Changes in Distribution of Lower Limb Alignment After Total Hip Arthroplasty for Crowe IV Developmental Dysplasia of the Hip.
The purpose of this study was to evaluate the distribution of lower limb alignment in Crowe IV developmental dysplasia of the hip (DDH) before and after total hip arthroplasty (THA). We retrospectively included 64 Crowe IV DDH patients (87 hips) who underwent THA between February 2010 and May 2019. Radiographic parameters were measured on full limb length standing anteroposterior radiographs, including hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), anatomical lateral distal femoral angle (aLDFA), and anatomical tibiofemoral angle (aTFA). HKA improved from 176.54°±3.52° preoperatively to 179.45°±4.31° at the last followup (P<0.001). According to the preoperative HKA, 40 hips were defined as knee valgus alignment. The majority of them were characteristic of a valgus mLDFA and a valgus or neutral mMPTA (35%, 47.5%). After THA, there were still 22 hips defined as knee valgus alignment. More than 50% of them were characteristic of a valgus mLDFA and a neutral mMPTA. Five hips (22.7%) revealed valgus alignment in both mLDFA and mMPTA. Twenty-one hips (24.1%) remained knee valgus alignment before and after surgery. One hip, defined as neutral alignment, preoperatively turned into valgus alignment after surgery. Both preoperative and postoperative sources of valgus alignment were mainly from the femoral side among Crowe IV DDH patients. THA mainly played a positive role in the reconstruction of lower limb alignment in these patients.


Increased retinoic acid responsiveness in lung carcinoma cells that are nonresponsive despite the presence of endogenous retinoic acid receptor (RAR) beta by expression of exogenous retinoid receptors retinoid X receptor alpha, RAR alpha, and RAR gamma.
Nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are thought to mediate most of the effects of retinoids on cell growth and differentiation. Despite expressing abundant levels of RAR beta mRNA, lung adenocarcinoma H1792 cells are resistant to the growth-inhibitory effects of all-trans-retinoic acid, suggesting that they have a defect in retinoid signaling. To determine whether transfection of exogenous receptors can restore retinoid responsiveness, we transiently transfected into H1792 cells coexpression vectors containing cDNAs of cell surface antigen CD7 and either RAR alpha, RAR beta, RAR gamma, or RXR alpha. The cells were then treated with retinoids and incubated with 5'-bromo-2'-deoxyuridine. Cells that express exogenous receptor were identified using antibodies against CD7, and cells that synthesized DNA were identified with anti-5'-bromo-2'-deoxyuridine antibodies using secondary antibodies with red and green fluorescence, respectively. RXR alpha and RAR alpha enhanced growth inhibition by all-trans-retinoic acid or 9-cis-retinoic acid, whereas RAR gamma was less effective, and RAR beta was ineffective. The effects of the transfected receptors were associated with antagonism of activator protein 1 (AP-1) activity. Studies with RXR alpha deletion and point mutants indicated that growth suppression is: (a) dependent on intact DNA-binding and ligand-binding regions but not on the NH2-terminal region, which contains a ligand-independent transactivation function; (b) dependent on RXR homodimer formation and transactivation of RXR response element; and (c) associated with AP-1 antagonism. These results demonstrate that transfected receptors can restore responsiveness to retinoids by antagonizing AP-1 in H1792 cells.


[Malignant histiocytofibroma of the bladder. A case report].
Malignant histiocytofibroma of the bladder is a rare (16 cases reported in the literature) and very aggressive sarcoma. It is sometimes associated with a haematological malignancy. The authors report a case of malignant histiocytofibroma of the bladder in a 72-year-old haemodialysed woman with a poor general status. She had a history of chemotherapy and radiotherapy for gastrointestinal lymphoma 6 years previously. Treatment consisted of palliative cystectomy for bladder pain and haematuria. A massive pelvic and abdominal wall recurrence occurred two months after cystectomy and the patient died. The authors review the 16 cases of malignant histiocytofibroma of the bladder reported in the literature. Histiocytofibroma is a tumour which requires aggressive treatment with a combination of radical surgery and systemic chemotherapy.


Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.


First- and second-order contributions to depth perception in anti-correlated random dot stereograms.
The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed-depth has been found using anti-correlated random-dot stereograms (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter.


The lateral spinal artery of the upper cervical spinal cord. Anatomy, normal variations, and angiographic aspects.
The lateral spinal artery corresponds to the most rostral extent of the posterolateral arterial axis of the spinal cord. It supplies the posterior and lateral aspects of the spinal cord, and courses anterior to the posterior roots of the upper cervical spinal nerves (C-1 to C-4), and posterior to the dentate ligament. The lateral spinal artery anastomoses rostrally with the branches of the posterior inferior cerebellar artery (PICA) at the restiform body and laterally with the extraspinal arteries at the emergence of each nerve. It may originate either from the vertebral artery or from the PICA lateral to the medulla. Certain variations will cause an unusual but normal enlargement of the vessel in a specific portion of its course; these variations include vertebral artery duplication, a C-1 or C-2 vertebral origin of the PICA, a C-1 or C-2 occipital origin of the PICA, and an intradural course of the vertebral artery at C-2. Knowledge of these variations in the arterial supply to the area allows for an understanding of the different anatomic peculiarities present and their angiographic importance.


Effects of industrial polystyrene foam insulation pads on the center of pressure and load distribution in the forefeet of clinically normal horses.
To evaluate the ability of industrial polystyrene foam insulation pads to redistribute loads placed on clinically normal weight-bearing structures of the foot and shift the location of the center of pressure palmarly in horses. 25 nonlame mature horses. Both forefeet from each horse were evaluated. Center of pressure data and solar load distribution patterns were recorded during a 5-second trial by use of a commercial pressure measurement system prior to placement of foam sole support and at 0, 6, 12, 24, and 48 hours after placement. Total contact surface area, contact pressure, peak contact pressure, and center of pressure positions were compared by use of a linear mixed model with repeated measurements. Total contact surface area was increased significantly at all time points, whereas contact pressure and peak contact pressure were significantly decreased at all time points following application of foam sole supports. Immediately following application of sole support, the position of the center of pressure was significantly moved cranially. However, by 48 hours, the center of pressure was significantly positioned more palmarly than prior to application of the foam supports. Results indicated that the use of foam sole supports may be an effective, economical, and immediate treatment for acute laminitis.


Neoplastic meningitis: How MRI and CSF cytology are influenced by CSF cell count and tumor type.
Although CSF cytology and MRI are standard methods to diagnose neoplastic meningitis (NM), this complication of neoplastic disease remains difficult to detect. We therefore reevaluated the sensitivity of gadolinium (GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology and the relevance of tumor type and CSF cell count. We retrospectively identified 111 cases of NM diagnosed in our CSF laboratory since 1990 with complete documentation of both MRI and CSF cytology. 37 had haematological and 74 solid neoplasms. CSF cell counts were increased in 74 and normal in 37 patients. In hematological neoplasms, MRI was positive in 49% and CSF cytology in 97%. In solid tumors, the sensitivity of MRI was 80% and of cytology 78%. With normal CSF cell counts, MRI was positive in 59% (50% hematological, 72% solid malignancies) and CSF cytology in 76% (92% in hematological, 68% in solid neoplasms). In cases of elevated cell counts, the sensitivity of MRI was 72% (50% for hematological, 83% for solid malignancies) and of CSF cytology 91% (100% for haematological and 85% for solid neoplasms). 91% of cytologically positive cases were diagnosed at first and another 7% at second lumbar puncture. Routine protein analyses had a low sensitivity in detecting NM. The high overall sensitivity of MRI was only confirmed for NM from solid tumors and for elevated CSF cell counts. With normal cell counts and haematological neoplasms, CSF-cytology was superior to MRI. None of the analysed routine CSF proteins had an acceptable sensitivity and specificity in detecting leptomeningeal disease.


First report of Escherichia coli O157 among Iraqi children.
We determined the prevalence of enterohaemorrhagic Escherichia coli, especially E. coli O157, and other enteropathogens among 200 children with bloody diarrhoea and 100 age-matched controls at two Baghdad hospitals. Bacterial and parasitic agents were found in 39.5% and 28.5% of cases, respectively; no pathogen was detected in 32%. E. coli O157 was identified in 11.5% and more than one pathogen was found in 15.5% of cases. The most common pathogens were enteropathogenic E. coli (EPEC) (5%); E. coli other than E. coli O157 or EPEC (15%); Entamoeba histolytica (25%) and Giardia lamblia (3.5%). All isolates of E. coli O157:H7 were sensitive to cephalexin, ciprofloxacin, gentamicin and nalidixic acid and resistant to erythromycin, polymyxin B and vancomycin. Resistance to 6 or more antimicrobial agents was common (50% of isolates).


Implicit Environmental Injustice in Global Trade: Based on the MRIO Model.
To answer these questions in light of the MRIO model, this paper presents a study of environmental injustice affecting the global economy. Practical ideas and lifespan measurements are often used in studies of the embodied carbon industry. The input-output table method is an important method for industrial embodied carbon research, which can be divided into the regional input-output table method, bilateral input-output table method, and multiregional input-output table method. Bilateral and multistakeholder consultations are more accurate than regional proposals. Therefore, when studying the carbon industry implied by the two countries, the input-output table of the two countries is usually used, and the multilateral input-output table is more reliable for determining the input-output calculation. Therefore, when studying local problems, it is advisable to adopt a variety of display strategies. The results show that in 2010, the carbon content of the carbon industry was 26,593 thousand tons, down 34.6% from 17,383 thousand tons in 2011, calculated at 2%. From 2012 to 2018, the carbon content grew from 31,051 tons in 2014 to 84,248 tons in 2018, with an average annual increase rate of 18%. The experimental results show that there is a large incidence of carbon emissions in the bilateral trade between China, the United States, and Japan. The expansion of export industries is the main reason for the increase in carbon emissions between the two industries. The role of technology has narrowed this difference to some extent.


Sedentarism, Physical Activity, Steps, and Neurotrophic Factors in Obese Children.
This study aimed to examine the associations of sedentary time, physical activity (PA) and step-related behaviors with neurotrophic growth factors. A total of 97 children with overweight/obesity age 8 to 11 yr participated in this study. Sedentary time, PA, and steps were measured by GT3X+ accelerometers in hip and nondominant wrist. Estimates of light, moderate, vigorous, and moderate-to-vigorous PA (MVPA) were obtained. Steps per daytime, peak 60-, 30-, and 1-min cadence were computed. The time accumulated (min·d) in different cadence bands of steps was also computed from hip accelerometer. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin growth factor-1 (IGF-1) were determined by the XMap technology (Luminex IS 100/200 system, Luminex Corporation, Austin, TX). Light PA, moderate PA, MVPA, and the peak 60-min cadence were positively related with BDNF concentrations (all P < 0.05), and only light PA to VEGF (P = 0.048). No association was observed for IGF-1 (P > 0.05). The associations of light PA with BDNF and VEGF disappeared (all P > 0.05) after performing analyses with nondominant wrist-placement data. However, moderate PA and MVPA remained significantly associated with BDNF (both P < 0.05). The time accumulated in cadence bands of 40 to 59 steps per day and 60 to 79 steps per day (i.e., walking at slow pace) was positively associated with plasma BDNF (all P < 0.05). In conclusion, PA is positively related to plasma BDNF, whereas no relationship was observed for VEGF or IGF-1. Higher amounts of time spent in slow walking cadence bands could increment BDNF levels. Exercise-based randomized controlled trials in children with overweight/obesity should be carried out to better understand the influence of PA behaviors on the neurotrophic factors.


Caring for the hypertensive newborn: a prospective evaluation of risk factors, clinical profile, management, and predictors of outcome of neonatal hypertension.
With the advancement of neonatal care and routine blood pressure monitoring, neonatal hypertension (NHT) has been increasingly recognised over the past few decades. NHT is known to cause target organ damage and risk of renal dysfunction later in life. However, diagnosis and management of NHT remain challenging, and there is a lack of evidence on the persistence of hypertension beyond the neonatal period and factors predicting its severity. This study aimed to identify risk factors, clinical profiles, predictors of the severity of hypertension, and short-term outcomes of NHT. A cohort of neonates diagnosed with hypertension requiring pharmacotherapy from September 2019 to July 2021 was prospectively enrolled. Demographic data, risk factors, the severity of hypertension, target organ damage, and follow-up for the persistence of hypertension at 3, 6, and 12 months of age were recorded. Of 1682 neonates admitted during this period, 34 had hypertension requiring pharmacotherapy, with a hospital incidence rate of 2%. Of these, 19 (55.9%) were preterm, 14 (41.2%) very low birth weight, and 15 (44.1%) were small for gestational age. Malignant hypertension was seen in 29 (85%) cases, moderate hypertension in 5 (15%) cases, and target organ damage (heart, brain, liver) was seen in 10 (29.4%) cases. On univariate and multivariate regression, an increasing total number of postnatal risk factors was an independent predictor of the occurrence of hypertensive crisis (OR = 3.5, p = 0.04; 95% CI 1.06-11.42). A significant positive correlation (p = 0.004) was observed between total number of postnatal risk factors and the duration of hospital stay. Renal causes of hypertension were identified significantly earlier (day 14 vs. 23, p = 0.01, 95% CI 2.5-17) and had shorter hospital stay (24 vs 45 days, p = 0.002, 95% CI 834). At 3 months follow-up, 7 (20.6%) babies were still requiring antihypertensive therapy, and 1 (3%) required antihypertensives at 6 and 12 months of age. Conclusion: NHT is a clinically important but underrecognised entity. Hypertension was seen in preterm, low birth weight neonates and associated with certain maternal and postnatal risk factors, with majority responding to a single drug. Neonates with multiple comorbid illnesses need careful monitoring for hypertension as they are at a higher risk of developing hypertensive crisis. Most NHT cases were normotensive at the time of discharge and did not require pharmacotherapy beyond the neonatal period. What is Known: • Neonatal hypertension (NHT) is an under-recognised entity, and the spectrum of clinical presentation varies from asymptomatic to severe target organ damage. • Hypertension is commonly seen in preterm, low birth weight neonates and associated with certain maternal and postnatal risk factor. What is New: • NHT is mostly transient, but intrauterine growth retardation, use of antenatal steroids, renal dysfunction due to congenital anomalies, drugs, and chronic lung disease may lead to the persistence of hypertension beyond the neonatal period. • Neonates with multiple comorbid illnesses need careful monitoring for hypertension as they are at a higher risk of developing hypertensive crisis. Three-fourths of hypertensive neonates respond to a single antihypertensive drug, and only one-fourth of patients required an additional drug to control hypertension. Most neonates respond to short duration of treatment, and only a few patients require long-term therapy.


Prevention of post-coronary artery bypass grafting (CABG) atrial fibrillation: efficacy of prophylactic beta-blockers in the modern era: a meta-analysis of latest randomized controlled trials.
Atrial fibrillation/flutter (AF) is a common complication of open heart surgery and ACC/AHA guidelines strongly recommend the use of prophylactic beta-blockers (BB) for its prevention. Several recent studies, however, have failed to show the desired protective effects of BB against post-coronary artery bypass grafting (CABG) AF. As the protocols of CABG, medical management of CAD (coronary artery disease) and demographic features of the patients undergoing open heart surgery have evolved significantly over the last two decades, we decided to perform a review of evidence from latest randomized controlled trials (RCTs) to confirm the efficacy of prophylactic BB. We searched for RCTs comparing the efficacy of prophylactic BB versus placebo/control against post-CABG AF. We limited our search to 1995 till present to reflect ongoing advancements in the protocols of CABG and the medical management of CAD. Initially, 34 trials were selected; however after certain exclusions only 10 RCTs were included in the final analysis. Prophylactic BB decreased the incidence of post-CABG AF from 32.8% in the control group to 20% in the prophylactic group with risk ratio (RR) of 0.50 with 95% CI of 0.36-0.69, P value < 0.001. In a subgroup analysis, carvedilol appears to be superior to metoprolol for the prevention of postoperative AF. Despite several limitations, this analysis confirms the efficacy of prophylactic BB against post-CABG AF in this era. We recommend continuing perioperative BB in the open heart surgery patients in the absence of contraindications.


Insurance coverage and health care spending by state-level Medigap regulations.
Medigap protects traditional Medicare (TM) beneficiaries against catastrophic expenses. Federal regulations around Medigap enrollment and pricing are limited to the first 6 months after turning 65 years old. Eight states institute regulations that apply to later enrollment; half use community rating (charging everyone the same premium) and half use both community rating and guaranteed issue (requiring insurers to accept any beneficiary irrespective of health conditions). We examined the impact of state-level Medigap regulations on insurance coverage and health care spending for Medicare beneficiaries. We used a retrospective cohort study design. Using the 2010-2016 Medicare Current Beneficiary Survey, we identified beneficiaries with TM only, TM + Medigap, or Medicare Advantage (MA) by state-level Medigap regulations. Outcomes were insurance coverage and health care spending. We used an instrumental variable approach to address endogenous insurance choice. We conducted 2-stage least squares regression while controlling for individual-level characteristics and area-level demographic characteristics. Then we used the recycled prediction methods to predict enrollment and spending outcomes for the 3 state-level Medigap regulation scenarios. Although enrollment in TM only was consistent across regulation scenarios, the scenario with community rating and guaranteed issue had lower Medigap enrollment and higher MA enrollment than the no-regulation scenario. Despite negligible health differences, TM + Medigap beneficiaries had higher Medicare spending than TM-only beneficiaries, suggesting moral hazard. Our findings suggest a link between additional regulations and lower Medigap and higher MA enrollment. Policy makers should consider the potential effects on insurance coverage, premiums, financial protection, and moral hazard when designing Medigap regulations.


Ranking populations in terms of inequality of health opportunity: A flexible latent type approach.
We offer a flexible latent type approach to rank populations according to unequal health opportunities. Building upon the latent-class method, an approch increasingly adopted to estimate health inequalities, our contribution is to let the number of socioeconomic groups considered vary to obtain an opportunity-inequality curve for a population that gives how the between-type inequality varies with the number of types. A population A is said to have less inequality of opportunity than population B if its curve is statistically below that of population B. This version of the latent class approach allows for a robust ranking of 31 European countries regarding inequality of opportunity in health.


Causes of mortality in diabetes mellitus: data from a tertiary teaching hospital in India.
Mortality studies can show the relative contribution of diabetes to mortality in the total population, and they can provide important descriptions of the changes in causes and frequency of diabetes mortality over time. To find the mortality pattern in people with diabetes admitted to a tertiary care hospital in a developing country, using underlying/contributory causes of death. In this retrospective study, mortality trends among people with diabetes admitted to Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India were reviewed by screening the hospital records of all people with diabetes who died over the last 9 years, carrying forward earlier observations from the same centre. Of 234 776 people admitted to the centre during the review period, 16 690 (7.11%) died; 741 (383 men) of these had diabetes mellitus mentioned on the death certificate. The mean (SD) age at death for people with diabetes was 60.07 (13.62) years in men and 57.36 (13.40) years in women. The leading contributory causes of death were infections (40.9%), chronic renal failure (33.6%), coronary artery disease (16.9%), cerebrovascular disease (13.2%), chronic obstructive pulmonary disease (6.9%), acute renal failure (6.2%), malignancy (4.2%), hypoglycaemia (3.5%) and diabetic ketoacidosis (3.4%). The cause of death could not be ascertained in 2.8% of cases; in 52.9%, 36.3% and 8.0% cases one, two and three or more causes, respectively, were recorded as the cause of death. The aetiological spectrum of mortality in people with diabetes at this Indian centre continues to be dominated by infections and renal failure, which is different from that in the developed world, where coronary artery disease and cerebrovascular disease are the principal causes of death in people with diabetes.


Pregnancy with Pemphigoid Gestationis: A Rare Entity.
Pemphigoid Gestationis (PG) is a rare autoimmune blistering disease with an incidence of 1/50000 pregnancies. Presentation in the second or third trimester is most common and tends to recur in subsequent pregnancies with earlier onset and a more severe course. Direct Immunofluorescence (DIF) staining is confirmatory on skin biopsy specimen. A 24-year-old female presented at 6 months period of gestation with increased blood pressure records. On examination, there were fresh bullous lesions along with old healed scar marks on the abdomen and limbs. Termination of pregnancy was done due to high BP. Patient delivered a fresh still birth weighing 750 gm. No postpartum flare ups were seen and she was discharged on prednisolone in a satisfactory condition.


Nonlinear resonant absorption effects on the design of resonance fluorescence lidars and laser guide stars.
Saturation effects may significantly reduce the backscattered signal expected for resonance fluorescence lidar systems. Saturation arises when the laser energy density within the layer is large enough to significantly alter the population densities of the atomic states within the layer. These altered state populations lead to nonlinear absorption of the laser energy resulting in reduced rate of fluorescence and increased rate of stimulated emission. The level of saturation is determined by the laser pulse length, pulse energy, beam-width, and linewidth. Analysis reveals that the saturation effects can be characterized by two parameters: the saturation time tau(s) and the rms laser linewidth Deltaomega(rms).The saturation time is the characteristic time of stimulated emission and is an indication of the level of saturation. The saturation time depends on pulse energy, pulse length, and beamwidth. The laser linewidth is important since it determines the effective absorption cross section of the atoms and also the percentage of atoms illuminated for an inhomogeneously broadened absorption line. The impact of saturation on lidar design is also examined. Design examples, including lidar systems for atmospheric research and laser guide stars for adaptive imaging applications in astronomy are studied in detail.


Associations of four circulating chemokines with multiple atherosclerosis phenotypes in a large population-based sample: results from the dallas heart study.
Specific chemokines contribute to vascular inflammation and may be useful biomarkers to detect atherosclerosis. The chemokines CXCL1 and CCL11 have previously been studied in animal or human models of atherosclerosis, while CXCL2 and CCL23 have not. Among 2,454 subjects enrolled in the Dallas Heart Study, a multi-ethnic population-based sample, we measured plasma CCL11, CCL23, CXCL1, and CXCL2, and associated levels with coronary artery calcium (CAC) by computed tomography, and aortic wall thickness, plaque burden, and compliance by magnetic resonance imaging. Elevated chemokine levels were defined as greater than or equal to the median for CCL11 and CCL23 and greater than or equal to the upper detection limit for CXCL1 and CXCL2. Elevated CCL23 (P < 0.01) and CXCL1 (P = 0.01), but not CCL11 and CXCL2, associated with CAC in univariable analyses. After adjustment for traditional risk factors, elevated CCL23 remained associated with CAC (OR 1.3, 95% CI 1.0-1.7; P = 0.02), while the association with CXCL1 was modestly attenuated (OR 1.4, 95% CI 1.0-2.1; P = 0.06). CCL23 also associated with aortic wall thickness, plaque, and compliance in univariable analyses (P < 0.05 for each), but these associations were attenuated after multivariable adjustment. The novel chemotactic protein, CCL23, which has not been previously studied in atherosclerosis, is independently associated with coronary atherosclerosis, suggesting that this chemokine merits further study in animal and human models.


Opioid-mediated regulation of A11 diencephalospinal dopamine neurons: pharmacological evidence of activation by morphine.
Dopamine (DA) neurons of the A11 diencephalospinal system represent the sole source of DA innervation to the spinal cord in mice, serving neuromodulatory roles in the processing of nociceptive input and movement. These neurons originate in the dorso-caudal diencephalon and project axons unilaterally throughout the rostrocaudal extent of the spinal cord, terminating predominantly in the dorsal horn. The density of A11 DA axon terminals in the lumbar region is greater in males compared to females, while in both sexes the activity of neurons terminating in the thoracic spinal cord is greater than those terminating in the lumbar region. The present study was designed to test the hypothesis that A11 DA neurons are activated by opioids. To test this hypothesis, male and female mice were systemically treated with agonists or antagonists acting at the μ-opioid receptor, and spinal cord concentrations of DA and its metabolite DOPAC were determined in the thoracic and lumbar spinal cord using high performance liquid chromatography coupled with electrochemical detection. Systemic administration of the μ-opioid agonist morphine led to a dose- and time-dependent increase in spinal cord DOPAC/DA ratio (an estimate of DA neuronal activity) in both male and female mice, with greater changes occurring in the lumbar segment. Blockade of opioid receptors with the opioid antagonist naloxone reversed the stimulatory effects of morphine on A11 DA neurons in both male and female mice, but had little to no effect on the activity of these neurons when administered alone. Present findings are consistent with the conclusion that spinal cord-projecting axon terminals of A11 DA neurons are activated by opioids in both male and female mice, most likely through a dis-inhibitory mechanism.


Minimum size limits and the reproductive value of numerous, young, mature female fish.
Fisheries management relies on various catch and effort controls to preserve spawning stock biomass and maximize sustainable yields while limiting fishery impacts on marine ecosystems. These include species-specific minimum or maximum size limits to protect either small non-reproductive subadults, a portion of reproductively mature adults, or large highly fecund individuals. Protecting size classes of mature fish is expected to yield a viable source of larvae for replenishing populations and reduce the risk of recruitment overfishing, yet size-specific recruitment contributions have rarely been assessed empirically. Here, we apply genetic parentage analysis to measure the reproductive success of a size-structured population of a commercially important species of coral grouper (Plectropomus maculatus-Serranidae) in no-take marine reserves (NTMRs) in the Great Barrier Reef Marine Park, Australia. Although the per capita reproductive success of individual fish increases rapidly with body length, the numerous young mature female fish, below the minimum size limit (MSL) (38 cm total length), were responsible for generating disproportionately large contributions (36%) towards larval replenishment of both fished and reserve reefs. Our findings indicate that MSLs are an effective harvest control measure to safeguard a portion of the spawning stock biomass for coral grouper and supplement recruitment subsidies assured from NTMRs.


Comparison of the protective effect of self-emulsifying peptide drug delivery systems towards intestinal proteases and glutathione.
The aim of this study was to evaluate the protective effect of self-emulsifying drug delivery systems (SEDDS) for therapeutic peptides towards intestinal proteases and reduced glutathione (GSH). Sodium docusate was applied as anionic surfactant for hydrophobic ion pairing with leuprorelin (LEU), insulin (INS) and desmopressin (DES). The complexes were loaded into SEDDS that were characterized regarding droplet size distribution and zeta potential. The release profile of the peptides was examined by dialysis membrane method. Enzymatic digestion studies were performed by applying α-chymotrypsin, trypsin and elastase. Furthermore, the protective effect of SEDDS towards degradation through thiol-disulfide exchange reactions was examined by addition of GSH. SEDDS showed a mean droplet size of 0.27-3.9μm and a zeta potential of -25 to -33mV. All formulations provided a sustained release of the peptides over 6h. Degradation of the model peptides by intestinal proteases and GSH could only be observed in the release medium. In the oily phase of SEDDS neither any of the proteases nor GSH was soluble (≤0.1%). Furthermore, no degradation of the model peptides by proteases and GSH took place in the oily phase of SEDDS. SEDDS can provide a 100% protective effect towards protease degradation and deactivation by GSH. According to this, SEDDS might be promising tools for oral delivery of peptide drugs.


Catalytically inactive Cas9 impairs DNA replication fork progression to induce focal genomic instability.
Catalytically inactive Cas9 (dCas9) has become an increasingly popular tool for targeted gene activation/inactivation, live-cell imaging, and base editing. While dCas9 was reported to induce base substitutions and indels, it has not been associated with structural variations. Here, we show that dCas9 impedes replication fork progression to destabilize tandem repeats in budding yeast. When targeted to the CUP1 array comprising ∼16 repeat units, dCas9 induced its contraction in most cells, especially in the presence of nicotinamide. Replication intermediate analysis demonstrated replication fork stalling in the vicinity of dCas9-bound sites. Genetic analysis indicated that while destabilization is counteracted by the replisome progression complex components Ctf4 and Mrc1 and the accessory helicase Rrm3, it involves single-strand annealing by the recombination proteins Rad52 and Rad59. Although dCas9-mediated replication fork stalling is a potential risk in conventional applications, it may serve as a novel tool for both mechanistic studies and manipulation of genomic instability.


MicroRNA-155 Expression Is Enhanced by T-cell Receptor Stimulation Strength and Correlates with Improved Tumor Control in Melanoma.
microRNAs are short noncoding RNAs that regulate protein expression posttranscriptionally. We previously showed that miR-155 promotes effector CD8+ T-cell responses. However, little is known about the regulation of miR-155 expression. Here, we report that antigen affinity and dose determine miR-155 expression in CD8+ T cells. In B16 tumors expressing a low-affinity antigen ligand, tumor-specific infiltrating CD8+ T cells showed variable miR-155 expression, whereby high miR-155 expression was associated with more cytokine-producing cells and tumor control. Moreover, anti-PD-1 treatment led to both increased miR-155 expression and tumor control by specific CD8+ T cells. In addition, miR-155 overexpression enhanced exhausted CD8+ T-cell persistence in the LCMV cl13 chronic viral infection model. In agreement with these observations in mouse models, miR-155 expression in human effector memory CD8+ T cells positively correlated with their frequencies in tumor-infiltrated lymph nodes of melanoma patients. Low miR-155 target gene signature in tumors was associated with prolonged overall survival in melanoma patients. Altogether, these results raise the possibility that high miR-155 expression in CD8+ tumor-infiltrating T cells may be a surrogate marker of the relative potency of in situ antigen-specific CD8+ T-cell responses.


ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation.
Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Our previous studies found that the activation of insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II (ANG II)-induced cardiomyocyte apoptosis. However, the detailed mechanism by which ANG II regulates IGF-IIR in heart cells remains elusive. In this study, we found that ANG II activated its downstream kinase JNK to increase IGF-IIR expression through the ANG II receptor angiotensin type 1 receptor. JNK activation subsequently led to sirtuin 1 (SIRT1) degradation via the proteasome, thus preventing SIRT1 from deacetylating heat-shock transcription factor 1 (HSF1). The resulting increase in the acetylation of HSF1 impaired its ability to bind to the IGF-IIR promoter region (nt -748 to -585). HSF1 protected cardiomyocytes by acting as a repressor of IGF-IIR gene expression, and ANG II diminished this HSF1-mediated repression through enhanced acetylation, thus activating the IGF-IIR apoptosis pathway. Taken together, these results suggest that HSF1 represses IGF-IIR gene expression to protect cardiomyocytes. ANG II activates JNK to degrade SIRT1, resulting in HSF1 acetylation, which induces IGF-IIR expression and eventually results in cardiac hypertrophy and apoptosis. HSF1 could be a valuable target for developing treatments for cardiac diseases in hypertensive patients.


Role of Scleral Contact Lenses in Management of Coexisting Keratoconus and Stevens-Johnson Syndrome.
To report the rare coexistence of keratoconus and Stevens-Johnson syndrome (SJS) managed with scleral contact lenses (ScCLs). This is a retrospective case series. Five patients (9 eyes) who had coexisting SJS and corneal ectasia were identified from the database during the 2-year period. Diagnosis of SJS was based on a positive history of drug reactions, signs of ocular surface disease, and the presence of keratinization of lid margins. Keratoconus was diagnosed by slit-lamp biomicroscopy. Five eyes of 3 patients had coexisting SJS and keratoconus and were dispensed with ScCLs (PROSE, prosthetic replacement of the ocular surface ecosystem; Boston Foundation for Sight, Needham Heights, MA). All these patients had photophobia. Visual acuity improved in all these patients with ScCL wear. Two patients (4 eyes) were excluded from this study because they had SJS with generalized corneal thinning from limbus to limbus, corneal opacification, and pannus. One patient developed deep vessels in the cornea on prolonged ScCL wear. Reduction in the ScCL wear schedule and change of material with a higher Dk resulted in regression of vascularization. Case 3 developed conjunctival congestion and was uncomfortable wearing ScCLs, although visual acuity was 20/40. He discontinued using ScCL wear. Keratoconus, a noninflammatory condition of the cornea coexisted with inflammatory SJS. Managing such patients with ScCLs may improve vision and comfort.


[Commission of inquiry scrutinized complications of carotid surgery. Half of the complications could be explicable by errors or dubious indications].
As carotid endarterectomy is a prophylactic procedure, it would seem particularly important to analyze complications with an aim to avoiding them. All carotid endarterectomies in Sweden are registered, and all serious complications (death and permanent neurological deficit) are analyzed in detail, classified and discussed within the profession. During the period 1994-1996 the frequency was 4.3 percent (technical causes in 17 percent, contraindications in 8 percent and dubious indications in 21 percent, but correct indication and surgery in 54 percent). Thus, even when conditions are optimal there is a certain price to pay for the prevention of ischemic stroke.


Primary malignant melanoma of the colon and the importance of an adequate anatomopathological analysis.
Primary malignant melanoma of the colon is an extremely rare tumor due to the absence of melanoblasts in this segment of the digestive tract. We report the case of a patient presenting an ulcerated lesion with a neoplastic appearance in the dentate line during a coloscopy. After chemotherapy and radiotherapy, surgical amputation was performed. The study of the surgical specimen described an invasive malignant melanoma located in the submucosa without involvement of the overlying epithelium or the muscularis propria, nor vascular or lymph node invasion, and with tumor free margins. The patient was presented to the melanoma committee, which determited follow up in consultations. This case strengthens the importance of a good anatomopathological study to prevent delays in diagnosis and appropriate treatment.


PRISMS: the story of a pivotal clinical trial series in multiple sclerosis.
The PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study was initiated in 1994, at which time there were few disease-modifying drugs for multiple sclerosis (MS). The PRISMS series of studies has since provided up to 8 years of clinical, magnetic resonance imaging (MRI), safety, and immunogenicity data on the use of subcutaneous (sc) interferon (IFN) beta-1a in patients with relapsing-remitting MS. This review is the first collation of all these data in one article, with a look ahead to the next generation of studies involving the new formulation of sc IFN beta-1a. Published efficacy, safety, and immunogenicity data, in terms of prospectively defined endpoints and later post hoc analyses, from years 1-8 of the PRISMS series are summarized and collated for the first time. Some of the studies of sc IFN beta-1a that evolved from the PRISMS studies are also discussed. In the 2-year, double-blind, randomized, placebo-controlled study, IFN beta-1a (22 or 44 mcg three times weekly [tiw]) was associated with significantly lower relapse rates, disability progression, and MRI burden of disease compared with placebo (p <or= 0.05). Subsequently, in the 2-year extension, patients previously receiving placebo were re-randomized to active treatment, and a further 2 years of open-label treatment confirmed good long-term safety and therapeutic efficacy. Follow-up visits at years 7 or 8 (68.2% of initial population) demonstrated a continued benefit for patients originally randomized to the 44-mcg dose compared with those receiving the 22-mcg dose or whose treatment had been delayed by 2 years. Neutralizing antibodies were more common in patients receiving the 22-mcg dose and attenuated treatment efficacy during years 1-4. Class I and long-term data from PRISMS support the use of sc IFN beta-1a tiw as a first-line treatment for MS, as evidenced by sustained efficacy rates, acceptable safety profiles, and high patient retention rates.


Maize Canopy Apparent Photosynthesis and 13C-Photosynthate Reallocation in Response to Different Density and N Rate Combinations.
Appropriate planting density and nitrogen (N) supply are critical factors optimizing yield in crop cultivation. To advance the knowledge of maize plants under different density and N rate combinations, responses of canopy apparent photosynthesis (CAP), and assimilate redistribution characters (by 13CO2 stable isotope tracing) were investigated. In this study, two maize varieties DH618 and DH605 were grown at various planting densities (6.75, 8.25, 9.75, and 11.25 pl m-2) and N application rates (0, 180, 270, 360, and 540 kg ha-1) during 2013-2015. Maize grain yield (GY) was maximized at a density of 9.75 pl m-2 with 180-360 kg ha-1 N during the three study years. Maize GY, biomass, CAP, leaf area index (LAI), and 13C-photosynthate reallocation all responded more intensively to density than N rate, but the N response differed between varieties. We established links among CAP, LAI and biomass, and GY and kernel number per unit area (KNA). CAP depended on high LAI and enzyme activities for photosynthesis, yet both N deficiency and N excess had inhibitory effects. Besides, relations between 13C-photosynthate reallocation and yield components were executed. High density increased the 13C-photosynthate distribution in vegetative organs but reduced the allocation in ear, while N supply moderated the response. Based on our results, maize plants with greater CAP, more 13C-photosynthate distribution to ears, and less 13C-photosynthate distribution to stems under different density and N rate combinations could improve KNA and achieve a greater GY consequently.


The role of contaminants in hexachlorobenzene toxicity.
Hexachlorobenzene (HCB) is hepatotoxic, causing a porphyria with an acquired deficiency of uroporphyrinogen decarboxylase. Conflicts have arisen regarding the toxicological significance of impurities in samples of HCB. In female rats, unpurified practical-grade HCB from Eastman Kodak Company was more porphyrogenic than a sample from Aldrich Chemical Company that had been recrystallized from benzene. To determine whether specific inducers of hepatic microsomal cytochrome P1-450, such as 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), contributed to the difference in toxicity of these samples, induction of porphyria and activities of the cytochrome P1-450-dependent mono-oxygenase, ethoxyresorufin-O-deethylase (ERR), were compared in rats receiving HCB (0.2% w/w) or TCDD (10 micrograms/kg initial dose, then 2.5 micrograms/kg weekly). Porphyria occurred in the former but ERR activity was induced about four times more in the latter. The relative potency of crude and purified HCB samples in inducing ERR activity was further evaluated in C57Bl/6 and DBA/2 mice; ERR activity was three times higher in C57Bl/6 than in DBA/2 mice treated with 0.01% w/w HCB. ERR activity was also higher in C57Bl/6 mice treated with impure than in those treated with purified HCB. These results show that undefined impurities can be important determinants of the biological effects of HCB samples and suggest that these effects are partly mediated via the Ah receptor. However, porphyria induced by HCB appears to be independent of HCB impurities and not solely dependent on induction of the cytochrome-P1-450 mono-oxygenases.


Construction of a high-density genetic map and identification of loci controlling purple sepal trait of flower head in Brassica oleracea L. italica.
Some broccoli (Brassica oleracea L. italic) accessions have purple sepals and cold weather would deepen the purple color, while the sepals of other broccoli lines are always green even in cold winter. The related locus or gene is still unknown. In this study, a high-density genetic map was constructed based on specific locus amplified fragment (SLAF) sequencing in a doubled-haploid segregation population with 127 individuals. And mapping of the purple sepal trait in flower heads based on phenotypic data collected during three seasons was performed. A genetic map was constructed, which contained 6694 SLAF markers with an average sequencing depth of 81.37-fold in the maternal line, 84-fold in the paternal line, and 15.76-fold in each individual population studied. In all of the annual data recorded, three quantitative trait loci (QTLs) were identified that were all distributed within the linkage group (LG) 1. Among them, a major locus, qPH.C01-2, located at 36.393 cM LG1, was consistently detected in all analysis. Besides this locus, another two minor loci, qPH.C01-4 and qPH.C01-5, were identified near qPH.C01-2, based on the phenotypic data from spring of 2018. The purple sepal trait could be controlled by a major single locus and two minor loci. The genetic map and location of the purple sepal trait of flower heads provide an important foundation for mapping other compound traits and the identification of the genes related to purple sepal trait in broccoli.


Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment.
Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects. Seventy-five patients with probable AD, 96 individuals with MCI, and 53 age-matched and sex-matched healthy control subjects were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-terminus, C-terminus, and full-length BACE1. Compared with healthy control subjects, plasma BACE1 activity (Vmax) significantly increased by 53.2% in subjects with MCI and by 68.9% in patients with probable AD. Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD. Plasma BACE1 activity is significantly increased in MCI converters and patients with probable AD. The sensitivities and specificities of BACE1 activity for the patients were 84% and 88%, respectively. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.


Characterization of antimicrobial-resistant phenotypes and genotypes among Salmonella enterica recovered from pigs on farms, from transport trucks, and from pigs after slaughter.
The main objectives of this study were to determine antimicrobial resistance patterns among Salmonella serotypes and to evaluate the role of transport trucks in dissemination of antimicrobial-resistant strains of Salmonella. Salmonella from groups of nursery and finishing pigs on farms, from trucks, and from pigs after slaughter were compared using serotyping, patterns of antimicrobial resistance, and pulsed-field gel electrophoresis patterns. The five farms included in the study yielded 858 isolates representing 27 Salmonella serovars. The most common resistance observed (80% of all isolates) was to tetracycline; resistance to ampicillin (42%), chloramphenicol (31%), amoxicillin/clavulanic acid (30%), and piperacillin (31%) also were common. We found a correlation between serovar and antimicrobial resistance. High correlation was found between Salmonella Typhimurium var. Copenhagen and chloramphenicol resistance (Spearman rank correlation, rho = 0.7). Multidrug resistance was observed primarily in Salmonella Typhimurium var. Copenhagen (94%) and Salmonella Typhimurium (93%) and was much less common in the other common serovars, including Salmonella Derby (7%) and Salmonella Heidelberg (8%). Of the 225 isolates exhibiting the most common pentaresistance pattern in this study, amoxicillin/clavulanic acid-ampicillin-chloramphenicol-piperacillin-tetracycline, 220 (98%) were Salmonella Typhimurium var. Copenhagen, and 86% of the isolates of this serovar had this pattern. Isolates from the trucks were similar, based on pulsed-field gel electrophoresis patterns, to those from the cecum and mesenteric lymph nodes of pigs on two of the farms, suggesting the probable infection of pigs during transport. Class I integrons were also common among various serovars.


Enhanced dissolution and bioavailability of raloxifene hydrochloride by co-grinding with different superdisintegrants.
The present study investigated the effect of co-grinding raloxifene HCL (RHCL) with different superdisintegrants, namely crospovidone (CP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), using a ball mill, in order to determine the potential effect on dissolution rate and bioavailability of raloxifene hydrochloride (RHCL). The dissolution studies of the co-ground compositions and the corresponding physical mixtures were carried out in U.S. Pharmacopeia (USP) Type II apparatus. The solid state interactions of the co-ground and the physical mixtures were evaluated by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The pharmacokinetics of co-ground mixture (1 : 5 RHCL : CP) and milled RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague-Dawley rats. DSC studies showed that the crystalline nature of RHCL was reduced after co-grinding with superdisintegrants, while co-grinding with CP resulted in significant particle-size reduction of the mixture. Significant enhancement in dissolution rate was observed with co-ground mixture of RHCL with CP (1 : 5). The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with co-ground mixture of RHCL, CP (1 : 5) compared to animals treated with milled RHCL. Co-grinding of RHCL with CP, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability.


Fibrous dysplasia in children and its management.
The purpose of this review is to provide a comprehensive overview into the diagnosis and management of fibrous dysplasia (FD) in children. FD is a mosaic disorder arising from somatic Gαs variants, leading to impaired osteogenic cell differentiation. Fibro-osseous lesions expand during childhood and reach final disease burden in early adulthood. The mainstay of treatment focuses on surgical correction of skeletal deformities, physiatric care, and medical management of associated hyperfunctioning endocrinopathies. Bisphosphonates may be helpful to treat bone pain, but do not alter lesion quality or progression. Emerging evidence suggests that the RANKL inhibitor denosumab may be effective in improving lesion activity and mineralization, however further studies are needed to determine the potential utility of this and other novel therapies, particularly in children with FD. Management of children with FD has unique challenges related to skeletal growth and age-related lesion progression. Inclusion of children in clinical research is critical to develop effective treatment strategies to treat FD lesions and prevent their development.


A perspective on partially hydrolyzed protein infant formula in nonexclusively breastfed infants.
The World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life to provide optimal nutrition in this critical period of life. After this, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to 2 years of age or beyond. For nonbreastfed infants, infant formula is an available option to provide the nutrition needed. Infant formula is usually prepared from industrially modified cow's milk and processed to adjust for the nutritional needs of infants. However, cow's milk is one of the most common causes of food allergy, affecting 2%-5% of all formula-fed infants during their first year of life. One strategy to prevent cow's milk allergy in nonbreastfed infants is the use of partially hydrolyzed formula (pHF) in high-risk infants, which are infants born in families with atopic disease. However, based on an epidemiological study, approximately half of the infants who develop allergy are not part of the at-risk group. This is because the non-at-risk group is significantly larger than the at-risk group and the non-at-risk infants have approximately 15% risk of developing allergies. This study aimed to evaluate the effects of partially hydrolyzed whey formula (pHF-W) in nonbreastfed infants and determine whether pHF-W can prevent atopic disease in high-risk infants and can be used as routine starter formula regardless of the allergy risk status.


Prevalence and factors associated with use of smokeless tobacco in young Swiss men.
Smokeless tobacco is of increasing interest to public health researchers and policy makers. This study aims to measure prevalence of smokeless tobacco use (nasal dry snuff, snus and chewing tobacco) among young Swiss men, and to describe its correlates. We invited 13 245 young men to participate in this survey on socio-economic and substance use data. Response rate was 45.2%. We included 5720 participants. Descriptive statistics and multivariable-adjusted logistic regression were performed. Mean age of participants was 19.5 years. Self-reported use once a month or more often was 8% for nasal dry snuff, 3% for snus and negligible for chewing tobacco. In multivariable-adjusted logistic regression, the odds for nasal dry snuff use increased in non daily smokers [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.90-3.05], compared with non smokers, participants reporting risky weekly drinking volume (OR 3.93, 95% CI 1.86-8.32), compared with abstinents, and binge drinking once a month or more often (OR 7.41, 95% CI 4.11-13.38), compared with never binge drinking. Nasal dry snuff use was positively associated with higher BMI, average or above family income and German language, compared with French, and negatively associated with academic higher education, compared with non higher education, and occasional cannabis use, compared with no cannabis use. Correlates of snus were similar to those of nasal dry snuff. One in 12 young Swiss men use nasal dry snuff and 3% use snus. Consumption of smokeless tobacco is associated with a cluster of other risky behaviours, especially binge drinking.


A functional dermatan sulfate epitope containing iduronate(2-O-sulfate)alpha1-3GalNAc(6-O-sulfate) disaccharide in the mouse brain: demonstration using a novel monoclonal antibody raised against dermatan sulfate of ascidian Ascidia nigra.
Oversulfated chondroitin sulfate (CS), dermatan sulfate (DS), and CS/DS hybrid structures bind growth factors, promote the neurite outgrowth of hippocampal neurons in vitro, and have been implicated in the development of the brain. To investigate the expression of functional oversulfated DS structures in the brain, a novel monoclonal antibody (mAb), 2A12, was generated against DS (An-DS) from ascidian Ascidia nigra, which contains a unique iD disaccharide unit, iduronic acid (2-O-sulfate)alpha1-->3GalNAc(6-O-sulfate), as a predominant disaccharide. mAb 2A12 specifically reacted with the immunogen, and recognized iD-enriched decasaccharides as minimal structures. The 2A12 epitope was specifically observed in the hippocampus and cerebellum of the mouse brain on postnatal day 7, and the expression in the cerebellum disappeared in the adult brain, suggesting a spatiotemporally regulated expression of this epitope. Embryonic hippocampal neurons were immunopositive for 2A12, and the addition of the antibody to the culture medium significantly reduced the neurite growth of hippocampal neurons. In addition, two minimum 2A12-reactive decasaccharide sequences with multiple consecutive iD units were isolated from the An-DS chains, which exhibited stronger inhibitory activity against the binding of various growth factors and neurotrophic factors to immobilized embryonic pig brain CS/DS chains (E-CS/DS) than the intact E-CS/DS, suggesting that the 2A12 epitope at the neuronal surface acts as a receptor or co-receptor for these molecules. Thus, we have selected a unique antibody that recognizes iD-enriched oversulfated DS structures, which are implicated in the development of the hippocampus and cerebellum in the central nervous system. The antibody will also be applicable for investigating structural alterations in CS/DS in aging and pathological conditions.


Characterization of sphingosine 1-phosphate-induced actions and its signaling pathways in rat hepatocytes.
Sphingosine 1-phosphate (S-1-P) and lysophosphatidic acid (LPA) stimulated glycogen phosphorylase, a rate-limiting enzyme responsible for glycogenolysis, in association with Ca2+ mobilization and phospholipase C (PLC) activation in rat hepatocytes. S-1-P, but not LPA, also inhibited adenosine 3',5'-cyclic monophosphate accumulation reflecting adenylyl cyclase inhibition. S-1-P-induced PLC activation, Ca2+ mobilization, and phosphorylase activation were markedly enhanced by primary culture of the cells for 24 h, whereas the inhibitory adenosine 3',5'-cyclic monophosphate response was unchanged by increasing culture time. Activation of the PLC-Ca2+ system during primary culture was specific to the lysosphingolipid; PLC and Ca2+ responses to LPA and NaF were unchanged or slightly attenuated by increasing culture time. Pertussis toxin treatment almost completely suppressed the S-1-P-induced inhibition of adenylyl cyclase but hardly influenced the lipid-induced activation of PLC and its cascade reactions. We conclude that S-1-P, through an LPA receptor-independent mechanism, stimulates two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of adenylyl cyclase, through distinct S-1-P receptor-transducer systems, resulting in the modulation of glycogenolysis in rat hepatocytes.


Electric pulse-induced fusion of 3T3 cells in monolayer culture.
Swiss mouse 3T3-C2 fibroblasts, grown to confluence in monolayer culture, are shown to fuse when exposed to electric fields. Exposure to five repetitive electric pulses of about 1 kilovolt per centimeter with a duration of 50 microseconds caused approximately 20 percent of the cells to become fused (multinucleate) when 1 millimolar magnesium was present in the medium. The effects of minimum thresholds of field strength, pulse duration, and number of pulses were determined. Cell disruption was observed when the electric field exceeded 2.0 kilovolts per centimeter or the pulse was of longer duration than 120 microseconds.


The applicability of hormonal effects on atherosclerosis in animals to heart disease in postmenopausal women.
The discrepancy between estrogen's beneficial cardiovascular effects found in animal studies and observational studies in women compared with the recently published randomized clinical trials have stimulated a great deal of controversy. Possibilities for the discrepancy include the age of the women, number of years postmenopausal, and amount of atherosclerotic complication (necrosis and inflammation) present when hormone therapy is initiated. Many of the previous benefits of estrogens noted in both animal studies and observational studies were found in primary prevention studies that experimentally refer to a decrease in the progression of atherosclerosis extent rather than prevention of clinical events, which often occur in women with undiagnosed atherosclerotic plaques. In support of this notion, animal studies in which artery damage was present prior to hormone treatment, due to either consumption of an atherogenic diet or balloon injury of the endothelium, found no benefit with estrogen treatment. These animal studies are consistent with the lack of protection found in secondary prevention studies in women. Other areas of concern deal with the route of hormone delivery or dose of hormones used. Higher doses of oral estrogens may result in increased risk of inflammation and thrombosis. Future studies should be directed at studying hormone therapy in relevant ages of women (perimenopausal women) using the lowest effective doses of hormones and comparing oral and parenteral forms of delivery.


The application of risk assessment methods in making veterinary public health and animal health decisions.
The newly emerging discipline of quantitative risk assessment has wide application in the field of veterinary public health and animal health. Regulatory authorities are increasingly faced with public policy decisions that must assess the risks of new technology or practices relative to the potential benefits, thereby establishing a level of acceptable risk. The elements of risk are a choice of action, a probability of loss and a magnitude of loss. Perceived risk and actual risk are seldom equivalent; adoption of the methodologies used in technological and human health risk assessments will allow veterinary regulators to make better decisions. Determination of levels of acceptable risk are increasingly dependent on quantitative models, and examples are presented for evaluation of different post-mortem meat inspection systems, estimating disease risks associated with animal embryo transfer and formulating national border protection strategies. All models have some degree of subjectivity, and the decisions made by regulators and risk managers should incorporate a wide knowledge of the risk assessment process, as well as the conditions of use that will occur in the real world.


Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue.
In spite of advances in the molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease due to a deficiency of type VII collagen at the basement membrane zone (BMZ) of stratified epithelium, current therapy is limited to supportive palliation. Gene delivery has shown promise in short-term experiments; however, its long-term sustainability through multiple turnover cycles in human tissue has awaited confirmation. To characterize approaches for long-term genetic correction, retroviral vectors were constructed containing long terminal repeat-driven full-length and epitope-tagged COL7A1 cDNA and evaluated for durability of type VII collagen expression and function in RDEB skin tissue regenerated on immune-deficient mice. Type VII collagen expression was maintained for 1 year in vivo, or over 12 epidermal turnover cycles, with no abnormalities in skin morphology or self-renewal. Type VII collagen restoration led to correction of RDEB disease features, including reestablishment of anchoring fibrils at the BMZ. This approach confirms durably corrective and noninjurious gene delivery to long-lived epidermal progenitors and provides the foundation for a human clinical trial of ex vivo gene delivery in RDEB.


Amlodipine (150 mg) Poisoning: A Case Study.
Treatments of patients with amlodipine (a calcium channel blocker, CCB) overdose/poisoning remain challenging and death is certain if not intervened timely. Furthermore, for the society, the availability and common use of this drug can drive more vulnerable groups, especially children, towards an accidental/suicidal poisoning. Herein, we describe the case of an 18 year-old-adolescent girl who took 150 mg of amlodipine with the suicidal intentions and was admitted in our hospital approximately 4-hours after the ingestion. She developed circulatory failure and tachypnea. Decontamination, calcium, glucagon, and dual vasopressors were started, however, persistent hypotension led to the initiation of hyperinsulinemiceuglycemia therapy. She recovered fully and discharged without any complications in few days. This case educates not only about the successful use of variant drugs in the management of CCB overdose/poisoning, but also calls for the attention of the society for a safe storage of often used drugs, especially away from the children/adolescents.


Impact of COVID-19 on lifestyle and mental wellbeing in a drought-affected rural Australian population.
The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented social and economic disruption, accompanied by the enactment of a multitude of public health measures to restrain disease transmission. These public health and social measures have had a considerable impact on lifestyle and mental wellbeing, which has been well studied with metropolitan populations. However, limited literature concerning such effects on a selectively rural population is presently available. Additionally, the use of a standardised scoring system for lifestyle may be valuable for an overall assessment of lifestyle that may be incorporated into clinical practice. This study examined the associations between psychological distress and changes in SNAPS health behaviours (smoking, nutrition, alcohol, physical activity, sleep) since the onset of COVID-19 in Australia. A cross-sectional anonymous survey was distributed online to adults in the Western New South Wales Primary Health Network in August 2020 and included measures of psychological distress, income, disposition and lifestyle factors during the pandemic as well as changes to lifestyle due to COVID-19. A novel Global Lifestyle Score (GLS) was generated as a holistic assessment of lifestyle across multiple domains. The survey was completed by 304 individuals (modal age group 45-54 years, 86.8% female). High distress on the Kessler-5 scale was present in over one-third of participants (n=95, 33.7%). Detrimental change was reported for sleep (22.7%), nutrition (14.5%), alcohol (16.7%), physical exercise (34.0%) and smoking (24.7%) since the onset of the pandemic. Changes in sleep, nutrition, physical activity and smoking were associated with distress. Participants with a poor lifestyle (GLS) during the pandemic were significantly more distressed. Perceived COVID-19 impact was associated with high distress, drought impact and loss of income. Participants who reported negative impact from both COVID-19 and drought were significantly more distressed than those reporting a negative impact from drought alone or neither event. High rates of distress among rural Australians during the COVID-19 pandemic was linked to low GLS, worsening lifestyles and loss of income. Healthy lifestyle strategies should be considered by health professionals for the management of crisis-related distress. Further research may explore the impact of COVID-19 on a larger study population with a greater proportion of male participants and to examine the effect of modifying lifestyle factors in reducing distress in the context of a stressor such as this pandemic.


Design of Peptide-Based Nanovaccines Targeting Leading Antigens From Gynecological Cancers to Induce HLA-A2.1 Restricted CD8+ T Cell Responses.
Gynecological cancers are a leading cause of mortality in women. CD8+ T cell immunity largely correlates with enhanced survival, whereas inflammation is associated with poor prognosis. Previous studies have shown polystyrene nanoparticles (PSNPs) are biocompatible, do not induce inflammation and when used as vaccine carriers for model peptides induce CD8+ T cell responses. Herein we test the immunogenicity of 24 different peptides, from three leading vaccine target proteins in gynecological cancers: the E7 protein of human papilloma virus (HPV); Wilms Tumor antigen 1 (WT1) and survivin (SV), in PSNP conjugate vaccines. Of relevance to vaccine development was the finding that a minimal CD8+ T cell peptide epitope from HPV was not able to induce HLA-A2.1 specific CD8+ T cell responses in transgenic humanized mice using conventional adjuvants such as CpG, but was nevertheless able to generate strong immunity when delivered as part of a specific longer peptide conjugated to PSNPs vaccines. Conversely, in most cases, when the minimal CD8+ T cell epitopes were able to induce immune responses (with WT1 or SV super agonists) in CpG, they also induced responses when conjugated to PSNPs. In this case, extending the sequence around the CD8+ T cell epitope, using the natural protein context, or engineering linker sequences proposed to enhance antigen processing, had minimal effects in enhancing or changing the cross-reactivity pattern induced by the super agonists. Nanoparticle approaches, such as PSNPs, therefore may offer an alternative vaccination strategy when conventional adjuvants are unable to elicit the desired CD8+ T cell specificity. The findings herein also offer sequence specific insights into peptide vaccine design for nanoparticle-based vaccine carriers.


Impacts, Perceptions and Management of Climate-Related Risks to Cage Aquaculture in the Reservoirs of Northern Thailand.
Weather is suspected to influence fish growth and survival, and be a factor in mass mortality events in cage aquaculture in reservoirs. The purpose of this study was to identify the important climate-related risks faced by cage aquaculture farms; evaluate how these risks were currently being managed; and explore how farmers might adapt to the effects of climate change. Fish farmers were interviewed across the northern region of Thailand to get information on impacts, perceptions and practices. Drought or low water levels, heat waves, cold spells and periods with dense cloud cover, each caused significant financial losses. Perceptions of climate-related risks were consistent with experienced impacts. Risks are primarily managed in the short-term with techniques like aeration and reducing feed. In the mid-term farmers adjust stocking calendars, take financial measures and seek new information. Farmers also emphasize the importance of maintaining good relations with other stakeholders and reservoir management. Larger farms placed greater importance on risk management than small farms, even though types and levels of risk perceived were very similar. Most fish farms were managed by men alone, or men and women working together. Gender differences in risk perception were not detected, but women judged a few risk management practices as more important than men. Fish farmers perceived that climate is changing, but their perceptions were not strongly associated with recently having suffered impacts from extreme weather. The findings of this study provide important inputs to improving risk management under current and future climate.


[Preliminary study of peroxidlipid in edible oils and fats].
In this article we report that peroxidlipid in edible oil-fats is extracted by using thylene glycol and measured by using TBA colorimetric method. This method is simple, rapid and has a high degree of accuracy with CV of 4.5%. The contents of peroxidlipid have been studied for certain edible oil-fats before and after high heat. The results showed that the contents of LPO were markedly increased after high heating.


Negative asymmetry parameter in plasmonic core-shell nanoparticles.
Plasmonic nanoparticles with a dielectric-metal core-shell morphology exhibit hybridized modes where the surface plasmon polaritons at the outer and inner surfaces of the shell couple. We demonstrate that suitably tailoring the interference of such hybrid surface plasmon polariton modes leads to composite subwavelength nanospheres with negative asymmetry parameters and strong scattering in the optical frequency range. As a result, for a low density collection of scatterers an anomalous regime occurs, where the extinction mean free path is longer than the transport mean free path. Explicit results for silver-coated nanospheres are presented.


Gadolinium-based contrast media does not improve the staging of neuroblastoma image-defined risk factors at diagnosis.
Neuroblastoma risk stratification relies on prognostic risk factors and image-defined risk factors (IDRFs). Evaluating neuroblastoma typically involves magnetic resonance imaging (MRI) with gadolinium-based contrast media (GBCM, "contrast"). However, there are concerns regarding adverse effects and cost of GBCM. We aimed to assess the impact of intravenous GBCM on interobserver agreement for neuroblastoma staging on baseline MRI. We reviewed baseline MRI scans of 50 children with abdominopelvic neuroblastomas confirmed by histopathology. Duplicate sets of images were created, with post-contrast T1-weighted sequences removed from one set. Four pediatric radiologists independently analyzed the scans in a randomized manner. They recorded primary tumor size, presence of IDRFs, and metastatic lesions. Agreement among the reviewers was measured using kappa and Fleiss kappa statistics. Mean age of included children was 3.3 years (range: 0.01-14.9 years), and 20 [40%] were females. Mean tumor size was 5.7 cm in greatest axial diameter. Pre-contrast versus post-contrast MRI showed excellent agreement for tumor measurement. Overlapping confidence intervals (CIs) were seen in nearly all categories of interobserver agreement on the presence or absence of individual IDRFs, with agreement ranging from poor to substantial, regardless of the presence of contrast. The overall interobserver agreement on the presence of at least one IDRF was substantial with contrast (kappa = .63; 95% CI: .52-.75) and moderate without contrast (kappa = .5; 95% CI: .39-.61); although the overlapping CIs suggest a lack of meaningful difference. Similarly, interobserver agreement on the presence or absence of individual sites of metastatic disease ranged from poor to substantial. The interobserver agreement on the overall determination of presence of metastatic disease was fair with contrast (kappa = .49; 95% CI: .38-.61) and moderate without contrast (kappa = .71; 95% CI: .59-.826). Contrast does not improve tumor size measurement or radiologist agreement on the presence or absence of IDRFs or metastatic disease in children with newly diagnosed neuroblastoma.


Shared decision making in sarcopenia treatment.
The implementation of shared decision making (SDM) in management of sarcopenia is still in its nascent stage, especially compared to other areas of medical research. Accumulating evidence has highlighted the importance of SDM in older adults care. The current study overviews general SDM practices and explores the potential advantages and dilemmas of incorporating these concepts into sarcopenia management. We present common patient decision aids available for sarcopenia management and propose future research directions. SDM can be effectively integrated into daily practice with the aid of structured techniques, such as the "seek, help, assess, reach, evaluate" approach, "making good decisions in collaboration" questions, "benefits, risks, alternatives, doing nothing" tool, or "multifocal approach to sharing in shared decision making." Such techniques fully consider patient values and preferences, thereby enhancing adherence to and satisfaction with the intervention measures. Additionally, we review the barriers to and potential solutions to SDM implementation. Further studies are required to investigate measurement and outcomes, coordination and cooperation, and digital technology, such as remote SDM. The study concludes that sarcopenia management must go beyond the single dimension of "Paternalism" choice. Integrating SDM into clinical practice offers promising opportunities to improve patient care, with patient-centered care and partnership of care approaches positively impacting treatment outcomes.


Transcriptional repression of the growth-associated T alpha1 alpha-tubulin gene by target contact.
In this report, we address the molecular mechanisms that regulate axonal growth by focusing on the gene for one of the major axonal cytoskeletal proteins, T alpha1 alpha-tubulin. During the developmental growth of sympathetic neurons, transcription of a beta-galactosidase transgene driven by the T alpha1 promoter (T alpha1:nlacZ) was high until the time of target innervation and neuronal maturation, when it decreased significantly. In mature animals, T alpha1:nlacZ transcription remained relatively low until target contact was experimentally disrupted; when facial motoneurons were axotomized, T alpha1:nlacZ transgene expression increased, was maximal for 1-7 days, and, if neurons regenerated and reinnervated their target musculature, returned to control levels by 49 days. In contrast, if regeneration and reestablishment of target contact were inhibited, transgene expression remained elevated. To determine whether this increased transcription was due to the loss of target contact or to axonal loss, we transected sympathetic neurons that project to the eye either close to or far from their cell bodies. In both cases, when target contact was severed, T alpha1:nlacZ transcription increased. These experiments indicate that transcription of the T alpha1 alpha-tubulin promoter is repressed by target contact in both developing and mature neurons. We suggest that this repression is due to a target-derived "stop-growth" factor that retrogradely signals to regulate transcription of this and other genes that are required for axonal growth.


Valosin-containing protein phosphorylation at Ser784 in response to DNA damage.
The response of eukaryotic cells to DNA damage includes the activation of phosphatidylinositol-3 kinase-related kinases (PIKK), such as ATM, ATR, and DNA-dependent protein kinase (DNA-PK). These three kinases have very similar substrate specificities in vitro, but in vivo, their substrates overlap only partially. Several in vivo substrates of ATM and ATR have been identified and almost all of them are involved in DNA damage-induced cell cycle arrest and/or apoptosis. In contrast, few in vivo substrates of DNA-PK have been identified. These include histone H2AX and DNA-PK itself. We identify here valosin-containing protein (VCP) as a novel substrate of DNA-PK and other PIKK family members. VCP is phosphorylated at Ser784 within its COOH terminus, a region previously shown to target VCP to specific intracellular compartments. Furthermore, VCP phosphorylated at Ser784 accumulated at sites of DNA double-strand breaks (DSBs). VCP is a protein chaperone that unfolds and translocates proteins. Its phosphorylation in response to DNA damage and its recruitment to sites of DNA DSBs could indicate a role of VCP in DNA repair.


Prevalence study of tongue lesions in a Hungarian population.
The aim of the study was to assess the prevalence of tongue lesions in a district population, in Budapest, called regularly for X-ray lung examinations. Oral examinations of 7820 individuals were performed, 42% were over 60 yr of age, 42.9% were men and 57.1% women. Tongue alterations were found in 18.52% of the examined individuals, more frequently in women than in men. Lingua fissurata has been diagnosed in 8.8%, geographic tongue in 3.0% of the examined subjects. Atrophic lesions of the tongue were found in 6.37%, among them 5.42% central papillary atrophy (median rhomboid glossitis): 0.35% of the total sample. Manifest clinical symptoms of oral Candidiasis were found in 2.15% of the total sample, and in 4.28% of patients with tongue lesions. The occurrence of oral leukoplakia and lichen in patients with tongue lesions was respectively 0.47 and 0.07%. The prevalence of tongue alterations was consistent with the literary data, the oral screening attached to the X-ray lung examinations proved to be useful in detecting changes of the oral mucosa.


BEM46 shows eisosomal localization and association with tryptophan-derived auxin pathway in Neurospora crassa.
BEM46 proteins are evolutionarily conserved, but their functions remain elusive. We reported previously that the BEM46 protein in Neurospora crassa is targeted to the endoplasmic reticulum (ER) and is essential for ascospore germination. In the present study, we established a bem46 knockout strain of N. crassa. This Δbem46 mutant exhibited a level of ascospore germination lower than that of the wild type but much higher than those of the previously characterized bem46-overexpressing and RNA interference (RNAi) lines. Reinvestigation of the RNAi transformants revealed two types of alternatively spliced bem46 mRNA; expression of either type led to a loss of ascospore germination. Our results indicated that the phenotype was not due to bem46 mRNA downregulation or loss but was caused by the alternatively spliced mRNAs and the peptides they encoded. Using the N. crassa ortholog of the eisosomal protein PILA from Aspergillus nidulans, we further demonstrated the colocalization of BEM46 with eisosomes. Employing the yeast two-hybrid system, we identified a single interaction partner: anthranilate synthase component II (encoded by trp-1). This interaction was confirmed in vivo by a split-YFP (yellow fluorescent protein) approach. The Δtrp-1 mutant showed reduced ascospore germination and increased indole production, and we used bioinformatic tools to identify a putative auxin biosynthetic pathway. The genes involved exhibited various levels of transcriptional regulation in the different bem46 transformant and mutant strains. We also investigated the indole production of the strains in different developmental stages. Our findings suggested that the regulation of indole biosynthesis genes was influenced by bem46 overexpression. Furthermore, we uncovered evidence of colocalization of BEM46 with the neutral amino acid transporter MTR.


Plasticity of human adipose-derived stem cells - relevance to tissue repair.
In contrast to cold blooded vertebrates, the ability to regenerate morphologically and functionally complex structures is limited in adult mammals. Recruitment of progenitor cells is a key step in the regenerative process. The possibility of repairing missing or diseased tissues in humans has been potentiated by the increasing understanding of somatic stem cells, their plasticity and the possibility of modulating it, that could be harnessed either to stimulate endogenous repair or to engineer the required tissue. Here, we focus on human mesenchymal stem cells (MSCs), important players in tissue homeostasis in healthy organisms, with a particular emphasis on those derived from the adipose tissue (ADSCs). While a mark of MSC identity is the ability to differentiate into osteoblasts, chondrocytes and adipocytes, there is evidence that their potential goes beyond these three mesenchymal lineages. We discuss some differentiation and modulatory properties of MSCs and provide an overview of our recent work on ADSCs from paediatric patients (pADSCs) that has shown their ability to give raise to non-mesenchymal cells, consistent with a significant plasticity. Finally, we present novel data indicating that both mesenchymal lineages (adipogenic, chondrogenic and osteogenic) and neural and epithelial lineages can originate from clonal lines that like the parental line express markers of pluripotency as well as the stromal cell marker, GREM1. Together these data support the existence of pADSC multipotent stem cells.


[Vertebral hydatidosis: case report].
Hydatidosis caused by echinococcus granulosus may affect any organ in the body, with the lungs and the liver as the most commonly affected organs. Vertebral compromise resulting from echinococcus granulosus has a low prevalence and accounts for less than 1% of bone compromise. We report the case of a 50 year-old female who presented at the Trauma Service with progressive low back pain with 5 months of duration that irradiated to the right lower limb, and led to neurologic compromise of the limb. Imaging studies showed spondylodiscitis at T12-L1, confirmed by a biopsy. Treatment of this condition is both orthopedic and surgical. The recurrence rate is high, between 30 and 40%. The objective of describing this case is to propose the differential diagnosis of a vertebral mass of unknown origin and provide details as to how to manage this condition.


Examining structural changes in Asian offices market.
It is complicated to measure the effects of various economic events on office markets within a non-parameter modeling framework. In response to this issue, a non-parametric statistical method-wavelet analysis is introduced in this study. Based on this innovative technique, we not only could detect the abrupt change points with a comparatively small data sample, but also could evaluate the impact from the abrupt change points by reconstructing the wavelet coefficient/de-noising the raw data, which had never been considered in previous studies of office markets. Our empirical results suggest that the wavelet reconstruction method, to some extent, makes it easier for the detection of the existence of structural change points. More interestingly, our findings also indicate that free market economies (i.e. Hong Kong and Singapore) are mainly influenced by the effects of global events, whereas the actual (net) impact on socialist economies (i.e. Beijing and Shanghai), depends on both the openness of the economies, and the magnitude of counter domestic forces put in place.


Should a hotter paramagnet transform quicker to a ferromagnet? Monte Carlo simulation results for Ising model.
For quicker formation of ice, before inserting inside a refrigerator, heating up of a body of water can be beneficial. We report first observation of a counterpart of this intriguing fact, referred to as the Mpemba effect (ME), during ordering in ferromagnets. By performing Monte Carlo simulations of a generic model, we have obtained results on relaxation of systems that are quenched to sub-critical state points from various temperatures above the critical point. For a fixed final temperature, a system with higher starting temperature equilibrates faster than the one prepared at a lower temperature, implying the presence of ME. The observation is extremely counter-intuitive, particularly because of the fact that the model has no in-built frustration or metastability that typically is thought to provide ME. Via the calculations of nonequilibrium properties concerning structure and energy, we quantify the role of critical fluctuations behind this fundamental as well as technologically relevant observation.


Can preoperative spiral CT scans alone determine the feasibility of endovascular AAA repair? A comparison to angiographic measurements.
To determine whether computed tomography (CT) alone can be used for excluding patients from endovascular repair for abdominal aortic aneurysms (AAA). Among 71 patients evaluated for endovascular AAA repair using spiral CT imaging and angiography, 31 were selected who had both studies performed within 6 months of each other using a graduated measuring catheter or guidewire. Measurements of aneurysm neck diameter, neck length, and infrarenal aortic length were made from the CT and angiographic images using handheld calipers with calibration markers as guides. Infrarenal aortic length and neck length were determined from CT images by multiplying the width of the cuts by the number of slices between the lowest renal artery and the aortic bifurcation or the top of the aneurysm, respectively. CT neck diameter measurements differed significantly from the angiographic dimensions (6.3 +/- 5.1-mm mean difference, p < 0.001). In the majority of patients (25, 81%), CT neck diameters were larger (mean 7.3 +/- 3.8 mm). The mean difference in neck length measurements was 0.5 +/- 15.9 mm (p = NS). Twenty-two (71%) patients had aortic length measurements that were longer on the angiogram (mean 15.4 +/- 17.2 mm, p = NS). Five patients who would have been excluded as candidates based on overestimated CT neck diameter measurements subsequently underwent successful endovascular aneurysm repair. Considerable discrepancies exist between preoperative neck diameter and infrarenal aortic length measurements obtained from CT scans and angiograms used to evaluate candidates for endovascular aortic aneurysm repair. CT alone may not be adequate for predicting the feasibility of endovascular AAA repair.


Non-small cell lung cancer-derived soluble mediators and prostaglandin E2 enhance peripheral blood lymphocyte IL-10 transcription and protein production.
Studies suggest that IL-10 may contribute to tumor-associated immunosuppression. In the current study we evaluated the capacity of human non-small cell lung cancer (NSCLC) cell lines to induce PBL IL-10 production. We observed a 10- to 100-fold increase in human PBL IL-10 production following exposure to NSCLC cell supernatants. The tumor-induced increase in PBL IL-10 production was partially blocked by pretreatment of the tumors with the PG inhibitor indomethacin. NSCLC lines were found to constitutively produce PGE2. Exogenous PGE2 also induced PBL IL-10 production in a dose- and time-dependent manner. Both PGE2 and NSCLC supernatant-induced PBL IL-10 production were due to an increase in the IL-10 mRNA transcriptional rate. To evaluate the significance of tumor-induced lymphocyte IL-10 production, the capacity of PBL to produce IFN-gamma during culture in tumor supernatants was assessed in the presence of specific anti-IL-10 mAb. We found enhanced PBL IFN-gamma production following anti-IL-10 treatment. These in vitro studies imply that NSCLC-induced PBL IL-10 production may serve to shift the Th1/Th2 cytokine axis at the tumor site and thus inhibit cell-mediated anti-tumor immune responses. These findings identify a mechanism by which lung cancer cells may escape host immune surveillance. We conclude that NSCLC-derived soluble mediators, including PGs, may play an immunoregulatory role through induction of lymphocyte IL-10 production.


[Effect of polychlorocamphene on the organs and their neural apparatus in pregnant animals].
Experiments conducted on pregnant albino rats showed that in daily oral administration of polychlorokamphene--a chlorine organic compound widely used in agriculature--in a dose of 12 mg/kg (1/20 LD50) there was interrelation between the structural and the enzymatic changes in the nerve elements of the organs under study. They consisted in the focality of the affection of the nervous structures of the brain cortex, and in increase in the destructive processes involving the nervous structures of the heart, uterus, spinal cord at the end of pregnancy. A peculiar enzymatic reconstruction with the preservation of the activity of the cholinesterase (CE)-positive pericellular structures (whose number was markedly decreased in comparison with control) was noted against the background of reduction of the CE activity. The prevalence of destructive processes by the end of pregnancy was conditioned by a considerable accumulation of the preparation in the heart, uterus, and the brain (as shown by thin-layer chromatography). The presence of polychlorkamphene in the organs of fetuses pointed to disturbances in the permeability of the transplacental barrier and to a possible influence of the preparation on the development of the fetal nervous system.


Risk factors for suicide and attempted suicide among young people.
Suicide rates in young people have increased during the past three decades, particularly among young males, and there is increasing public and policy concern about the issue of youth suicide in Australia and New Zealand. This paper summarises current knowledge about risk factors for suicide and suicide attempts in young people. Evidence about risk factors for suicidal behaviour in young people was gathered by review of relevant English language articles and other papers, published since the mid-1980s. The international literature yields a generally consistent account of the risk factors and life processes that lead to youth suicide and suicide attempts. Risk factor domains which may contribute to suicidal behaviour include: social and educational disadvantage; childhood and family adversity; psychopathology; individual and personal vulnerabilities; exposure to stressful life events and circumstances; and social, cultural and contextual factors. Frequently, suicidal behaviours in young people appear to be a consequence of adverse life sequences in which multiple risk factors from these domains combine to increase risk of suicidal behaviour. Current research evidence suggests that the strongest risk factors for youth suicide are mental disorders (in particular, affective disorders, substance use disorders and antisocial behaviours) and a history of psychopathology, indicating that priorities for intervening to reduce youth suicidal behaviours lie with interventions focused upon the improved recognition, treatment and management of young people with mental disorders.


Dopaminergic transplantation for Parkinson's disease: current status and future prospects.
Cell-based therapies that involve transplantation into the striatum of dopaminergic cells have attracted considerable interest as possible treatments for Parkinson's disease (PD). However, all double-blind, sham-controlled, studies have failed to meet their primary endpoints, and transplantation of dopamine cells derived from the fetal mesencephalon is associated with a potentially disabling form of dyskinesia that persists even after withdrawal of levodopa (off-medication dyskinesia). In addition, disability in advanced patients primarily results from features such as gait dysfunction, freezing, falling, and dementia, which are likely due to nondopaminergic pathology. These features are not adequately controlled with dopaminergic therapies and are thus unlikely to respond to dopaminergic grafts. More recently, implanted dopamine neurons have been found to contain Lewy bodies, suggesting that they are dysfunctional and may have been affected by the PD pathological process. Collectively, these findings do not bode well for the short-term future of cell-based dopaminergic therapies in PD.