Au-Ag alloy nanoparticle-incorporated AgBr plasmonic photocatalyst.
A solid-phase photochemical method produces Au-Ag alloy nanoparticles (NPs) with a sharp size distribution and varying composition in AgBr crystals (Au-Ag@AgBr). These features render Au-Ag@AgBr promising as a material for the plasmonic photocatalyst further to provide a possibility of elucidating the action mechanism due to the optical tunability. This study shows that the visible-light activity of Au-Ag@AgBr for degradation of model water pollutant is very sensitive to the alloy composition with a maximum at the mole percent of Au to all Ag in AgBr (y) = 0.012 mol%. Clear positive correlation is observed between the photocatalytic activity and the quality factor defined as the ratio of the peak energy to the full width at half maximum of the localized surface plasmon resonance band. This finding indicates that Au-Ag@AgBr works as a local electromagnetic field enhancement-type plasmonic photocatalyst in which the Au-Ag NPs mainly promotes the charge separation. This conclusion was further supported by the kinetic analysis of the light intensity-dependence of external quantum yield.


Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE.
IL-2 is crucial for the production of CD4(+)CD25(+) T regulatory (Treg) cells while important for the generation of effective T cell-mediated immunity. How to exploit the capacity of IL-2 to expand Treg cells, while restraining activation of T effector (Teff) cells, is an important and unanswered therapeutic question. Dexamethasone (Dex), a synthetic glucocorticoid steroid, has been reported to suppress IL-2-mediated activation of Teff cells and increase the proportion of Treg cells. Thus, we hypothesized that glucocorticoids may be useful as costimulants to amplify IL-2-mediated selective expansion of Treg cells. We show in this study that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive Foxp3(+)CD4(+)CD25(+) T cells in murine peripheral lymphoid tissues. In a myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) mouse model, we observed that splenic CD4(+)CD25(+) T cells failed to suppress the proliferation of CD4(+)CD25(-) T cells. Pretreatment with Dex/IL-2 remarkably increased the proportion of CD4(+)FoxP3(+) cells and partially restored the function of splenic CD4(+)CD25(+) T cells, and inhibited the development of EAE. Therefore, the combination of glucocorticoid and IL-2, two currently used therapeutics, may provide a novel approach for the treatment of autoimmune diseases, transplant rejection and graft-vs.-host disease.


[Microflora of the Black Sea mussel Mytilus galloprovincialis L].
The microbial cenosis in the mantle fluid and stomach of mussels is similar in its biochemical characteristics to the microflora of sea water.


The influence of ambient ozone on the incidence of bone fractures especially among the elderly.
Elevated levels of breatheable ozone will reduce the amount of UV radiation in the range of 280-305 nm reaching the surface of earth. This range of UV converts the provitamin 7-dehydrocholesterol to vitamin D, within the human. Since most typical diets contain low levels of vitamin D, the role of UV related vitamin D synthesis in the skin is considered to provide very important contributions to the total vitamin D content of the blood. Thus, elevated levels of ambient ozone should result in a decreased level of vitamin D synthesis which may be expressed as an increase in the incidence of histological osteomalacia and ultimately bone fractures, especially among the elderly.


Association study of apolipoprotein L-I Lys166Glu and Ile244Met gene variants with obesity in Chinese subjects.
ApoL-I is a newly found component of high-density lipoprotein, and has a potential role in lipid metabolism. This study was mainly to examine the possible association of the ApoL-I gene polymorphism with obesity and plasma lipid levels in the Chinese population. Three hundred nineteen Han Chinese (109 obese and 210 nonobese control subjects) in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphism analysis. The Lys and Glu allele frequencies of the apoL-I gene at the Lys166Glu site in obese and nonobese control groups were 0.830, 0.170 and 0.814, 0.186, respectively. The Ile and Met allele frequencies of the gene at Ile244Met site in the obese and the control groups were 0.844, 0.156 and 0.831, 0.169, respectively. The 166Glu and 244Met allele frequencies of the two polymorphisms in obese subjects were not different from those in the controls, respectively (p>0.05). In the nonobese group, subjects with genotype Lys/Lys at the Lys166Glu site or Ile/Ile at the Ile244Met site had a higher serum mean concentration of triglyceride (TG) as compared with those of corresponding Glu or Met allele carriers (p<0.05). In addition, serum apoC-III and apoE levels were affected by genotypes of Lys166Glu and Ile224Met polymorphisms, respectively, in the control group (all p<0.05). The current study, for the first time, provides evidence that Lys166Glu and Ile244Met polymorphisms in apoL-I gene are associated with TG, apoC-III, and apoE levels in nonobese Chinese. However, these polymorphisms are not associated with obesity in the population.


Passive Disease Surveillance of Alpine Chamois (Rupicapra r. rupicapra) in Slovenia between 2000 and 2020.
In this paper, we provide an overview of the causes of death of Alpine chamois (Rupicapra r. rupicapra) diagnosed in the national passive health surveillance of chamois in Slovenia. From 2000 to 2020, 284 free-ranging chamois provided by hunters were necropsied at the Veterinary Faculty, University of Ljubljana, Slovenia. Depending on the results of complete necropsy, histopathological, bacteriological, parasitological, and virological examinations, a descriptive data analysis was performed. The most common causes of death in chamois were infectious diseases (82.2%), followed by non-infectious diseases (11.8%). Of all the causes of death, parasitic infections accounted for 70.3%, trauma for 9.7%, and bacterial infections for 9.3% of all cases. Less common diseases were viral infections, neoplasms, winter starvation, and metabolic disorders.


Successful management of ivermectin-induced blindness in an African lion (Panthera leo) by intravenous administration of a lipid emulsion.
Ivermectin is widely used in veterinary practice for the treatment of ecto- and endo-parasites. In wildlife, an extra-label use this parasiticide is sometimes associated with toxicity. Different treatment regimens have been used in ivermectin toxicosis. The present report describes a successful reversal of ivermectin toxicity by intravenous administration of a commercially available lipid emulsion in a captive African lion (Panthera leo). A 2-year old captive African lion (Panthera leo) weighing ~130 kg was presented with acute neurological impairment and bilateral blindness that had developed 24 h after ivermectin exposure. The animal was treated with a commercially available lipid emulsion along with supportive therapy and experienced complete recovery. To our knowledge, this is the first case report of the use of lipid emulsion in the management of ivermectin induced blindness in an African lion and it appears that intravenous lipid emulsion may be an effective therapy in ivermectin toxicity in lions. Further testing in expanded clinical trials is clearly warranted.


Effect of staphylokinase concentration of plasminogen activation.
Activation of Glu- and Lys-plasminogen by various concentrations of recombinant staphylokinase (SAK) were studied by the generation of amidolytic activity from the chromogenic substrate S-2251(H-D-Val-Leu-Lys-pNA) and by SDS-PAGE analysis. Surprisingly, excess SAK decreased and fixed the rate of S-2251 hydrolysis in a mixture of Lys-plasminogen and SAK. Since the effect of SAK on S-2251 hydrolysis by plasma was similar, the hydrolysis kinetics by free plasmin and plasmin-SAK complex were studied. Hydrolysis by either enzyme form followed Michaelis-Menten kinetics with a Km of 0.38 mM for plasma and 3.74 mM for SAK-plasmin complex. The catalytic rate constant was 22.7 s-1 for plasmin and 21.0 s-1 for the SAK-plasmin complex. With excess SAK and vigorous removal of plasmin activity from plasminogen, the pre-activation lag period differed greatly between Glu- and Lys-plasminogen. Based on the different substrate specificity of plasmin and plasmin-SAK complex, we analyzed the Glu-plasminogen activation with either catalytic or excess SAK. With excess SAK, almost no Lys-plasminogen was detectable and whole Glu-plasminogen was converted directly to Glu-plasmin, then gradually to Lys-plasmin. In contrast, Lys-plaminogen appeared rapidly with catalytic amount of SAK. These results suggest that inhibition of Glu-plasminogen to Lys-plasminogen to Lys-plasminogen conversion in the plasminogen-SAK complex in the presence of excess SAK prolonged the initial lag phase of activation.


Fixation of tendon grafts for collateral ligament reconstructions: a cadaveric biomechanical study.
To compare the biomechanical properties of 4 methods of fixation of tendon grafts to bone as used for ligament reconstructions. Thirty-two metacarpals were harvested from fresh-frozen cadavers and stripped of soft tissue. Flexor tendons were harvested from the same cadavers and cut into 2-mm-wide strips. Each tendon was fixed to a metacarpal head at the site of origin of a collateral ligament. Four different methods of fixation were tested. In group 1 the tendon was fixed to the bone with a 4.0-mm Arthrex bio-tenodesis interference screw (Arthrex, Inc., Naples, FL). In group 2 the tendon was passed through a bone tunnel and fixed with a 3.2-mm mini-Acutrak screw (Acumed, LLC, Hillsboro, OR) that was inserted in interference mode. In group 3 the tendon was passed through a bone tunnel and fixed with sutures tied over a polyethylene button. In group 4 the tendon was fixed with a mini-Mitek bone suture anchor (Mitek Worldwide, Norwood, MA). All specimens were clamped into a linear loading machine and loaded until failure. Statistical analysis was performed by 1-way analysis of variance testing. The differences in maximal tensile strength and stiffness were statistically significant when comparing any 2 groups. The Arthrex biotenodesis interference screw was the strongest and stiffest fixation method, followed by the Acutrak screw inserted in interference mode. Next was the suture tied over a button method. The mini-Mitek bone suture anchor was the weakest. Interference screw fixation of tendons to bone has statistically significant higher pullout strength and stiffness than 2 other commonly used fixation methods. The use of interference screws for fixation of tendon grafts to bone for hand ligament reconstructions is a promising new surgical technique.


Atypical diabetes associated with inclusion formation in the R6/2 mouse model of Huntington's disease is not improved by treatment with hypoglycaemic agents.
The R6/2 transgenic mouse model of Huntington's disease (HD) develops a progressive neurological phenotype that involves severe motor and cognitive dysfunctions. Although not a cardinal sign, diabetes has been described in R6/2 mice. It is not clear, however, whether the diabetes contributes to the HD-like phenotype of R6/2 mice. In our study we found that the severity of diabetes in R6/2 mice was associated with the progressive formation of ubiquinated inclusions in pancreatic beta cells. Diabetes is dissociated from early motor and cognitive dysfunctions and did not correlate with motor impairment and survival of R6/2 mice. However, chronic behavioural testing (at a level higher than that which is reported to improve several aspects of the R6/2 phenotype) exacerbated the onset of diabetes. Pharmacological treatment of the diabetes was attempted using two oral hypoglycaemic agents commonly used by diabetics. The mice responded acutely to glibenclamide (which induces exocytosis of insulin) but not to rosiglitazone (which induces sensitization to insulin). This supports the suggestion that the diabetes in R6/2 mice is caused by an impairment in insulin release rather than insulin insensitivity. However, chronic treatment with these hypoglycaemic agents had no effect on either the course of the diabetes or the disease in R6/2 mice.


Osteogenesis imperfecta.
Osteogenesis Imperfecta is a heritable disorder characterized by bone fragility and low bone mass, with a wide spectrum of clinical expression. This review gives an update on its classification, the recent developments in the understanding of its pathophysiological mechanisms, and the current status of bisphosphonate therapy. Other therapeutic approaches and future directions of research are briefly discussed.


Aurora Observations from the Principality of Transylvania from the 16th to the 18th Century CE.
We focused on the period from about 1500 CE to 1800 CE and present a compilation of 78 different auroral sightings for the period from the geographical area of the former Principality of Transylvania, then part of the Kingdom of Hungary, and we give source quotations in English translation. Of the 78 potential aurorae, 23 are missing from the catalog of Rethly and Berkes (1963) and are introduced here for the first time into the scientific discourse on past solar activity. The region of Transylvania located around 46° northern latitude is a good geographical indicator for an auroral oval extending unusually far towards the Equator. The reports of seven celestial phenomena from Transylvania during the period of the Maunder minimum (1645 - 1715), which are considered genuine northern lights at a medium to very high probability level, suggest that even during this time of greatly reduced solar activity, aurorae penetrated down to near 45° latitude. Three of these potential aurorae, however, fall within the 18th century, when the Sun was already recovering from the deep minimum phase. Comparing the distribution of potential auroral sightings in Transylvania from the 16th to the 18th century clearly shows, in comparison with other aurora catalogs and with reconstructed solar activity, that high selectivity due to the historical-source situation (incomplete chronicles, lost reports, and lack of scientific interest on the part of chroniclers) makes statements about actual long-term distributions almost impossible. Furthermore, the catalog of Rethly and Berkes is shown to be rather incomplete and to contain several doubtful entries.


New oral Xa and IIa inhibitors: updates on clinical trial results.
Heparins and VKAs have been the cornerstones of anticoagulation therapy for several decades and these agents have become most important drugs in the primary and secondary prevention of venous and arterial thromboembolic disease. Although effective, their use has been hampered by numerous limitations. In the search for new agents matching the 'ideal' anticoagulant profile, a number of different steps in the coagulation cascade have been targeted, including direct thrombin inhibition, and direct inhibition of Factor Xa. There are currently a host of promising new agents at various stages of development and clinical evaluation. With potential benefits including predictable efficacy, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, these new agents are set to improve the management of thromboembolic disorders.


Value judgments in the analysis and synthesis of evidence.
To describe the principal role of value judgments in the analysis and synthesis of evidence as they are involved in systematic reviews, meta-analyses, and health technology assessments. Using the tools of conceptual analysis, we characterize three main types of value judgments and propose an outline of how to enhance the appropriate role of value judgments in the process of analyzing and synthesizing evidence. The production, analysis, and synthesis of evidence involve value judgments characterized as preferences of persons or groups that cannot be validated by appeal to facts alone. Because preferences across individuals can vary, value judgments can be a source of bias in science and unwarranted variation in the application of scientific evidence. However, it is not possible or desirable to eliminate all value judgments in the process from production to synthesis of evidence. With respect to the value judgments that shape the analysis and synthesis of evidence, review authors should disclose and justify choices related to the three key value judgments outlined in this paper. Authors should also highlight how their value judgments differ from the stated or implicit value judgments of previously published reviews on the same topic.


Maternal magnesium therapy, neonatal serum magnesium concentration and immediate neonatal outcomes.
The fetus is exposed to magnesium administered to the pregnant mother. However, there is controversy regarding magnesium-related neonatal adverse outcomes, largely driven by a limited understanding of the factors that influence neonatal serum magnesium concentrations and associated outcomes. The objective of this study was to examine the relationship between antenatal maternal magnesium dose and serum concentrations, neonatal serum magnesium concentration and immediate neonatal outcomes. A retrospective study was conducted at a community-based teaching hospital. Neonatal serum magnesium concentrations within 48 h of birth were used to stratify magnesium-exposed neonates into three groups: group 1: <2.5 mg dl-1, group 2: ⩾2.5 to <4.5 mg dl-1, and group 3:⩾4.5 mg dl-1. Immediate neonatal outcomes were compared between the three groups. Total maternal magnesium dose and serum magnesium concentrations before the delivery were correlated with neonatal serum magnesium concentrations and outcomes. Of the 304 mother-baby dyads between 24 and 34 weeks gestation, 237 received antenatal magnesium. Neonatal serum magnesium concentration was 3.14±0.83 mg dl-1 in exposed and 1.96±0.42 mg dl-1 in unexposed neonates (P<0.001). Compared with group 2, neonates had higher odds of grade 3 or 4 intraventricular hemorrhage in group 1 (adjusted odds ratio (AOR) 5.95 (95% confidence interval (CI) 1.05 to 33.66)) and group 3 (AOR 8.42 (95% CI 1.35 to 52.54)). Group 3 neonates also had increased odds of periventricular leukomalacia (AOR: 5.37 (95% CI 1.02 to 28.28) compared with group 2 neonates. Predictors of neonatal serum magnesium concentrations included maternal magnesium dose (r=0.66, P<0.0001), duration of therapy (r=0.70, P<0.0001) and serum concentration (r=0.72, P<0.001). The between-group differences highlight that there is a therapeutic range of neonatal serum magnesium concentrations for neuroprotective effects of antenatal magnesium sulfate, while concentrations outside of this range may be associated with adverse neonatal outcomes. Further studies are needed to determine the optimal dose and duration of maternal magnesium to minimize adverse neonatal outcomes.


Total testosterone may not decline with ageing in Korean men aged 40 years or older.
It is generally believed that gonadal function in men declines with ageing. However, observations on ageing-related decrease in total testosterone (TT) are not consistent. The aim of this study is to examine the ageing-related changes of testosterone and to investigate the influence of the ageing-related factors on TT. Changes of TT with ageing were observed in longitudinal design in a single health promotion centre. A total of 220 Korean men aged ≥40 years were included between 2002 and 2011. TT assay was repeated for all subjects, with an interval of ≥3 years. Information of medical history and lifestyle habits was collected. Anthropometry and blood pressure were measured. TT, glucose, creatinine, highly sensitive C-reactive protein, liver enzymes and lipid profiles were tested. Mean TT level did not decline significantly with ageing during median 4·3 years follow-up (18·1 vs 17·8 nm, P = 0·439). Longitudinal change of TT was approximately + 0·8% per year. TT was negatively correlated with body mass index (BMI), waist circumference and glucose. With mixed effects model, diabetes (P = 0·038) and BMI (P = 0·007) affected TT level, but age and follow-up interval did not. TT did not change significantly in 220 Korean men for a median 4·3 years follow-up. TT was not influenced by the age and follow-up interval. BMI and diabetes mellitus affected TT decline.


Detecting DNA methylation using the methylated CpG island amplification and microarray technique.
Methylated CpG island amplification and microarray (MCAM) is a two-color array technique that quantifies DNA methylation by hybridizing equimolar amounts of treated vs. control cell-line DNA to an array platform. Sample preparation, hybridization, and scanning are performed over 1 week, but multiple samples can be prepared simultaneously, allowing for high-throughput processing and data acquisition. One microarray slide is required for each sample assayed, with a control sample hybridized with each test sample.


Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells.
Involvement of peroxisome proliferator activated receptor gamma (PPARgamma) in the growth response of colon cancer cells has been suggested. To investigate the characteristics of PPARgamma induced apoptosis in colon cancer cells. The effects of ligands for each of the PPAR subtypes (alpha, delta, and gamma) on DNA synthesis and cell viability were examined in HT-29 colon cancer cells. Modulation of apoptosis related gene expression by PPARgamma ligands was screened with cDNA arrays, and the results were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. PPARalpha, PPARdelta, and PPARgamma were all expressed in HT-29 cells. PPARgamma ligands, 15-deoxy-delta(12,)(14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ), suppressed DNA synthesis of HT-29 cells whereas ligands for PPARalpha and PPARdelta had no significant effects. Both 15d-PGJ2 and TGZ induced HT-29 cell death in a dose dependent manner which was associated with an increase in fragmented DNA and was sensitive to a caspase inhibitor. Among several genes selected by cDNA array screening, quantitative RT-PCR analysis confirmed downregulation of c-myc expression and upregulation of c-jun and gadd153 expression by 15d-PGJ2 and TGZ. PPARgamma induced apoptosis was antagonised by the presence of serum in the culture medium, and interaction between PPARgamma signalling and cell survival signalling through the phosphatidylinositol 3-kinase pathway was suggested. As c-myc is an important target gene of the adenomatous polyposis coli (APC)/beta-catenin and/or APC/gamma-catenin pathway, activation of PPARgamma signalling appears to compensate for deregulated c-myc expression caused by mutated APC. The present results suggest the potential usefulness of PPARgamma ligands for chemoprevention and treatment of colon cancers.


Abortion Providers on Politically Engaging Patients.
For decades, abortion providers have lamented the lack of patients' voices in the abortion rights movement. Given the millions of women who have received abortions, the absence of this large constituency, providers assert, has been politically costly. Underlying this disappointment is a parallel question that reflects a philosophical divide among abortion providers: are attempts to politically engage abortion patients a desired or appropriate element of care? We interviewed providers from 14 abortion clinics, representing a range of approaches to care, patient volume, and geographic locations. We transcribed and analyzed the interviews to identify themes related to whether, why, and how providers worked to politically engage their patients. We found that many respondents limited or avoided political engagement with patients, believing that such efforts interfered with patient care or comfort, were not a priority given limited time, and were not something in which patients were interested. Many participants were unclear as to what political work they could pursue as nonprofit facilities. In contrast, other providers believe political outreach helped patients to more fully understand their care experiences, could influence future patients' access to care, and was an important part of the way they cared for patients. These varying approaches reflect divergent ways of and reasons for engaging abortion patients politically. Future research should consider if the act of obtaining an abortion could be understood as low-level engagement with the abortion rights movement, particularly as abortion access is increasingly limited and patients might be considered potential activists.


Assessing the Need for Hospitalization in Order to Conduct a Psychiatric Evaluation as part of Criminal Law Procedure.
In criminal law, psychiatrists are consulted regarding the "insanity defense" and the defendant's competency to stand trial. Court-ordered hospital admissions for such evaluations are on the increase, creating a major burden on the health system. To assess, in a hospital setting, whether hospitalization of the defendant is necessary for conducting a psychiatric evaluation. A 6 month prospective observational study exploring the phenomenon was conducted at the Beer Yaakov Mental Health Center. The psychiatrist was asked both at the initiation and at the end of the assessment process whether the subject was competent to stand trial and responsible for his/her actions and if hospitalization was necessary in order to conduct the evaluation. During the study period there were 112 admissions with a court request for a psychiatric evaluation. In 73 of the cases (65.2%) the evaluating psychiatrist believed there was no need for hospitalization. This assessment did not change by the end of the hospitalization in all cases. Employment and alcohol use were the only factors associated with a lower need for hospitalization (OR 0.24, 95% CI 0.07-0.77, and OR 0.34, 95% CI 0.13-0.90, respectively). In the majority of cases, based on the evaluating psychiatrist's responses, the evaluation could have been conducted without need for hospitalization. The findings indicate that an outpatient unit designated to write court-requested psychiatric evaluations could significantly reduce the rates of hospital admissions for this purpose.


Expanding the phenotype of cardiovascular malformations in Adams-Oliver syndrome.
We describe a newborn with a phenotype consistent with Adams-Oliver syndrome and truncus arteriosus. Although cardiovascular malformations associated with this syndrome have been previously published in the literature, this is the first description of truncus arteriosus in a patient with Adams-Oliver syndrome. We review other reports of Adams-Oliver syndrome previously described with cardiovascular malformations, consider possible genetic and embryologic mechanisms, and emphasize the need for cardiology consultation when a diagnosis of Adams-Oliver syndrome is suspected in the differential diagnosis.


Local recurrence after laparoscopic radiofrequency ablation of malignant liver tumors: Results of a contemporary series.
The aims of this study were to determine the incidence of Local recurrence (LR) in patients at long-term follow-up after laparoscopic RFA (LRFA) and also to determine the risk factors for LR from a contemporary series. Patients undergoing LRFA between 2005 and 2014 by a single surgeon were reviewed. Demographic and perioperative data were analyzed from a prospective database. LRFA was performed on 316 patients with 901 lesions. Median follow-up was 25 months, with 76% of whom completed at least one year of follow-up. The LR rate was 18.4%. The LR in patients followed for less than 12 months was 13.8%, 20.3% for 12 months, and 19.7% for 18 months (P = 0.02). One-fourth of the LRs developed after the 1st year. Morbidity was 8.9% and mortality 0.3%. Tumor type, size, ablation margin, and surgeon experience affected LR, with tumor type, size, and ablation margin being independent. This study shows that 14% of malignant liver tumors will develop LR within a year after LRFA. Additional 4% of the lesions will demonstrate recurrence within 1 cm of the ablation zone, mostly as part of a multifocal recurrence. Ablation margin is the only parameter that the surgeon can manipulate to decrease LR.


An alternative approach to tract dilation using optic urethrotome in percutaneous nephrolithotomy.
Percutaneous removal of renal or ureteral calculi requires fluoroscopic guidance of nephrostomy tube insertion, tract dilation and stone manipulation. We introduce an effective method of nephrostomy tract dilation with optic urethrotomy under direct visual control, which protects the patient and medical personnel from fluoroscopic exposure without further increasing the incidence of immediate and delayed vascular complications. In our series of 70 patients (73 kidneys) only 1 (1.4 per cent) had hypovolemic shock, with no kidney loss or operative mortality encountered. Of the kidneys 69 were operated on in 1 and 4 in 2 sessions. There was only 1 failure, for a success rate of 98.6 per cent and the stones were reached in all cases.


Inactivation of alpha(2)-Macroglobulin by Activated Human Polymorphonuclear Leukocytes.
The proteolytic activity of trypsin releases the dye Remazol Brilliant Blue from its high molecular weight substrate, the skin powder (Hide Powder Azure, Sigma), with an increase in absorbance at 595 nm. Active alpha(2)- macroglobulin (80 mug/ml) totally inhibits the proteolytic activity of trypsin (14 mug/ml) by trapping this protease. But after a 20 min incubation of alpha(2)-macroglobulin at 37 degrees C with 2 x 10(6) human polymorphonuclear leukocytes activated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (10(-7) M) and cytochalasin B (10(-8) M), 100% of trypsin activity was recovered, indicating a total inactivation of alpha(2)-macroglobuHn. Incubation with granulocyte myeloperoxidase also inactivates alpha(2)-macroglobulin. Hypochlorous acid, a by-product of myeloperoxidase activity, at a concentration of 10(-7) M also inactivates alpha(2)-macroglobulin, which indicates that an important cause of alpha(2)-macroglobulin inactivation by activated polymorphonuclear leukocytes could be the activity of myeloperoxidase.


The effect of low-flow cardiopulmonary bypass on cerebral function: an experimental and clinical study.
Systemic flow rates (Q) during nonpulsatile hypothermic cardiopulmonary bypass (CPB) that are consistent with preservation of cerebral function have not to our knowledge been objectively defined. The effect of a sequential reduction in flow rates on cerebral cortical metabolism and function was evaluated in 6 mongrel dogs during hypothermic (25 degrees C) CPB. Cerebral function was assessed using somatosensory cortical evoked potentials (SSEP); cerebral metabolism was assessed by adenosine triphosphate (ATP) and lactate content of snap-frozen gray matter biopsies taken from the hemisphere contralateral to that monitored for SSEP. A progressive decline in ATP levels was observed during flow reduction with virtually complete depletion of ATP at 0.25 L min-1 m-2(p = .0003). The significant (p = .028) dependence of cortical ATP levels on perfusion pressure was no longer evident after adjusting for the effects of flow rate. Lactate levels increased during flow reduction (p = .028), especially at flow rates less than 0.5 L min-1 m-2. Somatosensory neural transmission remained intact until flow was reduced to 0.25 L min-1 m-2 in 5 animals and until total circulatory arrest in 1, at which time loss of the signal occurred. In addition, 5 patients were subjected to brief periods of low-flow CPB (Q = 1.0 L min-1 m-2) at 21 degrees to 25 degrees C. SSEPs remained intact during flow reduction, and postoperative neurologic evaluation was normal in all patients. We conclude that, in the absence of cerebral vascular disease, the flow rate threshold for incurring functional cerebral injury during hypothermic (25 degrees C) nonpulsatile CPB is less than 1.0 L min-1 m-2.(ABSTRACT TRUNCATED AT 250 WORDS)


Estrogen receptor positive breast cancer identified by 95-gene classifier as at high risk for relapse shows better response to neoadjuvant chemotherapy.
A 95-gene classifier (95-GC) recently developed by us can predict the risk of relapse for ER-positive and node-negative breast cancer patients with high accuracy. This study investigated association of risk classification by 95-GC with response to neoadjuvant chemotherapy (NAC). Tumor biopsy samples obtained preoperatively from 72 patients with ER-positive breast cancer were classified by 95-GC into high-risk and low-risk for relapse. Pathological complete response (pCR) rate was numerically higher for high-risk (15.8%) than low-risk patients (8.8%) although the difference was not statistically significant. Pathological response evaluated in terms of the pathological partial response (pPR) rate (loss of tumor cells in more than two-thirds of the primary tumor) showed a significant association (P=0.005) between the high-risk patients and a high pPR rate. Besides, external validation study using the public data base (GSE25066) showed that the pCR rate (16.4%) for high-risk patients (n=128) was significantly (P=0.003) higher than for low-risk patients (5.7%) (n=159). These results demonstrate that the high-risk patients for relapse show a higher sensitivity to chemotherapy and thus are likely to benefit more from adjuvant chemotherapy.


Cost effectiveness of EUS for preoperative localization of pancreatic endocrine tumors.
Endoscopic ultrasonography (EUS) is highly accurate in the localization of small pancreatic tumors. We determined the cost effectiveness of EUS used early in the preoperative evaluation of pancreatic endocrine tumors. In a study with a case-control design, 36 patients (19 men, 17 women) who underwent preoperative EUS were matched retrospectively with 36 patients who underwent surgical exploration immediately before the introduction of EUS. The number, cost, and effectiveness of preoperative localization studies, days of hospitalization, and surgical and anesthesia times were assessed. The EUS group had reduced charges for preoperative localization studies: $2620 versus $4846 per patient (p < 0.05), largely because of reductions in the number of diagnostic angiograms and venous sampling procedures performed. Surgical and total anesthesia times were decreased, as were the number of preoperative admissions for angiographic procedures. The cost-effectiveness ratio for the EUS group was $3144 per tumor localized compared with $5628 per tumor localized for the group treated before EUS became available (p < 0.05). EUS is highly accurate in the localization of pancreatic neuroendocrine tumors and is cost effective when used early in the preoperative localization strategy. EUS decreased the need for additional invasive tests and avoided unnecessary morbidity and resource consumption. EUS should play a primary role in preoperative localization of pancreatic neuroendocrine tumors.


Chlorhexidine-loaded polysulfobetaine/keratin hydrogels with antioxidant and antibacterial activity for infected wound healing.
Multifunctional hydrogel dressings are promising for wound healing. In the study, chlorhexidine(CHX) loaded double network hydrogels were prepared by free radical polymerization of sulfobetaine and oxidative self-crosslinking of reduced keratin. The introduced keratin and CHX endowed hydrogels with cytocompatibility, antioxidant capability as well as enhanced antibacterial activity due to the antifouling property of polysulfobetaine. These hydrogels exhibited acidity, glutathione(GSH), and trypsin triple-responsive release behaviors, resulting in the accelerated release of CHX under wound microenvironments. Intriguingly, the freeze-drying hydrogels could be ground to powders and sprinkled on the irregular wound bed, followed by absorbing wound fluid to reform hydrogel in situ. These xerogel powders were more convenient for sterilization, formulation, and storage. Further, these xerogel powders could be rejected after being mixed with an appropriate amount of water. In vivo infected wound healing confirmed that the xerogel powder dressing significantly promoted collagen deposition and reduced inflammation, thereby accelerating the closure and regeneration of skin wounds. Taken together, these degradable xerogel powders have great potential applications for wound healing.


Amino acid sequence of Kalinowaski's Tinamou (Nothoprocta kalinowskii) hemoglobin and the rate of evolution of bird alphaD-globin.
Two hemoglobin components are recognized in erythrocytes of the adult Tinamou. We determined the amino acid sequences of Tinamou alphaD-, alphaA-, and beta-globins from intact globin chains and several chemically cleaved fragments. A remarkable feature of Tinamou hemoglobin was a deletion in the alphaD-globin chain. This has not been reported in the literature, except in pigeon embryonic alphaD-globin. The amino acid sequences of Tinamou globin were highly similar to those of Ostrich and Rhea hemoglobin. Comparison between Tinamou, Ostrich, and Rhea that suggested the evolution speed of globin, alphaD = alphaA > beta, was related with the early appearance birds. The important residues in Tinamou hemoglobin as the heme contact and oxygen binding regions were highly conserved in other species.


Gastrointestinal nematodes in grazing dairy cattle from small and medium-sized farms in southern Poland.
This study aimed to estimate the prevalence of gastrointestinal nematodes and the intensity of infection in grazing dairy cattle from small and medium-sized farms in southern Poland. The level of antibodies against Ostertagia ostertagi in the bulk tank milk (BTM) from the animals was also assessed. Rectal fecal samples collected from 361 cows on 20 farms were examined using Willis-Schlaaf flotation and the McMaster method. BTM samples were tested for the presence of O. ostertagi antibodies using ELISA. Multiplex PCR was used to identify the third-stage larvae (L3) of gastrointestinal nematodes derived from the culture of pooled fecal samples from sampled farms. Gastrointestinal nematode eggs were found in the samples from 18 of the 20 herds with a prevalence range from 20.4 to 94.5%. The average number of eggs excreted in the feces of the herds was 200 eggs per gram (EPG). Antibodies to O. ostertagi were found in 20 of the examined herds (100%), of which 6 had optical density ratios (ODR) greater than 0.5. PCR results showed the presence of three nematode species: Ostertagia ostertagi, Cooperia oncophora and Oesophagostomum radiatum.


Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model.
Tumor necrosis factor alpha is a proinflammatory cytokine that has been proved to play a crucial role in inducing posttransplantation lung injury. The present study was performed to determine whether pirfenidone, a new nonpeptide drug with potent anti-tumor necrosis factor alpha activity, promotes protection against acute allograft injury through inhibiting pulmonary inflammatory responses in a rat model of orthotopic lung transplantation. Three transplant groups were formed: isografts, untreated allografts, and allografts treated with pirfenidone (0.5% chow starting on day 1 after transplantation). The implants were harvested on day 21 after transplantation. Acute cellular rejection grade and degree of allograft injury were evaluated on the basis of hematoxylin-and-eosin staining. The pulmonary inflammatory response and inflammation-induced oxidative stress were assessed on the basis of neutrophil accumulation (myeloperoxidase immunoreactivity and enzymatic activity) and iron deposition (Prussian blue staining). In addition, circulating levels of tissue necrosis factor alpha in all animals were measured. The degree of allograft injury was significantly reduced in pirfenidone-treated allografts relative to untreated allografts (P < .01). The beneficial effect of pirfenidone was associated with decreased lung myeloperoxidase immunoreactivity (P < .05) and enzymatic activity (P < .01). Moreover, the untreated allografts contained a high concentration of iron, which was strikingly reduced by pirfenidone. Treatment with pirfenidone resulted in a lower level of plasma tissue necrosis factor alpha, which correlated positively with lung myeloperoxidase enzymatic activity (P < .0001). These results suggest that pirfenidone, with its anti-tissue necrosis factor alpha activity, reduced neutrophil recruitment and iron accumulation, hence limiting the acute lung allograft injury.


Prediction model for low birth weight and its validation.
To evaluate the factors associated with low birth weight (LBW) and to formulate a scale to predict the probability of having a LBW infant. This hospital based case-control study was conducted in a tertiary care university hospital in North India. The study included 250 LBW neonates and 250 neonates with birth weight ≥2,500 g. Data were collected by interviewing mothers using pre-designed structured questionnaire and from hospital records. Factors significantly associated with LBW were inadequate weight gain by the mother during pregnancy (<8.9 kg), inadequate proteins in diet (<47 g/d), previous preterm baby, previous LBW baby, anemic mother and passive smoking. The prediction model made on these six variables has a sensitivity of 71.6 %, specificity 67.0 %, positive LR 2.17 and negative LR of 0.42 for a cut-off score of ≥29.25. On validation, it has a sensitivity of 72 % and specificity of 64 %. It is possible to predict LBW using a prediction model based on significant risk factors associated with LBW.


A study of blood usage by diagnoses in a Korean university hospital.
There is paucity of comprehensive data on the blood usage with regard to diagnostic categories of Asian recipients. The purpose of this study is to analyse data for blood usage in a korean university hospital in order to obtain additional information on transfusion practices in relation to diagnoses. Data of information on patients discharged during the period from March 1996 to February 2002, who have received packed red blood cells (RBC), fresh frozen plasmas (FFP), and platelet components (PLT) were extracted from the computerized registers. We used only the principal four-digit diagnostic categories of the Tenth Revision of International Classification of Diseases. A total of 397 489 units of blood components (RBC 171 916 units; FFP 69 301 units; and PLT 156 272 units) were transfused for 17.2% of all discharged patients. Acute myeloid leukaemia, liver cell carcinoma, advanced gastric cancer, alcoholic or other unspecified cirrhosis of liver were the top 5 diagnoses related with the highest usage of blood component. The results showed a different blood usage pattern compared to those of previous studies. These provide a baseline transfusion practice at our institution, and the data would help in predicting future blood needs in a variety of diagnostic categories.


Assessment of oral health status among endosulfan victims in endosulfan relief and remediation cell - A cross-sectional survey.
Endosulfan is a highly toxic agrichemical used in the cashew plantations. The Stockholm Convention held in April 2011 recommended a global ban on the manufacture and use of endosulfan because of its adverse effects on human health and the environment. Its impact on the quality of food, water, and beverages; and its ability to cause neurobehavioral disorders, congenital malformations in female subjects, and abnormalities related to the male reproductive system are studied, but however information regarding the oral health of endosulfan victims is scant. To assess the oral health status of the endosulfan victim in rehabilitation center. A cross sectional study on 18 subjects of 4-50 years of age were interviewed and examined using modified WHO oral health assessment proforma (1997) in Endosulfan Relief and Remediation Cell in Kokkada, Belthangady Taluk, Dakshina Kannada district, Karnataka, India. Among the subjects, 10 (>50%) were found to be in age group <20 years. The overall oral health status of the endosulfan victim's in rehabilitation center considered to be poor, as many of the subjects suffered from major medical problems like mental retardation, physical disabilities etc. This study emphasizes the need for special attention from government and voluntary organization to improve overall health status of the victims.


Publisher Correction: A systematic review of the caries prevalence among children living in Chernobyl fallout countries.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Patients' characteristics and providers' attitudes: predictors of screening pregnant women for illicit substance use.
This study's aim was to determine how patients' and providers' characteristics affect hospital providers' decisions to screen pregnant and postpartum women for illicit substances. A retrospective design was used. Participants included all low-income women (N = 1,100) who delivered at an urban teaching hospital over a 12-month period and the providers (N = 40) who provided prenatal and delivery care for these women. The medical records of the women were abstracted to obtain demographic, medical, social, and substance use information. Providers were interviewed to obtain data on their attitudes. The outcome was a dichotomous indication of whether patients were screened for illicit substances. Multivariate logistic regression analyses found that women who were single (OR = 7.1), Black (OR = 1.9), received prenatal care at the prenatal clinic (OR 5.6), saw fewer providers (1.1), or had a placental abruption (OR 15.8), preterm labor (OR = 3.0), inadequate prenatal care (OR = 4.9), a history of involvement with Child Protective Services (OR = 3.9), a high social/Mental Health Risk Factor Score (OR = 1.4), a past or present history of illicit drug use (OR = 6.7), or a present history of tobacco use (OR = 1.7) were more likely to be screened than women without these characteristics. Women whose providers scored medium (OR = 2.5) or high (OR = 2.5) on the Professionalism Scale were more likely to be screened than women whose providers scored low on this scale. Providers' decisions to screen pregnant women for illicit substance use are influenced by both patients' characteristics and providers' personal attitudes. Hospital protocols might help reduce the potentially biased impact of attitudes on screening decisions.


Precision, accuracy, and data acceptance criteria in biopharmaceutical analysis.
Accuracy and precision are the most important criteria in the assessment of an analytical method, and monitoring quality control during sample analysis is essential to ensure the validity of reported results. Various approaches to testing accuracy, precision, and quality control were applied to 10 analytes from seven chromatographic bioanalytical methods. These methods include fixed interval bias and significance testing for accuracy; fixed interval percentage relative standard deviation (%RSD) and analysis of variance (ANOVA) approaches for precision; +/- 20% fixed range, 99% confidence interval, multiple rules, and range chart for individuals approaches for quality control acceptance criteria. Quality control approaches were also applied to the entire run and to a bracketed approach whereby results are considered valid only if bracketed by acceptable quality control. Accuracy and precision were assessed for six runs of each analyte at three concentrations established to represent the calibration range of the analytical method. Quality control acceptance criteria were evaluated using all data sets from each of the analytical methods collected during the course of running various numbers of real samples. The data suggest that the fixed interval bias criteria for accuracy was a more liberal method of accuracy assessment because three of the seven methods would have been rejected according to the significance testing criteria whereas all were acceptable by the fixed internal bias criteria. Precision can be effectively assessed for between- and within-run data by criteria set on unconfounded %RSD values or by separation of the sources of variation using an ANOVA approach applied to confounded data.(ABSTRACT TRUNCATED AT 250 WORDS)


ACh/dopamine crosstalk in motor control and reward: a crucial role for alpha 6-containing nicotinic receptors?
The midbrain dopaminergic system is a key element in the control of motor activity, cognition, and the motivational effects of drugs of abuse, including nicotine. In this issue of Neuron, Drenan et al. find that alpha6-containing nicotinic acetylcholine receptors might selectively activate mesolimbic and mesostriatal dopaminergic neurons, enhancing striatal dopamine release and its behavioral consequences.


[Current diagnostic methods in molecular classification of brain tumors at the Burdenko Neurosurgical Center].
DnA methylation has recently been accepted as the most reliable and effective method of diagnosing central nervous system (CNS) tumors. Healthy organs and tumors of different localizations have their own unique methylation structure. Determination of total tumor DNA methylome is the detection of all methylated nucleotides in a tumor. The "gold standard" for analyzing the methylation state of individual cytosines is bisulfite conversion, in which unmethylated cytosines are converted to uracils and read as thymines, while methylated cytosines are protected from conversion.


Intratympanic gentamicin as a treatment for drop attacks in patients with Meniere's disease.
Vertigo attacks in most cases of Meniere's disease (MD) are successfully treated with lifestyle changes and medication. However, approximately 6% of patients with MD develop drop attacks (DAs), a potentially life-threatening condition. Traditional treatment for DAs has been surgical labyrinthectomy. The objective of this study was to assess the effectiveness of intratympanic gentamicin for DAs in patients with MD. Retrospective charts review. All charts were reviewed from Meniere DA patients at our hospital during the 10-year period from 2002 to 2012 who had been treated with intratympanic gentamicin and had been followed for at least 1 year afterward. Twenty-four ears fulfilled inclusion criteria. The time for manifestation of DAs varied from 1 to 20 years after diagnosis (mean 10 years). A total of 83.3% of ears with intractable MD and DA achieved complete symptom control of DAs after the first intratympanic gentamicin cycle and 95.8% after the further injections. Among patients with no DA recurrence by the end of the study follow-up, the symptom-free interval varied from 12 to 120 months (mean: 43.5 months). All 15 patients with ≥ 24 months follow-up were still free of DAs. Elevated or absent vestibular evoked myogenic potential thresholds were more common in DA than in contralateral ears, and hearing loss was not a major complication of the treatment. Intratympanic gentamicin treatment appears to be a long-lasting and effective treatment for MD with DAs.


Constraint-induced aphasia therapy for patients with aphasia: A systematic review.
This study aimed to systematically evaluate the effects of constraint-induced aphasia therapy (CIAT) for aphasic patients reported by randomized controlled trials. Relevant randomized controlled trials were retrieved from 11 electronic databases. A methodological quality assessment was conducted in accordance with the Cochrane Handbook, and meta-analyses were performed by using RevMan 5.2. A descriptive analysis was conducted when the included trials were not suitable for a meta-analysis. A total of 12 trials were included. A statistically significant group difference was shown from the meta-analysis in the results measured by the Western Aphasia Battery (random-effects model, MD = 1.23, 95% CI = 0.31 to 2.14, P < 0.01). However, there were no statistically significant differences shown in the results of the Boston Naming Test (fixed-effects model, MD = -1.79, 95% CI = -11.19 to 7.62, P > 0.05) and Aachen Aphasia Test (fixed-effects model, MD = -1.11, 95% CI = -4.49 to 2.27, P > 0.05). The descriptive analysis showed positive results in language performances of naming, repetition, and comprehension. This systematic review indicated that CIAT was efficient for improving language performance with regard to naming, comprehension, repetition, written language, and oral language based on the current evidence. And this review provides some meaningful guides for clinical practice: expand the therapy duration to 2 or 3 h per day, focus on naming, and choose the best assessment tool. It also indicates a need for more rigorous, large-scale, and high-quality trials in the future.


Blue-green algae and selection in rotifer populations.
Observation in natural populations of the rotifer Asplanchna girodi suggested blue-green algae may have toxic effects on rotifers. The blue-greens Anabaena flos-aquae and Lyngbya sp. were isolated from a pond in Central Florida along with three electrophoretically identified genotypes of A. girodi. When tested Anabaena had marked effect on the reproductive rate of A. girodi and the effect was different among genotypes. Likewise, Lyngbya also depressed rotifer reproduction, but required an order of magnitude higher concentration to produce the same effects as Anabaena. The toxicity of these algae was corroborated by mouse bioassays. Results clearly show these blue-greens have the capacity to differentially reduce reproductive rates of rotifer genotypes. Because of this capability blue-greens could play an important role in the ecology of natural selection in rotifer populations.


Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats.
In view of subacute inhalation studies with cigarette smoke at high concentrations, the toxic properties of combinations of carbon monoxide and nicotine were investigated. Treating rats with fresh diluted cigarette smoke in an inhalation chamber, we established a smoking schedule that resulted in a certain death rate after 13 days. The mortality under the experimental conditions was taken as a measure for the toxicity of different combinations of carbon monoxide and nicotine. Since the absorption and therefore the toxicity of nicotine is pH dependent, the factorial experiments were performed under two pH conditions. The first experiments were conducted between pH 6.5 and 6.9 and then between pH 6.6 and 7.8 where the higher pH is due to the addition of nicotine base to the cigarette filler. After extensive mathematical treatment of the data, the following results were established: (a) Equations for the dose-response surface of CO and nicotine were computed. (b) R2 values (square of the multiple correlation coefficient) for the respective dose-response surfaces were between 87% and 94%. (c) From the respective equations the dose-response surfaces were drawn in the form of several computer plots. From the equations it becomes evident that, under the experimental conditions, there are no synergistic effects between carbon monoxide and nicotine. A simple additivity of the toxic effects was therefore postulated. On the other hand, it has been demonstrated that smoke pH plays an important role, because only from alkaline smoke does the absorption of nicotine seem sufficiently rapid for it to add to the acute toxicity of CO. The total particulate matter apparently does not contribute significantly to the toxicity of the smoke aerosol.


Renal and retroperitoneal metastasis from prostate adenocarcinoma: a case report.
Diffuse renal and retroperitoneal metastasis of prostatic origin is an uncommon spread pattern of prostate cancer. We described a 74-year-old male patient who was admitted because of dysuria and nocturia. Physical examination and imaging study indicated prostate mass, and laboratory analysis revealed elevated prostate specific antigen (PSA). The diagnosis of prostate cancer was established after biopsy. In the further evaluation, diffuse renal and retroperitoneal metastasis of prostate cancer was confirmed. Radiotherapy combined with endocrine therapy was given. Our present case emphasized that the routine metastatic work-up was quite necessary, since a small proportion of men with advanced prostate cancer might experience metastases in atypical sites.


Pentoxifylline and skin inflammation.
Cyclic nucleotide phosphodiesterase inhibitors, such as pentoxifylline, have been shown to beneficially influence a large number of inflammatory skin diseases. The biological effects of pentoxifylline on the production of proinflammatory cytokines, leukocyte-endothelial cell adhesion, chemokines and leukocyte-keratinocyte adhesion in skin inflammation are discussed.


Anaerobic bacteria: evaluation of disc susceptibility to four cephalosporins.
The disc diffusion technique was evaluated with 178 strains of anaerobes and four cephalosporins (cephalothin, cefamandole, cefazolin and cefoxitin). Good correlation in results was found in comparison with the agar dilution technique (p less than 0.001) with the exception of cefamandole and cefazolin against anaerobic cocci (p greater than 0.05). Choosing a breakpoint of 8 microgram/ml for distinguishing susceptible and resistant strains, we determined corresponding incubation, the rate of error is less than 1% for false susceptible and less than 5% for false resistant. However, some strains of anaerobic cocci required a 48 hour incubation period for allowing visible growth. Moreover, a great deal (60.5%) of overlapping zone diameters made interpretation of disc diffusion test difficult among Bacteroides fragilis strains classed as susceptible, intermediate and resistant occuring with cefoxitin. The results have shown that the cephalothin disk will not accurately predict susceptibility of B. fragilis to cefoxitin.


Quality-control analytical methods: considerations in compounding peroral solid dosage forms.
Pharmacists who are engaged in drug compounding have specific guidelines and standards that are outlined in the United States Pharmacopeia-National Formulary. Of the many dosage forms that are available for the compounder, capsules and tablets (peroral solids) represent the most stable and convenient formulations for drug combinations. Dosage units must remain consistent, and the uniformity of dosage units should be demonstrable. Specific standards for the uniformity of dosage units are outlined in United States Pharmacopeia Chapter 905, which was developed specifically for the pharmaceutical industry. The uniformity of dosage units can be demonstrated by either of two methods, Content Uniformity or Weight Variation. Weighing and blending activities are critical in compounding. Therefore, all efforts should be expended to prevent errors in weighing and other steps that could adversely affect the final preparation.


Correlation of the CT Compatible Stereotaxic Craniotomy with MRI Scans of the Patients for Removing Cranial Lesions Located Eloquent Areas and Deep Sites of Brain.
The first goal in neurosurgery is to protect neural function as long as it is possible. Moreover, while protecting the neural function, a neurosurgeon should extract the maximum amount of tumoral tissue from the tumour region of the brain. So neurosurgery and technological advancement go hand in hand to realize this goal. Using of CT compatible stereotaxy for removing a cranial tumour is to be commended as a cornerstone of these technological advancements. Following CT compatible stereotaxic system applications in neurosurgery, different techniques have taken place in neurosurgical practice. These techniques are magnetic resonance imaging (MRI), MRI compatible stereotaxis, frameless stereotaxy, volumetric stereotaxy, functional MRI, diffusion tensor (DT) imaging techniques (tractography of the white matter), intraoperative MRI and neuronavigation systems. However, to use all of this equipment having these technologies would be impossible because of economic reasons. However, when we correlated this technique with MRI scans of the patients with CT compatible stereotaxy scans, it is possible to provide gross total resection and protect and improve patients' neural functions.


The Society for Vascular Surgery Vascular Quality Initiative.
The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) is designed to improve the quality, safety, effectiveness, and cost of vascular health care. It uses the structure of a Patient Safety Organization to permit collection of patient-identified information but protect benchmarked comparisons from legal discovery. The SVS VQI is uniquely organized as a distributed network of regional quality groups to facilitate local translation of registry data into practice change while maintaining the power of a national registry. Detailed data specific to each commonly performed open and endovascular procedure are collected, both in-hospital and at ≥ 1 year of follow-up. Quality measures are reported to physicians and hospitals, which allow anonymous risk-adjusted benchmarking within regions or nationally. All specialties that perform vascular procedures are included, and international participation is encouraged. This review describes the current status of the SVS VQI.


Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion.
Previous studies have shown that neutrophils (PMNs) facilitate melanoma cell extravasation [M.J. Slattery, C. Dong, Neutrophils influence melanoma adhesion and migration under flow conditions, Intl. J. Cancer 106 (2003) 713-722] Little is known, however, about the specific interactions between PMNs, melanoma and the endothelium (EC) or the molecular mechanism involved under flow conditions. The aim of this study is to investigate a "two-step adhesion" hypothesis that involves initial PMN tethering on the EC and subsequent melanoma cells being captured by tethered PMNs. Different effects of hydrodynamic shear stress and shear rate were analyzed using a parallel-plate flow chamber. Results indicate a novel finding that PMN-facilitated melanoma cell arrest on the EC is modulated by shear rate, which is inversely-proportional to cell-cell contact time, rather than by the shear stress, which is proportional to the force exerted on formed bonds. Beta2 integrins/ICAM-1 adhesion mechanisms were examined and the results indicate LFA-1 and Mac-1 cooperate to mediate the PMN-EC-melanoma interactions under shear conditions. In addition, endogenously produced IL-8 contributes to PMN-facilitated melanoma arrest on the EC through the CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) on PMN. These results provide new evidence for the complex role of hemodynamic forces, secreted chemokines and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC.


Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden.
We undertook this study to evaluate in patients with peripheral arterial disease (PAD) the relationship of endothelial dysfunction, which is directly related to progression and clinical complications of atherosclerosis, with variables including classic risk factors, inflammation, severity of peripheral circulatory impairment, and atherosclerotic burden. This cross-sectional study included outpatients seen in an academic angiologic unit. Eighty-eight consecutive patients with PAD (ankle/brachial index [ABI] < 0.90) were studied. The control group consisted of 30 age-matched and sex-matched healthy subjects. Main outcome measures were endothelial function in the form of brachial artery flow-mediated dilation (FMD), plasma levels of C-reactive protein (CRP) and fibrinogen, severity of PAD according to ABI, and atherosclerotic burden, ie, atherosclerosis in one leg or in two or more other sites. Compared with patients with FMD greater than 6.2% (ie, 5th percentile of FMD in control subjects), patients with FMD less than 6.2% had a similar prevalence of classic risk factors but higher median levels of CRP (1.6 vs 6.0 mg/L; P <.01) and fibrinogen (200 vs 374 mg/dL; P <.01). The two inflammatory markers were negatively correlated with FMD (P <.01). ABI was higher in patients with FMD greater than 6.2% than in those with worse endothelial function (0.72 +/- 0.15 vs 0.62 +/- 16; P <.01); there was no difference with respect to atherosclerotic burden. Multivariate analysis showed that the association of CRP, fibrinogen, and ABI with FMD less than 6.2% was unrelated to classic risk factors. In a second model, which included CRP, fibrinogen, and ABI, all three variables were independently related to FMD less than 6.2%. Inflammation and severity of circulatory impairment are implicated in the pathophysiology of dysfunctional endothelium in PAD.


Hearing Mechanisms and Noise Metrics Related to Auditory Masking in Bottlenose Dolphins (Tursiops truncatus).
Odontocete cetaceans are acoustic specialists that depend on sound to hunt, forage, navigate, detect predators, and communicate. Auditory masking from natural and anthropogenic sound sources may adversely affect these fitness-related capabilities. The ability to detect a tone in a broad range of natural, anthropogenic, and synthesized noise was tested with bottlenose dolphins using a psychophysical, band-widening procedure. Diverging masking patterns were found for noise bandwidths greater than the width of an auditory filter. Despite different noise types having equal-pressure spectral-density levels (95 dB re 1 μPa(2)/Hz), masked detection threshold differences were as large as 22 dB. Consecutive experiments indicated that noise types with increased levels of amplitude modulation resulted in comodulation masking release due to within-channel and across-channel auditory mechanisms. The degree to which noise types were comodulated (comodulation index) was assessed by calculating the magnitude-squared coherence between the temporal envelope from an auditory filter centered on the signal and temporal envelopes from flanking filters. Statistical models indicate that masked thresholds in a variety of noise types, at a variety of levels, can be explained with metrics related to the comodulation index in addition to the pressure spectral-density level of noise. This study suggests that predicting auditory masking from ocean noise sources depends on both spectral and temporal properties of the noise.


Preventing collateral damage.
In pigs, nitrate supplements can protect salivary glands from the damage caused by radiation therapy to the head and neck.


HP1: a functionally multifaceted protein.
HP1 (heterochromatin protein 1) is a nonhistone chromosomal protein first discovered in Drosophila melanogaster because of its association with heterochromatin. Numerous studies have shown that such a protein plays a role in heterochromatin formation and gene silencing in many organisms, including fungi and animals. Cytogenetic and molecular studies, performed in Drosophila and other organisms, have revealed that HP1 associates with heterochromatin, telomeres and multiple euchromatic sites. There is increasing evidence that the different locations of HP1 are related to multiple different functions. In fact, recent work has shown that HP1 has a role not only in heterochromatin formation and gene silencing, but also in telomere stability and in positive regulation of gene expression.


Sulfondiimidamides unlocked as new S(VI) hubs for synthesis and drug discovery.
Despite their promise as drug targets, access to nitrogen-rich S(VI) compounds has been a significant synthetic challenge. In this issue of Chem, Zhang and Willis explore a new class of S(VI) compounds-sulfondiimidamides-providing robust strategies toward their synthesis, derivation, and promise as new sulfonamide bioisosteres.


Evidence for recombination in the envelope gene of maedi-visna virus.
Frequent recombination occurs during replication in all retroviruses examined. This increases the genetic variation in the retroviral population and may be of importance in the evolution of the virus. Maedi-visna virus (MVV), a retrovirus of sheep, has a highly variable envelope gene. In a previous experiment, 20 sheep were infected with an uncloned strain of MVV and virus was isolated at regular intervals for 7 years. We sequenced the envelope genes of a number of these strains and found evidence for recombination that may have contributed to the observed high frequency of antigenic variants.


Exercise-induced changes in mitral regurgitation in patients with prior myocardial infarction and left ventricular dysfunction: relation to mitral deformation and left ventricular function and shape.
The aim of this study was to assess the relationship between exercise-induced changes in mitral regurgitation (MR) and echocardiographic characteristics of mitral deformation, global left ventricular (LV) function and shape at rest and after exercise. Forty consecutive patients with ischaemic MR due to prior myocardial infarction (MI), ejection fraction <45% in sinus rhythm underwent exercise-echocardiographic testing. Exercise-induced changes in effective regurgitant orifice (ERO) were compared with baseline and exercise-induced changes in mitral deformation and global LV function and shape. There was significant correlation between exercise-induced changes in ERO and changes in coaptation distance (r=0.80, P<0.0001), tenting area (r=0.79, P<0.0001) and mitral annular diameter (r=0.65, P<0.0001), as well as in end-systolic sphericity index (r=-0.50, P=0.001, respectively), and wall motion score index (r=0.44, P=0.004). In contrast, exercise-induced changes in ERO were not related to the echocardiographic features at rest. By stepwise multiple regression model, the exercise-induced changes in mitral deformation were found to independently correlate with exercise-induced changes in ERO (generalized r(2)=0.80, P<0.0001). Exercise-induced changes in severity of ischaemic MR in patients with LV dysfunction due to prior MI were independently related to changes in mitral deformation.


Studies on the oxidative half-reaction of xanthine oxidase.
The oxidative half-reaction of xanthine oxidase is reexamined with regard to the generation of the superoxide anion. By using cytochrome c reduction to monitor superoxide, it is found that the stoichiometry of superoxide produced to enzyme reoxidized is 2:1, significantly greater than previously reported (Olson, J. S., Ballou, D. P., Palmer, G., and Massey, V. (1974) J. Biol. Chem. 249, 4350-4362). Furthermore, the kinetics of superoxide-dependent cytochrome c reduction exhibits a pronounced lag during the rapid phase of enzyme reoxidation and a limiting rate identical with that of the slow phase of enzyme reoxidation. This indicates that superoxide is generated only in the last steps of the sequential removal of reducing equivalents from the enzyme by molecular oxygen. Experiments with the two-electron-reduced enzyme indicate that it too produces two superoxide ions for each molecule of enzyme reoxidized, demonstrating that it is the last two electrons to leave the enzyme in the course of reoxidation that form superoxide. The sequential scheme for the oxidative half-reaction must therefore be 6 leads to 4 leads to 2 leads to 1 leads to 0, where the numbers reflect the number of reducing equivalents in each intermediate. Using this scheme, both enzyme reoxidation and cytochrome c reduction can be accurately simulated. Reasons for the different behavior of the two-electron-reduced xanthine oxidase compared to the six- and four-electron-reduced enzyme are discussed.


Association of daily and time-segmented physical activity and sedentary behaviour with mental health of school children and adolescents from rural Northeastern Ontario, Canada.
Physical activity (PA) and sedentary behaviour (SED) have been linked to the mental health of children and adolescents, yet the timing of behaviours may play a role in this relationship and clarifying this could inform interventions. We explored cross-sectional associations of PA and SED in varying time segments throughout the school day with the mental health of school-aged children and adolescents from rural Northeastern Ontario, Canada. A total of 161 students (56% female, M = 10.3 years old) wore accelerometers for 8 days (7 nights) and completed a self-report survey (parent reported for children younger than 11). Mental health was measured using the Strengths and Difficulties Questionnaire. Accelerometer-measured SED, light PA (LPA), and moderate and vigorous PA (MVPA) were estimated in the time-segments before school (06:00-08:44), school time (08:45-15:04), after school (15:05-16:59), and evenings (17:00-21:59). Associations were tested with multilevel linear regressions while adjusting for confounding factors. Students spent 72.6 min in MVPA, 209.0 min in LPA, and 621.0 min in SED per day. Daily SED was associated with less conduct problems (β = -0.27, p < 0.05). Evening LPA was inversely associated with hyperactivity (β = -1.45, p < 0.05), while SED was associated with hyperactivity and with peer problems before school (β = 1.70 and β = 1.01, respectively, p < 0.05), and during school (β = -0.83 and β = -0.57, respectively, p < 0.05). No associations were observed for MVPA, emotional symptoms, or prosocial behaviour. In conclusion, displacing SED with LPA in some specific periods of the day may benefit the mental health of students; taking this into account could strengthen interventions.


Plastics in the Anthropocene: A multifaceted approach to marine pollution management.
The Anthropocene, defined by human-induced environmental transformations, presents a critical challenge: plastic pollution. This complex problem, particularly prominent in coastal and marine environments, requires integrated and adaptive responses. This opinion paper examines global efforts across policy interventions, scientific innovations, and public education, highlighting both advancements and hurdles in managing this problem. These include enforcement limitations in policy implementation, scalability and cost issues in scientific innovations, and challenges in effecting large-scale behavioral change through public education. The complexities inherent in managing plastic litter in coastal and marine environments are further discussed, emphasizing the necessity for an integrated approach. This approach involves interdisciplinary collaboration, adaptive management, stakeholder engagement, policy integration, sustainable financing, resilience building, capacity enhancement, technological innovation, policy reform, ecosystem-based management, disaster risk reduction, and advocacy. The management of plastic pollution in the Anthropocene requires strategic planning, innovative thinking, and unified global efforts, ultimately providing an opportunity to redefine our relationship with the planet and steer toward a more sustainable future.


Anatomic update on the 3-dimensionality of the subdermal septum and its relevance for the pathophysiology of cellulite.
Cellulite is an aesthetic condition affecting the appearance of skin in specific body regions. When reviewing past literature, a 2-D image of a subdermal septum was created most likely due to the applied cross-sectional investigative methodology. Despite practitioners being aware of the 3-D nature of the subdermal architecture, this is not reflected in the present scientific literature. The aim of this anatomic review is to summarize the past literature and to provide an update on the 3-dimensionality of a subdermal septum with a specific focus on the pathophysiology of cellulite. This review is based on the literature search performed in the PubMed database using the keywords: cellulite (n = 777), cellulite, AND pathophysiology (n = 53). The articles obtained were screened and those focusing on "cellulitis" or other non-cellulite-related topics were additionally excluded resulting in a total of n = 38 relevant articles which were evaluated for the purpose of this anatomic review. The skin is comprised of two fat layers (superficial and deep), separated by the superficial fascia. The dynamic 3-D interplay between retinacula cutis, fascia, and fat, with anatomic differences between men and women, highlights a complex anatomic construct with direct implications for the formation and treatment of cellulite. The 3-dimensionality of a subdermal septum provides important clinical clues to understanding the underlying mechanisms and pathogenesis of cellulite. The 3-D approach, in contrast to the past 2-D models, presents a robust foundation for understanding and developing future cellulite therapeutic strategies.


Recombinant expression of aryl hydrocarbon receptor for quantitative ligand-binding analysis.
Recombinant expression of the aryl hydrocarbon receptor (AhR) yields small amounts of ligand-binding-competent AhR. Therefore, Spodoptera frugiperda (Sf9) cells and baculovirus have been evaluated for high-level and functional expression of AhR. Rat and human AhR were expressed as soluble protein in significant amounts. Expression of ligand-binding-competent AhR was sensitive to the protein concentration of Sf9 extract, and coexpression of the chaperone p23 failed to affect the yield of functional ligand-binding AhR. The expression system yielded high levels of functional protein, with the ligand-binding capacity (Bmax) typically 20-fold higher than that obtained with rat liver cytosol. Quantitative estimates of the ligand-binding affinity of human and rat AhR were obtained; the Kd for recombinant rat AhR was indistinguishable from that of native rat AhR, thereby validating the expression system as a faithful model for native AhR. The human AhR bound TCDD with significantly lower affinity than the rat AhR. These findings demonstrate high-level expression of ligand-binding-competent AhR, and sufficient AhR for quantitative analysis of ligand binding.


Fabrication and detection of tissue engineered bone aggregates based on encapsulated human ADSCs within hybrid calcium alginate/bone powder gel-beads in a spinner flask.
Traditional treatment for bone diseases limits their clinical application due to undesirable host immune rejection, limited donator sources and severe pain and suffering for patients. Bone tissue engineering therefore is expected to be a more effective way in treating bone diseases. In the present study, hybrid calcium alginate/bone powder gel-beads with a uniform size distribution, good biocompatibility and osteoinductive capability, were prepared to be used as an in-vitro niche-like matrix. The beads were optimized using 2.5% (w/v) sodium alginate solution, 4.5% (w/v) CaCl2 solution and 5.0mg/mL bone powder using an easy-to-use method. Human ADSCs were cultured and induced into chondrocytes and osteoblasts, respectively. The cells were characterized by histological staining showing the ADSCs were able to maintain their characteristic morphology with multipotent differentiation ability. ADSCs at density of 5 × 10(6)cells/mL were encapsulated into the gel-beads aiming to explore cell expansion under different conditions and the osteogenic induction of ADSCs was verified by specific staining. Results demonstrated that the encapsulated ADSCs expanded 5.6 folds in 10 days under dynamic condition via spinner flask, and were able to differentiate into osteoblasts (OBs) with extensive mineralized nodules forming the bone aggregates over 3 weeks postosteogenic induction. In summary, hybrid gel-beads encapsulating ADSCs are proved to be feasible as a new method to fabricate tissue engineered bone aggregation with potential to treat skeletal injury in the near future.


Conditioned taste aversion in vasopressin-deficient rats (Brattleboro strain).
Brattleboro rats are homozygous for diabetes insipidus (DI), lacking the ability to synthesize vasopressin. Previous studies reported learning deficits in DI rats on passive avoidance tasks using footshock. Other studies, however, could not replicate these results. In two experiments, we studied the learning of DI and control Long Evans (LE) rats in a different avoidance paradigm: conditioned taste aversion (CTA). In the first experiment a mild CTA to saccharin was established gradually using low levels of an illness-inducing agent (lithium chloride). In the second experiment a strong CTA was established in one acquisition trial and the extinction of the conditioned aversion was followed for 12 trials. The two experiments found no differences between the DI and LE rats in either the magnitude or the rate of acquisition and extinction of the CTA. These results suggest that vasopressin is not involved in the acquisition and retention of CTA, and support previous studies indicating that vasopressin may not be involved in avoidance learning.


Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides.
The transactivator responsive region (TAR) present in the 5'-NTR of the HIV-1 genome represents a potential target for antiretroviral intervention and a model system for the development of specific inhibitors of RNA-protein interaction. Earlier, we have shown that an anti-TAR polyamide nucleotide analog (PNA(TAR)) conjugated to a membrane transducing (MTD) peptide, transportan, is efficiently taken up by the cells and displays potent antiviral and virucidal activity [B. Chaubey, S. Tripathi, S. Ganguly, D. Harris, R. A. Casale and V. N. Pandey (2005) Virology, 331, 418-428]. In the present communication, we have conjugated five different MTD peptides, penetratin, tat peptide, transportan-27, and two of its truncated derivatives, transportan-21 and transportan-22, to a 16mer PNA targeted to the TAR region of the HIV-1 genome. The individual conjugates were examined for their uptake efficiency as judged by FACScan analysis, uptake kinetics using radiolabeled conjugate, virucidal activity and antiviral efficacy assessed by inhibition of HIV-1 infection/replication. While FACScan analysis revealed concentration-dependent cellular uptake of all the PNA(TAR)-peptide conjugates where uptake of the PNA(TAR)-penetratin conjugate was most efficient as >90% MTD was observed within 1 min at a concentration of 200 nM. The conjugates with penetratin, transportan-21 and tat-peptides were most effective as an anti-HIV virucidal agents with IC50 values in the range of 28-37 nM while IC50 for inhibition of HIV-1 replication was lowest with PNA(TAR)-transportan-27 (0.4 microM) followed by PNA(TAR)-tat (0.72 microM) and PNA(TAR)-penetratin (0.8 microM). These results indicate that anti-HIV-1 PNA conjugated with MTD peptides are not only inhibitory to HIV-1 replication in vitro but are also potent virucidal agents which render HIV-1 virions non-infectious upon brief exposure.


Test-retest validity of acoustic pharyngometry measurements.
Acoustic reflectometry is a relatively new technique that quantifies upper airway obstruction. The oropharyngeal airway is geometrically complex and variable; therefore establishing a standard operating protocol and understanding the possible sources of artifacts are of great importance in obtaining reliable results. This work aims at assessing the repeatability of pharyngeal cross-sectional area measurements obtained from normal and snoring individuals. Twenty adult normal volunteers (16 men and 4 women; mean age, 35.9 years) and 10 adult snorers (9 men and 1 woman; mean age, 36.4 years) were examined by acoustic reflectometry following the developed standard operating protocol. Measurements of pharyngeal cross-sectional area are analyzed in 2 groups. In normal subjects where mean pharyngeal cross-sectional area in the first session was 3.187 cm(2), in the second session (same-day test-retest), the mean pharyngeal cross-sectional area was 3.239 cm(2), and in the third session 7 to 10 days later (day-to-day test-retest), it was 3.245 cm(2) (P > 0.4). In a second group of snoring patients where mean pharyngeal cross-sectional area in the first session was 2.244 cm(2), in the second session, mean pharyngeal cross-sectional area was 2.237 cm(2), and mean pharyngeal cross-sectional area in the third session (7 to 10 days later) was 2.238 cm(2) (P > 0.9). These results show that repeatability of acoustic reflection results can be achieved following the standard operating protocol. The study results add to the reliability of this technique in assessing the pharyngeal airway in patients with snoring and obstructive sleep apnea.


The expression of a tumor suppressor gene JDP2 and its prognostic value in hepatocellular carcinoma patients.
The c-Jun dimerization protein 2 (JDP2) belongs to the activator protein-1 (AP-1) family and functions as a repressor of the AP-1 complex by dimerizing with other c-Jun proteins. Thus, JDP2 plays an important role in the repression of AP-1-driven biological processes, such as differentiation and proliferation. Recent studies have suggested that JDP2 may function as a tumor suppressor through its suppressive action against the AP-1 complex, which is known to drive oncogenic signals in several human malignancies. In this study, we used immunohistochemistry to examine the JDP2 expression in 211 cases of hepatocellular carcinoma (HCC) and analyzed the potential link of JDP2 expression to the clinicopathological features of HCC patients. Clinical parameter analysis showed that high expression of JDP2 was significantly correlated with smaller tumor size (P=.002) and early stage HCC (P=.039). Moreover, Kaplan-Meier survival analysis showed that high expression of JDP2 was significantly associated with better survival in HCC patients (P=.006). Taken together, our results showed that JDP2 may serve as a tumor suppressor in HCC and could therefore serve as a good prognostic marker for patients with HCC.


Disruption in the space-time continuum: why digital ethnography matters.
There is increasing interest in the use of ethnography as a qualitative research approach to explore, in depth, issues of culture in health professions education (HPE). Our specific focus in this article is incorporating the digital into ethnography. Digital technologies are pervasively and increasingly shaping the way we interact, behave, think, and communicate as health professions educators and learners. Understanding the contemporary culture(s) of HPE thus means paying attention to what goes on in digital spaces. In this paper, we critically consider some of the potential issues when the field of ethnography exists outside the space time continuum, including the need to engage with theory in research about technology and digital spaces in HPE. After a very brief review of the few HPE studies that have used digital ethnography, we scrutinize what can be gained when ethnography encompasses the digital world, particularly in relation to untangling sociomaterial aspects of HPE. We chart the shifts inherent in conducting ethnographic research within the digital landscape, specifically those related to research field, the role of the researcher and ethical issues. We then use two examples to illustrate possible HPE research questions and potential strategies for using digital ethnography to answer those questions: using digital tools in the conduct of an ethnographic study and how to conduct an ethnography of a digital space. We conclude that acknowledging the pervasiveness of technologies in the design, delivery and experiences of HPE opens up new research questions which can be addressed by embracing the digital in ethnography.


Three lysine residues in the common β chain of the interleukin-5 receptor are required for Janus kinase (JAK)-dependent receptor ubiquitination, endocytosis, and signaling.
Eosinophils are multifunctional leukocytes implicated in the pathogenesis of numerous inflammatory diseases including allergic asthma and hypereosinophilic syndrome. Eosinophil physiology is critically dependent on IL-5 and the IL-5 receptor (IL-5R), composed of a ligand binding α chain (IL-5Rα), and a common β chain, βc. Previously, we demonstrated that the βc cytoplasmic tail is ubiquitinated and degraded by proteasomes following IL-5 stimulation. However, a complete understanding of the role of βc ubiquitination in IL-5R biology is currently lacking. By using a well established, stably transduced HEK293 cell model system, we show here that in the absence of ubiquitination, βc subcellular localization, IL-5-induced endocytosis, turnover, and IL-5R signaling were significantly impaired. Whereas ubiquitinated IL-5Rs internalized into trafficking endosomes for their degradation, ubiquitination-deficient IL-5Rs accumulated on the cell surface and displayed blunted signaling even after IL-5 stimulation. Importantly, we identified a cluster of three membrane-proximal βc lysine residues (Lys(457), Lys(461), and Lys(467)) whose presence was required for both JAK1/2 binding to βc and receptor ubiquitination. These findings establish that JAK kinase binding to βc requires the presence of three critical βc lysine residues, and this binding event is essential for receptor ubiquitination, endocytosis, and signaling.


Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.
Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.


Iron(II) coordination complexes with panchromatic absorption and nanosecond charge-transfer excited state lifetimes.
Replacing current benchmark rare-element photosensitizers with ones based on abundant and low-cost metals such as iron would help facilitate the large-scale implementation of solar energy conversion. To do so, the ability to extend the lifetimes of photogenerated excited states of iron complexes is critical. Here, we present a sensitizer design in which iron(II) centres are supported by frameworks containing benzannulated phenanthridine and quinoline heterocycles paired with amido donors. These complexes exhibit panchromatic absorption and nanosecond charge-transfer excited state lifetimes, enabled by the combination of vacant, energetically accessible heterocycle-based acceptor orbitals and occupied molecular orbitals destabilized by strong mixing between amido nitrogen atoms and iron. This finding shows how ligand design can extend metal-to-ligand charge-transfer-type excited state lifetimes of iron(II) complexes into the nanosecond regime and expand the range of potential applications for iron-based photosensitizers.


Glucocorticoid therapy for the induction of pulmonary maturity in severely hypertensive gravid women.
Twenty hypertensive gravid women who had their pregnancies terminated for maternal indications because of the severity of pre-eclampsia or chronic hypertension were studied. They were treated at 27 to 33 weeks of gestation with 48 hours of betamethasone therapy prior to delivery. There was one antepartum fetal death, and it is believed that this death was preventable. There was an incidence of respiratory distress syndrome (RDS) of 23% with two neonatal deaths secondary to RDS, for a treated neonatal survival of 85.7%. All losses were from mothers with pre-eclampsia. Pregnancy-related hypertension is not thought to be an absolute contraindication to glucocorticoid therapy for the induction of pulmonary maturity.


Priming with MF59 adjuvanted versus nonadjuvanted seasonal influenza vaccines in children - A systematic review and a meta-analysis.
Identifying optimal priming strategies for children <2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children. We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs. Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p < 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6). Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.


Clarifying the Relationship between Trichotillomania and Anxiety.
Although research has consistently linked unidimensional anxiety with Trichotillomania (TTM) severity, the relationships between TTM severity and anxiety dimensions (i.e., cognitive and somatic anxiety) are unknown. This knowledge gap limits current TTM conceptualization and treatment. The current study examined these relationships with data collected from ninety-one adults who participated in a randomized clinical trial for TTM treatment. To examine whether the Beck Anxiety Inventory (BAI; Beck, Epstein, Brown, & Steer, 1988) could be used to measure multidimensional anxiety in TTM samples, we conducted a factor analysis. Results showed four emergent factors, including a cognitive factor and three somatic factors (neurophysiological, autonomic, and panic). Based on prior research, it was hypothesized that TTM severity would be related to the cognitive anxiety dimension and that psychological inflexibility would mediate the association. Hypotheses were not made regarding the relationship between TTM severity and somatic anxiety. Regression analyses indicated that only cognitive dimensions of anxiety predicted TTM severity and that psychological inflexibility mediated this relationship. Implications for the conceptualization and treatment of TTM are discussed.


A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells.
In this study, screening by LC-MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments. Antiproliferative assays using mammalian cancerous cells revealed that 1 inhibits the proliferation of HL-60 human promyelocytic leukemia cells. Cell cycle analysis showed an increased accumulation of cells in the G0/G1 phase after treatment with 1. Results of immunoblotting assays revealed that 1 reduced the expression levels of cyclin-dependent kinase 4 (CDK4), CDK6, retinoblastoma protein (Rb), and phosphorylated Rb, whereas it induced cyclin-dependent kinase inhibitor 1B (p27/Kip1) expression.


Getting back on track: evaluation of a brief group psychoeducation intervention for women completing primary treatment for breast cancer.
Patients with breast cancer experience unmet informational and psychosocial needs at the end of treatment. A brief psychoeducational intervention delivered at this transition may help to address some of the challenges these women face. The purpose of this study was to test the effectiveness of a single-session group psychoeducational intervention (GBOT group) compared with standard print material (usual care). In this randomized controlled trial, 442 patients with breast cancer who were completing their adjuvant radiotherapy were recruited and randomized to receive either usual care, which includes standard print material (CRL group n = 226) or usual care and the GBOT group intervention (INT group n = 216). Participants completed measures at baseline and again at 3 and 6 months post-intervention. The INT group showed significant improvement in their knowledge regarding the re-entry transition period (d = 0.31) and in their feelings of preparedness for re-entry (d = 0.37). There were no differences between the groups over time on health-related distress or mood. Results support the effectiveness of providing a single-session group psychoeducational intervention as a first-step approach to supportive care for women at the end of breast cancer treatment.