The association between 17-hydroxyprogesterone caproate use and postpartum hemorrhage.
To evaluate whether receipt of 17α-hydroxyprogesterone caproate within seven days of delivery is associated with increased risk of postpartum hemorrhage. This was a retrospective cohort study of women who were receiving 17α-hydroxyprogesterone caproate for preterm birth prevention and delivered between 2010 and 2014. Women were dichotomized by whether a dose of 17α-hydroxyprogesterone caproate was administered within seven days of delivery. Demographic and clinical characteristics were examined, including obstetric history and details of 17α-hydroxyprogesterone caproate receipt. Bivariable analyses were used to compare the frequency of postpartum hemorrhage in women stratified by 17α-hydroxyprogesterone caproate receipt within seven days of delivery. Multivariable analysis was used to adjust for potential confounders. Of 221 women who met inclusion criteria, 93 (42%) received 17α-hydroxyprogesterone caproate within seven days of delivery and 18 (7.8%) experienced a postpartum hemorrhage. No differences were observed in the frequency of postpartum hemorrhage between women who did and did not deliver within seven days of 17α-hydroxyprogesterone caproate injection (9.7% vs 7.0%, p=0.478). These findings persisted after adjusting for potential confounders (aOR for PPH 2.9, 95% CI, 0.5-15.8). Recent receipt of 17α-hydroxyprogesterone caproate for prevention of recurrent preterm birth is not associated with risk of postpartum hemorrhage.


Detecting benthic community responses to pollution in estuaries: a field mesocosm approach.
Biological stress responses in individuals are used as indicators of pollution in aquatic ecosystems, but detecting ecologically relevant responses in whole communities remains a challenge. We developed an experimental approach to detect the effects of pollution on estuarine communities using field-based mesocosms. Mesocosms containing defaunated sediments from four estuaries in southeastern Australia that varied in sediment contamination were transplanted and buried in sediments of the same four estuaries for six weeks. Mesocosm sediment properties and metal concentrations remained representative of their source locations. In each estuary, fauna communities associated with sediments derived from the site with the highest metal concentrations were significantly different from other communities. This pattern was evident for some of the individual taxa, in particular the polychaete Capitella sp. Consistent responses across estuaries suggest numbers of individuals, and especially Capitella sp., could be used to identify contaminated sediments in estuaries with similar fauna and site characteristics.


Ochronotic arthropathy.
Ochronotic arthropathy is the musculoskeletal manifestation of alkaptonuria. an uncommon inherited metabolic disorder associated with various clinical and radiologic abnormalities due to the deposition of homogentisic acid. We report on a 35-year-old man with ochronotic arthropathy who presented with the main characteristic radiological findings. The differential diagnosis of this rare condition is discussed with a review of the literature.


Ovigerity, selective predation, and variable diel vertical migration in Euchaeta elongata (Copepoda: Calanoida).
We present a statistical analysis of a previously published (Yen, 1983) but heretofore unanalyzed data set on the vertical distributions and diel vertical migration (DVM) of adult females of the marine planktonic copepod Euchaeta elongata in Dabob Bay, Washington, USA. Non-ovigerous females were strongly migratory on all four dates sampled, residing between 75-175 m during the day and at shallower depths during the night, commonly entering the upper 50 m of the water column. In contrast, ovigerous females were non-migratory or weakly migratory, largely remaining between 100-175 m both day and night, and entering the upper 50 m of the water column only rarely. Thus non-ovigerous females always migrated much more strongly, as measured by both amplitude of migration and the proportion of animals migrating, than did ovigerous females. These results led us to hypothesize that differential susceptibility to visually orienting predators was the cause of these differences in DVM behavior in female E. elongata, and we subsequently undertook an experimental study of the feeding selectivity of the copepod's natural predator, Pacific herring (Clupea harengus pallasi). Pacific herring exhibited a highly significant preference for ovigerous over nonovigerous adult female E. elongata. The demographic consequences of variable DVM in adult female E. elongata were investigated by way of life table analyses. Results indicated that under conditions of thermal stratification of the water column there is a distinct demographic disadvantage (reduced rate of realized population growth) incurred by non-migratory or weakly migratory ovigerous females due to delayed egg development at cooler subsurface temperatures. We conclude that ovigerous female E. elongata remain at depth both day and night to avoid visually orienting predators, and that such behavior must afford the copepod a demographic advantage of no less than a 26% reduction in adult mortality to offset the demographic cost of delayed egg development.


Sulfonilamidothiopyrimidone and thiopyrimidone derivatives as selective COX-2 inhibitors: synthesis, biological evaluation, and docking studies.
Newly synthesized sulfonilamidothiopyrimidone derivatives and a subset of 14 sulfonilamidothiopyrimidones and thiopyrimidones selected by an MTT assays cell viability guided selection from an in house collection were evaluated to determine the inhibitory effect on the PGE(2) formation in human peripheral blood lymphocytes (PBLs) using commercial ELISA. The newly synthesized sulfonilamidothiopyrimidone derivatives showed interesting pharmacological activities. Preliminary in vitro assays showed that compounds 2-5 are endowed with very high activity. Compound 2 was the most active as hCOX-2 inhibitor. The observed effects were not due to an inhibition of cell proliferation as proved by the BrdU assay. Western blot of COX-2 confirmed the inhibition on the PGE(2) secretion. Further evidence on the inhibitory potential and selectivity as COX-2 inhibitors of the selected compounds came from the in vitro screening. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data. Compounds 2-5 were able to fit into the active site of COX-2 with highest scores and interaction energies. Furthermore, compound 2, which showed an inhibition of around 50% on PGE(2) production, was the best scored in all the docking calculations carried out.


Concordances and correlations between chronological, dental and bone ages: A retrospective study in French individuals.
Bone and dental maturations are subject to physiological, environmental and pathological variables and are unique to each individual. Numerous methods for age estimation appeared to answer a new demand explained by the contemporary migratory movements and the increase of the crime rates. The objective of this study was to observe the relationships between skeletal and dental maturation stages to estimate which methods can be applied to a French population. This retrospective study was based on panoramic and cephalometric radiographs belonging to 192 (101 females and 91 males) orthodontic patients aged between 9 and 19 years, inhabitants of the Provence-Alpes-Côte d'Azur region. The Demirjian method based on dental calcification was used to estimate dental age. For the assessment of skeletal maturity and bone age, the Cervical Vertebral Maturation (CVM) method (Baccetti et al.) and its computerized version (Decocq et al.) were used. Spearman's correlation tests were performed to estimate the correlation between dental calcification stages and those of cervical vertebral maturation among the study population. The methods of Lin's concordance correlation coefficient and Bland and Altman were used to analyze the concordance between bone, dental and chronological ages. A moderate but statistically significant correlation was obtained between dental and skeletal developmental stages (R = 0.383-0.618). The tooth showing the highest correlation with vertebral stages was the second molar for both sexes. Earlier vertebral maturation stage affiliation was observed in girls. The results confirmed that bone and dental maturations can be assessed to estimate relevant biological ages for children in orthodontic or forensic contexts.


Trends in Hospitalization Rates, Major Causes of Hospitalization, and In-Hospital Mortality in Rheumatoid Arthritis in the United States From 2000 to 2014.
To evaluate national trends in hospitalizations and in-hospital mortality in rheumatoid arthritis (RA). National Inpatient Sample from 2000-2014 and United States Census data were used to study temporal trends in adult RA hospitalizations, reasons for hospitalizations, and in-hospital mortality. The data represented 183 983 hospitalizations with a primary diagnosis of RA. The annual rates of hospitalization for the primary diagnosis of RA decreased from 76.54 admissions per 1 million in 2000 to 29.96 per 1 million in 2014 (P trend < 0.0001). The hospital mortality rate declined from 0.70% to 0.41% (P trend < 0.0001) in this group. With a primary or nonprimary diagnosis of RA, the mortality rate ranged between 1.95 and 2.87 (P trend 0.08). For a nonprimary diagnosis of RA, we noted that the proportion of hospitalizations with a diagnosis of myocardial infarction (6.4% in 2000 to 4.6% in 2014; P < 0.001) significantly decreased, but the absolute number of hospitalizations significantly increased. In contrast, the proportion and the absolute number of hospitalizations with any diagnosis of sepsis, congestive heart failure, lung disease, and urinary tract infection increased significantly. We also noted a significant increase in the actual rate and proportions for hospitalizations for hip and knee arthroplasty. Among in-hospital deaths when RA was a nonprimary diagnosis, the most common primary diagnosis was pneumonia (12.5 %) in 2000, whereas sepsis accounted for the most deaths in 2014 (31.4%). We observed that hospitalization rates and in-hospital mortality rates in patients with RA have changed significantly over the past 15 years.


Bacterial flora in relation to cataract extraction. I. Material, methods and preoperative flora.
The conjunctival flora of 499 patients was studied the day before cataract extraction, no antibiotics or chemotherapeutical agents had been used before admission. Staphylococcus albus was by far the most common micro-organism (95.4%), followed by corynebacteria (44%), Staphylococcus aureus (14.9%), gram-negative bacilli (7.8%) and pneumo-streptococci (4.4%). Corynebacteria was isolated more frequently in the presence of S. albus, while S. aureus and gram-negative bacilli were found more frequently in the absence of S. albus. No relationship could be demonstrated between the occurrence of pneumo-streptococci and S. albus. The flora of the nose and skin of the face were studied and compared with the conjunctival flora, and a similarity could be observed. Furthermore, strains of S. aureus isolated at the same time from the two or three regions, in most cases, showed the same bacterio-phage type complex. The conjunctival flora was further correlated with sex, age, season, and number of polymorphonuclear neutrophils recovered from the conjunctival fluid. The incidence of corynebacteria and gram-negative bacilli was found to be higher in males, while corynebacteria was the only organism to show seasonal variation, i.e. was isolated more frequently in the second and third quarters of the year. No correlation could be found between age or number of neutrophils.


Acute hemolytic reaction by anti-Wra: Case report and review of the hemovigilance database of a tertiary care hospital.
Wra is the most common LIA in white population. The incidence of Wra antigen in Spanish population has been estimated to be 1 in 785 in blood donors, while anti-Wra was found in 2.7 % and 3.6 % of healthy donors and transfused patients respectively. Severe, even fatal hemolytic transfusion reactions and hemolytic disease of the newborn caused by anti-Wra have been reported. Since the reagent red blood cells used for antibody screening usually lack Wra antigen, the anti-Wra is not detected and hemolytic reaction could occur if transfusion is performed by type and screen approach. We report an acute hemolytic reaction due to anti-Wra in a patient with negative antibody screening. We have also reviewed the records of the hospital hemovigilance database in order to collect the previous hemolytic cases due to anti-Wra. During a 21-year period 461,539 red blood cell units have been transfused to 81,614 patients in our hospital. Alloimmnunization was detected in 3840 patients (0.83 %) and anti-Wra was detected in 22 patients (1/3709), 10 of whom had other alloantibodies, and only in 1 occasion (this case) has been implicated in mild hemolytic acute transfusion reaction. In our experience, the risk of fatal hemolytic reaction due to LIA in hospitals with blood services using the type and screen policy is extremely low.


An effective method of isolating microvascular endothelial cells from the human dermis.
Dermal microvascular endothelial cells (DMECs) play central roles in inflammation and angiogenesis and have become important cell models for studying various skin diseases. However, primary DMECs are difficult to culture and often contaminated by mesenchymal stem cells, fibroblasts, and other stromal cells. Surgically removed superfluous foreskin was first cut into pieces, digested with two types of enzymes, and dispersed into single cells. Cells obtained from the dermis were then subjected to Percoll density gradient centrifugation and cells located between densities 1.033 and 1.047 g/ml were further purified with endothelial growth medium containing decreasing concentrations of puromycin. Obtained HDMECs were identified by microscopy, flow cytometry, quantitative reverse-transcription polymerase chain reaction, western blot analysis, and immunofluorescent staining. The expression of CD31 (PECAM-1), CD34, VEGFR2, VWF (Von Willebrand Factor), VE-Cadherin (CD144), and NOS was positive. HDMECs were found to have abilities of angiogenesis and uptake of acetylated low-density lipoprotein. Growth curves and cell viability were analyzed, and a growth pattern consisting of the "latency phase-logarithmic growth phase-stagnation phase" was determined. In this study, a simple, rapid, effective, and low-cost method is established to isolate HDMECs from the foreskin with a purity of over 91% and high viability. The method showed good repeatability and allowed a stable passage. This study provides technical support and theoretical guidance for studying the physiological characteristics of HDMECs, the pathogenesis of the skin associated, and other microvascular diseases.


Effect of treatment with certain flavonoids on Mengo virus-induced encephalitis in mice.
Among the four flavonoids tested quercetin and morin proved to be significantly effective against lethal Mengo virus-induced encephalitis in mice when the drugs were adminsitered orally (p.o.). With subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. Quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four days. Single injections of the full daily dose of drug failed to prevent deaths in mice. Treatment must be begun at the time of, or prior to, virus inoculation. Delayed initiation of treatment was ineffective in preventing mortality.


Feasibility of sustained low efficiency dialysis in critically sick pediatric patients: A multicentric retrospective study.
Sustained low-efficiency dialysis (SLED) has emerged as a cost effective alternative to Continuous Renal Replacement Therapy in the management of hemodynamically unstable adult patients with acute kidney injury. The objective of the study was to document the SLED practices in these centers, and to look at the feasibility, and tolerability of SLED in critically sick pediatric patients. It was a retrospective record review from January 2010 to June 2016 done in four tertiary pediatric nephrology centers in India. All pediatric patients undergoing SLED in the collaborating centers were included in the study. Basic demographic data, prescription parameters and outcomes of patients were recorded. During the study period a total of 68 children received 211 sessions of SLED. PRISM score at admission in patients was 13.33 ± 9.15. Fifty-seven patients were ventilated (84%). Most of the patients had one or more organ system involved in addition to renal (n = 64; 94%). Heparin free sessions were achievable in 153 sessions (72%). Out of 211 sessions, 148 sessions were on at least one inotrope (70.1%). Overall premature terminations had to be done in 27 sessions (13% of all sessions), out of which 7 sessions had to be terminated due to circuit clotting (3.3%). Intradialytic hypotension or need for inotrope escalation was seen in 31 (15%) sessions but termination of the session for drop in BP was required in only 20 (9%) sessions. SLED is a feasible method of providing renal replacement in critically ill pediatric patients.


Personalized nutrition communication through ICT application: how to overcome the gap between potential effectiveness and reality.
The potential effectiveness of personalized nutrition communication through the Internet is promising in terms of addressing personal relevance, flexibility, interactive options and amount of people that can be reached. However, little research on the contribution to behaviour change has been done. The MyFood program at Wageningen University aims at providing insight into strategies to implement personalized nutrition communication through interactive tools. In this article we present the framework for research on social acceptance of personalized nutrition communication through interactive computer technology as part of the MyFood program.


The projection of the nucleus reticularis tegmenti pontis and adjacent regions of the pontine nuclei to the central cerebellar nuclei in the cat.
The projection of the nucleus reticularis tegmenti pontis (NRTP) and the pontine nuclei (NP) to the central cerebellar nuclei (CCN) was investigated by means of anterograde transport of tritiated leucine. Although termination was found in all the CCN, it was most pronounced in the lateral nucleus and the lateral aspect of the posterior interposed nucleus. The extreme lateral aspect of the anterior interposed nucleus and the caudal part of the fastigial nucleus received a projection of modest intensity. Termination in the infracerebellar nucleus and group Y is likely to be present but could not be confirmed with certainty from the light microscopical material. The contribution from the NP was small and originated from the dorsolateral and dorsal paramedian subdivisions of the NP. Within the NRTP the total area giving rise to projections to the CCN was extensive, and the origin of the projections to the individual CCN overlapped considerably. The projection of the NRTP to the ventrocaudal part of the lateral nucleus was found in conjunction with a projection to the ventrolateral part of the posterior interposed nucleus. Both projections seemed to branch off the fiber bundle terminating in the ventral paraflocculus. Similar correlations could be established in the projection of the NRTP to the dorsal paraflocculus and crus II of the ansiform lobule with other parts of the lateral and posterior interposed nuclei. It was concluded that the transverse, lobular organization of mossy fibers, which differs fundamentally from the longitudinal, modular organization of climbing fibers, is maintained in the collateral projection to the CCN. The results are further discussed in relation to the corticonuclear projection and the engagement of the NRTP and different parts of the CCN in pontocerebellar circuits.


The effects of orthodontic materials on the accuracy of periapical radiography-based caries detection.
To investigate the influence of orthodontic materials on the assessment of proximal caries using periapical radiography. Forty non-cavitated and restoration-free human premolars and molars ranging from sound teeth to teeth containing various grades of lesions were embedded with approximal contacts into silicon blocks. Periapical radiographs were obtained using combinations of two orthodontic materials (three bracket and two archwires). Images were obtained using a Planmeca ProX™ (Planmeca®, Helsinki, Finland). Two observers assessed the images. Intraobserver and interobserver agreement was computed using an intraclass correlation coefficient. Receiver operating characteristic (ROC) analysis was used to calculate the true positive value, true negative value, and the area under the ROC curve (AUC). Intraobserver agreement ranged from 0.483 to 0.768. Interobserver agreement ranged from 0.383 to 0.718. The AUC, sensitivity and specificity were 0.792, 71.23% and 87.10% in the control group (without bracketing), respectively. The highest area under the curve (AUC) value (0.792) was obtained from the without bracket group. The lowest AUC value (0.659) belonged to the stainless steel bracket and steel wire group. A decrease in the AUC values was observed for the control group (without bracketing) compared to the stainless steel bracket and steel wire group (P = 0.040). The addition of a stainless steel bracket with stainless steel wire combination makes it difficult to the diagnose the interproximal tooth caries by periapical radiography.


Correlation between magnetic resonance imaging (MRI) findings and the new bone formation factor Dkk-1 in patients with spondyloarthritis.
In recent years, MRI has been regarded as a major diagnostic tool for spondyloarthritis (SpA), and anti-TNF therapy has been widely confirmed as an effective treatment strategy. This study was designed to investigate the correlation between the secreted protein dickkopf-1 (Dkk-1) and abnormal findings on magnetic resonance imaging (MRI) through a prospective study of 30 cases of SpA. Thirty patients with active SpA were included, all treated with recombinant human tumor necrosis factor (TNF) receptor-antibody fusion protein (YiSaiPu) injection at 50 mg/week for 6 months. All patients were also examined for their clinical, serological, and imaging manifestations of the condition before and after treatment. In patients receiving TNF inhibitor treatment, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and clinical activity indices BASDAI, BASFI, BASMI, ASDAS-CRP were significantly decreased (p < 0.01). Serum Dkk-1 concentration was also significantly decreased (p < 0.05), as were the scores of bone marrow edema of the sacroiliac joints and the spine (p < 0.05). The score of sacroiliac joint backfill was significantly increased (p < 0.05), and the baseline and changes in the serum Dkk-1 concentration were significantly correlated with the baseline and changes in spinal bone marrow edema levels. Inhibition of the level of serum Dkk-1 by TNF inhibitors may be the molecular basis for inhibiting the formation of new bone in SpA patients. In addition, spinal marrow edema may have significance for predicting new bone formation.


Investigating highly crosslinked macroporous resins for solid-phase synthesis.
The washing efficiencies of a chromophore and the reaction rates of a classical esterification reaction are improved with macroporous resins (MRs) relative to a classical Merrifield resin. Furthermore, Wacker-oxidation of a MR bound alkene yielded the expected methylketone product whereas an alkene bound to a low-crosslinked Merrifield resin gave no product, a function of the relative permeability of each of these resins to the aqueous solvent conditions employed.


Localization of Drosophila nasutoides satellite DNAs in metaphase chromosomes.
Metaphase chromosomes of D. nasutoides were hybridized in situ with 3H-cRNA synthesized from the four satellites which make up 50--60% of the total DNA of this species. All four satellites were localized in the large, metacentric, heterochromatic chromosome four. They did not, however, appear to hybridize to centromeric or other constitutive heterochromatin, nor did they, with the exception of satellite I, seem to hybridize in the specific regions of chromosome four which, on the basis of C, Q, and H banding and AT contents, were predicted to contain some of these satellites.--Comparison of grain patterns with the results of fluorescent staining indicated that satellite-bearing heterochromatin was not always associated with other fractions of constitutive heterochromatin in interphase nuclei and was, at least partially, decondensed in some larger nuclei.


Changes in ethanol consumption by C3H and CF1 mice with age.
Water or a 3% alcohol solution was offered for 4 weeks to groups of male C3H mice initially aged 3, 13, 20 and 60 weeks, and to male CF1 mice from age 10 weeks until they died. Differences in the consumption depended on age and the rate at which response patterns to the solution develop.


Retinal artery occlusion in a healthy pregnant patient.
We report a case of branch retinal artery occlusion (BRAO) in a healthy pregnant woman. A 29-year-old pregnant woman presented with decreased vision in her left eye. She had a pale retina with macular edema consistent with BRAO. An extensive workup was performed to determine an etiologic factor. All test results were within normal limits except for her factor VIII activity. Her visual acuity improved from finger counting to 20/30 over 2 months without any treatment. This case suggests that BRAO can occur in healthy patients without any systemic or ocular disorders. BRAO can occur in healthy patients without any systemic or ocular disorders, despite an extensile evaluation.


Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population.
Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes in order to explaining the association between these polymorphisms and we also investigated the association between these variants and ischemic stroke risk to determine whether gene-gene interaction between these genes increases the susceptibility of ischemic stroke or its subtypes. A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction. The additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression. At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR = 0.657, 95%CI = 0.437-0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR = 0.812, 95%CI = 0.657-0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR = 5.203, 95% CI = 1.519-5.159, P = 0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR = 1.404, 95% CI = 1.019-1.934, P = 0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke and other subtypes. At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX - 1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke and other subtypes.


[Morphological changes in scoliosis during growth. Study in the human spine].
To analyse the pathological substrate of human scoliotic spine during growth. We studied two spines obtained at the autopsy of two patients suffering from untreated scoliosis. Sample A (a girl of 13 years and 2 months) and sample B (a boy of 14 years and one month). On the conventional radiological study the curves were measured using the method of Cobb, and the vertebral rotation with the Pedriolle method. A CT scan and analysis of the posterior asymmetry were also performed. The bone structure, growth plate, subchondral bone were evaluated in the histological study, as well as the presence and distribution of fibrous tissue. Levels from C7 to L5 were studied in sample A, and levels from T2 to L4 in sample B. There was no evidence of vertebral deformity in the frontal, sagittal or axial planes, except for T5 in sample A, where wedging into the concavity in the frontal plane was observed. The deformity originated in the intervertebral discs. Endochondral ossification of the epiphyseal cartilage showed increased activity on the side of the convexity of the curve. Neurocentral cartilage was present at thoracic and cervical level, having disappeared at lumbar level. No asymmetry was observed in the neurocentral cartilage. The deformity begins in the intervertebral discs, producing distortions in the epiphyseal cartilage. Those changes may influence the end of growth and therefore the deformity of the scoliotic vertebrae, basically resulting in wedging and rotation of the vertebrae.


Long-term maintenance therapy with cyclosporine and posttreatment survey in severe psoriasis: results of a multicenter study. German Multicenter Study.
Although cyclosporine has been found to be effective therapy for severe psoriasis, only limited data exist about efficacy and safety during long-term treatment with a low-dose regimen. Furthermore, little is known about the course of psoriasis after drug withdrawal. Our purpose was to assess the results of long-term therapy with cyclosporine for severe psoriasis with particular regard to efficacy and safety, as well as the disease course after stopping treatment. A multicenter study of 217 patients treated with 1.25, 2.5, or 5.0 mg/kg per day of cyclosporine was performed. Duration of treatment ranged from 6 to 30 months followed by a posttreatment period of 3 months. Efficacy was assessed by the Psoriasis Area and Severity Index and safety was monitored by clinical and laboratory investigations. Patients with severe psoriasis showing a reduction in the Psoriasis Area and Severity Index of 75% with their individual dose of cyclosporine maintained clinical improvement during continuous maintenance therapy. Newly occurring side effects were less frequent during the maintenance phase than in the induction phase. After withdrawal of cyclosporine, worsening of psoriasis requiring antipsoriatic therapy was seen in about half of the patients. Cyclosporine is effective for long-term therapy for severe psoriasis and does not lead to severe deterioration of the disease after drug withdrawal.


Proposal for pathogenesis-based treatment options to reduce calcium oxalate stone recurrence.
Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30% and 50% despite technological and scientific advances. Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities. Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence. All relevant literature up to October 2020, listed in PubMed is reviewed. Clinical guidelines endorse the use of evidence-based medications, such as alkaline agents and thiazides, to reduce urinary mineral supersaturation and recurrence. However, there may be additional steps during stone pathogenesis where medications could moderate stone risk. Idiopathic calcium oxalate stones grow attached to Randall's plaques or plugs. Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs. The renin-angiotensin-aldosterone system (RAAS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, and NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome have all been implicated at specific steps during stone pathogenesis in animal models. In addition to supersaturation-reducing therapies, the use of anti-oxidants, free radical scavengers, and inhibitors of NADPH oxidase, NLRP3 inflammasome, and RAAS may prove beneficial for stone prevention. Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats. Although clinical evidence for their use in stone prevention in humans is limited, experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.


Tracheobronchitis caused by Aeromonas veronii biovar sobria after near-drowning.
A 19-year-old man developed an acute tracheobronchitis shortly after having been rescued from a near-drowning in a river where previous investigations had demonstrated the presence of 500 c.f.u. ml(-1) of Aeromonas sp. in the water. An isolate of Aeromonas veronii biovar sobria was identified as the causative agent of the tracheobronchitis. The causality was supported by the massive growth of A. veronii in bronchial secretion, the presence of a type III secretion system in the bacterial isolate, and the strong haemolytic activity of the strain on blood agar.


Genetic characteristics of mumps viruses isolated in Korea from 2007 to 2012.
Mumps is a vaccine-preventable viral disease. Despite vaccine coverage of >95%, the incidence of mumps has increased in Korea since 2007. This study aimed to genetically characterize mumps virus (MuV) strains that circulated in Korea between 2007 and 2012 to determine the factors underlying mumps outbreaks. MuV was isolated from 175 clinical specimens between 2007 and 2012 in Korea. Upon analysis of the SH gene in Korean mumps virus isolates, three different genotypes were identified: I, H, and F. The MuV genotypes I and H co-circulated in Korea, and eight isolates of Korean genotype F were found within the same time period in 2008. An analysis of HN amino-acid sequence data showed that Korean isolates had no changes in their glycosylation sites. At putative neutralizing epitope sites, the Jeryl-Lynn strain showed 4-5 different amino acid sequences from those observed in Korean isolates. Korean isolates of genotypes I and H shared distinctive point mutations on putative neutralizing epitope positions in each genotype. This report describes the genetic characteristics of MuV strains circulating in Korea and provides information on endemic mumps infections. This information may be important to help prevent mumps and control outbreaks of mumps in Korea. J. Med. Virol. 88:1479-1486, 2016. © 2016 Wiley Periodicals, Inc.


Chlorella vulgaris α-L-arabino-α-L-rhamno-α,β-D-galactan structure and mechanisms of its anti-inflammatory and anti-remodelling effects.
Microalgal exopolysaccharides (EPSs) are given great attention due to their potential biotechnology applications. Purified C. vulgaris EPS was subjected to compositional and sugar linkage analyses, and partial acid hydrolysis. Hydrolysate separation by gel chromatography afforded oligosaccharide fractions. Both, EPS and oligomers were studied by NMR spectroscopy. Data suggest very complex highly branched α-L-arabino-α-L-rhamno-α,β-D-galactan structure. Backbone repeating unit is formed by →2)-α-L-Rha (1 → 3)-α-L-Rha(1 → sequence, highly branched by long 1,6-linked α-D-Galp side chains, further branched at C2, C3 or C4 by α-L-Araf, α-D-Galf and β-D-Galf residues. α-L-Araf form longer 1,2-linked chains branched at C3, C4 or C5. Galf residues are localized as terminal units predominantly in the β configuration, while α-D-Galp and α-L-Araf may be partially O-methylated. Ex vivo biological assays showed increased interleukin-12 (IL-12) and interferon-gamma (INF-γ) levels corresponding to transforming growth factor beta (TGF-β) decrease in guinea pig model experimental asthma. These facts point to the anti-remodelling effect of Chlorella EPS and suggest its possible application in the treatment of asthma and chronic obstructive pulmonary disorder.


Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration.
The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking.


A cluster of fever and hypotension on a surgical intensive care unit related to the contamination of plasma expanders by cell wall products of Bacillus stearothermophilus.
To evaluate an outbreak of fever and hypotension after cardiac surgical procedures and the role of polygeline, a plasma expander. Unmatched case-control study. A six-bed cardiac surgery intensive care unit (SICU) of the Hospital Clinic of Barcelona (Spain), a 940-bed public teaching hospital. Eight cases and 25 control patients admitted to the SICU over a 4-week epidemic period. Development of hypotension (systolic blood pressure < or = 90 mm Hg or a drop of 40 mm Hg from baseline systolic blood pressure) and fever (axillary temperature > 38.5 degrees C) within 24 hours of a cardiac surgical procedure. The single risk factor significantly different between cases and controls was the total volume of polygeline used throughout the surgical procedure for extracorporeal circulation: a median of 1,250 mL (mean, 1,312.5 +/- 842.5 mL) in cases versus 500 mL (mean, 566.0 +/- 159.9 mL) in controls (P = .0029). By multiple logistic regression analysis, polygeline use was the single risk factor significantly related to the outcome (odds ratio, 8.75; CI95, 1.36 to 56.2; P = .01). Neither blood cultures from patients nor cultures of the polygeline used yielded growth of any microorganism. Stopping use of the implicated polygeline lot controlled the outbreak. Use of polygeline was associated with an outbreak of fever and hypotension in a SICU. Information from the manufacturer indicated the likelihood of contamination of the product with Bacillus stearothermophilus components. The manufacturer has since changed the production and control processes, and no further adverse events have been seen.


Measurement of the response of psoriasis to short-term application of anthralin.
Thirty-six patients with psoriasis were treated with short-term application of anthralin in three studies. (I) In thirteen patients 2% anthralin was applied daily to lesions on one arm for 60 min; (2) in ten patients 4% anthralin was applied daily to lesions on one-half of the body for 30 min; (3) in thirteen patients 2% anthralin was applied daily to lesions on one-half of the body for 30 min and the strength was increased to 4% and then 8% at intervals of 3 or more days, according to tolerance. Comparison was made with the response to conventional daily treatment with 0.05% to 1% anthralin. Progress was compared clinically by days to clearing, by measurements of plaque thickness with Harpenden calipers, by the frequency and severity of burning, and by patient preference. There was no significant difference in the times to clinical clearance between short-term and conventional anthralin treatments and the rate of decrease of plaque thickness was likewise similar. There was an excellent correspondence between time to reach half plaque thickness and the time for each plaque to clear clinically. There was increased burning with all the short-term treatments but the patients still preferred it. We conclude that short-term treatment with anthralin is as effective as continuous application, but that the increased burning is likely to limit its usefulness.


Associations of vitamin D with novel and traditional anthropometric indices according to age and sex: a cross-sectional study in central southern China.
Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. Level V, cross-sectional descriptive study.


Caries prevalence in Danish pre-school children delivered vaginally and by caesarean section.
The mode of delivery may significantly influence the diversity and composition of the oral microflora and facilitate early acquisition of mutans streptococci. The aim was to compare caries prevalence and experience in 3-year-old children delivered vaginally and by caesarean section (C-section). The study had an observational cohort protocol based on extracted information from governmental databases and nationwide registers concerning birth, social and educational levels and dental status. Children born at the Copenhagen University Hospital in 2005 were eligible and the final study group with complete information consisted of 594 children, 443 delivered vaginally and 151 by C-section. The total caries prevalence was 8% and no significant difference was displayed between the groups. When only the children with caries (dmfs > 0) were compared, those delivered by C-section had a higher mean value in comparison with those delivered vaginally (dmfs 6.8 vs 3.2), but the difference was not statistically significant. There was a significant relationship between caries prevalence and low family income in the total study group (OR = 5.8, p < 0.05). Within the limitations of this observational cohort study, caries prevalence in 3-year-old children was not related to the mode of delivery. However, the tendency of more severe caries in the C-section group justifies further studies, preferably with a prospective design.


Selection of a PD-1 blocking antibody from a novel fully human phage display library.
Programmed cell death protein 1 (PD-1) is an immunoregulatory target which is recognized by different monoclonal antibodies, approved for the therapy of multiple types of cancer. Different anti-PD-1 antibodies display different therapeutic properties and there is a pharmaceutical interest to generate and characterize novel anti-PD-1 antibodies. We screened multiple human antibody phage display libraries to target novel epitopes on the PD-1 surface and we discovered a unique and previously undescribed binding specificity (termed D12) from a new antibody library (termed AMG). The library featured antibody fragments in single-chain fragment variable (scFv) format, based on the IGHV3-23*03 (VH ) and IGKV1-39*01 (Vκ) genes. The D12 antibody was characterized by surface plasmon resonance (SPR), cross-reacted with the Cynomolgus monkey antigen and bound to primary human T cells, as shown by flow cytometry. The antibody blocked the PD-1/PD-L1 interaction in vitro with an EC50 value which was comparable to the one of nivolumab, a clinically approved antibody. The fine details of the interaction between D12 and PD-1 were elucidated by x-ray crystallography of the complex at a 3.5 Å resolution, revealing an unprecedented conformational change at the N-terminus of PD-1 following D12 binding, as well as partial overlap with the binding site for the cognate PD-L1 and PD-L2 ligands which prevents their binding. The results of the study suggest that the expansion of antibody library repertoires may facilitate the discovery of novel binding specificities with unique properties that hold promises for the modulation of PD-1 activity in vitro and in vivo.


Employing multiple-attribute utility technology to evaluate publicity activities for cancer information and counseling programs in Japan.
Cancer Information and Support Centers (CISCs), which are set up at designated cancer care hospitals (DCCHs) according to the national cancer control programs in Japan, are expected to provide cancer patients and their families with information and counseling, but their public recognition remains low. Therefore, it is necessary to evaluate the publicity activities of CISCs. In this study, we evaluated two types of activities for publicizing CISCs conducted inside and outside one of the DCCHs ('Inside Activity' and 'Outside Activity', respectively) by multi-attribute utility technology (MAUT). Seven types of stakeholders, including physicians (n = 5), nurses (n = 4), CISC cancer counselors (n = 5), executives (n = 5), office department staff (n = 5), and licensed social insurance consultants in the hospital (n = 5), as well as patients and citizens (n = 19) were involved in the evaluation. Eight goals of the program for publicizing CISCs were determined. The utility score for each goal was separately calculated for Inside Activity and Outside Activity, and those of the eight goals were summed up to obtain an overall utility score for each activity. Finally, no substantial difference in overall utility score was found between the activity types (Inside Activity = 82.00 vs. Outside Activity = 81.18). It is implied that omitting or reducing either activity should be avoided in streamlining publicity activities at the CISCs. Despite the limited external validity of the finding, the methodology presented in this study is widely applicable to evaluate other multifaceted programs under an increasingly tight budget in the oncology setting. As the MAUT approach enables us to obtain numerical data for priority settings, it will contribute to rationalized healthcare management, especially in the oncology setting in which objective evaluations of the national cancer-related control programs are lacking and a broad range of stakeholders is involved.


Synthesis, characterization, and in vitro cytotoxicity of some gold(I) and trans platinum(II) thionate complexes containing water-soluble PTA and DAPTA ligands. X-ray crystal structures of [Au(SC4H3N2)(PTA)], trans-[Pt(SC4H3N2)2(PTA)2], trans-[Pt(SC5H4N)2(PTA)2], and trans-[Pt(SC5H4N)2(DAPTA)2].
A series of gold(I) and platinum(II) complexes of the type [Au(SR)(P)] and trans-[Pt(SR) 2(P) 2] [SR = 2-thiopyridine (SPy), 2-thiopyrimidine (SPyrim); P = 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)] were prepared and characterized, and their in vitro cytotoxicities against a panel of seven human cancer cell lines were evaluated. The highly water soluble gold(I) complexes [Au(SR)(P)] [P = PTA and SR = SPy ( 1), SPyrim ( 2); P = DAPTA and SR = SPy ( 3), SPyrim ( 4)] showed low cytotoxicity, while the platinum(II) complexes trans-[Pt(SR) 2(P) 2] [P = PTA and SR = SPyrim ( 5), SPy ( 6); P = DAPTA and SR = SPyrim ( 7), SPy ( 8)] demonstrated potent cytotoxicity for ovarian, colon, renal, and melanoma cancer cell lines on the basis of a comparison with ID 50 values for some established cytotoxic drugs. Single crystals of 2, 5, 6, and 8 suitable for X-ray structural characterization were obtained, and the study revealed the trans configuration for 5, 6, and 8 in their solid states.


Restricting the ageing degradation of the mechanical properties of gamma irradiated UHMWPE using MWCNTs.
Property degradation of the medical grade polymers after gamma irradiation is the primary concern that limits longevity of them. Though the conventional antioxidant material helps to reduce the degradation but it limits the degree of crosslinking of the polymer. The objective of the present work is to study the influence of multi walled carbon nanotubes (MWCNTs) on restricting the degradation of mechanical properties of medical grade ultra high molecular weight polyethylene (UHMWPE) after its irradiation. UHMWPE was reinforced by chemically treated MWCNTs at different concentrations such as 0.5, 1.0, 1.5, and 2.0 wt%. The test samples were then subjected to Co⁶⁰ gamma irradiation with an integral dose of 25, 50, 75 and 100 kGy in air. The mechanical properties of irradiated samples were evaluated within 10 days, 60 and 120 days after irradiation. It was observed that the mechanical properties of virgin UHMWPE and nanocomposites were enhanced immediately after irradiation but they were found to be reduced at later stages. It was also observed that the presence of MWCNTs limited the ageing degradation of the mechanical properties of UHMWPE. Raman spectroscopic and TEM studies confirmed the formation of irradiation induced defects on the MWCNTs. Electron spin resonance studies showed that the relative radical intensity of virgin UHWMPE was reduced significantly with an increase of MWCNTs concentration confirming the radical scavenging ability of them. It is concluded that MWCNTs restricted the ageing degradation of irradiated UHMWPE.


Intravital imaging of osteocyte integrin dynamics with locally injectable fluorescent nanoparticles.
Osteocytes are the resident mechanosensory cells in bone. They are responsible for skeletal homeostasis and adaptation to mechanical cues. Integrin proteins play a prominent role in osteocyte mechanotransduction, but the details are not well stratified. Intravital imaging with multiphoton microscopy presents an opportunity to study molecular level mechanobiological events in vivo and presents an opportunity to study integrin dynamics in osteocytes. However, fluorescent imaging limitations with respect to excessive optical scattering and low signal to noise ratio caused by mineralized bone matrix make such investigations non-trivial. Here, we demonstrate that ultra-small and bright fluorescent core-shell silica nanoparticles (<7 nm diameter), known as Cornell Prime Dots (C'Dots), are well-suited for the in vivo bone microenvironment and can improve intravital imaging capabilities. We report validation studies for C'Dots as a novel, locally injectable in vivo osteocyte imaging tool for both non-specific cellular uptake and for targeting integrins. The pharmacokinetics of C'Dots reveal distinct sex differences in nanoparticle intracellular dynamics and clearance in osteocytes, which represents a novel topic of study in bone biology. Integrin-targeted C'Dots were used to study osteocyte integrin dynamics. To the best of our knowledge, we report here the first evidence of osteocyte integrin endocytosis and recycling in vivo. Our results provide novel insights in osteocyte biology and will open up new lines of investigation that were previously unavailable in vivo.


A new synthesis of N-alkyl 3-acetyl-4-methoxycarbonylmethyl-2-methyl-1,4-dihydropyridines utilizing sec-aminodienyl esters with acetylacetone.
The reactions of sec-aminodienyl esters 3 with acetylacetone (4) afforded N-alkyl 3-acetyl-4-methoxycarbonylmethyl-2-methyl-1,4-dihydropyridines 5 and enamines 6, providing a new azaelectrocyclization reaction.


Opportunities for learning in the surgical workplace and how they can be exploited: a practical guide.
Training times and the working week have been shortened but the amount needed to be learned remains the same. This article demonstrates how trainees in surgery can incorporate learning opportunities into their normal working day.


Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer.
To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.


Readability, relevance and quality of the information in Spanish on the Web for patients with rheumatoid arthritis.
Education is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. To assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. The search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre-established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. The Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. There is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA.


Primary Production in the Kara, Laptev, and East Siberian Seas.
Understanding of the primary production of phytoplankton in the Kara Sea (KS), the Laptev Sea (LS), and the East Siberian Sea (ESS) remains limited, despite the recognized importance of phytoplankton in the Arctic Ocean. To address this knowledge gap, we conducted three NABOS (Nansen and Amundsen Basins Observational System) expeditions in 2013, 2015, and 2018 to measure in situ primary production rates using a 13C-15N dual-tracer method and examine their major controlling factors. The main goals in this study were to investigate regional heterogeneity in primary production and derive its contemporary ranges in the KS, LS, and ESS. The daily primary production rates in this study (99 ± 62, 100 ± 77, and 56 ± 35 mg C m-2 d-1 in the KS, LS, and ESS, respectively) are rather different from the values previously reported in each sea mainly because of spatial and regional differences. Among the three seas, a significantly lower primary production rate was observed in the ESS in comparison to those in the KS and LS. This is likely mainly because of regional differences in freshwater content based on the noticeable relationship (Spearman, rs = -0.714, p < 0.05) between the freshwater content and the primary production rates observed in this study. The contemporary ranges of the annual primary production based on this and previous studies are 0.96-2.64, 0.72-50.52, and 1.68-16.68 g C m-2 in the KS, LS, and ESS, respectively. Further intensive field measurements are warranted to enhance our understanding of marine microorganisms and their community-level responses to the currently changing environmental conditions in these poorly studied regions of the Arctic Ocean.


Revisiting survival at sea from a nutrition and food perspective: rationalizing the rations.
This study examines the design of food rations for survival at sea required by the International Maritime Organization through the Life Saving Appliances (LSA) Code, as implemented by Transport Canada. Energy demand and body fat reserves were estimated for the Canadian population based on demographic and anthropometric data. It was determined that caloric content of food rations could be drastically decreased without potential harm to survivors of a marine abandonment. Coupled with ration reformulation, such decrease could be an opportunity to extend safe survival conditions to up to 5 days versus 2 days as currently provisioned by the LSA Code.


Kinetics of the interaction of sulfate and hydrogen phosphate radicals with small peptides of glycine, alanine, tyrosine and tryptophan.
The kinetics and mechanism of the oxidation of Glycine (Gly), Alanine (Ala), Tyrosine (Tyr), Tryptophan (Trp) and some di-(Gly-Gly, Ala-Ala, Gly-Ala, Gly-Trp, Trp-Gly, Gly-Tyr, Tyr-Gly), tri-(Gly-Gly-Gly, Ala-Gly-Gly) and tetrapeptides (Gly-Gly-Gly-Gly) mediated by sulfate (SO(4) (-)) and hydrogen phosphate (HPO(4) (-)) radicals was studied, employing the flash-photolysis technique. The substrates were found to react with sulfate radicals (SO(4) (-), produced by photolysis of the S(2)O(8)(2-)) faster than with hydrogen phosphate radicals (HPO(4) (-), generated by photolysis of P(2)O(8)(4-) at pH = 7.1). The reactions of the zwitterions of the aliphatic amino acids and peptides with SO(4) (-) radicals take place by electron transfer from the carboxylate moiety to the inorganic radical, whereas those of the HPO(4) (-) proceed by H-abstraction from the alpha carbon atom. The phenoxyl radical of Tyr-Gly and Gly-Tyr are formed as intermediate species of the oxidation of these peptides by the inorganic radicals. The radical cations of Gly-Trp and Trp-Gly (at pH = 4.2) and their corresponding deprotonated forms (at pH = 7) were detected as intermediates species of the oxidation of these peptides with SO(4) (-) and HPO(4) (-). Reaction mechanisms which account for the observed intermediates are proposed.


Effects of 2,4-dichlorophenol on the expression of vitellogenin and estrogen receptor genes and physiology impairments in Chinese rare minnow (Gobiocypris rarus).
2,4-Dichlorophenol (2,4-DCP) is known as a toxicant, but unknown as an environmental endocrine disruptor. In the present work, Chinese rare minnow (Gobiocypris rarus) was exposed to 0.03, 0.3, and 3 mg/L 2,4-DCP for 3 d and 0.1, 0.3, and 1 mg/L 2,4-DCP for 21 d, respectively. Endpoints including somatic index, vitellogenin (VTG) mRNA and protein level, estrogen receptor (ER) mRNA and histopathology were measured. In the 3-d exposure experiment, the effect concentrations were 0.3 mg/L and above, and in 21-d exposure, the effect concentrations were 0.1 mg/L and above. When exposed to the effect concentrations, GSI was significantly reduced for both male and female, ER mRNA was upregulated in male and downregulated in female. There were no significant variations of VTG mRNA in both male and female in 3-d exposure and in male in 21-d exposure. However, VTG mRNA in female in 21-d exposure was upregulated, corresponding to an increase of VTG protein in serum. Histopathological observation showed that ovaries were degenerated in the effect concentrations, where follicular atresias were more frequently observed. Because the sex hormones related genes and toxicological endpoints were affected in the dose-dependent manner, the results suggest that 2,4-DCP could be a potential endocrine disruptor and might cause adverse effects in female sex organs through interruption of ER-mediated processes.


Danggui-Jakyak-San enhances hippocampal long-term potentiation through the ERK/CREB/BDNF cascade.
Danggui-Jakyak-San (DJS), a traditional herbal prescription, has long been used to treat gerontological disorders due to insufficient blood supply. Previously, we reported that DJS increased hippocampal neurogenesis and enhanced learning and memory. However, the precise mechanism of DJS and its effects on learning and memory are still not well understood. In this study, we investigated the effect of DJS on hippocampal long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory. To understand the effect of DJS on LTP, we used acute mouse hippocampal slices and delivered one train of high frequency stimulation (100 Hz, 100 pulses). Western blots were used to analyze the changes in protein levels induced by DJS. Morris water maze test was used to evaluate the effect of DJS on spatial long-term memory. DJS enhanced LTP in the Schaffer-collateral pathway of the hippocampus in a concentration-dependent manner. Extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) were activated by DJS. Moreover, brain-derived neurotropic factor (BDNF) was also increased by DJS. Blockade of ERK1/2 activation with PD198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LTP enhancement. In vivo, DJS improved spatial long-term memory and upregulated the hippocampal CREB/BDNF cascade. These results suggest that DJS enhances hippocampal LTP and spatial memory through the ERK/CREB/BDNF cascade.


Measurement of slow diffusion coefficients of molecules with arbitrary scalar couplings via long-lived spin states.
New experiments are described for the determination of very slow diffusion constants by nuclear magnetic resonance (NMR) using long-lived (singlet) states. These experiments are suitable for molecules or conformations featuring a wide range of J-couplings.


Expert Surgeons Can Be Distinguished From Trainees, and Surgical Proficiency Can Be Defined, Using Validated Metrics and Shoulder Models.
Experts at performing arthroscopic shoulder Bankart procedures can be distinguished from surgical trainees using validated metrics and a cadaveric or simulator model. The combination of performance metrics plus models generates a tool that can be used to precisely and accurately define a performance threshold and assess whether or not a surgeon is proficient at performing a procedure. A tool that can be used to judge surgical expertise has implications for training and credentialing. Experienced surgeons make fewer mistakes and are faster than novices.


Thymoma patients with or without myasthenia gravis have increased Th17 cells, IL-17 production and ICOS expression.
Thymoma associated myasthenia gravis (TAMG) is a small disease subgroup with autoantibodies against the acetylcholine receptor. The aim of this study was to assess the role of T helper (Th) cells in TAMG compared to thymoma patients without MG (TOMA) and healthy controls (HC). Peripheral blood cells were used for intracellular cytokine measurements and phenotyping of CD4+ Th cells. IL-21 and IL-4 productions and peripheral Th cells were higher in TAMG compared to TOMA patients and HC. Increases of ICOS and Th17 population were detected both in TAMG and TOMA groups. Higher IL-10 and Th1 population have been observed related to thymectomy. ICOS expression and Th17 induced by thymoma may contribute to the development of TAMG.


Altered environment and risk of malaria outbreak in South Andaman, Andaman & Nicobar Islands, India affected by tsunami disaster.
Pools of salt water and puddles created by giant waves from the sea due to the tsunami that occurred on 26th December 2004 would facilitate increased breeding of brackish water malaria vector, Anopheles sundaicus. Land uplifts in North Andaman and subsidence in South Andaman have been reported and subsidence may lead to environmental disturbances and vector proliferation. This warrants a situation analysis and vector surveillance in the tsunami hit areas endemic for malaria transmitted by brackish water mosquito, An. sundaicus to predict the risk of outbreak. An extensive survey was carried out in the tsunami-affected areas in Andaman district of the Andaman and Nicobar Islands, India to assess the extent of breeding of malaria vectors in the habitats created by seawater flooding. Types of habitats in relation to source of seawater inundation and frequency were identified. The salinity of the water samples and the mosquito species present in the larval samples collected from these habitats were recorded. The malaria situation in the area was also analysed. South Andaman, covering Port Blair and Ferrargunj sub districts, is still under the recurring phenomenon of seawater intrusion either directly from the sea or through a network of creeks. Both daily cycles of high tides and periodical spring tides continue to cause flooding. Low-lying paddy fields and fallow land, with a salinity ranging from 3,000 to 42,505 ppm, were found to support profuse breeding of An. sundaicus, the local malaria vector, and Anopheles subpictus, a vector implicated elsewhere. This area is endemic for both vivax and falciparum malaria. Malaria slide positivity rate has started increasing during post-tsunami period, which can be considered as an indication of risk of malaria outbreak. Paddy fields and fallow land with freshwater, hitherto not considered as potential sites for An. sundaicus, are now major breeding sites due to saline water. Consequently, there is a risk of vector abundance with enhanced malaria transmission potential, due to the vastness of these tsunami-created breeding grounds and likelihood of them becoming permanent due to continued flooding in view of land subsidence. The close proximity of the houses and paucity of cattle may lead to a higher degree of man/vector contact causing a threat of malaria outbreak in this densely populated area. Measures to prevent the possible outbreak of malaria in this tsunami-affected area are discussed.


Flavonoid composition of Juniperus oblonga Bieb.
Juniperus oblonga Bieb is widely spread in the Caucasus Mountains, particularly in its eastern and southern regions. Diuretic effect of juniper berries is determined by the presence of volatile oils and polyphenol complex, particularly flavonoids. Flavonoids were extracted from raw material with 70% ethanol and then with ethyl acetate. Column chromatography of ethyl acetate fraction on polyamide yielded 5 compounds, which were identified on the basis of physicochemical constants of parent compounds and products of acid hydrolysis and alkaline degradation of aglycones and on the basis of UV-spectroscopy as apigenin, isoquercitrin, apigenin-7-glucoside, quercetin-3-rutinoside, and scutellarin-7-glucoside. Quantitative composition of flavonoid in equivalent to rutin concentration in Juniperus oblonga Bieb was 0.910±0.007% (UV-spectrophotometry data).


Caprine arthritis encephalitis virus (CAEV) replicates productively in cultured epididymal cells from goats.
The transmission of CAEV from male goats has not been well studied and the target cells that support viral replication are not well characterized. Epididymal epithelial cells (EECs) are important and play a key role in the fertility and motility of spermatozoa. During their transit, spermatozoa incorporate several EEC-produced proteins into their plasma membranes to stabilize them and prevent premature acrosomal reaction. This intimate interaction between spermatozoa and EECs may increase the likelihood of the infection of semen with CAEV if epididymal tissue is productively infected and sheds the virus into the duct. The aim of this study was to examine whether goat EECs are susceptible to CAEV infection in tissue culture. Cells were isolated from epididymides obtained from goats that were sampled from a certified-CAEV-free herd. Cultured cells were then inoculated with a molecularly-cloned isolate of CAEV (CAEV-pBSCA). Inoculated cells developed cytopathic effects (CPE), showing numerous multinucleated giant cells (MGC) in cell-culture monolayers. Expression of CAEV proteins was detected by immunofluorescence using an anti-p28, Gag-specific antibody. The culture medium of inoculated cells was shown to contain high titers (10(6) tissue culture infectious doses 50 per ml (TCID50/ml)) of infectious, cytopathic virus when assayed using indicator goat synovial membrane (GSM) cells. Our findings clearly demonstrate that cells of the buck genital tract are targets of CAEV and are thus a potential reservoir that sheds infectious CAEV into the semen of infected animals. These data suggest the use of sperm from CAEV-free goat males for artificial insemination in genetic selection programs to minimize CAEV dissemination.


Influence of carotid and aortic baroreceptors on neurosecretory neurons in supraoptic nuclei.
(1) The effects of arterial baroreceptor stimulation on the activity of 'identified' neurosecretory cells in supraoptic nuclei (SON) of the hypothalamus were investigated in anesthetized cats. (2) Stimulation of baroreceptors by distension of an 'isolated' carotid sinus greatly inhibited SON activity. A linear relationship was found to exist between stimulus intensity (an increase in the sinus pressure) and the degree of inhibition of SON neuron activity. This inhibitory effect was abolished by section of the sinus nerve. (3) The inhibitory effect of baroreceptors on SON neuron activity was most pronounced in the first 5 sec during stimulation, and the effect became less when the stimulus lasted for a long period. At the end of stimulation there was a transient reversal of the response. (4) The excitation of aortic baroreceptors by occluding descending aorta strongly inhibited SON neuron activity. (5) Occlusion of carotid arteries augmented the SON neuron activity. Electrical stimulation of the sinus nerve caused an excitation or an inhibition of SON neurons, depending on the stimulus intensities. Apparently these stimuli produced different degrees of excitation in baro- and chemoreceptors. (6) Combination of chemo- and baroreceptor stimulations revealed that the excitatory effect exerted by chemoreceptor stimulation on SON neurons was reversed or blocked by baroreceptor activation, indicating the powerful inhibitory influence of baroreceptors.


Putative relationship between hormonal status and serum pyrrolidone carboxypeptidase activity in pre- and post- menopausal women with breast cancer.
In breast cancer, hormonal changes are rather constant in post-menopausal women since they tend to vary only over long time spans. However, in pre-menopausal women, the development of breast cancer is associated with hormonal physiological variations. The aim of the present work was to analyse the changes in circulating levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pre- and post-menopausal women that were healthy or with breast cancer, and their connection to serum pyrrolidone carboxypeptidase (Pcp) activity. We observed significant changes in the hormonal profile in post-menopausal women with breast cancer compared to the control group. In pre-menopausal women, we found significant changes in circulating GnRH levels with respect to the healthy group. Our present results support the existence of neuroendocrine misregulation that could be involved in tumour progression, with Pcp being a potentially new pharmacological target in breast cancer treatments.


Detecting changes in natural resources using Land Condition Trend Analysis data.
The Land Condition Trend Analysis (LCTA) program is the US Army's standard for land inventory and monitoring, employing standardized methods of natural resources data collection, analyses, and reporting designed to meet multiple goals and objectives. Critical to using LCTA data in natural resources management decisions is the ability of the LCTA protocols to detect changes in natural resources. To quantify the ability of LCTA protocols to detect resource changes, power analysis techniques were used to estimate minimum detectable effect sizes (MDES) for selected primary and secondary management variables for three Army installations. MDES for a subset of primary variables were estimated using data from 27 installation LCTA programs. MDES for primary and secondary variables varied widely. However, LCTA programs implemented at larger installations with lower sampling intensities detected changes in installation resources as well as programs implemented at smaller more intensively sampled installations. As a national monitoring program that is implemented at individual installations, LCTA protocols provide relatively consistent monitoring data to detect changes in resources despite diverse resource characteristics and implementation constraints.


Structural changes measured by X-ray scattering from human flap endonuclease-1 complexed with Mg2+ and flap DNA substrate.
Human flap endonuclease-1 (FEN-1) is a member of the structure-specific endonuclease family and is essential in DNA replication and repair. FEN-1 has specific endonuclease activity for repairing nicked double-stranded DNA substrates that have the 5'-end of the nick expanded into a single-stranded tail, and it is involved in processing Okazaki fragments during DNA replication. Magnesium is a cofactor required for nuclease activity. We used small-angle x-ray scattering to obtain global structural information pertinent to nuclease activity from FEN-1, the D181A mutant, the wild-type FEN-1. 34-mer DNA flap complex, and the D181A.34-mer DNA flap complex. The D181A mutant, which has Asp-181 replaced by Ala, selectively binds to the flap structure, but has lost its cleaving activity. Asp-181 is thought to be involved in Mg2+ binding at the active site (Shen, B., Nolan, J. P., Sklar, L. A., and Park, M. S. (1996) J. Biol. Chem. 271, 9173-9176). Our data indicate that FEN-1 and the D181A mutant each have a radius of gyration of approximately 26 A, and the effect of Mg2+ on the scattering from the proteins alone is insignificant. The 34-mer DNA fragment was constructed such that it readily forms a 5'-flap structure. The formation of the flap conformation of the DNA substrate was evident by both the extrapolated Io scattering and radius of gyration and was supported by NMR spectrum and nuclease assays. In the absence of magnesium, the FEN-1.34-mer DNA flap complex has an Rg value of approximately 34 A, whereas the D181A.34-mer DNA flap complex self-associates, suggesting that a significant protein conformational change occurs by addition of the flap DNA substrate and that Asp-181 is crucial for proper binding of the protein to the DNA substrate. A time course change in the scattering profiles arising from magnesium activation of the FEN-1.34-mer DNA flap complex is consistent with the protein completely releasing the DNA substrate after cleavage.


Effect of prenatal exposure to fine particulate matter and intake of Paracetamol (Acetaminophen) in pregnancy on eczema occurrence in early childhood.
The goal of the study was to test the hypothesis that prenatal Paracetamol exposure increases the risk of developing eczema in early childhood and that this association may be stronger in children who are exposed in fetal period to higher concentrations of fine particulate matter (PM2.5). The study sample consisted of 322 women recruited from January 2001 to February 2004 in the Krakow inner city area who gave birth to term babies and completed 5-year follow-up. Paracetamol use in pregnancy was collected by interviews and prenatal personal exposure to PM2.5 over 48 h was measured in recruited women in the second trimester of pregnancy. After delivery, every three months in the first 24 months of the newborn's life and every 6 months later, a detailed standardized face-to-face interview on the infant's health was administered to each mother by trained interviewers. During the interviews at each of the study periods after birth, a history of eczema was recorded. The incident rate ratio (IRR) for frequency of eczema events over the follow-up was estimated from the Poisson regression model and the overall effect of main exposure variables on eczema was assessed by odds ratios (ORs) by the logistic model. The estimated relative risk of eczema occurring whenever in the follow-up was related significantly neither with prenatal Paracetamol nor higher PM2.5 exposure, however, their joint effect was significant (OR interaction term=6.04; 95%CI: 1.04-35.16). Of potential confounders considered in the analysis only damp/moldy home significantly increased the risk of eczema (OR=1.53; 95%CI: 1.14-2.05). In contrast, there was an inverse significant association between the presence of older siblings and eczema (OR=0.55; 95%CI: 0.35-0.84). The joint effect of the main exposure variables significantly increased frequency of eczema events (IRR=1.78, 95%CI: 1.22-2.61). In conclusion, the findings of the study suggest that Paracetamol use by mothers in pregnancy is not an independent risk factor for eczema in children, however, even very small doses of Paracetamol taken in pregnancy may contribute to the occurrence of allergic symptoms in early childhood if there is prenatal co-exposure to higher airborne fine particulate matter.


Effectiveness of daily eccentric contractions induced via kilohertz frequency transcutaneous electrical stimulation on muscle atrophy.
The effects of daily repeated bouts of concentric, isometric, or eccentric contractions induced by high frequency (kilohertz) transcutaneous electrical stimulation in ameliorating atrophy of the soleus muscle in hindlimb unloaded rats were determined. Five groups of male rats were studied: control, hindlimb unloaded for 2 weeks (HU), or HU plus two daily bouts of concentric, isometric, or eccentric high-frequency electrical stimulation-induced contractions of the calf musculature. Soleus mass and fiber size were smaller, the levels of phosphorylated Akt1 and FoxO3a lower, and atrogin-1 and ubiquitinated proteins higher in the HU, and the HU plus concentric or isometric contraction groups than in the control group. In contrast, daily bouts of eccentric contractions maintained these values at near control levels and all measures were significantly different from all other HU groups. These results indicate that daily bouts of eccentric contractions induced by high-frequency stimulation inhibited the ubiquitin-proteasome catabolic pathway and enhanced the Akt1/FoxO3a anabolic pathway that resulted in a prevention of the atrophic response of the soleus muscle to chronic unloading.


A thermo-responsive and photo-polymerizable chondroitin sulfate-based hydrogel for 3D printing applications.
The aim of this study was to design a hydrogel system based on methacrylated chondroitin sulfate (CSMA) and a thermo-sensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate)-polyethylene glycol triblock copolymer (M15P10) as a suitable material for additive manufacturing of scaffolds. CSMA was synthesized by reaction of chondroitin sulfate with glycidyl methacrylate (GMA) in dimethylsulfoxide at 50°C and its degree of methacrylation was tunable up to 48.5%, by changing reaction time and GMA feed. Unlike polymer solutions composed of CSMA alone (20% w/w), mixtures based on 2% w/w of CSMA and 18% of M15P10 showed strain-softening, thermo-sensitive and shear-thinning properties more pronounced than those found for polymer solutions based on M15P10 alone. Additionally, they displayed a yield stress of 19.2±7.0Pa. The 3D printing of this hydrogel resulted in the generation of constructs with tailorable porosity and good handling properties. Finally, embedded chondrogenic cells remained viable and proliferating over a culture period of 6days. The hydrogel described herein represents a promising biomaterial for cartilage 3D printing applications.


The time is now: addressing the need for training in maternal critical care medicine.
Amongst many high-income countries, indirect medical conditions (e.g. cardiovascular disease, sepsis) now account for the majority of maternal deaths. In response to this concerning rise in indirect causes of maternal deaths, professional societies have developed guidelines that regionalize high-risk obstetric care and prioritize critical care expertise as a requirement for designated 'top' maternity hospitals. Critical care proficiency is mandated by the Accreditation Council for Graduate Medical Education for graduating obstetric anesthesiology fellows. Despite these requirements, no formal obstetric critical care educational curricula or fellowship pathways, combining critical care medicine and obstetric anesthesiology, currently exist. Dual subspecialty training in both obstetric anesthesiology and critical care medicine represents one strategy to improve the care of critically-ill obstetric patients and reduce maternal mortality and morbidity, which is one of the pressing healthcare issues of our time.


Pesticide contamination of the coastline of Martinique.
In January and February 2002, the presence of certain agricultural pesticides throughout the coastline of the Caribbean island of Martinique was investigated. The tropical climate of the French West Indies is suitable for banana production, which requires intensive use of pesticides. An inventory of all pesticides used on the island (compounds and tonnage) was compiled. Surveys and analyses revealed the presence of pesticides in the plumes of seven rivers. The organochlorine chlordecone and metabolites of aldicarb were detected at nearly all of the monitored sites, even though the use of chlordecone has been prohibited since 1993. Two triazines (ametryn and simazine) were also identified. The concentrations of carbamates and triazines detected in the water and sediment samples from Martinique are comparable to those reported for mainland France. Chlordecone concentrations in the sediment and particulate matter samples were, however, particularly high in the samples from Martinique. Toxicological implications are discussed. Of particular concern are the high levels of chlordecone (which is bioaccumulating and carcinogenic) and further monitoring of this compound is recommended, especially in fish and other sea-food products.


The interconversion kinetics, equilibrium, and solubilities of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981.
The pH dependence of the interconversion kinetics, equilibrium, and solubilities of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981 ([R-(R*,R*)]-2-(4-fluorophenyl)- beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl ]- 1H-pyrrole-1-hepatonic acid), are important considerations when choosing and developing one of the forms of these compounds. Over a pH range of 2.1 to 6.0 and at 30 degrees C, the apparent solubility of the sodium salt of CI-981 (i.e., the hydroxyacid form) increases about 60-fold, from 20.4 micrograms/mL to 1.23 mg/mL, and the profile yields a pKa for the terminal carboxyl group of 4.46. In contrast, over a pH range of 2.3 to 7.7 and also at 30 degrees C, the apparent solubility of the lactone form of CI-981 varies little, and the mean solubility is 1.34 (+/- 0.53) micrograms/mL. The kinetics of interconversion and the equilibrium between the hydroxyacid and the lactone forms have been studied as a function of pH, buffer concentration, and temperature at a fixed ionic strength (0.5 M) using a stability-indicating HPLC assay. The acid-catalyzed reaction is reversible, whereas the base-catalyzed reaction can be treated as an irreversible reaction. More specifically, at pH < 6, an equilibrium favoring the hydroxyacid form is established, whereas at pH > 6, the equilibrium reaction is no longer detectable and greatly favors the hydroxyacid form.(ABSTRACT TRUNCATED AT 250 WORDS)


A critical examination of team-teaching of health care administration courses: student, faculty, and administration perspective.
There are several teaching techniques adopted by faculty in order to provide information to students in the most effective manner. One of the relatively new teaching techniques is known as team-teaching. It has been observed that over the recent years this form of teaching has been gaining increasing interest and popularity among academicians. Nevertheless, there seems to be a great deal of confusion associated with team-teaching format. This paper attempts to clarify the various definitions and concerns that are associated with this form of teaching. The pros and cons of this form of teaching are discussed in detail.


Suprapubic prostatectomy. The removable purse string: a continuing comparative analysis of 300 consecutive cases.
Mortality rates, length of hospitalization, transfusion requirements, weights of excised tissue, complications and operating time are analyzed in this series of 300 patients who underwent suprapubic prostatectomies in which a removable purse-string closure of the bladder neck was used. The results are compared to those in other studies. The mortality rate in our study is the lowest reported to date for a large series. We believe that this technically simple operation, which has the most adaptability for combination with conjunctive operations, low transfusion requirements, few long-term complications and which can be done rapidly, is the most desirable method to remove benign prostates of 40 gm. or larger. We believe that there should be acceptance of broader indications for its use and that greater emphasis should be placed on teaching this procedure in urological training programs.


Structural and spectral studies of palladium(II) and platinum(II) complexes derived from N,N,N,N-tetradentate macrocyclic ligands.
Palladium(II) and platinum(II) complexes having the general composition [M(L)] X2 (where M=Pd(II) and Pt(II), L=3,4,12,13-tetraphenyl-2,5,11,14,19,20-hexaaza tricyclo [188.8.131.52.(6-10)] cosa-1(19), 2,4,6,8,10,(20),11,13,15,17-decaene (L1); 3,4,13,14-tetraphenyl-2,5,12,15-tetraaza tricyclo [11,0,0,(6-11)] cosa-1(16),2,4,7,9,6(11),12,14,17, 19-decaene (L2); 2,3,8,9-tetraphenyl-1,4,7,10-tetraaza cyclododeca-1,3,7,9-tetraene (L3) and X=Cl(-)) have been synthesized. The ligands were characterized on the basis of elemental analyses, IR, 1H NMR and EI mass spectral studies while that of the complexes were characterized on the basis of elemental analyses, molar conductance measurements, magnetic susceptibility measurements, IR, and electronic spectral techniques. All the complexes were found to be diamagnetic. The structures consist of monomeric units in which the Pd(II) and Pt(II) atoms exhibit square planar geometry.


Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.
Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.


Lymphatic pathways and rate of absorption of 131I-albumin from pericardium of dogs.
Labeled albumin diluted to 4.0 ml with normal saline solution was instilled into the pericardium of 14 dogs. Lymph from the right lymphatic duct (RD) and thoracic duct (TD) was collected at intervals as well as blood samples, and radioactivity measured.


Problems involving the determination of the column-only band broadening in columns producing narrow and tailed peaks.
We have investigated which of the different existing peak variance read-out methods (including the effect of a deconvolution pre-treatment method) are most suited to eliminate the system contribution from the total observed band broadening observed in LC systems. Emphasis is put on the most demanding case, i.e., the measurement of non-retained component peaks, which typically are very narrow and tailed. The problem with such peaks is that the method that is generally considered to be the only mathematically correct method (i.e., the method of moments) leads to peak variance values that are so strongly dominated by the tail of the peak that they become highly exaggerated and practically meaningless (i.e., they are dominated by the peak width at 10 or 12σt, which corresponds to resolutions and peak purities that are so high they are never pursued in practice). Interestingly, filtering away the extra-column contribution from the entire peak shape using peak deconvolution (wherein not only the second order moment is corrected but also all other moments) produces corrected 4σt- and half height peak widths that are physically meaningful, i.e., the corrected values allow to make sufficiently accurate predictions of how the peak width at 4σt and at half height changes when the column length changes. This result now allows to navigate away from the classical method of moments to define the column plate height, and resort to plate heights based on the practically much more relevant 4σt- and 5σt-widths, provided theses are corrected via peak deconvolution.


Long-term cancer survivors treated with multiple courses of repeat radiation therapy.
Through recent advances in cancer care, the number of long-term survivors has continuously increased. As a result, repetitive use of local radiotherapy for curative or palliative indications might have increased as well. This analysis aims to describe patterns of care and outcome of patients treated with multiple courses of repeat radiotherapy. All patients treated with radiotherapy between 2011 and 2019 at our department of Radiation Oncology were included into this analysis. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. Demographics, cancer and treatment characteristics and overall survival of patients having undergone multiple radiotherapy courses (minimum n = 5) were evaluated. The proportion of cancer patients treated with a minimum five courses of radiotherapy increased continuously from 0.9% in 2011 to 6.5% in 2019. In the 112 patients treated with a minimum of five radiotherapy courses, the primary tumor was lung in 41.9% (n = 47), malignant melanoma in 8.9% (n = 10) and breast in 8.0% (n = 9) of cases. A median interval of 3 years (maximum 8 years) elapsed between the first and the last radiotherapy course. The maximum number of courses in a single patient were n = 10. Treatment intent was curative or palliative in 46.4% and 53.6% for the first radiotherapy, respectively. The proportion of curative intent decreased to 11.6% at the 5th, and the last radiotherapy course was following a palliative intent in all patients. Five-year overall survival measured from the 1st radiotherapy course was 32.7%. Median overall survival was 3.3, 2.4, 1.3, and 0.6 years when measured from the 1st, the 1st palliative, the 5th and last course of radiotherapy, respectively. A continuously increasing number of patients is treated with multiple courses of radiotherapy throughout their long-term cancer survivorship.


Effects of glucocorticosteroids on cultured human skin fibroblasts. III. Transient inhibition of cell proliferation in the early growth stages and reduced susceptibility in later growth stages.
An immediate depression of the rate of cell proliferation occurred upon addition of glucocorticosteroids to cultures of human skin fibroblasts in the early growth stages. A reduced sensitivity or even insensitivity of the fibroblasts to growth inhibition inhibition was found upon the addition of the steroids at later stages of cell growth, when the cell density has increased. The inhibition in the early growth stages is transient and is most pronounced if the cultured medium is not renewed. This transient inhibition is not due to the development of steroid-resistant cell lines, and resembles the effect called tachyphylaxis, as is also observed in vasoconstriction tests.


Carotid artery wall stiffness is increased in patients with small vessel disease: A case-control study.
Cerebral ischemic small-vessel disease (SVD), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (MRI), is a progressive disease associated with an increased risk of stroke, dementia and death. Increased arterial stiffness has been associated with ischemic stroke and cerebral SVD independently of common vascular risk factors. The aim of the study was to analyze arterial stiffness in our patients with symptomatic SVD. In a cross-sectional study design we included 30 patients with clinical and MRI evidence of cerebral SVD and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. Patients were evaluated at the Ultrasound Laboratory at the Neurology Clinic, Clinical Center of Serbia in Belgrade, during a three-month period (from September 1st to December 1st 2012). Baseline demographic and vascular risk factors were recorded. All patients underwent standard carotid ultrasound scans with measuring of intima-media thickness (IMT) and analysis of atheromatous plaques. Internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (BSI) value. There were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p > 0.05). Patients in SVD group had significantly higher mean IMT (p = 0.0093) and mean BSI (p < 0.0001) than subjects in the control group. No significant correlation was detected between IMT and BSI in SVD group (r = 0.168; p = 0.376). Brain lesions severity correlated with BSI (r = 0.733; p < 0.0001). Arterial stiffness is increased in symptomatic patients with SVD, independently of vascular risk factors and IMT.


[Deciphering Hypoplastic Myelodysplastic Syndrome and Aplastic Anemia via In-Depth Analysis of Lymphocyte Subsets].
To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM). The lymphocyte subsets in hypo-MDS (n=25) and AA (n=33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed. The percentage of CD8+T cells in AA group was significantly higher than that in hypo-MDS group (P=0.001), while the percentage of CD4+ T cells and the CD4+/CD8+ ratio in AA group were obviously lower than those in hypo-MDS group (P=0.015 and 0.001, respectively). Furthermore, the proportion of CD4+ and CD8+ activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group (P=0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8+ naive T (TN) cells in AA patients was remarkably higher (P=0.044). And hypo-MDS patients had declined lymphocyte counts (P=0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients (P=0.019, 0.023, 0.027 and 0.045, respectively). In this study it was confirmed that the percentages of CD4+ and CD8+ TA cells, memory Tregs and CD8+ TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.