Effect of high levels of the rotifer Lecane inermis on the ciliate community in laboratory-scale sequencing batch bioreactors (SBRs).
Due to its ability to feed on filamentous bacteria, the rotifer Lecane inermis has already been recognized as a potential control agent of activated sludge bulking, which is usually caused by the excessive growth of filamentous microorganisms. However, their effectiveness depends, in part, on their abundance. We studied the influence of high densities of L. inermis on the protozoan community in activated sludge from a wastewater treatment plant (WWTP) in 4 laboratory-scale sequencing batch bioreactors (SBRs). Two treatments and two controls were subjected to nutrient removal system in process similar to that used in a WWTP. The experiment lasted 9 days and was repeated in 24-h cycles, including phases of agitation with feeding, aeration and agitation and sedimentation with decantation at the end of the cycle. In total, 32 taxa were identified, among which 25 were ciliated protozoa, 4 were amoebae, 2 were flagellates, and one was a nematode. Rotifers were then introduced to 2 bioreactors at a final concentration of 500ind.mL(-1), and the taxonomic composition and abundance of the activated sludge microfauna were assessed 2, 5 and 8 days thereafter. The mean density of ciliates on the first day of experiment was 12,610ind.mL(-1) and diminished to 4868±432ind.mL-±432ind.mL(-1) in the control and 5496±638ind.mL(-1) in the rotifer-treated group on the last day. Thus, even extremely high densities of artificially introduced rotifers did not negatively affect the protozoan community. On the contrary, the protozoan community was more diverse in the treatment group than in the control.


Contrast-enhanced dual energy mammography with a novel anode/filter combination and artifact reduction: a feasibility study.
To demonstrate the feasibility of contrast-enhanced dual-energy mammography (CEDEM) using titanium (Ti) filtering at 49 kVp for high-energy images and a novel artefact reducing image-subtraction post-processing algorithm. Fifteen patients with suspicious findings (ACR BI-RADS 4 and 5) detected with digital mammography (MG) that required biopsy were included. CEDEM examinations were performed on a modified prototype machine. Acquired HE and low-energy raw data images were registered non-rigidly to compensate for possible subtle tissue motion. Subtracted CEDEM images were generated via weighted subtraction, using a fully automatic, locally adjusted tissue thickness-dependent subtraction factor to avoid over-subtraction at the breast border. Two observers evaluated the MG and CEDEM images according to ACR BI-RADS in two reading sessions. Results were correlated with histopathology. Seven patients with benign and eight with malignant findings were included. All malignant lesions showed a strong contrast enhancement. BI-RADS assessment was altered in 66.6 % through the addition of CEDEM, resulting in increased overall accuracy. With CEDEM, additional lesions were depicted and false-positive rate was reduced compared to MG. CEDEM using Ti filtering with 49 kVp for HE exposures is feasible in a clinical setting. The proposed image-processing algorithm has the potential to reduce artefacts and improve CEDEM images. • CEDEM with a titanium filter is feasible in a clinical setting. • Breast thickness-dependent image subtraction has the potential to improve CEDEM images. • The proposed image-processing algorithm reduces artefacts.


Bladder training after surgery for stress urinary incontinence: is it necessary?
Eighty-nine consecutive patients with a clinically and urodynamically proved diagnosis of genuine stress urinary incontinence entered this study. Forty women had a revised Pereyra procedure and 49 had a Burch retropubic urethropexy. All had a suprapubic Bonnano catheter for postoperative bladder drainage. Postoperatively, patients were randomly allocated to "bladder training" (N = 44) or "nonbladder training" (N = 45) protocols. "Bladder training" consisted of scheduled clamping and unclamping of the catheter, whereas the "nonbladder training" patients had continuous bladder drainage throughout their postoperative period. Postvoiding residual urine volume was measured twice daily after the patient had voided with a symptomatically full bladder. The catheter was removed once residual volume was 50 mL or less. The bladder training protocol had no effect on resumption of spontaneous voiding after surgery. There was no significant change in length of postoperative bladder catheterization or in urinary tract infection rate among women with or without bladder training.


Patients With Previous COVID-19 Infection Can Safely Undergo Primary Total Joint Arthroplasty.
The COVID-19 virus is believed to increase the risk of diffusing intravascular coagulation. Total joint arthroplasty (TJA) is one of the most common elective surgeries and is also associated with a temporarily increased risk of venous thromboembolism (VTE). However, the influence of a history of COVID-19 infection on perioperative outcomes following TJA remains unknown. Therefore, this study sought to determine what effect a history of COVID-19 infection had on outcomes following primary TJA. A retrospective case-control study using the national database was performed to identify all patients who had a history of COVID-19 and had undergone TJA, between 2019 and 2020. Patients who had a history of both were 1:1 matched to those who did not have a history of COVID-19, and 90-day outcomes were compared. A total of 661 TKA and 635 THA patients who had a history of COVID-19 were 1:1 matched to controls. There were no differences in demographics and comorbidities between the propensity-matched pairs in both TKAs and THAs studied. Previous COVID-19 diagnosis was noted in 28.3% of patients 5 days within TJA and in 78.6%, 90 days before TJA. Patients who had a previous diagnosis of COVID-19 had a higher risk of pneumonia during the postoperative period for both THA and TKA (6.9% versus 3.5%, P < .001 and 2.27% versus 1.21%, P = .04, respectively). Mean lengths of stay were also greater for those with a previous COVID-19 infection in both cohorts (TKA: 3.12 versus 2.57, P = .027, THA: 4.52 versus 3.62, P < .001). Other postoperative outcomes were similar between the 2 groups. COVID-19 infection history does not appear to increase the risk of VTE following primary TJA, but appears to increase the risk of pneumonia in addition to lengths of stay postoperatively. Individual risk factors should be discussed with patients, to set reasonable expectations regarding perioperative outcomes.


Cold-specific and light-stimulated expression of a wheat (Triticum aestivum L.) Cor gene Wcor15 encoding a chloroplast-targeted protein.
Wcor15, a member of the wheat cold-responsive (Cor) gene family, has been isolated and characterized. The deduced polypeptide WCOR15 (MW=14.7 kDa) showed high homology to the previously identified wheat and barley COR proteins. Southern blot analysis using diploid, tetraploid and hexaploid wheat and diploid Aegilops species showed that the wheat and related wild genomes possessed multiple copies of Wcor15 homologues. Five copies were assigned to the homologous group 2 chromosomes by nulli-tetrasomic analysis. Northern blot analysis showed that expression of Wcor15 was specifically induced by low-temperature. Homologous transcripts accumulated in leaves, and light markedly increased their steady-state levels. Bombardment-mediated transient expression analysis of a chimeric CaMV 35S::Wcor15-GFP construct showed protein-targeting to epidermal guard cell chloroplasts in excised spiderwort leaves. A promoter of Wcor15 contained at least three CRT/DRE-like sequence motifs found in Arabidopsis Cor genes and induced the reporter GUS gene expression in leaves of transgenic tobacco plants under low-temperature and light conditions. These results suggest that the functional Cor gene system involving the CRT/DRE cis-element is conserved in both monocotyledonous and dicotyledonous plants.


Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration.
Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.


Proteomic study of calpain interacting proteins during skeletal muscle aging.
Aging is associated with a progressive and involuntary loss of muscle mass also known as sarcopenia. This condition represents a major public health concern. Although sarcopenia is well documented, the molecular mechanisms of this condition still remain unclear. The calcium-dependent proteolytic system is composed of calcium-dependent cysteine proteases named calpains. Calpains are involved in a large number of physiological processes such as muscle growth and differentiation, and pathological conditions such as muscular dystrophies. The aim of this study was to determine the involvement of this proteolytic system in the phenotype associated with sarcopenia by identifying key proteins (substrates or regulators) interacting with calpains during muscle aging. Immunoprecipitations coupled with proteomic analyses and protein identification by mass spectrometry have been undertaken. Reverse co-immunoprecipitation, cellular colocalisation by confocal microscopy and calpain-dependent in vitro proteolysis of several of the identified proteins have been also carried out. We identified ATP synthase subunit alpha and alpha actinin 3 as key partners of calpains during muscle aging. Such interactions would suggest that calpains are implicated in many processes altered during aging including cytoskeletal disorganisation and mitochondrial dysfunction.


Comparative performance evaluation of conventional and two-phase hydrophobic stirred tank reactors for methane abatement: Mass transfer and biological considerations.
This study demonstrated for the first time the capability of methanotrophs to grow inside silicone oil (SO200) and identified the optimum cultivation conditions for enrichment of hydrophobic methanotrophs (high dilution rates (D) and low CH4 transfer rates). The potential of the hydrophobic methanotrophs enriched was assessed in a single-phase stirred tank reactor (1P-STR) and in a two-phase stirred tank reactor (2P-STR). Different operational conditions were systematically evaluated in both reactors (SO200 fractions of 30 and 60 %, stirring rates of 250 and 500 rpm, and D of 0.1-0.35 day(-1) with and without biomass retention). The results showed that the TPPB only supported a superior CH4 abatement performance compared to the 1P-STR (40% enhancement at 250 rpm and 25% enhancement at 500 rpm) at a D of 0.3 day(-1) due to the retention of the biocatalytic activity inside the SO200, while the 1P-STR achieved higher elimination capacities (EC up to ≈3 times) than the TPPB under the rest of conditions tested (ECmax = 91.1 g m(-3) h(-1) ). Furthermore, the microscopic examination and DGGE-sequencing of the communities showed that the presence of SO200 influenced the microbial population structure, impacting on bacterial biodiversity and favoring the growth of methanotrophs such as Methylosarcina. Biotechnol. Bioeng. 2016;113: 1203-1212. © 2015 Wiley Periodicals, Inc.


Revisiting respect for persons: conceptual analysis and implications for clinical practice.
In everyday conversations, professional codes, policy debates, and academic literature, the concept of respect is referred to frequently. Bioethical arguments in recent decades equate the idea of respect for persons with individuals who are capable of autonomous decision-making, with the focus being explicitly on 'autonomy,' 'capacity,' or 'capability.' In much of bioethics literature, respect for persons is replaced by respect for autonomy. Though the unconditional respect for persons and their autonomy (irrespective of actual decision-making capacity) is established in Kantian bioethics, current argument and debates often revolve around a thin concept of autonomy, focusing on capacity and capability: persons are owed respect because they are 'rational beings' or with a focus on 'agency' and 'decision-making abilities.' However, these aspects alone are insufficient while engaging the concept of respect for persons, particularly in healthcare settings. This paper sets out to explore if the concept of respect for persons-as opposed to a thin concept of autonomy-could help us engage better in healthcare practices. We shall probe the practical value of the experiential aspect of respect-understood as the recognition of persons as respect-worthy through certain dispositions and deliberative acts-by reflecting on instances in clinical practice that tend to be dismissed as negligible or even unavoidable in a stressful environment such as a busy hospital. We shall argue that these instances are far from trivial but carry moral significance and express an unacceptable-disrespectful-attitude that can compromise the moral habitus in hospital settings. In our conclusion, we call for practicing recognition respect in the health professional-patient encounter by focussing on manners, attitudes, and behaviors. Furthermore, we call for continuous medical ethics education programs to address the moral significance of disrespectful behaviors and their manifestations in particular socio-cultural contexts.


Application of the BC1 RNA gene promoter for short hairpin RNA expression in cultured neuronal cells.
BC1 RNA is a neuronal cell-specific non-messenger RNA transcribed by RNA polymerase III (Pol III). We previously reported that the transcription of BC1 RNA is controlled both by intragenic promoters for Pol III and by a 5'-flanking region containing several unique cis-elements that are possible members of the Pol II transcription system. In this study, we chose beta-secretase (BACE1) as a target and applied the promoter to produce a short hairpin RNA (shRNA) for RNA interference (RNAi) in cultured neuronal cells. A plasmid vector in which the promoter was linked to a target sequence functioned in rodent NG108-15 cells and suppressed BACE1 protein expression, but did not function in non-neuronal NIH3T3 cells. It was also effective in rat primary hippocampal neurons. We further showed that the promoter can be active in human neuroblastoma SH-SY5Y cells and reduced expression of targeted protein, although the BC1 RNA gene is a rodent-specific gene. The use of this vector-based system for shRNA expression may be an important component of future development of neuronal cell-selective RNAi in both transgenic and therapeutic applications.


Transcatheter closure of patent foramen ovale in patients with paradoxical embolism: intermediate-term risk of recurrent neurological events.
Closure of patent foramen ovale (PFO) has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. We report our preliminary intermediate results of patients who underwent transcatheter PFO closure for paradoxical embolism using DAS-Angel Wings occluder or Amplatzer devices. Eighteen patients (8 male/10 female) underwent catheter closure of their PFOs at a median age of 42 years. The complete closure rate was 67% immediately after the procedure and 100% at a mean follow-up interval of 2.2 +/- 1.8 years. The mean fluoroscopy time and procedure time in the Amplatzer group were 8.5 +/- 3.2 min and 65 +/- 21 min, respectively, which were significantly shorter than those of DAS-Angel Wings group (18.9 +/- 4.7 min and 137 +/- 28 min, respectively). There were no recurrent embolic neurological events following device placement in this subset of patients. No complications were encountered either during or after the closure procedure. In conclusion, transcatheter closure of PFO seems to be an effective alternative therapy in the prevention of presumed paradoxical emboli. Further study is needed to identify patients most likely to benefit from this intervention.


Competition in mixtures of susceptible and resistant genotypes of Chondrilla juncea differentially infected with rust.
Plants of two genotypes of Chondrilla juncea (skeleton weed), one susceptible to and the other resistant to one isolate of the rust Puccinia chondrillina, were grown as pure and mixed populations both in the presence and absence of rust. Weights of individual plants were obtained at two harvests, one when the plants were rosettes and the other when flowering had begun. Distributions of plant weights of each genotype became progressively more positively skewed with time, with rust infection of plants of the susceptible genotype and with increasing competition between plants of both genotypes. The results show that genetic differences may be an important factor in determining which individuals become dominant or are suppressed in competing mixtures, and that differential disease pressure may alter dominance of individuals in plant populations.


IL-4 receptor expression by SAC-activated B-lymphocytes: its role in B-cell proliferation and the effect of cyclosporine (CsA), prednisolone and verapamil.
Expression of the IL-4 receptor was studied in a highly purified population of human B-lymphocytes stimulated by Staphylococcus aureus, cowan I (SAC). Flow cytometric analysis showed that incubation with SAC in the absence of detectable levels of IL-2, IL-4 and IL-6 resulted in a striking increase in cellular binding of IL-4. The SAC-stimulated B-cells responded to exogenous IL-4 by DNA synthesis. This response was unaffected by CsA or prednisolone, but was inhibited by the Ca2+ channel blocker verapamil.


Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-coverting enzyme in vivo.
Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.


Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK.
Glucocorticoids are highly effective in the control of many inflammatory and immune diseases. Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, the molecular basis for the inhibitory effect of glucocorticoids on mucin overproduction, a hallmark of chronic respiratory diseases, still remains unclear. Here we show that glucocorticoids markedly inhibit up-regulation of MUC5AC induced by NTHi, a major human bacterial pathogen causing chronic obstructive pulmonary disease and otitis media. Inhibition of NTHi-induced MUC5AC expression by dexamethasone occurs at the level of p38 MAPK via glucocorticoid receptor. Moreover, glucocorticoids up-regulate MKP-1 expression, which in turn leads to p38 dephosphorylation and the subsequent inhibition of NTHi-induced MUC5AC expression. These studies provide new insight into the molecular mechanism underlying glucocorticoid therapy and may lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.


Action of thiazide on renal interstitial calcium.
Although thiazides increase urinary sodium excretion, they also decrease urinary calcium excretion. Recent studies in our laboratory have shown that increased dietary salt significantly reduces interstitial fluid calcium in Dahl salt-sensitive (DS) rats, and this was associated with a rise in blood pressure and increased urinary calcium excretion. Owing to the vasorelaxant actions of increased extracellular fluid calcium, we reasoned that the antihypertensive action of hydrochlorothiazide (HCTZ), a commonly used thiazide, may be the result of increased interstitial fluid calcium as a consequence of decreased urinary calcium excretion. To test this hypothesis, DS and Dahl salt-resistant (DR) rats were given high salt alone or in combination with HCTZ for 1 week. Renal cortical interstitial fluid calcium was determined by the zero net flux method. High salt decreased cortical interstitial fluid calcium (1.69 +/- 0.25 vs. 1.13 +/- 0.05 mmol/l; P < 0.05) in DS rats as previously reported; thiazide treatment had no effect on the high salt interstitial fluid calcium response in salt-sensitive animals. However, thiazide decreased interstitial fluid calcium in DS on a normal salt diet. Cortical interstitial fluid calcium was unchanged by dietary salt in DR rats, and thiazide did not alter this interstitial fluid calcium response. We interpret these data to mean that (i) short-term thiazide treatment does not reduce blood pressure by restoring renal cortical interstitial fluid calcium concentration and (ii) a decrease in renal cortical interstitial fluid calcium may not contribute to the increased renal vasoconstriction seen in salt-sensitivity.


Creation of Multimeric Single-Domain Antibodies Using Bacterial Superglues.
Multimerization of single-domain antibodies (sdAbs) is instrumental for construction of antibody molecules with high avidity, extended in vivo half-life, and tailor-made biological activity. Two-component superglues, based on bacterium-derived peptides (Tags) and small protein domains (Catchers) that form isopeptide bonds when in close proximity, enable the creation of multimers by simply mixing of the individual components. Here, we provide detailed methods for the construction of sdAbs and scaffolds bearing genetically fused superglue components and their assembly into multimeric complexes.


Malignant Otitis Externa: A Retrospective Analysis and Treatment Outcomes.
The purpose of this study was to analyze previous treatments and outcomes in patients with malignant otitis externa (MOE) retrospectively. The efficacy of medical and surgical treatments was also evaluated. This study included 25 patients diagnosed with MOE and treated at the Department of Otorhinolaryngology, Ege University School of Medicine between 2006 and 2017. The duration of hospitalization, Hemoglobin A1c (HbA1c) levels of the patients, erythrocyte sedimentation rate (ESR), source of the infection, complications, and previous medical and surgical treatments were also retrospectively assessed. The mean age of the patients (7 females and 18 males) was 69.68±11.29 years. The mean length of hospital stay in patients with HbA1c levels ≤6 and in patients with HbA1c levels >6 was 26.86 and 33.39 days, respectively. The mean hospitalization time was significantly longer in patients with HbA1c levels >6 (p<0.05). Additionally, elderly patients (age>65 years) had a significantly longer hospital stay in our study (p<0.05). ESR was found to be 52.76±32.49 (9-108) mm/h at the first examination and 14.92±1.22 (4-32) mm/h at the time of discharge. MOE is an aggressive disease that requires conservative management, and ESR proved to be a good indicator of treatment response. Long-term antibiotherapy are recommended for treatment.


[The study of the inflammation of the airway in bronchial asthma by cytological and chemical analysis in the fluid phase of samples taken by sputum induction].
In recent years the study of samples of bronchial biopsies and bronchoalveolar lavage fluid has made it possible to show the existence of significant airway mucosal inflammation, even in cases of mild bronchial asthma. This has led to a renewed interest in the use of sputum to assess airway inflammation non-invasively. Sputum induction has recently been proposed as a non-invasive alternative to bronchoscopy for the collection of airway secretions from asthmatic subjects. Sputum induction yields satisfactory samples of sputum in the great majority of asthmatic subjects, and both differential cell counts and the measurement of molecular markers of inflammation in the sputum fluid phase are feasible. In this paper we review studies where these measurements have been taken from subjects who were asthmatic, affected by other respiratory pathologies or healthy, and we assess their validity. Finally, we consider possible future clinical applications of sputum measurement of airway inflammation in asthma.


Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results.
Nutrient interactions with prescription drugs are a topic of ongoing basic and clinical research. Pomegranate juice and a 1-g capsule containing pomegranate extract were evaluated in vitro and in vivo as inhibitors of cytochrome P450 2C9 (CYP2C9), with flurbiprofen serving as the index substrate. Fluconazole was the positive control inhibitor. The in vitro 50% inhibitory concentration (IC(50)) values for pomegranate juice and extract were below 1% (vol/vol), with no evidence of mechanism-based (irreversible) inhibition. In clinical studies, flurbiprofen pharmacokinetics were unchanged by pomegranate juice or extract as compared to a low-polyphenol placebo control beverage. However, fluconazole significantly reduced the oral clearance of flurbiprofen. Despite inhibition of CYP2C9 in vitro, pomegranate juice and extract had no effect on CYP2C9 activity in human subjects, and can be consumed by patients taking CYP2C9 substrate drugs with negligible risk of a pharmacokinetic interaction.


ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma.
Gene expression profiling revealed ADAM9 to be distinctly overexpressed in pancreatic ductal adenocarcinoma (PDAC). We examined the relevance of ADAM9 expression in PDAC diagnosis and prognosis. A total of 59 infiltrating PDACs, 32 specimens from patients with chronic pancreatitis, 11 endocrine tumours and 24 acinar cell carcinomas were immunohistochemically analysed for ADAM9 expression. Staining for ADAM9 was detected in 58 out of 59 (98.3%) PDACs and in two out of 24 (8.3%) acinar cell carcinomas, but not in endocrine tumours. In the non-neoplastic pancreas, whether normal or chronically inflamed, ADAM9 was expressed in centroacinar and intralobular duct cells, but not in interlobular duct cells and their hyperplastic lesions. Pancreatic ductal adenocarcinomas showing cytoplasmic ADAM9 expression correlated with poor tumour differentiation and also with shorter overall survival than in cases showing only an apical membranous staining pattern (P=0.001). Multivariate analysis identified cytoplasmic ADAM9 expression as an independent marker of shortened survival in a set of 42 curatively (R0) resected PDAC (P<0.05, hazard ratio 2.85, 95% confidence interval: 1.21-6.71). The results show that ADAM9 expression distinguishes PDACs from other solid pancreatic tumours. In addition, cytoplasmic ADAM9 overexpression is associated with poor differentiation and shortened survival. Therefore, ADAM9 overexpression might contribute to the aggressiveness of PDACs.


Multi-analytical characterisation of blotting sands on documents from religious orders in Portugal (16th-19th centuries).
Too little is known about areia de escrever, i.e., blotting sands, the intriguing particles sprinkled on freshly written scripts to accelerate the drying time of the ink. Blotting sands constitute a valuable but underestimated historical source. This work investigated the blotting sands used on the account books of the religious houses scattered across continental Portugal and Madeira Island (16th-19th centuries). The sands were mainly composed of different minerals, predominately black sands, but in a few cases, minerals were found mixed with gums, paper cocoons or bone shavings. The combined use of SEM-EDS, µ-Raman and FT-IR techniques uncovered the materials' chemical or mineralogical composition and morphology. This approach, allied with image analysis and statistics complemented with multivariate analysis, allowed us to look for trends between the samples and hypothesise about their provenance. Heavy minerals, such as ilmenite, hematite and almandine, were identified as major components, together with other silicates (e.g. quartz). Samples were dominated by medium-sized grains with shape features indicating texturally mature sediments resulting from a medium-to-long sedimentary transport. Due to shorter geological transport distances, Madeira Island was the exception, with more angular grains. This work allowed us to uncover blotting sands, value them as historical sources, and establish a roadmap for their use in Portugal, aiming to pave the way towards a more global context in Europe.


Cerebral blood flow and oximetry response to blood transfusion in relation to chronological age in preterm infants.
Preterm infants frequently receive blood transfusion (BT) and the aim of this study was to measure the effect of BT on cerebral blood flow and oxygenation in preterm infants in relation to chronological age. Preterm infants undergoing intensive care recruited to three chronological age groups: 1 to 7 (Group 1; n=20), 8 to 28 (Group 2; n=21) & ≥29days of life (Group 3; n=18). Pre and post-BT anterior cerebral artery (ACA) time averaged mean velocity (TAMV) and superior vena cava (SVC) flow were measured. Cerebral Tissue Haemoglobin Index (cTHI) and Oxygenation Index (cTOI) were measured from 15-20min before to 15-20min post-BT using NIRS. Vital parameters and blood pressure were measured continuously. Mean BP increased significantly, and there was no significant change in vital parameters following BT. Pre-BT ACA TAMV was higher in Group 2 and 3 compared to Group 1 (p<0.001). Pre-BT ACA TAMV decreased significantly (p≤0.04) in all 3 groups; pre-BT SVC flow decreased significantly in Group 1 (p=0.03) and Group 3 (p<0.001) following BT. Pre-BT cTOI was significantly lower in Group 3 compared to Group 1 (p=0.02). cTHI (p<0.001) and cTOI (p<0.05) increased significantly post-BT in all three groups. PDA had no effect on these measurements. Baseline cTOI decreases and ACA TAMV increases with increasing chronological age. Blood transfusion increased cTOI and cTHI and decreased ACA TAMV in all groups. PDA had no impact on the baseline cerebral oximetry and blood flow as well as changes following blood transfusion.


Immediate effects of alkaline infusion in infants with respiratory distress syndrome.
Nineteen infants with acidosis associated with RDS were studied following the infusion of: (1) 0.58M (7%) THAM over 30 seconds; (2) molar bicarbonate over 30 seconds; (3) molar bicarbonate over 2 minutes; and (4) molar bicarbonate over 5 minutes. PaC02 fell after THAM; PaC02 rose sharply after bicarbonate and remained elevated 10 minutes after infusion. The pH rose abruptly in all infants and remained significantly elevated 10 minutes after infusion. Pa02 changes were variable; no infant had immediate improvement in Pa02. The changes in osmolality, hematocrit, and colloid osmotic pressure describe the immediate osmotic hemodilution following the infusion of hypertonic base.


[Increased pulmonary arterial and venous pressure].
Increases in pressure in the pulmonary arteries or pulmonary veins may be the result of a variety of underlying diseases. Noninvasive imaging plays a crucial role not only for identification, but also for differential diagnosis. This article provides a comparative review of the signs of increased pulmonary arterial and pulmonary venous pressure in chest X‑ray and computed tomography (CT). Typical signs of a pulmonary arterial or pulmonary venous pressure increase in chest X‑ray and CT facilitate diagnosis of pulmonary hypertension (e.g., enlargement of central pulmonary arteries) and interstitial or alveolar pulmonary edema (e.g., Kerley lines/thickened interlobular septae or butterfly edema). A basic understanding of imaging findings and underlying pathophysiology helps in establishing the differential diagnosis. Chest X‑ray and CT are essential for diagnosis of patients with suspected increased pulmonary arterial or pulmonary venous pressure.


A comparison study of corneal topographic changes following 20-, 23-, and 25-G pars plana vitrectomy.
To evaluate and compare corneal topographic changes following pars plana vitrectomy with the 23-gauge (G) and 25-G transconjuntival sutureless vitrectomy system as well as the standard 20-G vitrectomy system. We prospectively evaluated corneal topographic changes in 45 eyes of 45 patients divided into three groups according to vitrectomy system used (20-, 23-, and 25-G). All patients underwent computer-assisted videokeratography using an EyeSys System 3000 topographer preoperatively and at one week, one month, and three months postoperatively. In the 20-G vitrectomy group, we found statistically significant postoperative changes in corneal curvature parameters with an average steepening of 0.98 ± 0.18 D (P<0.001) and 0.93 ± 0.21 D (P<0.001) at one week and one month, respectively. No statistically significant difference was observed at the three-month follow-up visit. In the 23- and 25-G groups, no statistically significant changes in corneal curvature parameters were observed at any postoperative follow-up visit. Twenty-three-gauge and 25-gauge transconjunctival sutureless vitrectomy did not induce topographic corneal changes following surgery, whereas 20-G vitrectomy was found to induce transient topographic corneal changes that had returned to preoperative levels at three months postoperatively.


Biological evolution requires an emergent, self-organizing principle.
In this perspective review, we assess fundamental flaws in Darwinian evolution, including its modern versions. Fixed mutations 'explain' microevolution but not macroevolution including speciation events and the origination of all the major body plans of the Cambrian explosion. Complex, multifactorial change is required for speciation events and inevitably requires self-organization beyond what is accomplished by known mechanisms. The assembly of ribosomes and ATP synthase are specific examples. We propose their origin is a model for what is unexplained in biological evolution. Probability of evolution is modeled in Section 9 and values are absurdly improbable. Speciation and higher taxonomic changes become exponentially less probable as the number of required, genetically-based events increase. Also, the power required of the proposed selection mechanism (survival of the fittest) is nil for any biological advance requiring multiple changes, because they regularly occur in multiple generations (different genomes) and would not be selectively conserved by the concept survival of the fittest (a concept ultimately centered on the individual). Thus, survival of the fittest cannot 'explain' the origin of the millions of current and extinct species. We also focus on the inadequacies of laboratory chemistry to explain the complex, required biological self-organization seen in cells. We propose that a 'bioelectromagnetic' field/principle emerges in living cells. Synthesis by self-organization of massive molecular complexes involves biochemical responses to this emergent field/principle. There are ramifications for philosophy, science, and religion. Physics and mathematics must be more strongly integrated with biology and integration should receive dedicated funding with special emphasis for medical applications; treatment of cancer and genetic diseases are examples.


Behavioral observation and intracerebral electrochemical recording following administration of amphetamine in rats.
Intracerebral electrochemistry (chronoamperometry) was performed on rats that were administered 1, 4, and 8 mg/kg doses of amphetamine. Graphpoxy working electrodes were implanted bilaterally in nucleus accumbens (ACC) and ventral anterior stratum (VAS). Following drug injection, locomotor and stereotyped behaviors were observed. Intracerebral electrochemical signals reliably increased following injection of amphetamine. The magnitude of these increases did not change significantly across the dose range tested for VAS electrodes. ACC electrodes had increases similar in magnitude to VAS electrodes at 1 and 4 mg/kg. At 8 mg/kg increases obtained from ACC electrodes were significantly lower than those recorded from VAS. Onset of the change in electrochemical signal paralleled the onset of activity or stereotypy but the subsequent declines in signal and behavior were only loosely correlated. At the 4 mg/kg dose, the magnitude of signal increase from striatum was negatively correlated with indices of stereotypy and positively correlated with locomotor counts.


The biasing effects of appearances go beyond physical attractiveness and mating motives.
The influence of appearances goes well beyond physical attractiveness and includes the surprisingly powerful impact of "face-ism" - the tendency to stereotype individuals based on their facial features. A growing body of research has revealed that these face-based social attributions bias the outcomes of labor markets and experimental economic games in ways that are hard to explain via evolutionary mating motives.


The incidence of pulmonary embolism (PE) after spinal fusions.
Pulmonary embolism (PE) is a rare but serious event that may occur after spinal surgery. To correlate PE incidence after spinal arthrodesis with surgical approach, region of spine operated, and primary spinal pathology. To identify PE incidence trends in this population. The Nationwide Inpatient Sample was queried using ICD-9 codes (81.01-81.08) for spinal fusion procedures over a 21-year period (1988-2008). Other data points included PE occurrence, surgical approach, spinal region, surgical indication, and mortality. Multivariate and relational analyses were performed. 4,505,556 patients were identified and 9530 had PE (incidence=0.2%). PE patients had higher odds of combined A/P surgical approaches than posterior approaches (OR=1.97; 95% CI=1.66-2.33), and PE incidence was higher in thoracic versus cervical or lumbar fusions (OR=2.54; 95% CI=2.14-3.02). PE was more likely with vertebral fracture (OR=1.85; 95% CI=1.53-2.23) and SCI with vertebral fracture (OR=4.59; 95% CI=3.72-5.70) than without trauma. Between 1988 and 2008, the PE incidence remained stable for patients with intervertebral disk degeneration and scoliosis, but increased for patients with vertebral fracture, and SCI with vertebral fracture. There was greater inpatient mortality with occurrence of a PE (OR=12.92; 95% CI=10.55-14.41). Although the incidence of PE in spinal arthrodesis patients is only 0.2%, there is a higher incidence after combined A/P approaches, thoracic procedures, and trauma surgical procedures. Despite the overall PE incidence remaining stable since 1988, incidence steadily increased among trauma patients. Further research is needed to explain these trends, given the context of changing patient populations and improving surgical techniques and prophylaxis measures. Greater caution and prophylaxis among trauma patients may be warranted.


A comparison of standard dual-tip hemodialysis catheter split lumen hemodialysis catheter.
To compare a split lumen (SLC) with the standard dual-tip hemodialysis catheter (DTC). The patients who underwent DTC insertion or SLC insertion were enrolled. Initial catheter dwell times (ICDT) and catheter-related complications were compared. SLC (n=80) and DTC (n=133) were enrolled. ICDT was 71.94 days (SLC) and 68.55 days (DTC) (P=.76). Catheter migration was detected in 10.5% and 12.4% (SLC) and in 1.7% and 2.0% (DTC) (P=.0026). SLC did not extend the ICDT compared to DTC. Furthermore, SLC was more prone to catheter-related complications, particularly catheter migration, than DTC.


Detection and treatment of at-risk mental state for developing a first psychosis: making up the balance.
The at-risk mental state (ARMS) has been substantially researched and used as the basis for new clinical settings and strategies over the past two decades. However, it has also caused controversy and intense debate. In this Review, we assess available evidence and propose future directions. Accumulating research suggests that a blend of clinical staging and profiling, which naturally incorporates ARMS, might be a better guide for treatment of patients in different stages of psychiatric illness than the categorical DSM and ICD systems. Furthermore, clinical staging, with its emphasis on balancing risks and benefits, could help to prevent premature treatment or overtreatment with psychotropic drugs. Meta-analyses and reviews show that treatment of ARMS leads to a significant reduction in transition rate to a first psychosis. The debate about stigma associated with ARMS is based on scarce published work. The few studies that have been done suggest that stigma (including self-stigma) arises largely from negative societal views on psychiatric disorders and, depending on the setting and approach, not from engagement in treatment for ARMS per se. The evidence base suggests that definition of ARMS is an important step in implementation of clinical staging and profiling in psychiatry. However, more research across traditional diagnostic boundaries is needed to refine these clinical phenotypes and link them to biomarkers with the goal of personalised stepwise care. Health-system reform is overdue and a parallel process to support this approach is needed, which is similar to how physical forms of non-communicable disease are treated.


Immunocytochemical demonstration of neuropeptides in the fish-gill parasite, Diclidophora merlangi (Monogenoidea).
Using the indirect immunofluorescence technique, immunoreactivity (IR) to three mammalian and one invertebrate regulatory peptide has been demonstrated in the nervous system of the monogenean gill parasite Diclidophora merlangi. IR to pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY) and FMRFamide was evident throughout central and peripheral nervous tissues, whereas vasoactive intestinal polypeptide (VIP)-IR was confined to a portion of the longitudinal ventral nerve cords. Staining patterns revealed the orthogonal arrangement of the nervous system consisting of paired cerebral ganglia, connecting post-pharyngeal commissure, three pairs of longitudinal nerve cords and associated neurones. PP-IR, PYY-IR and FMRFamide-IR were intense throughout the central nervous system of the worm. A small plexus of nerve fibres and somata in each peduncle was immunoreactive for FMRFamide and provided innervation to each of the eight posterior clamps. In the peripheral nervous system, PP-IR, PYY-IR and FMRFamide-IR occurred in an extensive nerve-net with fine, possibly sensory nerve endings in the tegument. PP-IR was also present in nerve fibres in the walls of the ootype, seminal vesicle and uterus. PYY- and FMRFamide-IRs, while evident in nerve fibres of the ootype wall, were also present in a distinct population of cells that encircles the ootype, and which are linked to it by fine cytoplasmic connectives. The majority of these somata were bipolar or multipolar. PYY-IR and FMRFamide-IR were also associated with nerve fibres and bipolar cells in the wall of the vitelline reservoir. Regulatory peptides would appear to play an integral role in neuronal functioning and egg development in D. merlangi.


Identification of critical residues of subunit H in its interaction with subunit E of the A-ATP synthase from Methanocaldococcus jannaschii.
The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral stalks connecting the A(1) and A(0) sections. Structural analyses of the N-terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our initial NMR structural calculations for H1-47 indicate that amino acid residues 7-44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1-47 interact specifically with the N-terminal domain E1-100 of subunit E. A more detailed picture regarding the residues of E1-100 involved in this association was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N-terminal amino acids of H1-47, and this has been confirmed by fluorescence correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the central stalk subunit F in the presence and absence of E101-206 show no obvious interaction between the C-terminal domain of E and subunit F. The data presented provide, for the first time, structural insights into the interaction of subunits E and H, and their arrangement within A(1)A(0) ATP synthase.


Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia.
To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second-generation antipsychotics (SGAs) than those with PTSD alone. National serial cross-sectional study. Veterans Health Affairs inpatient and outpatient settings. Veterans aged 65 and older with PTSD (excluding schizophrenia or bipolar disorder) with or without concomitant dementia who received care from the Veterans Health Administration between 2003 and 2010 were identified using International Classification of Diseases, Ninth Revision, codes (N = 93,068; 11.1% with dementia). Trends in SGA prescribing and odds of being prescribed an SGA were determined using a multivariable logistic regression model adjusted for clinical, sociodemographic, and geographic covariates. Between 2004 and 2009, SGA prescribing declined annually from 7.0% to 5.1% of elderly veterans with PTSD without dementia and 13.2% to 8.9% in those with dementia; findings over time consistently indicated that veterans with PTSD and dementia had at least twice the odds of being prescribed an SGA as those without PTSD (odds ratios 2.03 (95% confidence interval (CI) = 1.82-2.26) to 2.33 (95% CI = 2.10-2.58). Although the prescribing of SGAs to elderly veterans with PTSD has decreased, prescribing an SGA to those with dementia remained consistently higher than for those with PTSD alone and is problematic given the high prevalence of medical comorbidities in this aging population coupled with the lack of compelling evidence for effectiveness of SGAs in individuals with dementia.


[Standardized ultrasound follow-up of callus distraction of the mandible].
Up to now the clinical follow-up in mandibular callus distraction was supported by radiologic methods, although low-mineralized structures are only insufficiently described by X-rays. Mandibular callus distraction was performed on 14 patients suffering from uni- or bilateral mandibular hypoplasia, using either intra- or extraoral devices. The clinical follow-up was supplemented by standardized sonographic investigations. With the exception of postoperative pin placement control, which was done by using X-rays, all interesting items of treatment could be visualized by sonography. We found a reliable correlation between sonographically measured distances and distances measured on the device. Due to early detection of complications, a premature ossification was detected in one case and an infection was diagnosed in another, using ultrasound. Sonography proved to enhance the possibilities of monitoring in mandibular callus distraction treatment and can be recommended in clinical routine.


Cytotoxicity of a recombinant ricin-A-chain fusion protein containing a proteolytically-cleavable spacer sequence.
Chimeric proteins composed of ricin toxin A chain (RTA) and staphylococcal protein A (PA) have been produced in E. coli. Constructs consisting of N-terminal RTA and C-terminal PA (RTA-PA) or N-terminal PA and C-terminal (PA-RTA) were capable of binding to immunoglobulin G (via PA) and of specifically depurinating 28 S ribosomal RNA (via RTA). However, neither fusion protein was cytotoxic to antigen-bearing target cells in the presence of an appropriate monoclonal antibody presumably because the RTA could not be released from the PA within the cytosol where the ribosomal substrate of RTA is located. The overcome this, a short amino acid sequence from diphtheria toxin was engineered between the RTA and PA to produce a disulfide-linked loop containing a trypsin sensitive cleavage site. Cleavage of this fusion protein with trypsin converted the RTA-DT-PA to the two chain form consisting of RTA linked by a disulfide bond to PA. The cleaved fusion protein was highly toxic to Daudi cells coated with anti-immunoglobulin antibody suggesting that the RTA could be released from the PA by reduction within the cytosol.


Measurement of cerebral blood flow and volume with positron emission tomography during isoflurane administration in the hypocapnic baboon.
Using positron emission tomography, cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured after the addition of isoflurane (1.3 vols %, end-tidal concentration) to neuroleptanesthesia (fentanyl/droperidol) in hypocapnic baboons. The study was designed to determine whether isoflurane, when administered during hypocapnia, acted as a cerebral vasodilator to increase either CBF or CBV. Mean arterial pressure was maintained within 10% of preisoflurane levels with an angiotensin infusion. In the first protocol (A), CBF and CBV were measured as close together in time as possible in order to detect divergent effects of isoflurane on these variables. When PaCO2 was reduced from 40 mmHg to 25 mmHg, CBF decreased from 44 +/- 4 to 31 +/- 4 ml.100 g-1.min-1 (P less than 0.05) and CBV decreased from 3.1 +/- 0.3 to 2.6 +/- 0.3 ml/100 g (P less than .05). Neither CBF nor CBV was significantly changed by the addition of isoflurane. In the second protocol (B), serial CBV scans were performed frequently during the addition of isoflurane in a fashion designed to detect transient changes in CBV at the time isoflurane was first added to the breathing circuit. Induction of hypocapnia again reduced CBV from 3.1 +/- .3 to 2.7 +/- .2 ml/100 g, (P less than .05) and addition of isoflurane did not change CBV. From these results the authors conclude that in the normal hypocapnic baboon the addition of 1.3% isoflurane does not significantly change cerebral blood flow or volume.


Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity.
The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15,550 cases and 444,007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.


In silico Identification of Novel SARS-CoV-2 Main Protease and Nonstructural Protein 13 (nsp13) Inhibitors through Consensus Docking and Free Binding Energy Calculations.
A new strain of a novel disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recently declared a pandemic by the World Health Organization (WHO). The virus results in significant mortality and morbidity across the planet; therefore, novel treatments are urgently required. Recently deposited crystallographic structures of SARS-CoV-2 proteins have ignited the interest in virtual screenings of large databases. In the current study, we evaluated the inhibitory capacity of the IMPPAT phytochemical database (8500 compounds) and the SuperDRUG2 dataset (4000 compounds) in SARS-CoV-2 main protease and helicase Nsp13 through consensus-based docking simulations. Glide and GOLD 5.3 were implemented in the in silico process. Further MM/GBSA calculations of the top 10 inhibitors in each protein were carried out to investigate the binding free energy of the complexes. An analysis of the major ligand-protein interactions was also conducted. After the docking simulations, we acquired 10 prominent phytochemicals and 10 FDAapproved drugs capable of inhibiting Nsp5 and Nsp13. Delphinidin 3,5,3'-triglucoside and hirsutidin 3-O-(6-O-p-coumaroyl)glucoside demonstrated the most favorable binding free energies against Nsp5 and Nsp13, respectively. In conclusion, the analysis of the results identified that the phytochemicals demonstrated enhanced binding capacities compared to the FDA-approved database.


Structural changes induced by antineoplastic therapies: keys to evaluate tumor response to treatment.
The criteria to define therapeutic response in oncology are those proposed by Miller, characterized by four response categories (complete response, partial response, no change, progression of disease), and based upon both measurable and non-measurable (and otherwise assessable) morphological parameters in comparison with baseline and subsequently modified following the Response Evaluation Criteria In Solid Tumors. In addition to these classical morphological criteria, we review the predictive value of structural changes in the evaluation of response to antineoplastic therapies. The goal of the present review is to evaluate in detail structural variations (calcification, fibrosis, differentiation, necrosis, cavitation, vascularization, edema, and pseudocapsule formation) induced by therapy, and to ascertain their significance in terms of biological evolution of the neoplastic process.


The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1'-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer.
3-(1'-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T1 , T2 relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.


Discovery of new biomarkers for malignant mesothelioma.
Malignant mesothelioma is an asbestos-induced, aggressive tumour with limited treatment options and very poor outcome. Currently, there are no tumour biomarkers in widespread clinical use for this disease. Soluble mesothelin is the most intensively investigated mesothelioma biomarker and has been approved by the US FDA primarily as a tool for monitoring patient response and progression. Mesothelin is elevated in the blood and effusions of patients with mesothelioma, and is rarely elevated in people with benign disease with normal renal function. However, the sensitivity of mesothelin limits its use as a stand-alone tool for the screening of the asymptomatic asbestos-exposed population-one of the primary aims of mesothelioma biomarker studies. Thus, there is an intense research effort focused on the identification of new and/or novel biomarkers for mesothelioma. Some of the challenges associated with biomarker discovery in mesothelioma are discussed.


Entheseal involvement in systemic disorders.
The objective of this study is to review the data on entheseal involvement in systemic disorders. A Pubmed search utilizing the indexing terms "enthesis" and "enthesitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. A number of cadaver-based studies, as well as studies using ultrasonography and magnetic resonance imaging, have detailed new distinct aspects of enthesis physiology and pathology in a variety of rheumatic and non-rheumatic systemic disorders. Major progress has been done in characterization of separate components of the enthesis organ, imaging of entheses, elaboration of the role and features of entheseal disease in spondyloarthropathies, juvenile idiopathic arthritis, osteoarthritis, familial Mediterranean fever, hyperuricemia, and other systemic conditions. The knowledge acquired and summarized herein shows that entheses can be affected in various ways in variety of medical disorders with different pathogenesis. Better understanding of the risk factors, mechanisms and natural history of enthesopathies is warranted. The current progress in the understanding of entheseal involvement in systemic disorders represents just the first step in resolving the entheses-related enigmas.


Experience with percutaneous transhepatic fiberoptic choledochoscopy for retained stones in the biliary tract. Report on 15 patients.
Residual choledochal stones in 11 patients and stones in the intrahepatic bile ducts in 5 patients were successfully removed by the use of the fiberoptic choledochoscope (FCH-6T), introduced percutaneously into the intrahepatic biliary tract. The reasons for the use of percutaneous transhepatic extraction were: (1) unsuccessful endoscopic papillotomy; (2) unsuccessful choledochoscopic removal via the T-tube tract; (3) high surgical risk; (4) the presence of percutaneous transhepatic biliary drainage for acute cholangitis and acute pancreatitis. All stones were extracted through the liver or the papilla of Vater after crushing them. All minor complications such as pain, vomiting, or fever resolved without further therapy. Percutaneous transhepatic choledochoscopy proved safe and effective for the removal of retained choledochal stones and was essential for the treatment of stones in the intrahepatic bile ducts.


The efficacy of stretching for prevention of exercise-related injury: a systematic review of the literature.
The objective of this study was to conduct a systematic analysis of the literature to assess the efficacy of stretching for prevention of exercise-related injury. Randomized clinical trials (RCTs) and controlled clinical trials (CCTs) investigating stretching as an injury prevention measure were selected. A computer-aided search of the literature was conducted for relevant articles, followed by assessment of the methods of the studies. The main outcome measures were scores for methodological quality based on four main categories (study population, interventions, measurement of effect, and data presentation and analysis) and main conclusions of authors with regard to stretching. One RCT (25%) and three CCTs (100%) concluded that stretching reduced the incidence of exercise-related injury. Three RCTs (75%) concluded that stretching did not reduce the incidence of exercise-related injury. Only two studies scored more than 50 points (maximum score=100 points) indicating that most of the studies selected were of poor quality. Neither of the two highest scoring RCTs showed positive effects for stretching. Due to the paucity, heterogeneity and poor quality of the available studies no definitive conclusions can be drawn as to the value of stretching for reducing the risk of exercise-related injury.


Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD.
We have previously shown that tiotropium at 18 mug reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. The present study was designed to gain further insight into the duration of improvements. A randomized, double-blind, placebo-controlled, parallel-group study was conducted in 261 COPD patients (mean age, 62.5 +/- 7.4 years [+/- SD]; 189 men and 72 women; mean FEV1, 1.2 +/- 0.4 L [43 +/- 12.7% predicted]). On day 0 (first dose), day 21, and day 42 of treatment, pulmonary function tests were performed before and 1 h 20 min after dosing, followed by a constant work rate cycle ergometry test (75% maximum work capacity) to symptom limitation at 2.25 h after dosing. On day 42, an additional constant work rate cycle ergometry test was performed at 8 h after dosing. Adjusted mean (+/- SE) endurance time (ET) on day 42 was 803 +/- 40 s (tiotropium), vs 568 +/- 42 s (placebo) at 2.25 h after dosing (primary end point; treatment difference, 236 +/- 58 s; p = 0.0001) and 665 +/- 40 s (tiotropium) vs 494 +/- 42 s (placebo) at 8 h after dosing (treatment difference, 171 +/- 58 s; p = 0.0035). Adjusted mean dyspnea intensity at isotime on day 42 was 4.60 +/- 0.16 Borg units (tiotropium), vs 5.65 +/- 0.16 Borg units (placebo) at 2.25 h after dosing (p < 0.001), and 5.54 +/- 0.17 Borg units (tiotropium) vs 6.51 +/- 0.18 Borg units (placebo) at 8 h after dosing (p < 0.001). Adjusted mean pre-exercise inspiratory capacity (IC) on day 42 was 2.41 +/- 0.03 L (tiotropium) vs 2.19 +/- 0.03 L (placebo) at 2.25 h after dosing (p < 0.001), and 2.31 +/- 0.03 L (tiotropium) vs 2.16 +/- 0.03 L (placebo) at 8 h after dosing (p < 0.001). The significant increase in IC with tiotropium compared with placebo was maintained throughout exercise. The present study confirms that tiotropium reduces lung hyperinflation at rest and during exercise, reduces exertional dyspnea, and improves symptom-limited exercise tolerance in COPD patients. Furthermore, this study shows that this improvement is present at 2.25 h and at 8 h after dosing after 6 weeks of treatment.


Bilateral ossifying fibroma affecting the jaws: Literature review, rare case report.
Ossifying fibroma (OF) is a benign lesion could occur in different areas of the body and contain fibers, cells and non-organic materials in non specific amounts. It is growing could be slow or rapid and according to this an array of treatment options must be considered to avoid future complications. In this article, we present a case report of a 40-year-old female patient who visited the dentist with the intention of having a normal check up. Bilateral lesion was observed in the mandible, the patient had no medical history of trauma. The lesion was removed surgically and analyzed histologically and the result was ossifying fibroma in both sides. Ossifying fibroma is a rare tumor to be found in the oral cavity, and the family of fibro-osseous lesions (FOLs) has in general the same pathologic features and differ from each other in clinical view so the definitive diagnosis is based on mixture of all these elements. The treatment is complete surgical excision. 11 cases were discovered and archived since 1968 until now, the distribution of cases is nearly equal in the oral cavity, and the infection of females is higher than males.


Estimation of trochanteric soft tissue thickness from dual-energy X-ray absorptiometry.
Low body mass index is considered to be an important risk factor for fractures in postmenopausal women, in part reflecting its association with lower bone mineral density (BMD). In contrast, obesity is thought to be protective against fracture because of higher BMD and reduced transmitted force of falls as a result of soft tissue padding. Dual-energy X-ray absorptiometry (DXA) is most widely used for the assessment of osteoporosis. We hypothesized that trochanteric soft tissue thickness, as measured directly on whole-body DXA scans, could be estimated using the regional measures of anteroposterior tissue thickness from hip and spine DXA. We identified 376 adult patients who underwent DXA evaluation of the lumbar spine, hip, and whole body at the same visit. The population was randomly divided into 2 equal-sized subgroups, one used to derive prediction equations for trochanteric soft tissue thickness and the other for independent validation. Compared with the actual measurement from the whole-body scans in the validation cohort, the DXA-based estimate gave an unbiased prediction of trochanteric soft tissue thickness (adjusted R² was 0.60 with a standard error of the estimate of 1.35cm), which was significantly better than estimation obtained without DXA information (p < 0.001). Area under the curve discrimination for trochanteric soft tissue thickness in the lowest and highest tertiles was 0.901 (95% confidence interval: 0.849-0.953) and 0.859 (95% confidence interval: 0.805-0.915), respectively. Model-based prediction of trochanteric soft tissue thickness in the lowest and highest tertiles had sensitivities of 78.5% and 91.9% and specificities of 64.4% and 86.8%, respectively. We conclude that regional DXA scans of the spine and hip can be used to estimate the trochanteric soft tissue thickness.


A new marine bacterial laccase with chloride-enhancing, alkaline-dependent activity and dye decolorization ability.
A bacterial laccase gene designated as lac21 was screened from a marine microbial metagenomic library of the South China Sea based on sequence screening strategy. The protein encoded by lac21 shared less than 40% sequence identities with all of the laccases found. Lac21, which was recombinantly expressed in Escherichia coli, showed high activity toward syringaldazine at an optimum pH of 7.5 and temperature of 45°C. Lac21 was stable at pH values ranging from 5.5 to 9.0 and temperatures lower than 40°C. Interestingly, chloride enhanced the laccase activity, with concomitant increase in substrate affinity. Furthermore, Lac21 has high decolorization capability toward azo dyes in the absence of redox mediators, with 80% of Reactive Deep Blue M-2GE (50mg/L) being decolorized by 15U/L enzyme after 24h incubation at 20°C. These unusual properties demonstrate that the new bacterial laccase Lac21 has potentials in specific industrial or environmental applications.


Simple construct evaluation with latent class analysis: An investigation of Facebook addiction and the development of a short form of the Facebook Addiction Test (F-AT).
In psychological research, there is a growing interest in using latent class analysis (LCA) for the investigation of quantitative constructs. The aim of this study is to illustrate how LCA can be applied to gain insights on a construct and to select items during test development. We show the added benefits of LCA beyond factor-analytic methods, namely being able (1) to describe groups of participants that differ in their response patterns, (2) to determine appropriate cutoff values, (3) to evaluate items, and (4) to evaluate the relative importance of correlated factors. As an example, we investigated the construct of Facebook addiction using the Facebook Addiction Test (F-AT), an adapted version of the Internet Addiction Test (I-AT). Applying LCA facilitates the development of new tests and short forms of established tests. We present a short form of the F-AT based on the LCA results and validate the LCA approach and the short F-AT with several external criteria, such as chatting, reading newsfeeds, and posting status updates. Finally, we discuss the benefits of LCA for evaluating quantitative constructs in psychological research.


Fluorescence assay for measuring lipid deposits on contact lens surfaces.
A simple fluorescence assay for estimating the propensity of the contact lens surface towards the uptake of lipids and formation of lipid deposits has been developed. The assay is based on the incubation of the contact lenses with an artificial tear-lipid mixture, staining of the lenses with a fluorescent lipid probe, Nile Red, and subsequent macroscopic imaging of the fluorescent lipid deposits on the contact lens surface with a thermoelectrically cooled charge-coupled device (CCD) camera. The results of the assay show that statistically significant differences in the formation of lipid deposits exist between the surfaces of different contact lens materials.


Laparoscopic treatment of complications from endoscopic retrograde cholangiopancreatography.
Complications after endoscopic retrograde cholangiopancreatography (ERCP) usually are treated endoscopically or by traditional surgical procedure. We present two cases of laparoscopic treatment. Patient l had mechanical jaundice. Ultrasound scan showed a common bile duct (CBD) extended to 11 mm, and ERCP disclosed a stone wedged up in the extrapancreatic part of the CBD. Endoscopic techniques did not help to remove the stone, and finally tore off the Dormia basket, leaving it in the bile ducts. After unsuccessful attempts at its endoscopic evacuation, laparoscopy was performed. A choledochoscope was introduced into the CBD, and the Dormia basket was removed. However, the removal of the stone "ingrown" in the wall of the CBD was not successful, leading to a laparotomy. Patient 2 had cholecysto- and choledocholithiasis. On ERCP, multiple stones filling the CBD were found. Combining ECRP with extracorporeal shock-wave lithotripsy, sphincterotomy, and mechanical lithotripsy did not lead to removal of all the stones, so an endoscopic biliary prosthesis was introduced. During consecutive ERCP, one of the prosthetic ends moved into the head of pancreas. Endoscopic attempts to remove it were unsuccessful, so laparoscopy was performed. During the operation, the CBD was incised, allowing all the remaining stones and the prosthetic device to be removed successfully. It seems that laparoscopic treatment currently may be an alternative to traditional surgery in the treatment of some complications after ERCP.


Early-onset Pseudomonas aeruginosa sepsis and Yersinia enterocolitica neonatal infection: a unique combination in a preterm infant.
The purpose of this communication is to report the occurrence of early-onset Pseudomonas aeruginosa sepsis and Yersinia enterocolitica neonatal infection. This case serves as a reminder of the changing spectrum of neonatal septicaemia.


Evaluation of the Efficacy of Single Anastomosis Sleeve Ileal (SASI) Bypass for Patients with Morbid Obesity: a Multicenter Study.
Single anastomosis sleeve ileal (SASI) bypass is a newly introduced bariatric and metabolic procedure. The present multicenter study aimed to evaluate the efficacy of the SASI bypass in the treatment of patients with morbid obesity and the metabolic syndrome. This is a retrospective, seven-country, multicenter study on patients with morbid obesity who underwent the SASI bypass. Data regarding patients' demographics, body mass index (BMI), percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), and improvement in comorbidities at 12 months postoperatively and postoperative complications were collected. Among 605 patients who underwent the SASI, 54 were excluded and 551 (390; 70.8% female) were included. At 12 months after the SASI, a significant decrease in the BMI was observed (43.2 ± 12.5 to 31.2 ± 9.7 kg/m2; p < 0.0001). The %TWL was 27.4 ± 13.4 and the %EWL was 63.9 ± 29.5. Among the 279 patients with type 2 diabetes mellitus (T2DM), complete remission was recorded in 234 (83.9%) patients and partial improvement in 43 (15.4%) patients. Eighty-six (36.1%) patients with hypertension, 104 (65%) patients with hyperlipidemia, 37 (57.8%) patients with sleep apnea, and 70 (92.1%) patients with GERD achieved remission. Fifty-six (10.1%) complications and 2 (0.3%) mortalities were recorded. Most complications were minor. All patients had 12 months follow-up. The SASI bypass is an effective bariatric and metabolic surgery that achieved satisfactory weight loss and improvement in medical comorbidities, including T2DM, hypertension, sleep apnea, and GERD, with a low complication rate.


Possible anticancer agents: QSAR analogs of glutamamide: synthesis and pharmacological activity of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides.
Based on our earlier QSAR prediction, a series of designed QSAR analogs of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides were synthesized as possible anticancer agents. Inhibitions of tumor cell proliferation of the compounds were tested in tumor cell line IMR-32. Anticancer activities of these compounds were also evaluated on Swiss Albino mice against Ehrlich Ascites Carcinoma (EAC) cells. Tumor weight inhibition and tumor cell inhibition were considered as anticancer activity parameters. QSAR analysis of these compounds was performed on the basis of a set of descriptors like physicochemical, topological, quantum chemical and DRAGON whole molecular descriptors. The study showed that the increase of length of substituent at R(2) position and the increase of dipole moment of the molecule decrease the anticancer activity of these compounds, presence of bromine atom at R(3) position and hydrophilic substitution at R(2) position are advantageous to the activity. Nucleophilic attack at atom number 14 is advantageous and electrophilic attack at atom number 15 is detrimental to anticancer activity. Atom number 2 is important and may be involved in dispersive interactions of the compounds with enzymes. The results offer an opportunity for further tailoring of these analogs for an active member.


Correction to: BRADSHAW: a system for automated molecular design.
The original version of this article unfortunately contained some mistakes in the references.


The shoot is important for high-affinity nitrate uptake in Egeria densa, a submerged vascular plant.
To understand the mechanisms of nitrate uptake by submerged vascular plants, a cDNA for a high-affinity nitrate transporter, NRT2, was isolated from Egeria densa, a submerged monocot. The deduced EdNRT2 protein was similar to the proteins of a conserved NRT2 group in higher plants. Real-time reverse transcription-PCR analysis revealed that after feeding whole plants with 0.2 mM nitrate, the EdNRT2 transcripts were induced in both shoots and roots within 0.5 h, reached the maximum by 1-3 h and then decreased. The EdNRT2 transcript levels in shoots were comparable to those in roots. When nitrate was applied separately to shoots and roots, the EdNRT2 transcripts were induced only in nitrate-treated organs and reached the maximum levels comparable to those in organs when nitrate was applied to whole plants. (15)N-nitrate feeding experiments demonstrated that both shoots and roots are responsible for nitrate uptake and that biomass and (15)N content in shoots was even higher than that in roots. We concluded that EdNRT2 is involved in high-affinity nitrate uptake by shoots and roots of E. densa, that nitrate is taken up independently by shoots and roots and that shoots play an important role in nitrate uptake from aquatic ecosystem.


Evaluation of four protocols for the detection and isolation of thermophilic Campylobacter from different matrices.
To identify the optimal method for detection of thermophilic Campylobacter at various stages in the food chain, three culture-dependent (direct plating, Bolton and Preston enrichment) and one molecular method (qPCR) were compared for three matrices: poultry faeces (n = 38), neck skin (n = 38) and packed fresh meat (n = 38). Direct plating was compared to enrichment with either Bolton broth (ISO 10272:2006-1) or Preston broth, followed by culture on two selective agars: modified charcoal cefoperazone desoxycholate agar (mCCDA) and Campyfood agar (CFA). Direct plating on CFA provided the highest number of positive samples for faeces and neck skin samples. Enrichment of meat samples in Preston followed by plating on mCCDA gave significantly higher number of positives than the recommended ISO method. Real-time qPCR yielded the highest number of positive samples. Direct plating on CFA is optimal for Campylobacter isolation from highly contaminated samples such as faeces or neck skin. When enrichment is required for less-contaminated samples such as poultry meat, Preston broth is the best choice. The maximum of detectable cells predicted by qPCR is a sensitive and powerful evaluation tool. The recommended ISO protocol had the least sensitivity, and application of this method could result in underreporting. We detected a high prevalence of Campylobacter on packed meat to be distributed, which suggests this is still a significant risk for consumers.


The Expanded Impact of Human Papillomavirus Vaccine.
Human papilloma virus (HPV) infection is the most common sexually transmitted infection in the United States. Some infections will result in anogenital warts and anogenital or oropharyngeal cancers. Preventing HPV infection is a public health priority to reduce cancer and HPV-associated complications. Prevention through vaccination is the most cost-effective and lifesaving intervention to decrease the burden of HPV-related cancers and other HPV-associated diseases. It is critical for pediatricians to make a strong recommendation for early and timely vaccination and completion of the 3-dose series. The goal of early vaccination is to immunize before first exposure to HPV virus.


Studies of the life-history and energetics of marine and brackish-water nematodes : II. Production, respiration and food uptake by Monhystera disjuncta.
An energy budget was constructed for the marine nematode Monhystera disjuncta. Respiration was measured with a modified Cartesian diver technique, in which the nematodes were kept in agar inside the diver 'head'. The relationship between respiration and body weight was: R =1.53 W0.75. Body growth was exponential during the juvenile phase, with a growth rate equal to 0.61 d-1. After maturation the growth rate fell to 0.17 d-1. Food uptake was measured in experiments with radiolabeled bacteria. In one series of experiments the accumulation of radiolabel in the nematodes was followed. In a second series the decrease in labeling was followed when pre-labeled nematodes fed on unlabeled bacteria. A model for label uptake permitted the calculation of assimilation efficiency and consumption rates. Consumption rates thus measured, correspond well to those calculated from the growth, reproduction and respiration rates. Assimilation efficiency was low, around 25%. Production efficiency (P/(P+R)) was high: 60% for the population at stable age distribution, and up to 75% for reproducing females. This seems to be a general feature in nematodes.


The measurement of cyclic AMP levels in biological preparations.
The radioreceptor method is sensitive, simple, and specific, requiring little, or no purification of sample prior to analysis. It is possible to process hundreds of samples in a matter of hours (sample throughput may be enhanced through the use of a cell harvester for rapid filtration of bound [3H]cAMP). Assays for endogenous cAMP and cAMP measured using a radioactive precursor give similar results in terms of fold stimulation. The main advantage of the former technique lies in the use of cells or tissues with poor uptake of [3H]adenine.


[Mismatch negativity in schizophrenia research. An indicator of early processing disorders of acoustic information].
Mismatch negativity (MMN) represents an event-related component of the auditory evoked potentials at about 100-250 ms, evoked by discernible changes in an ongoing uniform acoustic stimulation. The current paper reviews all recently published MMN studies in the field of schizophrenia research. A reduced MMN in schizophrenic patients is found in the majority of the studies. This deficit is likely to be related to the disorder, since antipsychotic medication seems to have little influence on these results. Interestingly, a reduced MMN is also found in first-degree relatives of patients. Clear evidence for a hemispheric lateralization of the MMN reduction in schizophrenic patients is lacking. A hypofunction of the N-methyl-D-aspartate (NMDA) receptor is discussed as a possible explanation of this deficit.


Genetic liability to schizophrenia measured by p300 in concordant and discordant monozygotic twins.
Differential effects of genes and environment can contribute to etiological heterogeneity in schizophrenia. Twins concordant and discordant for schizophrenia may differ in genetic predisposition to schizophrenia with concordant twins having a higher genetic liability and discordant twins having a lower genetic liability to schizophrenia. We aimed to investigate whether P300 amplitude (which has been postulated as a genetic marker for schizophrenia) reflected this heterogeneity. We compared P300 amplitudes across 36 monozygotic twin pairs (6 concordant for schizophrenia/schizoaffective disorder, 11 discordant and 19 healthy control pairs) performing an auditory oddball task, using multiple regression (age, gender, birth order, premorbid IQ as covariates). We further looked at the correlation between the Brief Psychiatric Rating Scale (BPRS) and P300 amplitude in affected twins, and compared concordant and discordant affected twins on the Global Assessment Scale (GAS). Multiple regression yielded a highly significant model (p = 0.004) though the explained variance was limited (21%). The main effect of the group on P300 amplitude was significant (p = 0.0001): affected concordant twins showed a significantly lower P300 amplitude as compared to affected discordant (p = 0.005, Cohen's d = 1.08) and control twins (p = 0.000, d = 1.16). Discordant affected and unaffected twins did not differ significantly from each other or from control twins. P300 did not correlate significantly with the BPRS and the affected groups did not differ across the GAS. Our results provide evidence for etiological heterogeneity within schizophrenia pointing to different pathophysiological mechanisms that may underlie more and less genetically determined forms of schizophrenia. They also indicate that P300 correlates with a differing degree of genetic liability to schizophrenia independently of the psychopathological status and even in the presence of similar functional profiles.


Measuring the Efficacy of a Pilot Public Health Intervention for Engaging Communities of Puerto Rico to Rapidly Write Hurricane Protection Plans.
The efficacy is measured for a public health intervention related to community-based planning for population protection measures (PPMs; ie, shelter-in-place and evacuation). This is a mixed (qualitative and quantitative) prospective study of intervention efficacy, measured in terms of usability related to effectiveness, efficiency, satisfaction, and degree of community engagement. Two municipalities in the Commonwealth of Puerto Rico are included. Community members consisting of individuals; traditional leaders; federal, territorial, and municipal emergency managers; municipal mayors; National Guard; territorial departments of education, health, housing, public works, and transportation; health care; police; Emergency Medical Services; faith-based organizations; nongovernmental organizations (NGOs); and the private sector. The intervention included four community convenings: one for risk communication; two for plan-writing; and one tabletop exercise (TTX). This study analyzed data collected from the project work plan; participant rosters; participant surveys; workshop outputs; and focus group interviews. Efficacy was measured in terms of ISO 9241-11, an international standard for usability that includes effectiveness, efficiency, user satisfaction, and "freedom from risk" among users. Degree of engagement was considered an indicator of "freedom from risk," measurable through workshop attendance. Two separate communities drafted and exercised ~60-page-long population protection plans, each within 14.5 hours. Plan-writing workshops completed 100% of plan objectives and activities. Efficiency rates were nearly the same in both communities. Interviews and surveys indicated high degrees of community satisfaction. Engagement was consistent among community members and variable among governmental officials. Frontline communities have successfully demonstrated the ability to understand the environmental health hazards in their own community; rapidly write consensus-based plans for PPMs; participate in an objective-based TTX; and perform these activities in a bi-lingual setting. This intervention appears to be efficacious for public use in the rapid development of community-based PPMs.


Platelet migration inhibition test for platelet antibodies. Parameters and simplified methodology.
A simplified methodology and parameters associated with the performance of a platelet migration inhibition test for the detection of antiplatelet-associated antibodies is described.


Effect of topical unoprostone isopropyl on optic nerve head circulation in controls and in normal-tension glaucoma patients.
To evaluate the effect of unoprostone isopropyl on microcirculation in the optic nerve head (ONH) of controls and patients with normal-tension glaucoma (NTG). Thirty healthy volunteers were randomly placed in a placebo group or a control group. For ten NTG patients, one eye was selected to receive the placebo drops and the contralateral eye received the unoprostone in a masked fashion. In both studies, the intraocular pressure (IOP) and the parameters of the blood hemodynamics of the ONH were obtained before and at 1 and 2 h after the instillation. Blood flow measurements were made with a scanning laser Doppler flowmeter. In both control subjects and NTG patients, the changes in the IOPs after the instillation of either unoprostone or the placebo were not significant because almost all of the NTG patients had IOPs lower than 15 mmHg. Although the hemodynamic parameters were not significantly changed in the placebo-treated eyes of the controls, the eyes of the controls treated with unoprostone had mean blood velocity and flow values that were significantly higher than the baseline values 1 and 2 h after instillation (P < 0.01). The velocity values of the controls treated with unoprostone were significantly higher than in those controls receiving the placebo at 2 h postinstillation (P = 0.027). The values for the three circulation parameters (volume, velocity, flow) were significantly higher than the baseline values after instillation in the eyes of the NTG patients treated with unoprostone (P < 0.05). In contrast, none of these parameters was significantly different from the baseline in the eyes of NTG patients treated with placebo. These results showed that unoprostone significantly increased microcirculation in the ONH in control subjects and in NTG patients without reducing the IOP significantly.


The Otto Aufranc Award. On the etiology of the cam deformity: a cross-sectional pediatric MRI study.
Femoroacetabular impingement (FAI) has been recognized as a common cause of hip pain as well as a cause of hip arthritis, yet despite this, little is known about the etiology of the cam morphology or possible risk factors associated with its development. The purposes of our study were to determine when the cam morphology associated with FAI developed in a cross-sectional cohort study of pediatric patients pre- and postphyseal closure using MRI and whether increased activity level during the period of physeal closure is associated with an increased likelihood that the cam deformity will develop. Alpha angles were measured at the 3 o'clock (anterior head-neck junction) and 1:30 (anterosuperior head-neck junction) positions in both hips with a cam deformity defined as an alpha angle ≥ 50.5° at the 3 o'clock position. Forty-four volunteers (88 hips) were studied: 23 with open physes (12 females, mean age 9.7 years; 11 males, age 11.7 years) and 21 with closed physes (five females, age 15.2 years; 16 males, age 16.2 years). Daily activity level using the validated Habitual Activity Estimation Scale was compared for patients in whom cam morphology did and did not develop. None of the 23 (0%) patients prephyseal closure had cam morphology, whereas three of 21 (14%, p = 0.02; all males) postclosure had at least one hip with cam morphology. Daily activity level was higher (p = 0.02) for patients with the cam morphology (7.1 hours versus 2.9 hours). Mean alpha angles at the 3 o'clock head-neck position were 38° (95% confidence interval [CI], 37.2°-39.1°) in the open physes group and 42° (95% CI, 40.16°-43.90°) in the closed physes group; at the 1:30 head-neck position, they were 45° (95% CI, 44.0°-46.4°) in the open physes group and 50° (47.9°-52.3°) in the closed physes group. The fact that cam morphology was present exclusively in the closed physeal group strongly supports its development during the period of physeal closure with increased activity level as a possible risk factor.


Molecular modeling study on the disassembly of dendrimers designed as potential antichagasic and antileishmanial prodrugs.
A molecular modeling study was carried out to investigate the most likely enzymatic disassembly mechanism of dendrimers that were designed as potential antichagasic and antileishmanial prodrugs. The models contained myo-inositol (core), L-malic acid (spacer), and active agents such as 3-hydroxyflavone, quercetin, and hydroxymethylnitrofurazone (NFOH). A theoretical approach that considered one, two, or three branches has already been performed and reported by our research group; the work described herein focused on four (models A and B), five, or six branches, and considered their physicochemical properties, such as spatial hindrance, electrostatic potential mapping, and the lowest unoccupied molecular orbital energy (E(LUMO)). The findings suggest that the carbonyl group next to the myo-inositol is the most promising ester breaking point.


Clinical characteristics of ocular toxocariasis in Eastern China.
To explore the clinical characteristics of patients with ocular toxocariasis in eastern China. The medical records of 35 cases of ocular toxocariasis in Fudan University Eye & ENT Hospital between May 2009 and April 2011 were retrospectively reviewed and analyzed. UBM, RetCam or fundus imaging, and high-frequency or conventional ultrasonography were performed in these patients. The mean patient age in our series of ocular toxocariasis was 11.86 ± 8.80 years. There were 28 children and seven adults, the majority residing in a rural area (88.57%). All cases were classified into three clinical subtypes: granuloma in the peripheral retina (60% of cases); granuloma in the posterior pole (28.57% of cases); and vitreous inflammation mimicking chronic endophthalmitis (5.71% of cases). We also identified an additional subtype with unique clinical features that we termed "combined type" presenting in 5.71% of our patients. This subtype exhibited granulomas in both the posterior pole and peripheral retina. RetCam fundus imaging was able to identify granulomas in the posterior and peripheral subtypes, 100% and 80.95% of cases respectively. Moreover, UBM combined with conventional ultrasonography identified granulomas in 95% of the peripheral subtype cases and in 100% of the posterior pole subtype cases. This is the first ocular toxocariasis series described in Chinese patients. Compared with reports from developed countries, the ocular features in our series were more severe and complicated, presenting with poorer visual acuity and a high rate of retinal detachment (45.7%). The application of RetCam and UBM during examination in ocular toxocariasis can provide valuable information in determining the severity of disease and features important in considering surgical procedures in such patients.


Exercise studies in patients with transposition of the great arteries after atrial repair operations (Mustard/Senning): a review.
Exercise evaluation studies of patients after atrial repair surgery for transposition of the great arteries, as in tetralogy of Fallot, represent only a small fraction of the 3970 Medline references (1966 to mid-1997) concerning this congenital heart lesion. We have abstracted data from 27 studies from 20 institutions reporting on measurements during exercise on work capacity, heart rate response, respiratory gas exchange, or radionuclide/radiographic systemic ventricular ejection fraction measurements in addition to resting pulmonary function measurements. These studies provide almost uniform general conclusions that even after 20 or more years of follow-up (1) most patients "report" that they are asymptomatic in performing usual levels of physical activities; (2) significant abnormalities are present, often in more than half of the patients studied, in one or more of the exercise measurements when compared to control subjects; and (3) the diminished exercise performance is related to a diminished cardiac output, results from diminished stroke volume but is also related to a blunted heart rate response.


Fractal dimensions of breast lesions on cytology smears.
In the present study, box-counting fractal dimensions of benign and malignant cells of breast tumors on cytology material were measured and compared. We selected fine-needle aspiration cytology smears of 14 cases of histopathology-proven infiltrating duct carcinomas and 7 cases of fibroadenoma of the breast. Five cells were randomly selected from each case. Box-counting fractal dimensions of all cells were measured with the help of an image cytometer (Leica, Cambridge, UK), using Quantimet 600 software (Leica). In total, 70 malignant cells and 35 benign cells were studied. The mean fractal dimensions of malignant cells and benign cells were 0.9571 +/- 0.1265 and 0.8354 +/- 0.1367, respectively. There was significant difference in the fractal dimension of malignant and benign cells (P = 0.006, Mann-Whitney nonparametric test). The measurement of fractal dimension may be helpful in discriminating malignant from benign cells. This may be another discriminating feature of malignant cells, along with classic image morphometry based on Euclidean geometry.


Interactions of platinum complexes, peptides, methionine and dehydrogenases.
Eight platinum-methionine complexes have been investigated as inhibitors of the alcohol (EC 18.104.22.168) and lactate (EC 126.96.36.199) dehydrogenase systems. While only one complex, Pt(Met)Cl2, had two halogen ligands on the platinum, all the complexes were able to inhibit both enzyme systems. Of the various methionine and histidine containing peptides evaluated, the dipeptide Met-Met gave the best protection against inhibition by N-alkyl-substituted ethylenediamine-platinum complexes. The histidine containing peptides gave a slight protection against the inhibition by beta-[Pt(Met)(NH3)Cl]Cl. Thus it appears that in the enzyme systems studied, the methionine acts as a strong ligand for platinum.


Muscle spindle activity following muscle tendon vibration in man.
Muscle spindle primary endings originating from the Tibialis anterior, Extensor Digitorum Longus and Lateral Peroneal muscles were recorded by the microneurographic technique. Their resting activity and stretch sensitivity after muscle tendon vibration (80 Hz, 30 s) were compared with those in the previbratory period. Most of the units (73%) exhibited a decreased spontaneous firing rate whereas a few others either conserved (13.5%) or increased (13.5%) their resting discharge after vibration. A complete recovery necessitated 40 s. The static stretch sensitivity of the units was decreased during the 3 s following vibration exposure and returned to the control level (about 14 s). The results are discussed in the light of previous psychophysiological studies reporting an altered position sense and a development of involuntary muscle contractions in postvibratory periods.