-assisted coiling.


[Periodontal osseous surgery: osteoplasty and osteotomy].
Elimination of the periodontal pocket is a prime objective of periodontal therapy. Normally the gingiva is consistent with the underlying bone, and aberration in gingival form can be corrected by gingivectomy or gingivoplasty if the gingiva is supported by good bony architecture. If periodontitis has caused marginal irregularities or septal deformities the complete elimination of the periodontal pocket is done by osteoplasty or osteoectomy. The Authors through a review of the literature have examined these surgical techniques.


Single-mode unidirectional-emission circular-side hexagonal resonator microlasers.
Circular-side hexagonal resonator (CSHR) microlasers connecting an output waveguide are proposed and demonstrated for enhancing the mode Q factor and realizing single-mode operation. Three-dimensional simulation results indicate that the CSHRs with an optimized deformation can greatly enhance mode Q factors. The CSHR microlasers with output waveguides are fabricated using a planar technology process. For a CSHR microlaser with a side length of 7.5 μm and an output waveguide width of 2 μm, single-mode operation is realized with a side-mode suppression ratio of 43 dB and a threshold current of 2.5 mA. Furthermore, flat small-signal modulation responses are obtained with a 3 dB bandwidth of 13 GHz.


An Intensified EMCCD Camera for Low Energy Gamma Ray Imaging Applications.
This paper presents the design and feasibility study of a very-high resolution gamma camera for detecting 27-35 keV X and gamma rays emitted by I-125 labelled radiotracers. This detector consists of a newly developed Electron-multiplying CCD (EMCCD) sensor and a de-magnifier tube coupled to a thin layer of scintillator. A prototype detector was developed and experimentally evaluated. This detector has a detection area of ~ 5 cm2. It provided an intrinsic spatial resolution of < 60 µm FWHM and a high signal-to-noise ratio for detecting the 27-35 keV photons, which ensures an excellent counting efficiency. This detector will be used as the key component for a single photon emission microscope (SPEM) system that is under development.


Fall risk screening and balance rehabilitation in elderly: a missing healthcare intervention in Pakistani healthcare system.
Elderly are one of the fastest-growing population globally and require significant healthcare services due to age-related deterioration in physiological systems. Poor postural control due to aging results in impaired balance leading to increase in frequency of falls, poor quality of life, and rise in disability and mortality rates. In Pakistan, due to lack of awareness, and resources, fall prevention and screening programmes for the elderly are lacking. Regular fall risk screening utilizing balance assessment tools, integration of fall prevention programmes and balance rehabilitation approach as part of elderly healthcare services can serve as tools to lower the incidence of falls in the elderly population of Pakistan. Moreover, integration of latest technology as part of balance rehabilitation can also be considered. The review aims to highlight appropriate strategies for fall risk screening and balance rehabilitation in an effort to promote an important healthcare intervention for elderly in Pakistan.


[Studies on the structure-activity relationship of retinoids--Hansch analysis and 3D-OSAR studies on specific ligands of retinoid x receptor].
Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retinoids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitative structure-activity relationships of specific ligands of RXR, we carried out mimesis of environment of ligands interacting with their receptor and, to some extent, mapping the topological and physico-chemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.


Mutagenic and cytotoxic properties of 6-thioguanine, S6-methylthioguanine, and guanine-S6-sulfonic acid.
Thiopurine drugs, including 6-thioguanine ((S)G), 6-mercaptopurine, and azathioprine, are widely employed anticancer agents and immunosuppressants. The formation of (S)G nucleotides from the thiopurine prodrugs and their subsequent incorporation into nucleic acids are important for the drugs to exert their cytotoxic effects. (S)G in DNA can be methylated by S-adenosyl-l-methionine to give S(6)-methylthioguanine (S(6)mG) and oxidized by UVA light to render guanine-S(6)-sulfonic acid ((SO3H)G). Here, we constructed single-stranded M13 shuttle vectors carrying a (S)G, S(6)mG, or (SO3H)G at a unique site and allowed the vectors to propagate in wild-type and bypass polymerase-deficient Escherichia coli cells. Analysis of the replication products by using the competitive replication and adduct bypass and a slightly modified restriction enzyme digestion and post-labeling assays revealed that, although none of the three thionucleosides considerably blocked DNA replication in all transfected E. coli cells, both S(6)mG and (SO3H)G were highly mutagenic, which resulted in G-->A mutation at frequencies of 94 and 77%, respectively, in wild-type E. coli cells. Deficiency in bypass polymerases does not result in alteration of mutation frequencies of these two lesions. In contrast to what was found from previous steady-state kinetic analysis, our data demonstrated that 6-thioguanine is mutagenic, with G-->A transition occurring at a frequency of approximately 10%. The mutagenic properties of 6-thioguanine and its derivatives revealed in the present study offered important knowledge about the biological implications of these thionucleosides.


Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis.
Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014). (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.


Re-description of the catfish species Liobagrus kingi Tchang, 1935 (Pisces: Amblycipitidae) from the upper Chang-Jiang basin, China.
The identity and validity of Liobagrus kingi Tchang, 1935 remain contentious to date due to its inaccurate original description. A re-description is provided here for this species based on our examination on its type, hitherto deposited in ASIZB and available topotypic material. It is confirmed that L. kingi is a species with a serrated posterior edge of the pectoral-fin spine and distinct from the sympatrically existing species L. nigricauda. Comments on former recognitions of specimens from the upper Chang-Jiang basin as L. kingi are presented.


[Mesenteric panniculitis].
A 70-year-old patient with a 6 x 6 x 12 cm mass involving the mesentery root is discussed. The pseudotumorous infiltration was detected by ultrasound done because of nonspecific abdominal symptoms and weight loss. Laparoscopic biopsy confirmed the diagnosis of mesenteric panniculitis. The primary histologic criterion is infiltration of the mesenterium by foamy lipid-laden macrophages, clusters of lymphocytes and fibrosis. The majority of cases follow a benign course and need no therapy, but co-existence of lymphoma has been reported. There have been few cases where panniculitis with progressive fibrosis changed into retractile mesenteritis with shortening of the mesenterium and compression of mesenteric vessels with partial or complete intestinal obstruction or ischemia requiring surgery. Few reported cases of severe and progressive disease have been treated with prednisone and azathioprine or cyclophosphamide.


[Detection of Middle East Respiratory Syndrome Coronavirus by Reverse-transcription Loop-Mediated Isothermal Amplification].
A simple, rapid and sensitive colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) was developed for rapid detection of Middle East respiratory syndrome coronavirus (MERS-CoV). The method employed six primers that recognized sequences of a nucleocapsid gene for amplification of nucleic acids under isothermal conditions at 63 degrees C for 60 min. Products were detected through a LA-320c Loopamp Turbidimeter (real-time RT-LAMP) or visual inspection of color change by pre-addition of Hydroxynaphthol Blue dye (visual RT-LAMP). Specificity of RT-LAMP was validated by detection of several human coronaviruses and common respiratory viruses. MERS-CoV real-time RT-LAMP had a linear correlation (R2) of 0.995 at 10(3)-10(6) copies. The limit of detection of real-time RT-LAMP, visual RT-LAMP and quantitative real-time PCR was 500, 1000 and 100 copies/reaction, respectively. The established RT-LAMP assay was demonstrated to be a rapid screening tool for MERS-CoV infection, and could be suitable in resource-limited clinical sites and for field studies.


Neuroprotective Effects of β-Asarone Against 6-Hydroxy Dopamine-Induced Parkinsonism via JNK/Bcl-2/Beclin-1 Pathway.
β-asarone, a major component of Acorus tatarinowii Schott, has positive effects in neurodegeneration disease, however, its effect on the Parkinson's disease (PD) remains unclear. In this study, the effects of β-asarone on behavioral tests, neurotransmitters, tyrosine hydroxylase (TH), and α-synuclein (α-syn) were investigated in 6-hydroxydopamine (6-OHDA) induced rats. Furthermore, the JNK/Bcl-2/Beclin-1 autophagy pathway was also studied. The results showed that β-asarone improved the behavioral symptoms of rats in the open field, rotarod test, initiation time, and stepping time. And it increased the HVA, Dopacl, and 5-HIAA levels in striatum but not the DA and 5-HT levels. After administration of β-asarone, the TH level was elevated but the α-syn was declined in rats. It inhibited the expressions of LC3-II, but increased the p62 expression in SN4741 cells. Moreover, it affected the expressions of Beclin-1, Bcl-2, JNK, and p-JNK in vivo. We deduced that β-asarone may firstly downregulate expressions of JNK and p-JNK, and then indirectly increase the expression of Bcl-2. And the function of Beclin-1 could be inhibited, which could inhibit autophagy activation. Collectively, all data indicated that β-asarone may be explored as a potential therapeutic agent in PD therapy.


Comparison between high-pass resolution perimetry and differential light sensitivity perimetry in patients with glaucoma.
High-pass resolution perimeters such as the Ophthimus (High Tech Vision, Malmö, Sweden) may provide an easier, faster assessment of the visual field than conventional perimeters such as the Humphrey (Humphrey Instruments Inc., San Leandro, CA, U.S.A.), which is based on differential light sensitivity. The Ophthimus provides global indices and statistical analyses conceptually similar to those produced by the Humphrey. In addition, the Ophthimus provides, as a unique parameter, the estimated neural capacity. Twenty-one patients with chronic open-angle glaucoma and reliable fields on both Humphrey and Ophthimus testing were evaluated. The results from the two different techniques were compared. The estimated neural capacity was correlated to global deviation and mean deviation at a statistically significant level. There were also correlations between mean deviation and global deviation and between pattern standard deviation and local deviation, but not between retest standard deviation and short-term fluctuation. It is not clear at this point if the neural capacity of the Ophthimus provides any clinically useful information over and above global deviation. Mean test time was shorter with the Ophthimus system than the Humphrey. Performance on the reliability indices was better for the Ophthimus. The Ophthimus may prove useful in following patients with glaucoma.


Evaluation of accuracy of plain radiography in determining the Risser stage and identification of common sources of errors.
Risser's sign is an established radiological marker for predicting growth potential in adolescent idiopathic scoliosis, but the accuracy of Risser's staging has been debated. This research was designed to evaluate the accuracy of Risser's staging and to identify causes of errors in Risser's staging. Plain radiographs of 89 adolescent idiopathic scoliosis patients were evaluated for Risser's stage using both the Original and French methods. A three-dimensional computed tomography (3D-CT) was used to evaluate the accuracy of the plain radiographs. Inter- and intra-observer reliability of both methods was assessed on radiographs and 3D-CT images using weighted kappa statistics. The concordance rate for Risser's staging between plain radiographs and 3D-CT images were calculated. The various sources of staging differences between the two imaging methods were noted, grouped, and analyzed to identify common error patterns. Intra- and inter-observer staging reliabilities on plain radiography were 0.91 and 0.94, respectively, using the Original method and 0.91 and 0.92, respectively, using the French method. Intra- and inter-observer reliabilities on 3D-CT were 0.98 and 0.99, respectively, using the Original method and 0.97 and 0.99, respectively, using the French method. Mean concordance rates between plain radiography and 3D-CT were 59.76% and 67.42% using the Original and French methods, respectively. Common sources of error leading to misinterpretation of Risser's staging were miscalculation of apophysis excursion, skip ossification, isolated non-linear ossification, micro-fusion, and pseudo-fusion. Risser's staging by plain radiography is reliable but not accurate. Variations in the iliac apophysis ossification and misinterpretation of apophysis fusion are the main sources of error.


Parameters, practices, and preferences for regulatory review of emerging biotechnology products in food and agriculture.
This paper evaluates the U.S. regulatory review of three emerging biotechnology products according to parameters, practices, and endpoints of assessments that are important to stakeholders and publics. First, we present a summary of the literature on variables that are important to non-expert publics in governing biotech products, including ethical, social, policy process, and risk and benefit parameters. Second, we draw from our USDA-funded project results that surveyed stakeholders with subject matter expertise about their attitudes towards important risk, benefit, sustainability, and societal impact parameters for assessing novel agrifood technologies, including biotech. Third, we evaluate the regulatory assessments of three food and agricultural biotechnology case studies that have been reviewed under U.S. regulatory agencies and laws of the Coordinated Framework for the Regulation of Biotechnology, including gene-edited soybeans, beef cattle, and mustard greens. Evaluation of the regulatory review process was based on parameters identified in steps 1 and 2 which were deemed important to both publics and stakeholders. Based on this review, we then propose several policy options for U.S. federal agencies to strengthen their oversight processes to better align with a broader range of parameters to support sustainable agrifood products that rely on novel technologies. These policy options include 1) those that would not require new institutions or legal foundations (such as conducting Environmental Impact Statements and/or requiring a minimal level of safety data), 2) those that would require a novel institutional or cross-institutional framework (such as developing a publicly-available website and/or performing holistic sustainability assessments), and 3) those that would require the agencies to have additional legal authorities (such as requiring agencies to review biotech products according to a minimal set of health, environmental, and socio-economic parameters). Overall, the results of this analysis will be important for guiding policy practice and formulation in the regulatory assessment of emerging biotechnology products that challenge existing legal and institutional frameworks.


Efforts toward the total synthesis of (-)-kendomycin.
[structure: see text] The synthesis of an advanced component leading to (-)-kendomycin is described. The synthetic scheme features the application of asymmetric conjugate addition methodology for the early generation of the C13-C14 (E)-trisubstituted olefin, providing an efficient assembly of the ansa chain. Condensation reactions probe two strategies for attachment of the aromatic system.


DNA origami applications in cancer therapy.
Due to the complexity and heterogeneity of cancer, the development of cancer diagnosis and therapy is still progressing, and a complete understanding of cancer biology remains elusive. Recently, cancer nanomedicine has gained much interest as a promising diagnostic and therapeutic strategy, as a wide range of nanomaterials possess unique physical properties that can render drug delivery systems safer and more effective. Also, targeted drug delivery and precision medicine have now become a new paradigm in cancer therapy. With nanocarriers, chemotherapeutic drugs could be directly delivered into target cancer cells, resulting in enhanced efficiency with fewer side-effects. DNA, a biomolecule with molecular self-assembly properties, has emerged as a versatile nanomaterial to construct multifunctional platforms; DNA nanostructures can be modified with functional groups to improve their utilities as biosensors or drug carriers. Such applications have become possible with the advent of the scaffolded DNA origami method. This breakthrough technique in structural DNA nanotechnology provides an easier and faster way to construct DNA nanostructures with various shapes. Several experiments proved that DNA origami nanostructures possess abilities to enhance efficacies of chemotherapy, reduce adverse side-effects, and even circumvent drug resistance. Here, we highlight the principles of the DNA origami technique and its applications in cancer therapeutics and discuss current challenges and opportunities to improve cancer detection and targeted drug delivery.


Prevalence of oral lesions in the 6-year-old pediatric population of Oviedo (Spain).
The present study investigates the prevalence of oral diseases in children in the city of Oviedo (Spain). A representative sample was selected from among the 6-year-old children in Oviedo (n= 786), involving a protocol developed for pediatric oral diseases. A total of 344 lesions were detected in 243 children. The most common disorder was saburral tongue (16,02%), followed by traumatisms (12.17%) and geographic tongue (4.48%). The prevalence of aphthous stomatitis was 2.24% and herpes labialis was 1,6%. Ankyloglossia was observed in 2.08% of cases, and a hypertrophic lip frenulum in 1.28%. In this study shows the prevalence of the lesions of the oral mucosa in the Spanish population of 6 year-old. Of the results of the present study comes off that the objectives sanitary oral publics and deprived in this field they should go focused toward: 1) the eradication of illnesses of local cause (language saburral, traumatic ulcerations, etc.) for their high prevalencia; and, 2) the precocious diagnosis of anomalies of the development (anquiloglosias and labial frenum) for their relationship with dysfunctions of the phonation and future malocclusions.


Parenting Stress After Deployment in Navy Active Duty Fathers.
Military fathers are being deployed, and leaving their families, for greater lengths of time and more frequently than ever before. The purpose of this study was to examine the impact of recent deployment on parenting stress in U.S. Navy fathers with young children. Of the 111 participants who completed the one-time study questionnaire at a large military outpatient clinic on the Eastern seaboard, 67.6% had returned from a ship-based deployment. Regression analyses were performed, using the Parenting Stress Index as the outcome variable, deployment elements (such as time away from home in the past 5 years) as predictors, and adjusting for other factors such as post-traumatic stress disorder (PTSD) and depression. Higher perceived threat and greater warfare exposure were both associated with increased parenting stress (p < 0.05) in the unadjusted model. These associations were greatly attenuated and no longer significant after adjustment for depression. In addition, rates of positive screens for PTSD and depression (17.1%) in this sample were higher than in other recent studies. In summary, these data indicate that various deployment factors are associated with increased parenting stress in Navy fathers back from deployment within the past year; these relationships are largely explained by depressive symptoms. Clinical implications are discussed.


The three-dimensional reconstruction of the XY chromosomal pair in human spermatocytes.
The spatial reconstruction of the XY pair of chromosomes from human spermatocytes has been made by the study of serial sections 1000 A in thickness. The sex pair during zygotene-pachytene forms a condensed mass of chromatin that has two filamentous, electron-opaque cores: the long and the short core. During early pachytene both cores have a common ending region, about 0.4-0.8 micro long. This common end is a synaptonemal complex, and each of the cores forms a lateral element of that complex. The cores become more convoluted during middle pachytene forming "ringlike bodies." Nucleoli from spermatocytes have three distinct regions: (a) granular; (b) dense fibrillar; and (c) clear intermediate. Occasional association of the XY pair and the heteropycnotic "basal knobs" results in apparent association of nucleoli and the sex pair in a minority of cells. The evidence presented is interpreted as a strong support of the hypothesis of homologous regions in the human XY pair.


[Aortocoronary bypass graft in coronary arterial stenosis with aortitis syndrome].
A 50-year old female who had aortitis syndrome with unstable angina due to severe coronary arterial narrowings is described. On the preoperative coronary arteriogram, 95% occlusion of the left anterior descending coronary artery (segment 6) and the left circumflex artery (segment 11), so-called "skip lesion" of aortitis syndrome, were revealed. The distal circumflex artery was well visualized through collateral vessels of the posterior descending branch of the right coronary artery. Therefore single aortocoronary bypass graft to the left anterior descending branch was done with good success. Postoperatively the patient has been completely free from anginal chest pain. Narrowing of the coronary artery due to aortitis syndrome is considered uncommon. Stenotic lesions have been reported to be limited mostly to the ostia and proximal segments of the coronary arteries, connecting to the aortic wall. Moreover, so-called "skip lesion" of the coronary artery as seen in this case is thought to be very rare.


Hospitalization of patients with heart failure: a population-based study.
To describe the clinical course of heart failure in a population-based sample of incident cases, and to identify factors predicting hospitalization and mortality. Three hundred and thirty-two incident cases were identified over 15 months; 208 inpatients and 124 outpatients. Thirty-eight inpatients died during the first hospital admission (case fatality 18%) leaving 294 at risk of subsequent hospitalization. Over an average follow-up of 19 months, 173 cases were hospitalized on 311 occasions. Two hundred and twenty-four (72%) of these admissions were unplanned, with 51% due to worsening heart failure. One hundred and ten cases died over the same period. Cases diagnosed as an inpatient had 26 more admissions for worsening heart failure per 100 cases during follow-up (95% CI 9 to 44) compared to cases diagnosed as an outpatient, and also a higher mortality (hazard ratio 3.1 (95% CI 1.9 to 5.1)). Age was the only factor associated with an increased risk of hospitalization for worsening heart failure, but age, functional class and serum creatinine were predictive of mortality. New cases of heart failure are at high risk of subsequent hospitalization, especially during the first months after diagnosis. Whilst predicting which patients will be hospitalized is difficult, interventions designed to reduce hospitalizations for worsening heart failure should be targeted at elderly inpatients with a new diagnosis.


Treatment of psoriatic arthritis: management recommendations.
Given the varied therapeutic options available for the management of psoriatic arthritis (PsA), recommendations for the management of PsA have been developed by several expert groups. These recommendations deal mainly with pharmacological treatments. At the international level, 2 recommendations sets are available: these have been developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and by the European League against Rheumatism (EULAR). These recommendations were published in 2009 and in 2012, respectively; and updates of these recommendations are currently ongoing. The first sets of recommendations dealt with non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease modifying drugs and tumour necrosis factor inhibitors; the 2015 sets of recommendations also deal with new drugs with other mechanisms of action, namely ustekinumab, secukinumab and apremilast. In the present paper, we will review these management recommendations.


[Rational diagnosis of endocrine forms of hypertension].
Primary aldosteronism, Cushing's syndrome and pheochromocytoma are the most frequent endocrine hypertensive disorders. Following biochemical confirmation of the clinical diagnosis, mainly non-invasive imaging techniques are necessary to determine the cause of the hormone excess. Diagnosis of primary aldosteronism is confirmed by analysis of aldosterone and renin in peripheral venous blood. Differentiation between adenoma and idiopathic adrenal hyperplasia usually is achieved by computed tomography and isotope scan. A reliable test for the biochemical confirmation of Cushing's syndrome is the determination of urine-free cortisol. In patients with equivocal results the dexamethasone suppression test is performed. Differential diagnosis between ACTH-dependent Cushing's syndrome (pituitary or ectopic) and primary adrenal disorders can be made by determination of plasma-ACTH and -cortisol. Non-invasive localization procedures include computed tomography of the abdomen, computed tomography or magnetic resonance imaging of the pituitary gland, sonography and isotope scan. Diagnosis of pheochromocytoma is based on elevated catecholamine levels in urine or plasma. The tumor is localized by ultrasound, computed tomography or isotope scan.


Central venous catheter care for the patient with cancer: American Society of Clinical Oncology clinical practice guideline.
To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low-molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy.


Distributions of vesicular glutamate transporters 1 and 2 in the visual system of tree shrews (Tupaia belangeri).
Vesicular glutamate transporter (VGLUT) proteins regulate the storage and release of glutamate from synapses of excitatory neurons. Two isoforms, VGLUT1 and VGLUT2, are found in most glutamatergic projections across the mammalian visual system, and appear to differentially identify subsets of excitatory projections between visual structures. To expand current knowledge on the distribution of VGLUT isoforms in highly visual mammals, we examined the mRNA and protein expression patterns of VGLUT1 and VGLUT2 in the lateral geniculate nucleus (LGN), superior colliculus, pulvinar complex, and primary visual cortex (V1) in tree shrews (Tupaia belangeri), which are closely related to primates but classified as a separate order (Scandentia). We found that VGLUT1 was distributed in intrinsic and corticothalamic connections, whereas VGLUT2 was predominantly distributed in subcortical and thalamocortical connections. VGLUT1 and VGLUT2 were coexpressed in the LGN and in the pulvinar complex, as well as in restricted layers of V1, suggesting a greater heterogeneity in the range of efferent glutamatergic projections from these structures. These findings provide further evidence that VGLUT1 and VGLUT2 identify distinct populations of excitatory neurons in visual brain structures across mammals. Observed variations in individual projections may highlight the evolution of these connections through the mammalian lineage.


Palliative care needs in hospitalized cancer patients: a 5-year follow-up study.
The aims of this study were to describe and compare diagnoses, symptoms, and care needs in palliative cancer patients in two medium-sized hospitals in a county council with no specialized palliative care available 24/7; to analyze the relationships between diagnosis and symptoms/care needs; and to compare results and trends from two datasets (from 2007 and 2012). The study was population-based with a cross-sectional design and was conducted at two acute care hospitals. We performed 142 one-day inventories (n = 2972) in 2007 and 139 in 2012 (n = 2843) to register symptoms, care needs, and diagnosis based on a questionnaire. Multiple logistic regression models were used in the analysis. During 2007 and 2012 combined, 10% (n = 589) of hospitalized patients were assessed as having cancer in a palliative phase. Prostate (12%) and colorectal (12%) cancers were most common. Pain (42%) and deterioration (42%) were the most prevalent symptoms and were associated with pancreas cancer in our regression models (p = 0.003 and p = 0.019, respectively). Other cancers had different associations: hematologic malignancies were associated with infections and blood transfusions (p < 0.001), breast cancer with pleurocentesis (p = 0.002), and stomach/esophagus cancer with nausea (p < 0.001). Nausea was more common in women than in men (p < 0.01). The mean number of symptoms/care needs was 2.9; patients with stomach/esophagus cancer had the highest number of symptoms/care needs (3.5). Acute care hospitals still play an important role for patients requiring palliative care. Symptoms and care needs were not strongly associated with specific diagnoses. Therefore, symptoms, rather than the specific cancer diagnoses, should be the focus of care.


Phenomic networks reveal largely independent root and shoot adjustment in waterlogged plants of Lotus japonicus.
Waterlogging imposes severe stress to the plant, and the interplay between root and aerial organs in the adjustment to this stress is poorly understood. A set of recombinant inbred lines (RILs) of Lotus japonicus (Gifu B-129 × Miyakojima MG-20) was subjected to control and waterlogging conditions for 21 d, and 12 traits related to leaf physiological functioning, root aerenchyma formation, shoot and root morphology, and dry mass accumulation were assessed to generate phenomic networks. The phenomic network became more complex under waterlogging as a result of the incorporation of root aerenchyma and dark-adapted Fv/Fm. Significant waterlogging-induced variation was found for stomatal conductance, dark-adapted Fv/Fm and aerenchyma. The RILs with stronger induction of aerenchyma in response to waterlogging tended to show reduced negative impact of this stress on root growth but suffered average impact on shoot growth. The RILs that retained higher stomatal conductance under waterlogging tended to retain higher dark-adapted Fv/Fm and shoot growth under waterlogging conditions but showed average impact on root traits. We propose a model where, although the stress experienced by the roots during waterlogging is transmitted to the shoot, shoots and roots deal with waterlogging in a less interdependent manner than often assumed.


Influence of the temperature on the cement disintegration in cement-retained implant restorations.
The aim of this study was to estimate the average disintegration temperature of three dental cements used for the cementation of the implant-supported prostheses. One hundred and twenty metal frameworks were fabricated and cemented on the prosthetic abutments with different dental cements. After heat treatment in the dental furnace, the samples were set for the separation to test the integration of the cement. Results have shown that resin-modified glass-ionomer cement (RGIC) exhibited the lowest disintegration temperature (p<0.05), but there was no difference between zinc phosphate cement (ZPC) and dual cure resin cement (RC) (p>0.05). Average separation temperatures: RGIC - 306 ± 23 °C, RC - 363 ± 71 °C, it could not be calculated for the ZPC due to the eight unseparated specimens. Within the limitations of the study, it could be concluded that RGIC cement disintegrates at the lowest temperature and ZPC is not prone to break down after exposure to temperature.


Tocopherol content of adipose tissue from vitamin E-deficient humans.
The high performance liquid chromatographic isolation of tocopherol with fluorometric quantitation, which we have previously described, has been extended to the analysis of needle aspiration biopsies of adipose tissue. Results are expressed relative to triglyceride content (ng tocopherol per mg triglyceride). In normal subjects adipose tissue content was 262 +/- 33; this value was increased two- to three-fold in normal persons ingesting additional vitamin E. Abetalipoproteinaemic patients have very low adipose tissue tocopherol values--about 10-20% of normal subjects; with massive supplementation of vitamin E (grams per day) a number of such patients have achieved normal tissue tocopherol concentrations. Patients with cholestatic liver disease and low plasma content of tocopherol also had low adipose tissue values; these could be increased by parenteral administration of vitamin E. Neuromuscular improvement noted in response to treatment with supplementary vitamin E has not as yet been correlated to the adipose tissue increment of tocopherol. While extensive observations on the intestinal absorption of tocopherol in humans have been reported, the mode of transfer from plasma lipoproteins to tissues has been less studied. Our results from patients with lipoprotein lipase deficiency and other abnormalities of lipid metabolism suggest that considerable transfer occurs during the initial catabolism of the chylomicrons.


Etiology of GVHD: alloreactivity or impaired cellular adaptation?
According to the self-nonself model of immunity, allogeneic T cells are considered as major cause of graft versus host disease (GVHD) following allogeneic stem cell transplantation (SCT). On the other hand, the danger model of immunity suggests that transplant-associated recipient tissue injury rather than donor-derived alloreactive T cells is the main cause of GVHD. What has been less appreciated are the early, both conditioning-dependent and conditioning-independent, events that impair homeostatic cellular adaptations and host-protective immune responses leading to the development of tissue-specific GVHD. The notion of gut injury precipitating in GVHD has been acknowledged by clinicians, with the shift to reduced intensity-conditioning regimens that prevent acute tissue injury and are less disruptive of tissue adaptation to T cell attack. Also, the role of host-protective immune response against pathogens in preventing GVHD has been shown by the lack of severe GVHD in germ free mice as well as an impaired anti-viral immune response during chronic GVHD. This article provides a brief review of the literature on GVHD and suggests that transplant-induced dysregulation of the protective immune response in the recipient of SCT is more important than allogeneic T cells in causing GVHD.


Osteonecrosis Related to Steroid and Alcohol Use-An Update on Pathogenesis.
Osteonecrosis (ON) is usually a progressive disease that negatively affects the quality of life and leads to significant disability. Most patients are aged 30-50 years and require multiple surgical interventions throughout their lifetime. In non-traumatic ON, alcohol abuse and corticosteroids are involved in up to 80% of cases. This narrative review aims to summarize data on their impact on healthy bone and the development of pathophysiological processes leading to ON development. We conducted EMBASE and MEDLINE database reviews to identify relevant research. We found that for both agents, the risk was time and dose-dependent. ON in alcohol and steroid use shared many pathogenetic mechanisms leading to the development of necrosis, including increased adipogenesis, the induction of chronic inflammation, vascular alterations, and impaired bone-cell differentiation. Because both alcohol and steroid use are modifiable factors, both general physicians and orthopedic surgeons should encourage patients to limit ethanol intake and avoid corticosteroid overuse. In the presence of ON, because both alcohol- and steroid-induced disease tend to be multifocal, addiction treatment and limiting steroid use are justified.


Photocatalytic reverse polarity Povarov reaction.
A visible light mediated iridium photocatalysed reverse polarity Povarov reaction of aryl imines and electron deficient alkenes is described. Operating via a putative nucleophilic α-amino radical, generated by a proton coupled electron transfer process, addition to a range of conjugated electron deficient alkene substrates affords substituted tetrahydroquinoline products in high yields and with typically good to excellent diastereoselectivity in favor of the trans diastereoisomer. Sub-stoichiometric quantities of Hantzsch ester were found to be key to initiate the overall redox-neutral, free radical cyclization cascade. This new reaction complements existing two electron Lewis acid mediated variants and expands the capabilities of imine umpolung chemistry to synthetically relevant cyclisation methodology.