Histiocyte-rich B-cell lymphoma.
This is the second report of histiocyte-rich B-cell lymphoma and the first case analyzed by flow cytometry and cytogenetic study. The immunophenotype determined by flow cytometry was that of a B-cell antigen-positive, surface immunoglobulin-negative B-cell lymphoma with 79% CD11c positive histiocytes. The lymphoid cells were composed of 76% neoplastic B-cells and 24% reactive T-cells. Immunohistochemical staining showed large numbers of histiocytes positive for CD68 and lysozyme in the lymph node and the bone marrow. Neoplastic lymphoid cells were positive for CD20, CD45, CD74 and CDw75. The monoclonality of the tumor cells was established by the evidence of rearrangements of the heavy chain and kappa light chain genes and a complex clonal cytogenetic abnormalities including t(8;14)(q11;q32). The tumor cells were large, pleomorphic lymphoid cells and showed no features resembling those of the L/H cells of Hodgkin's disease as previously reported. The rapidly progressive clinical course in the present case is consistent with the clinical features shown in the original study. The histiocytic component in this tumor is presumably recruited by a lymphokine with the nature of a growth factor from the tumor cells that may also be responsible for the rapid proliferation of the tumor cells and the aggressive clinical course. This entity merits special recognition because it leads to a predictable poor prognosis and because of its potential of being misdiagnosed as true histiocytic lymphoma.


Update: outbreaks of cyclosporiasis -- United States and Canada, 1997.
Since April 1997, CDC has received reports of outbreaks of cyclosporiasis in the United States and Canada (1,2). As of June 11, there have been 21 clusters of cases of cyclosporiasis reported from eight states (California, Florida, Maryland, Nebraska, Nevada, New York, Rhode Island, and Texas) and one province in Canada (Ontario). These clusters were associated with events (e.g., receptions, banquets, or time-place-related exposures [meals in the same restaurant on the same day]) that occurred during March 19-May 25 and comprise approximately 140 laboratory-confirmed and 370 clinically defined cases of cyclosporiasis. In addition, four laboratory-confirmed and approximately 220 clinically defined cases have been reported among persons who, during March 29-April 5, were on a cruise ship that departed from Florida. Approximately 70 laboratory-confirmed sporadic cases (i.e., cases not associated with events, the cruise, or recent overseas travel) have been reported in the United States and Canada. The most recent laboratory-confirmed sporadic case occurred in a person who had onset of symptoms on June 3.


[Language in autistic disorders].
Autism is a developmental disorder affecting social relationships, communication and flexibility of thought. These three basic aspects of autism may present in many different forms and degrees. Therefore autism should be considered to be a spectrum of autistic disorders rather than a single strictly defined condition. The spectrum of autistic disorders extends from intelligent individuals with acceptable social integration, to severely retarded patients with scarcely any social interaction. Language is almost always affected either in its formal aspects or in its usage. Autistic linguistic disorders form a specific language disorder (developmental dysphasia) and a pragmatic disorder linked both to the primary language problem and to the social cognitive deficit. We discuss the different linguistic syndromes observed in autistic patients with special emphasis on the semantic-pragmatic disorder.


Ecosystem Model Skill Assessment. Yes We Can!
Accelerated changes to global ecosystems call for holistic and integrated analyses of past, present and future states under various pressures to adequately understand current and projected future system states. Ecosystem models can inform management of human activities in a complex and changing environment, but are these models reliable? Ensuring that models are reliable for addressing management questions requires evaluating their skill in representing real-world processes and dynamics. Skill has been evaluated for just a limited set of some biophysical models. A range of skill assessment methods have been reviewed but skill assessment of full marine ecosystem models has not yet been attempted. We assessed the skill of the Northeast U.S. (NEUS) Atlantis marine ecosystem model by comparing 10-year model forecasts with observed data. Model forecast performance was compared to that obtained from a 40-year hindcast. Multiple metrics (average absolute error, root mean squared error, modeling efficiency, and Spearman rank correlation), and a suite of time-series (species biomass, fisheries landings, and ecosystem indicators) were used to adequately measure model skill. Overall, the NEUS model performed above average and thus better than expected for the key species that had been the focus of the model tuning. Model forecast skill was comparable to the hindcast skill, showing that model performance does not degenerate in a 10-year forecast mode, an important characteristic for an end-to-end ecosystem model to be useful for strategic management purposes. We identify best-practice approaches for end-to-end ecosystem model skill assessment that would improve both operational use of other ecosystem models and future model development. We show that it is possible to not only assess the skill of a complicated marine ecosystem model, but that it is necessary do so to instill confidence in model results and encourage their use for strategic management. Our methods are applicable to any type of predictive model, and should be considered for use in fields outside ecology (e.g. economics, climate change, and risk assessment).


Phase I dose escalation study of temsirolimus in combination with metformin in patients with advanced/refractory cancers.
Mammalian target of rapamycin (mTOR) inhibitors like temsirolimus may result in undesirable AKT upregulation. Metformin inhibits mTOR through different mechanisms and may enhance temsirolimus's antitumor activity. We conducted an open-label phase I dose escalation trial of this drug combination in patients with advanced/refractory cancers. Temsirolimus, 25 mg weekly, was combined with an escalating daily dose of metformin (level 1: 500; level 2: 1000; level 3: 1500; level 4: 2000 mg) by utilizing a standard 3 + 3 trial design. Treatment was administered in 28-day cycles following initial 2-week metformin titration during the first cycle. Twenty-one patients (median age, 56 years) with sarcoma (n = 8), colorectal (n = 3), endometrial (n = 4), uterine carcinosarcoma (n = 2), ovarian (n = 2), and other (n = 2) cancers were enrolled. Patients had received median of four prior systemic treatments. Two dose-limiting toxicities were observed (grade 3 mucositis, grade 3 renal failure); both patients continued treatment after dose modification. Fifty-six percent patients had stable disease as best response; clinical benefit rate was 22 %. Patients continued treatment for median of 11 weeks. Combination temsirolimus/metformin was well tolerated with modestly promising effectiveness among this heavily pretreated patient cohort. We recommend a dose of temsirolimus 25 mg weekly and metformin 2000 mg daily for phase II study.


Cyanobacterial extracellular antibacterial substances could promote the spread of antibiotic resistance: impacts and reasons.
Many studies have shown that antibiotic resistance genes (ARGs) can be facilitated by a variety of antibacterial substances. Cyanobacteria are photosynthetic bacteria that are widely distributed in the ocean. Some extracellular substances produced by marine cyanobacteria have been found to possess antibacterial activity. However, the impact of these extracellular substances on ARGs is unclear. Therefore, we established groups of seawater microcosms that contained different concentrations (1000, 100, 10, 1, 0.1, 0.01, and 0 μg mL-1) of cyanobacterial extracellular substances (CES), and tracked the changes of 17 types of ARGs, the integron gene (intI1), as well as the bacterial community at different time points. The results showed that CES could enrich most ARGs (15/17) in the initial stage, particularly at low concentrations (10 and 100 μg mL-1). The correlation analysis showed a positive correlation between several ARGs and intI1. It is suggested that the abundance of intI1 increased with CES may contribute to the changes of these ARGs, and co-resistance of CES may be the underlying reason for the similar variation pattern of some ARGs. Moreover, the results of qPCR and high-throughput sequencing of 16S rRNA showed that CES had an inhibitory impact on the growth of bacterial communities. High concentrations of CES were found to alter the structure of bacterial communities. Co-occurrence networks showed that bacteria elevated in the high concentration group of CES and might serve as the potential hosts for a variety of ARGs. In general, marine cyanobacteria could play an important role in the global dissemination of ARGs and antibiotic-resistant bacteria (ARBs).


[Change in the asymmetry of paired functions in pilots during flight].
The flight activity of a pilot brings about peculiar changes in the asymmetry of physiological functions whose pattern depends to a large extent on the initial state of asymmetry. An inflight change in the functional state and the interaction of paired structures of the cerebral hemispheres results in a reduction of the predominance of the leading hand in pilots with distinct asymmetry preflight and in an increase of opposite asymmetric fluctuations in pilots with insignificant asymmetry preflight.


Impact of Immunoglobulin Therapy in Intestinal Transplant Recipients With Posttransplantation Hypogammaglobulinemia.
Severe hypogammaglobulinemia (HGG) (IgG <400 mg/dL) following intestinal transplantation is common. Although IgG replacement therapy is commonly used, clinical outcomes associated with increasing IgG levels to >400 mg/dL are not well described. Kaplan-Meier analysis was performed to estimate survival, the log-rank test to compare survival distributions between groups, and the Fisher exact test to determine the association between HGG and rejection. A total of 23 intestinal transplant (IT) recipients with a median age of 2.3 years (range, 0.7-41 years) at the time of HGG diagnosis were included. The types of transplants were liver-small bowel (73.9%), liver-small bowel-kidney (8.7%), and small bowel only (17.4%). The 3-year survival after the diagnosis of HGG was 50.2% (95% confidence interval [CI] = 28.2%-68.7%). There was no difference in survival (P = .67) when patients were dichotomized based upon IgG level at last follow-up (IgG ≥400 mg/dL, n = 14; and IgG <400 mg/dL, n = 9). There was no also evidence of an association between survival and: total dose (P = .58), frequency (P = .11), and number of IgG doses administered (P = .8). There was no difference in survival between patients receiving (n = 12) or not receiving (n = 11) cytomegalovirus hyperimmunoglobulin (P = .10). Improved survival rates were not found in our IT recipients with severe HGG with immunoglobulin therapy to IgG levels of ≥400 mg/dL, even when cytomegalovirus hyperimmunoglobulin was administered.


Patterns of Use of Smartphone-Based Interventions Among Latina Breast Cancer Survivors: Secondary Analysis of a Pilot Randomized Controlled Trial.
Latina breast cancer survivors experience poorer health-related quality of life (HRQoL), greater symptom burden, and more psychosocial needs compared to non-Latina breast cancer survivors. eHealth platforms such as smartphone apps are increasingly being used to deliver psychosocial interventions to cancer survivors. However, few psychosocial eHealth interventions have been developed specifically for Latina breast cancer survivors. Further, little is known about how Latinas, in general, engage with eHealth interventions and whether specific participant characteristics are associated with app use in this population. We evaluated the use of 2 culturally informed, evidence-based smartphone apps for Latina breast cancer survivors-one that was designed to improve HRQoL and reduce symptom burden (My Guide) and the other to promote healthy lifestyle behaviors (My Health). The objectives of our study were to explore the patterns of use of the My Guide intervention app and My Health attention-control app among Latina breast cancer survivors. Eighty Latina breast cancer survivors were randomized to use the My Guide or My Health app for 6 weeks. Assessments were collected at baseline (T1), immediately after the 6-week intervention (T2), and 2 weeks after T2 (T3). Specific study outcomes included subdomains of HRQoL, symptom burden, cancer-specific distress, cancer-relevant self-efficacy, and breast cancer knowledge. On average, participants used their assigned app for more than 1 hour per week. Sociodemographic or psychological characteristics were not significantly associated with app use, except for employment status in the My Health group. Content related to common physical and emotional symptoms of breast cancer survivors as well as recommendations for nutrition and physical activity were most frequently accessed by My Guide and My Health participants, respectively. Lastly, clinically meaningful improvements were demonstrated in breast cancer well-being among low app users (ie, <60 minutes of use/week) of My Guide and social well-being among high app users (ie, ≥60 minutes of use/week) of My Health. The favorable rates of participant use across both apps suggest that Latina breast cancer survivors are interested in the content delivered across both My Guide and My Health. Furthermore, since sociodemographic variables, excluding employment status, and baseline HRQoL (psychological variable) were not related to app use, My Guide and My Health may be accessible to diverse Latina breast cancer survivors. ClinicalTrials.gov NCT03645005; https://clinicaltrials.gov/ct2/show/NCT03645005.


[Cultivation of monolayer cultures of primary and transplantable animal cells in a device with regulated growth conditions].
Primary, diploid and continuous cell lines were cultivated in the apparatus "Cellotron-1". Rashig's ring was used as an underlay in the apparatus. Fresh medium perfusion, pH control, the medium aeration, temperature control, as well as dissolved oxygen control were exercised in the cultivator. Various cell types have demonstrated a significant increase as compared to the control stationary cultivation: diploid green monkey embryo cells increased 7.5-fold for 5 days, continuous green monkey kidney cells 8-fold for 4 days, primary monkey kidney cells 2-fold for 7 days.


Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor Administration for Adult Stem Cell Transplantation.
The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration-approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34+ cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of ≥2 × 106 CD34+ cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 106 CD34+ cells/kg, the number of apheresis cycles required to achieve ≥2 × 106 CD34+ cells/kg, the median CD34+ cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group (P = .0111). The median number of plerixafor days to reach the collection goal of ≥2 × 106 CD34+ cells/kg was 1 day for each group (P = .323), and the median number of apheresis days to reach the collection goal was 2 days for the standard administration group compared with 1 day for the early administration group (P = .0156). Most adverse events were similar between the 2 groups except for fever, which occurred in 4.8% of the patients in the early administration group and none of the patients in the standard administration group. This study demonstrates plerixafor effectively mobilizes peripheral blood stem cells when given at an early administration time of 16 hours before apheresis compared with standard administration of 11 hours before apheresis. However, further prospective studies could strengthen these results.


[Cross-cultural validated adaptation of dysfunctional voiding symptom score (DVSS) to Japanese language and cognitive linguistics in questionnaire for pediatric patients].
Validated questionnaire for evaluation of pediatric lower urinary tract symptoms (LUTS) is of a great need. We performed cross-cultural validated adaptation of Dysfunctional Voiding Symptom Score (DVSS) to Japanese language, and assessed whether children understand and respond to questionnaire correctly, using cognitive linguistic approach. We translated DVSS into two Japanese versions according to a standard validation methodology: translation, synthesis, back-translation, expert review, and pre-testing. One version was written in adult language for parents, and the other was written in child language for children. Pre-testing was done with 5 to 15-year-old patients visiting us, having normal intelligence. A specialist in cognitive linguistics observed the response by children and parents to DVSS as an interviewer. When a child could not understand a question without adding or paraphrasing the question by the parents, it was defined as 'misidentification'. We performed pretesting with 2 trial versions of DVSS before having the final version. The pre-testing for the first trial version was done for 32 patients (male to female ratio was 19 : 13). The pre-testing for the second trial version was done for 11 patients (male to female ratio was 8 : 3). In DVSS in child language, misidentification was consistently observed for representation of time or frequency. We completed the formal validated translation by amending the problems raised in the pre-testing. The cross-cultural validated adaptation of DVSS to child and adult Japanese was completed. Since temporal perception is not fully developed in children, caution should be taken for using the terms related with time or frequency in the questionnaires for children.


Protein fouling behavior of carbon nanotube/polyethersulfone composite membranes during water filtration.
The protein fouling of membranes can be related to the hydrophobic and electrostatic interactions between proteins and the membrane material; i.e., protein fouling can be reduced by changing the membrane properties. In this study, multi-walled carbon nanotube/polyethersulfone (C/P) composite membranes were prepared via the phase inversion method in order to investigate protein fouling, with bovine serum albumin (BSA) and ovalbumin (OVA) used as the model protein for assessing the protein fouling behavior. The results show that the C/P composite membranes were fouled less compared to the bare polyethersulfone (PES) membrane at 4 h of static protein adsorption at neutral pH. Moreover, the irreversible fouling ratio of the C/P composite membranes was less than the bare PES membrane after 1 h of protein ultrafiltration, and the flux recovery ratio of the C/P composite membranes was higher than the bare PES membrane after 20 min of DI water filtration. Based on these results, C/P composite membranes were shown to have the potential to alleviate the effects of protein fouling, thereby enabling C/P composite membranes to be used for several runs of protein filtration after simple washing with water.


The role of platelet-activating factor in mesangial pathophysiology.
Platelet-activating factor (PAF) is a powerful proinflammatory mediator that displays an exceedingly diverse spectrum of biological effects. Importantly, PAF is shown to participate in a broad range of pathologic conditions. This review focuses on the role that PAF plays specifically in the pathophysiology of the kidney, the organ that is both a source and a target of PAF. Renal mesangial cells are responsible for glomerular PAF generation and, ultimately, are the victims of its excessive production. Mesangial pathology is widely acknowledged to reflect glomerular damage, which culminates in glomerulosclerosis and proteinuria. Therefore, modulation of mesangial cell responses would offer a pathophysiology-based therapeutic approach to prevent glomerular injury. However, the currently available therapeutic modalities do not allow for targeted intervention into these processes. A more profound understanding of the mechanisms that govern PAF metabolism and signaling in mesangial cells is important, because it could facilitate the quest for improved therapies for renal patients on the basis of PAF as a drug target.


Interpersonal Callousness from Childhood to Adolescence: Developmental Trajectories and Early Risk Factors.
Youth with a callous interpersonal style, consistent with features of adult psychopathy (e.g., lack of guilt, deceitful), are at risk for exhibiting severe and protracted antisocial behaviors. However, no studies have examined changes that occur in interpersonal callousness (IC) from childhood to adolescence, and little is known about the influence of early child, social, and contextual factors on trajectories of IC. The current study examined distinct patterns of IC across childhood and adolescence and associations with early risk factors. Participants were an at-risk sample of 503 boys (56% African American) assessed annually from around ages 7-15. Analyses examined child (anger dysregulation, fearfulness), social (peer, family, maltreatment), and contextual (psychosocial adversity) factors associated with teacher-reported IC trajectories across childhood and adolescence. Using latent class growth analysis, five trajectories of IC were identified (early-onset chronic, childhood-limited, adolescent-onset, moderate, low). Approximately 10% of boys followed an early-onset chronic trajectory, and a roughly equal percent of youth followed childhood-limited trajectory (10%) or an adolescent-onset trajectory (12%) of IC across development. Specifically, half of the boys with high IC in childhood did not continue to exhibit significant levels of these features into adolescence, whereas an equal proportion of youth with low IC in childhood demonstrated increasing levels during the transition to adolescence. Boys in the early-onset chronic group were characterized by the most risk factors and were differentiated from those with childhood-limited and adolescent-onset IC only by higher conduct problems, fearlessness, and emotional abuse/neglect. Findings are discussed in terms of developmental models of IC and several avenues for early targeted interventions.


The Third Half: A Pilot Study Using Evidence-Based Psychological Strategies to Promote Well-Being among Doctoral Students.
Over the last few years, various studies have reported decreasing well-being levels among doctoral students, who show a higher risk of suffering from psychological distress than the general population. Accordingly, European policies in higher education encourage well-being promotion programs among doctoral studies to enhance young researchers' well-being. However, programs using evidence-based practices for well-being promotion are not yet generalised in public universities. The present study describes a pilot experience designed to evaluate the efficacy of a well-being program among doctoral candidates of a public European university, the Autonomous University of Barcelona. 25 doctoral students (67% women) participated in a pre-post study consisting of six sessions of 3 h each and structured by the big five criteria coming from evidence-based practices for well-being promotion: outdoor green spaces exposure, physical activity, gamification, mentoring, positive and coaching psychology techniques. Results showed how participants experienced significant increases in several indicators of emotional well-being and decreased psychological distress after the Third Half program. These positive pilot results encourage further research and future replications to assess the impact of this evidence-based psychological program among the academic community. Results also lead the way towards the creation of healthier academic workplaces by implementing cost-effective interventions that improve researchers' psychosocial support and their overall well-being.


Enhancing Time-Frequency Analysis with Zero-Mean Preprocessing.
Side-channel analysis is a critical threat to cryptosystems on the Internet of Things and in relation to embedded devices, and appropriate side-channel countermeasure must be required for physical security. A combined countermeasure approach employing first-order masking and desynchronization simultaneously is a general and cost-efficient approach to counteracting side-channel analysis. With the development of side-channel countermeasures, there are plenty of advanced attacks introduced to defeat such countermeasures. At CARDIS 2013, Belgarric et al. first proposed time-frequency analysis, a promising attack regarding the complexity of computation and memory compared to other attacks, such as conventional second-order side-channel analysis after synchronization. Nevertheless, their time-frequency analysis seems to have lower performance than expected against some datasets protected by combined countermeasures. It is therefore required to study the factors that affect the performance of time-frequency analysis. In this paper, we investigate Belgarric et al.'s time-frequency analysis and conduct a mathematical analysis in regard to the preprocessing of frequency information for second-order side-channel analysis. Based on this analysis, we claim that zero-mean preprocessing enhances the performance of time-frequency analysis. We verify that our analysis is valid through experimental results from two datasets, which are different types of first-order masked Advanced Encryption Standard (AES) software implementations. The experimental results show that time-frequency analysis with zero-mean preprocessing seems to have an enhanced or complementary performance compared to the analysis without preprocessing.


[Treatment of obsessive-compulsive disorder in older patients - case studies].
Five patients aged 64 to 74 years with obsessive-compulsive disorder were treated successfully, one with cognitive behavioural therapy and four with a combination of antidepressants and cognitive behavioural therapy. The current multidisciplinary guidelines on anxiety treatment, which cover the age-range 18 to 65 years, are a good starting point for the treatment of obsessive compulsive disorder in older patients.


Extracting Contextual Semantic from a Concordance Containing Mathematical Definition.
With the increased penetration of screen reading software, effective audio rendering of equations can significantly assist in making many electronic mathematics documents accessible. However, linear syntactic rendering of equations not only creates a considerable cognitive load, even for relatively simple equations, but also becomes crucial in more advanced mathematical subjects where the precise and correct interpretation of symbols is essential. To overcome this challenge, we are working on a procedure to extract contextual semantics for mathematical expressions from the surrounding text. In this paper, we will present one of its modules: the Semantic Extractor. This module aids in extracting semantics from the concordance that contains valid mathematical definitions. This approach enables contextually aware audio rendering of complex mathematical expressions, rather than relying solely on syntactic rendering.


Identification of prognostic gene biomarkers for metastatic skin cancer using data mining.
Skin cancer is a common malignant tumor in China and throughout the world, and the rate of recurrence is considerably high, thus endangering the quality of life and health of patients, and increasing the economic burden and pressure to the families of those afflicted. Due to the limitations of traditional drug treatments, it is difficult to achieve the desired therapeutic effect of complete removal. However, targeted gene therapy may be a novel means of treating skin cancer, as the targeted nature of treatment may improve therapeutic outcomes. However, targeted gene therapy requires physicians to select the appropriate gene, which means suitable genetic biomarkers must be identified from complex genetic data. In the present study, the least absolute shrinkage and selection operator regression analysis method was used with 10-fold cross verification to reduce the dimensions of gene data in patients with skin cancer, and subsequently, 20 gene biomarkers were screened. A prognostic model was constructed using these 20 gene biomarkers, and the validity of the model was assessed using a training set and a verification set, which showed that the model performed well. Finally, gene function analysis of these 20 gene biomarkers was determined. Relevant studies were found to show that the genetic biomarkers identified in this paper may possess value for the follow-up clinical treatment of skin cancer.


[Painful lymphadenopathy after an insect bite-a case report].
Tularemia is a bacterial zoonosis which is commonly transmitted through tick or insect bites or contact with meat of infected animals. We report the case of a 36-year-old man who developed fever, chills, headaches, and a painful, unilateral, inguinal lymphadenopathy with a red-livid skin discoloration after an insect bite on his abdomen. Ulceroglandular tularemia was diagnosed through polymerase chain reaction (PCR) and serology. Treatment with doxycycline for 21 days resulted in an excellent outcome.


A double-blind cross-over trail of Prenazone and aspirin in the management of rheumatoid arthritis.
A double-blind cross-over trial of Prenazone 600 mg and Aspirin 4 g daily was carried out on 20 patients suffering with rheumatoid arthritis. The analgesic and anti-inflammmatory activity was indistinguishable from that of aspirin under the conditions of the trail. Twelve patients expressed a general preference for Prenazone and six for aspirin. Prenazone appeared to be well tolerated and free from serious side-effects. These results suggest that it will be a useful drug in the management of rheumatoid arthritis.


Outcomes of Infants Receiving Palivizumab Prophylaxis for Respiratory Syncytial Virus in Canada and Italy: An International, Prospective Cohort Study.
Respiratory syncytial virus (RSV) infection frequently results in RSV-related hospitalization (RSVH) in young infants. We examined the outcomes of palivizumab recipients within the Canadian Registry (CARESS) and the Torino-Verona Italian Registry over the 2002-2014 RSV seasons. RSVHs were captured during the study seasons. Premature infants who received palivizumab (≤35 completed weeks' gestational age; group1) were compared with infants given palivizumab for underlying disorders regardless of gestational age (group 2). Variables and between-group incidences were analyzed. Risk factors associated with RSVH were assessed by logistic regression. A total of 14,468 palivizumab-exposed infants were enrolled (group 1, n = 9093; group 2, n = 4856; miscellaneous, n = 519). RSVH was significantly more frequent in group 2 (211/4856, 4.34%) versus group 1 infants (216/9093, 2.37% [relative risk 1.93; 95% confidence interval (CI): 1.60-2.33; P < 0.0001]). Infants with neuromuscular disorders (7.88%), airway anomalies (5.95%), bronchopulmonary dysplasia (4.75%) and hemodynamically significant congenital heart disease (4.10%) had the highest RSVH incidences. After multivariable logistic regression, only neuromuscular disease [odds ratio [OR] 4.29; 95% CI: 2.30-8.00; P < 0.01], airway anomalies (OR 3.23; 95% CI: 1.92-5.43; P < 0.01), Down syndrome (OR 2.25; 95% CI: 1.31-3.89; P < 0.01), hemodynamically significant congenital heart disease (OR 2.24; 95% CI: 1.52-3.31; P < 0.001), prematurity ≤28 completed weeks' gestational age (OR 1.82; 95% CI: 1.29-2.58; P < 0.001) and bronchopulmonary dysplasia (OR 1.81; 95% CI: 1.31-2.50; P < 0.001) significantly predicted RSVH. No significant association was detected with the number of doses administered or the time elapsed after the previous dose. RSVH rates are higher in infants given palivizumab for reasons other than prematurity. It is uncertain whether these findings relate to inadequate current palivizumab dosing protocols or to a specific increased RSVH risk inherent in infants with severe underlying comorbidities.


Design of a decision-support architecture for management of remotely monitored patients.
Telehealth is the provision of health services at a distance. Typically, this occurs in unsupervised or remote environments, such as a patient's home. We describe one such telehealth system and the integration of extracted clinical measurement parameters with a decision-support system (DSS). An enterprise application-server framework, combined with a rules engine and statistical analysis tools, is used to analyze the acquired telehealth data, searching for trends and shifts in parameter values, as well as identifying individual measurements that exceed predetermined or adaptive thresholds. An overarching business process engine is used to manage the core DSS knowledge base and coordinate workflow outputs of the DSS. The primary role for such a DSS is to provide an effective means to reduce the data overload and to provide a means of health risk stratification to allow appropriate targeting of clinical resources to best manage the health of the patient. In this way, the system may ultimately influence changes in workflow by targeting scarce clinical resources to patients of most need. A single case study extracted from an initial pilot trial of the system, in patients with chronic obstructive pulmonary disease and chronic heart failure, will be reviewed to illustrate the potential benefit of integrating telehealth and decision support in the management of both acute and chronic disease.


Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists.
Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.


Molecular cloning, over-expression, developmental regulation and immunolocalization of fragminP, a gelsolin-related actin-binding protein from Physarum polycephalum plasmodia.
FragminP is a Ca2+-dependent actin-binding and microfilament regulatory protein of the gelsolin family. We screened a Physarum polycephalum cDNA library with polyclonal fragminP antibodies and isolated a cDNA clone of 1,104 bp encoding 368 amino acids of fragminP, revealing two consensus phosphatidylinositol 4,5 bisphosphate-binding motifs in the central part of the protein. The first methionine is modified by an acetyl group, and three amino acids were missing from the protein coded for by the cDNA clone. Full-length recombinant fragminP was generated by PCR, purified after over-expression from Escherichia coli and displayed identical properties to native Physarum fragminP. Northern blot analysis against RNA, isolated from cultures at various stages of development, indicated that fragminP is absent from amoebae and that expression is initiated at an early stage during apogamic development, in a similar way to that observed for the profilin genes. In situ immunolocalization of fragminP in Physarum microplasmodia revealed that the protein is localized predominantly at the plasma membrane, suggesting a role in the regulation of the subcortical actin meshwork. Our data indicate that we have isolated the plasmodium-specific fragminP cDNA (frgP) and suggest that, in each of its two vegetative cell types, P. polycephalum uses a different fragmin isoform that performs different functions.


Liver damage with non-narcotic analgesics.
Non-narcotic analgesics can produce a variety of hepatic lesions but clinically significant liver damage is uncommon with normal therapeutic use. The pattern of hepatotoxicity caused by the salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen) and the pyrazolones differs but many of these drugs can cause generalised reactions which involve the liver. Depending on the drugs in question, the risks of liver injury may be conditioned by factors such as age, sex, dose and duration of treatment. Hepatotoxicity associated with the use of salicylates and most NSAIDs has been reported most often in females with collagen diseases but this may simply reflect the greater use of these drugs in such patients. Paracetamol-induced liver damage occurs almost exclusively as a result of overdosage. Except for the microvesicular fatty changes in hepatocytes in patients with Reye's syndrome attributed to salicylate, the acute centrilobular necrosis caused by paracetamol in overdosage and the marked cholestasis produced by benoxaprofen, the pathological changes in hepatic reactions to non-narcotic analgesics are rather variable and nonspecific. About 50% of patients given salicylate in full anti-inflammatory dosage develop minor abnormalities of liver function. There is usually a mild to moderate increase in plasma aminotransferase activity with patchy necrosis and degeneration of hepatocytes. These changes are related to plasma salicylate concentration and are usually rapidly reversible. In a small minority of patients, particularly the young, liver damage is more severe and may be associated with liver failure, acidosis, hypoglycaemia and encephalopathy. This picture closely resembles Reye's syndrome. In overdosage, paracetamol can cause acute hepatic necrosis. Without specific treatment, some 8% of adults suffer severe liver damage with plasma aminotransferase activity greater than 1000 U/L and about 1% die with hepatic failure and encephalopathy. The administration of sulfhydryl compounds such as N-acetylcysteine within 8 to 10 hours effectively prevents liver damage and death. Liver damage has been attributed to the therapeutic use of paracetamol. However, in most reports the dose was excessive and many patients were chronic alcoholics (who seem to be at increased risk). In these cases the features were typical of acute overdosage. A consistent and characteristic pattern of hepatotoxicity is evident with relatively few non-steroidal anti-inflammatory and pyrazolone analgesics. A rank order of relative risk cannot be established and the incidence in relation to use is not known.(ABSTRACT TRUNCATED AT 400 WORDS)


Serum thymus and activation-regulated chemokine as disease activity and response biomarker in alopecia areata.
Serum thymus and activation-regulated chemokine/CCL17 (sTARC) is known as a good indicator for atopic dermatitis severity. Herein, we investigate whether sTARC correlates with severity and therapeutic response for alopecia areata (AA) in our 121 patients. The sTARC mean of AA totalis and universalis was significantly higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity-controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 ± 400.0 pg/mL) was significantly higher than that of the patchy type (344.0 ± 239.8 pg/mL), suggesting a potential role of TARC in active progression of diffuse AA. Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy. Then, we tested whether sTARC can predict prognosis after the pulse therapy and found that baseline sTARC in the poor responders (1025.5 ± 484.8 pg/mL) was significantly higher than that in the good responders (complete remission at 24 months after the pulse therapy, 347.8 ± 135.7 pg/mL), indicating sTARC as a response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally, to investigate TARC production in the affected hair follicles, we performed immunohistochemical double staining of TARC and CD68 using scalp skin specimens of diffuse AA with high titers of sTARC. The results showed their co-localization in the infiltrating cells around the AA hair follicles, suggesting that TARC is mainly produced from CD68(+) histiocytes. In conclusion, sTARC is a disease activity and response biomarker in AA, providing new insight beyond the T-helper 1/2 paradigm to solve the immunological pathogenesis of AA.


Impact of screening and antiretroviral therapy on anal cancer incidence in HIV-positive MSM.
The incidence of anal cancer is high in HIV-positive MSM. We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland. Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study and literature data. We assumed all men to be human papillomavirus infected. CD4 cell count trajectories were the main predictors of anal cancer. From 2016 we modeled cART coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the following four screening strategies: no screening, yearly anal cytology (Papanicolaou smears), yearly anoscopy and targeted anoscopy 5 years after CD4 count dropped below 200 cells/μl. Median nadir CD4 cell count of 6411 MSM increased from 229 cells/μl during 1980-1989 to 394 cells/μl during 2010-2015; cART coverage increased from 0 to 83.4%. Modeled anal cancer incidence peaked at 81.7/100 000 in 2009, plateaued 2010-2015 and will decrease to 58.7 by 2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly cytology, incidence declined to 38.2/100 000 by 2030, with yearly anoscopy to 32.8 and with CD4 cell count guided anoscopy to 51.3. The numbers needed to screen over 15 years to prevent one anal cancer case were 384 for yearly cytology, 313 for yearly anoscopy and 242 for CD4 cell count-dependent screening. Yearly screening of HIV-positive MSM may reduce anal cancer incidence substantially, with a number needed to screen that is comparable with other screening interventions to prevent cancer.


Acute Cerebellitis or Postinfectious Cerebellar Ataxia? Clinical and Imaging Features in Acute Cerebellitis.
Acute cerebellitis is a rare condition often considered within the group of acute postinfectious cerebellar ataxia despite its distinctive clinical and imaging features. We retrieved clinical, laboratory, and follow-up data of 15 children diagnosed with acute cerebellitis in our department between 2011 and 2019. There were 10 boys and 5 girls aged 3-15 years, median 9.5 years. The most common first symptoms were ataxia, vomiting, and headache. Magnetic resonance imaging (MRI) generally showed bilateral symmetrical T2 hyperintense changes with moderate swelling in the cerebellar cortex. Tonsillar herniation was present in 73.3% and obstructive hydrocephalus in 26.6%. Etiologic workup for infectious pathogens revealed Mycoplasma pneumoniae, influenza A virus, cytomegalovirus, and varicella zoster virus in 1 case each. Fourteen of 15 patients were treated with intravenous and/or oral steroids and 8 cases with intravenous immunoglobulin. No patient required surgical decompression. Neurologic examination median 12 months later revealed ataxia and dysmetria in 4 cases (27%), accompanied by memory difficulties, dysarthria or tremor. Follow-up magnetic resonance imaging (MRI; n = 12) showed diffuse cerebellar cortical T2-hyperintense signal changes in 11 cases and cerebellar atrophy in 9. The diagnosis of acute cerebellitis rather than acute postinfectious cerebellar ataxia should be considered when headache and vomiting accompany ataxia in a child. Acute cerebellitis heals with sequelae in about one-third of cases. The absence of fatalities in our series suggests early diagnosis, and steroid treatment can increase the chance of recovery. MRI results were not found to be predictive of outcome.


Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats.
This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans.


DNA content, mitotic activity, and incorporation of tritiated thymidine in the developing inner ear of the rat.
The rat inner ear is ectodermally derived from a region adjacent to the developing hindbrain. Beginning on day 8 of a 22-day gestational period, This zone of ectoderm first forms the otic placode, then the otocyst, and ultimately the definitive membranous labyrinth. This report provides an estimation of total DNA content of the developing inner ear, and hence an estimation of the total number of cells that comprise the inner ear at each developmental stage. The incorporation of 3H-thymidine indicates that most cells of the inner ear undergo DNA synthetic activity during gestational days 13 to 15. Radioautographic observations indicate a zone of DNA synthetic activity at the base of the outpocketing cochlear duct during early development. At the later stages of development, DNA synthesis is restricted to the cristae ampullares of the semicircular canals and the maculae of the utricle and the saccule. In contradistinction to the findings of other investigators, the statoacoustic ganglion complex undergoes terminal mitosis during gestational days 17 and 18. The gestational period between days 13 and 15 may prove to be a critical stage in normal otic development. The normal values of total DNA content and the number of cells that comprise the inner ear during development, established by these methods, can be compared with pathologic inner ears to provide quantitative means of assessing the damage in malformed inner ears. These values also form the baseline for future experimental studies of inner ear development.


Cesarean scar pregnancy - a new challenge for obstetricians.
Diagnosis and treatment of ectopic cesarean scar pregnancy has become a challenge for contemporary obstetrics. With an increase in the number of pregnancies concluded with a cesarean section and with the development of transvaginal ultrasonography, the frequency of cesarean scar pregnancy diagnoses has increased as well. The aim of the study is to evaluate various diagnostic methods (ultrasonography in particular) and analyze effective treatment methods for cesarean scar pregnancy. An ultrasound scan, Doppler examination and magnetic resonance imaging are all useful in early detection of asymptomatic cesarean scar pregnancy, thus enabling effective treatment and preservation of fertility. Dilatation and curettage is not recommended as it carries significant risk of bleeding and very high risk of hysterectomy and fertility loss. Systemic methotrexate treatment should not be applied on the routine basis due to its low efficacy, high risk of fertility loss and adverse effects. Local methotrexate therapy (under ultrasound or hysteroscopy guidance) should be considered a perfect management method as it offers fertility preservation in asymptomatic pregnant patients without concomitant hemodynamic disorders. Synchronous usage of several treatment methods is an effective way to manage cesarean scar pregnancy. The combination of local methotrexate with simultaneous aspiration of gestational tissues under ultrasound or hysteroscopy guidance seems optimal. Subsequently, the remaining gestational tissues can be removed hysteroscopically in combination with vascular coagulation at the implantation site. In more advanced cases, local methotrexate treatment should be considered followed by laparoscopic or laparotomic wedge resection with subsequent surgical correction of the cesarean section scar.


Enzyme activity of extracellular protein induced in Trichoderma asperellum and T. longibrachiatum by substrates based on Agaricus bisporus and Phymatotrichopsis omnivora.
Antagonistic Trichoderma spp. are used throughout the world for the biological control of soil-borne plant diseases. This approach has stimulated an on-going search for more efficient mycoparasitic strains with a high potential for producing extracellular lytic enzymes. This study compares the production of lytic enzymes by native strains of Trichoderma asperellum and Trichoderma longibrachiatum on substrates of differing complexity. The quantity of protein induced by Agaricus bisporus-based medium was higher than that induced by Phymatotrichopsis omnivora-based medium. In P. omnivora medium, T. asperellum exhibited higher chitinolytic and β-1,3-glucanolytic activities than T. longibrachiatum. The enzyme profile was related to the previously reported ability of these strains to inhibit the growth of several soil-borne plant pathogens. NAGase production was similar among the tested indigenous strains of T. longibrachiatum; T479 and T359 produced more endochitinase, T479 produced more glucanase, and T341 and T359 produced more β-1,3-glucanase. The detected variations in glucanase and β-1,3-glucanase activities suggest that the production of these enzymes is strongly influenced by the substrate. Strains T397 and T359 exhibited xylanase activity, which triggers defence mechanisms in plants. Thus, these strains may utilise an additional mechanism of biocontrol.


Why are there no FDA-approved treatments for female sexual dysfunction?
After many years of research, female sexual dysfunction (FSD) is still an unmet clinical need because no FDA-approved treatments are available for women. The bio-psychosocial model is essential to understand whether a candidate drug induces a meaningful effect over placebo on sexual symptoms with a significant impact on women's quality of life and partnership. Vasoactive agents, hormone therapy and psychoactive drugs have been investigated. Randomized placebo-controlled trials showing efficacy and safety, however, did not convince the FDA to approve either transdermal testosterone patch in postmenopausal women or the serotoninergic agent flibanserin in premenopausal women, for the treatment of hypoactive sexual desire disorder. The process of balancing efficacy and safety of a chronic treatment for a non-life threatening condition, such as FSD, is very difficult in women of any age, but there is some hope that the gender gap in sexual medicine will soon come to an end. Insightful research centered on women's needs and expectations and the availability of novel compounds, tested according to the new DSM-5 diagnostic criteria, will finally lead medical regulatory agencies to approve an effective and safe pharmacotherapy for FSD.


Differences in the corono-apical location of sinus tracts and buccal cortical bone defects between vertically root-fractured and non-root-fractured teeth based on periradicular microsurgery.
This retrospective study aimed to investigate whether the corono-apical location of sinus tracts differs according to the presence/location of vertical root fracture (VRF) in microsurgically treated root-filled teeth. The cases included were (1) anterior and premolar teeth without a preoperative diagnosis of VRF, (2) those with a periodontal probing depth of ≤3 mm, and (3) those for which preoperative cone-beam computed tomography (CBCT) scans and intraoperative video records were available. VRF was diagnosed intraoperatively. The locations of buccal cortical bone defects and fracture lines were categorized on video images, and the corono-apical sinus tract locations were determined by superimposing video images onto volume-rendered CBCT images. Eleven of the 78 teeth investigated had VRF, and there was no significant difference in the incidence of sinus tracts between vertically fractured and non-fractured teeth (Mann-Whitney U-test, P > 0.05). The location of the sinus tract was significantly more coronal in vertically fractured than in non-fractured teeth (Mann-Whitney U-test, P < 0.0001). The location of sinus tracts was high correlated with cortical bone defects (Spearman's correlation, P < 0.0001). In microsurgically treated anterior and premolar teeth with a normal probing depth, sinus tracts were located more coronally in vertically fractured than in non-fractured teeth, and were highly correlated with the location of cortical bone defects.


EcoDiet: A hierarchical Bayesian model to combine stomach, biotracer, and literature data into diet matrix estimation.
Although quantifying trophic interactions is a critical path to understanding and forecasting ecosystem functioning, fitting trophic models to field data remains challenging. It requires flexible statistical tools to combine different sources of information from the literature and fieldwork samples. We present EcoDiet, a hierarchical Bayesian modeling framework to simultaneously estimate food-web topology and diet composition of all consumers in the food web, by combining (1) a priori knowledge from the literature on both food-web topology and diet proportions; (2) stomach content analyses, with frequencies of prey occurrence used as the primary source of data to update the prior knowledge on the topological food-web structure; (3) and biotracers data through a mixing model (MM). Inferences are derived in a Bayesian probabilistic rationale that provides a formal way to incorporate prior information and quantifies uncertainty around both the topological structure of the food web and the dietary proportions. EcoDiet was implemented as an open-source R package, providing a user-friendly interface to execute the model, as well as examples and guidelines to familiarize with its use. We used simulated data to demonstrate the benefits of EcoDiet and how the framework can improve inferences on diet matrix by comparison with classical network MM. We applied EcoDiet to the Celtic Sea ecosystem, and showed how combining multiple data types within an integrated approach provides a more robust and holistic picture of the food-web topology and diet matrices than the literature or classical MM approach alone. EcoDiet has the potential to become a reference method for building diet matrices as a preliminary step of ecosystem modeling and to improve our understanding of prey-predator interactions.


Role of power Doppler sonography in evaluation of therapeutic response of the knee in juvenile rheumatoid arthritis.
The objective is to study the role of power Doppler sonography (PDS) in assessment of therapeutic response in juvenile rheumatoid arthritis (JRA) of knee joint. Thirty patients (age range 3-11 years) of JRA with knee joint involvement were selected for this study. Clinical assessment and ultrasound was done on the same day and repeated at the end of second and sixth month of therapy. All patients received naproxen (15-20 mg/kg/day) for a period of 6 months. Total clinical score (TCS) was calculated as sum of scores of pain, articular swelling and functional impairment. PDS was performed and degree of vascularity was assessed and graded. Total USG score was obtained by adding sum of scores of synovial effusion, synovial thickening and PDS. Results were compared between the total clinical score and the total ultrasound score and between clinical groups at baseline, end of second month and end of sixth month. There were statistically significant differences between clinical and ultrasound indices and confirmed that PDS is more sensitive in detection and follow-up of clinically silent cases of JRA. PDS holds great promise for detection of active synovial inflammatory disease in sub-clinical cases of JRA and is useful in objective assessment of therapeutic response.


Recombination of selectable marker DNA in Nicotiana tabacum.
A chimeric neomycin phosphotransferase II (NPT II) gene, which normally provides kanamycin resistance to transformed plant cells, was inactivated by in vitro deletions. Repair plasmids not containing plant-specific transcription signals but containing only the NPT II coding region (or parts of it) were used in co-transformation experiments involving direct DNA uptake into protoplasts isolated from Nicotiana tabacum. Recombination, or gene conversion mediated by homologous sequences produced active NPT II genes in about 1% of transformants, rendering these cells resistant to kanamycin. Analysis of the size of the active enzyme indicated that recombination had occurred producing an NPT II gene indistinguishable from the wild-type gene. Southern blot analysis revealed that the bulk of co-transformed donor plasmid DNA had suffered structural modifications; however, kanamycin resistance was inherited in a Mendelian fashion, indicating that at least one functional and structurally intact copy of the regenerated NPT II gene is integrated into the host genome.


Effects of chronic administration of delta-9-tetrahydrocannabinol on early embryogenesis of the mouse.
The effects of chronic administration of delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marihuana, on embryogenesis were investigated in the mouse treated with THC prior to sexual maturation. The study was designed to imitate the prolonged abuse of marihuana by sexually immature and adolescent girls. Female Swiss-Webster mice were injected, intraperitoneally, with THC 5 mg/kg per day or with the vehicle for 21 consecutive days, starting on the 30th day of life, which is prior to their sexual maturation. The dose of THC was approximately equivalent to that absorbed by a man smoking 1 to 2 marihuana cigarettes per day. Superovulation was then induced, and the mice were mated with untreated males. Ova were recovered from the oviducts just prior to the first cleavage division, and at about the time of the second cleavage division. The incidence of degenerative ova increased from 13.6% in the controls to 19.1% in the THC-treated group (P less than 0.001) at the time of the second cleavage division, but there was no difference in the incidence of morphologically abnormal ova between the two groups just prior to the first cleavage division. The rate of successful completion of the first cleavage division, but not the second cleavage division, was adversely affected by THC, resulting in accumulation of morphologically abnormal ova at the later stage. In view of the known disruptive effect of THC on the process of cell division, it was postulated that THC might have adversely affected meiosis, leading to the inability of the ova to undergo the first cleavage division.


Nomograms for calculation of oxygen consumption and respiratory exchange ratio.
Nomograms have been prepared whereby the respiratory exchange ratio may be derived from the concentrations of carbon dioxide and oxygen in expired gas and oxygen consumption from the volume and oxygen concentration of expired gas; they apply only to patients breathing room air. The nomogram for the respiratory exchange ratio has an error of less than 0.01, which is the limit of visual discrimination on the nomogram. The nomogram for oxygen consumption has an error of standard deviation 7.73 ml/min. This error may be substantially reduced by excluding cases with a respiratory exchange ratio outside the range 0.70-0.93. Under these conditions the maximum error was 10 ml/min, which is acceptable for a wide range of clinical purposes.


A clinician's expectation of the radiologist.
This personal viewpoint emphasizes the importance of establishing a dialogue between the clinician and the radiologist. Such a dialogue must be characterized by specificity and objectivity, and should foster a critical appraisal of attempts to solve our patients' problems.


Fine-needle aspiration biopsy of canine mammary gland tumours: a comparison between cytology and histopathology.
In the current study, a total of 90 mammary neoplasms obtained from 55 female dogs were used to determine the accuracy of fine-needle aspiration cytology in the diagnosis of canine mammary tumours and to investigate the feasibility of this technique for the differentiation of simple tumours from complex or mixed tumours. Three aspirations were performed on each mammary gland mass using a 22-gauge needle attached to a 5-ml syringe before the mammary glands were surgically excised and submitted for histopathological examination. Twenty-five (27.7%) of 90 samples were classified as insufficient/inadequate for diagnosis. Of the remaining 65 samples, six (9.2%) were benign, 51 (78.5%) were malignant tumours and 8 (12.3%) were suspicious. Histopathological examination of the 90 specimens revealed five (5.6%) benign, 84 (93.3%) malignant and one (1.1%) non-neoplastic lesion. The diagnostic accuracy, sensitivity and specificity of cytologic examination for diagnosing malignancy were 96.5%, 96.2% and 100%, respectively. However, when inadequate (n = 25) and suspicious (n = 8) samples were included, the diagnostic accuracy and sensitivity decreased to 63.3% and 60.7%, respectively, but no change was observed in the specificity. Furthermore, it was not possible to differentiate simple tumours from complex and mixed tumours because spindle cells were seen in both 28% of the simple tumours and 39.3% of the complex or mix tumours. In conclusion, we believe that fine-needle aspiration cytology of canine mammary tumours is a valuable diagnostic tool, although our results indicated lower accuracy when inadequate samples were taken into consideration.


Effect and interaction between wheat bran and zinc oxide on productive performance and intestinal health in post-weaning piglets.
The inclusion of fibre has been studied as an alternative to antimicrobials in weaning pig diets, while ZnO is used as an effective method to prevent post-weaning diarrhoea. However, it has not been investigated to what extent these two strategies interact with each other. The present study was designed to evaluate the effects of including wheat bran (WB) and ZnO alone or combined in the diet of early-weaning pigs on productive performance and microbial activity in the gastrointestinal tract (trial 1). A total of sixty-four piglets were distributed in a 2 × 2 factorial combination of two levels of WB (0 v. 40 g/kg) and ZnO (0 v. 3 g/kg) in the diet. The inclusion of ZnO in the diet improved the feed intake and growth of the animals and reduced the incidence of diarrhoea. The inclusion of WB increased SCFA concentrations and decreased Escherichia coli counts. However, simultaneous incorporation of WB and ZnO increased E. coli counts. Two in vitro trials were also designed to clarify hypotheses derived from the in vivo test: (1) the ability of WB and other fibre sources to bind E. coli in vitro (trial 2) and (2) the in vitro interactions between WB and ZnO with respect to E. coli growth (trial 3). We can conclude that incorporation of WB in the diet improved gut health by modulating the activity and composition of the microbial population. The negative interaction between WB and ZnO raises the interest of considering the inclusion of phytase enzymes to reduce the therapeutic levels of ZnO in post-weaning diets.


Animal lipocalin allergens.
Lipocalins represent the most important group of inhalant animal allergens. For some of them, three-dimensional protein structures have been resolved, but their functions are still elusive. Lipocalins generally display a low sequence identity between family members. The characterization of new lipocalin allergens has revealed however that some of them display a high sequence identity to lipocalins from another species. They constitute a new group of potentially cross-reactive molecules which, in addition to serum albumins, may contribute to allergic cross-reactions between animal dander of different species. However, the clinical relevance of cross-reactivity needs to be assessed. Further studies are needed to understand which of these animal lipocalins are the primary allergens and which are cross-reacting molecules. The use of single, well characterized allergens for diagnosis will allow the identification of the sensitizing animal, which is a prerequisite for specific immunotherapy.


Noise-bound method for detecting shadow-free scene changes in image sequences.
Many image processing applications are confounded by both sensor noise and cast shadows. All image sensors add noise to a captured image that can reduce algorithm sensitivity and performance, and global filters or fixed thresholds are often applied to limit their effects. Cast shadows can appear as scene changes and are difficult to adequately detect and remove from images and image sequences. We couple image-noise statistics with a dual-illumination shadow-detection algorithm to provide a novel color-based method for shadow-free scene-change detection whose performance is bound by metamerism and image noise, and has only one variable--the desired confidence interval for noise separation.


The role of ambulatory monitoring in postinfarction patients.
Ventricular premature contractions noted at the time of hospital discharge following myocardial infarction identify a population of patients at risk for late, sudden cardiac death. Patients with PVC's who are at exceptionally high risk can be identified by means of certain clinical and arrhythmic characteristics. Late ambulatory monitoring is the most effective single technique for identifying such individuals and for monitoring their response to anti-arrhythmic medication.


Differences in time to patient access to innovative cancer medicines in six European countries.
Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: -0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.


Evaluation of prescription pattern of analgesic use among ambulatory elderly in South-Western Nigeria.
Inappropriate prescribing of analgesics has a global impact on the health of elderly patients and the society. Empirical evidence on the prescription of analgesics among elderly Nigerians is scarce. The objective of the study was to evaluate the prescription pattern of analgesics and describe the co-prescribing of gastroprotective agents with non-steroidal anti-inflammatory drugs (NSAIDs) among elderly patients at the geriatric center, University College Hospital, Ibadan. A retrospective cross-sectional, hospital-based study was carried out among elderly patients (≥60 years) who were prescribed analgesics. Using a data extraction sheet, information on demographic characteristics, drug utilization pattern, and morbidities was obtained from patients' case files via electronic health records. A total of 337 patients case files were reviewed, the mean age was 72 ± 8.8 years, and 210 (62.3%) were females. There were a total of 2074 medications prescribed, with 733 (35.3%) being analgesics. Majority of the elderly patients (259, 76.9%) were on nonopioids, with 252 (74.8%) on NSAIDs. Paracetamol was the most commonly prescribed analgesics (181, 24.6%), followed by diclofenac/misoprostol (177, 24.1%), opioid analgesic prescribed was 88 (12.0%), with paracetamol/codeine 58 (65.9%), and tramadol 16 (18.2%) being the most prescribed opioid. A significant proportion of the hypertensive elderly patients (160, 78.8%; P < 0.036) were on NSAIDs. The oral route of administration (302, 89.6%) was the most common route of administration. Majority (310, 92%) of elderly patients taking NSAIDs had a co-prescription for gastroprotective agents. Majority of hypertensive patients were on NSAIDs. This calls for prompt awareness of rational analgesic use among the elderly to improve management and their survival.


[Applications of the Fragment Molecular Orbital Method in Drug Discovery].
Recently, ab initio quantum mechanical calculations have been applied to large molecules, including biomolecular systems. The fragment molecular orbital (FMO) method is one of the most efficient approaches for the quantum mechanical investigation of such molecules. In the FMO method, dividing a target molecule into small fragments reduces computational effort. The clear definition of inter-fragment interaction energy (IFIE) as an expression of total energy is another valuable feature of the FMO method because it provides the ability to analyze interactions in biomolecules. Thus, the FMO method is expected to be useful for drug discovery. This study demonstrates applications of the FMO method related to drug discovery. First, IFIE, according to FMO calculations, was used in the optimization of drug candidates for the development of anti-prion compounds. The second example involved interaction analysis of the human immunodeficiency virus type 1 (HIV-1) protease and a drug compound that used a novel analytical method for dispersion interaction, i.e., fragment interaction analysis based on LMP2 (FILM).


Comparison of headspace techniques for sampling volatile natural products in a dynamic system.
Commonly used dynamic sorption techniques for collecting biologically active volatile compounds have been compared. Solid phase microextraction (SPME) using two types of fibers (polydimethylsiloxane, PDMS, 100 microm, and carbowax/divinylbenzene, CW/DVB, 65 microm) was compared to purge and trap methods (Porapak Q, Tenax TA and charcoal) and a technique based on absorption in methanol in a cooling bath. Sampling was done in a stream of purified air (20 ml/min) in a closed and temperature-regulated (27 degrees C) glass tube, passing over a capillary tube containing a hexane solution of tridecane, heptadecane, 1-octen-3-ol, 1-hexadecanol, ethyl tetradecanoate, alpha-pinene, linalool, terpinen-4-ol, cis-verbenol, verbenone, beta-caryophyllene, E,E-farnesol, and geranylgeraniol. With all of the methods, the sampling was performed for a period of 30 min before extraction and analysis was done on a GC-FID system. In general, SPME gave a higher response for all compounds except for alpha-pinene, which was only extracted by the CW/DVB fiber. Purge and trap methods and methanol absorption gave the same response for all substances extracted. None of the methods extracted hexadecanol and geranylgeraniol under the conditions used. However, the SPME equipped with the PDMS coating extracted heptadecane, E,E-farnesol and ethyl tetradecanoate. Our results show that SPME, when selecting the fibers to fit the polarity and volatility of the compounds, is an outstanding extraction method compared to purge and trap and methanol absorption, especially for a qualitative analysis. The best conditions for storing fibers exposed to compounds of high volatility were at low temperatures (6 degrees C) in sealed vials, while the worst way was to leave the exposed fiber unprotected at room temperature (22 degrees C). The dynamic sampling system was effectively tested on a fruiting body of a polypore fungus (Ganoderma applanatum) emitting 1-octen-3-ol, and again SPME showed to be the most sensitive technique.


Acceptability of child adoption as management option for infertility in Nigeria: evidence from focus group discussions.
Infertility remains a global health challenge with devastating psycho-social consequences in many African communities. Adoption that may serve as an alternative strategy for the affected couples is not widely practiced. This study was conceptualized to assess the acceptability of child adoption as a management option by Nigerians. Twelve focus group discussions were held involving three communities stratified into inner core, transitory and peripheral, within Ibadan metropolis, South-Western Nigeria from May to July 2008. The participants were purposively selected based on gender and age group. The barriers mentioned were cultural practices, stigmatization, financial implications, and procedural bottle-necks. Measures suggested to curb these negative attitudes were advocacy, community mobilization and enactment of supportive law that will protect all parties involved.


Development and validation of an intervention package to improve lifejacket wear for drowning prevention among occupational boaters on Lake Albert, Uganda.
Occupational drowning is a growing public health concern globally. The human cost of fishing is highest in sub-Saharan Africa. Although lifejackets prevent drowning, the majority of boaters in Uganda do not wear them. We developed and validated a peer-to-peer training manual to improve lifejacket wear among occupational boaters on Lake Albert, Uganda. The intervention was developed in three stages. In stage one, we conducted baseline studies to explore and identify aspects of practices that need to change. In stage two, we held a stakeholder workshop to identify relevant interventions following the intervention functions of the behaviour change wheel (BCW). In stage three, we developed the content and identified its implementation strategies. We validated the intervention package using the Content Validity Index for each item (I-CVI) and scale (S-CVI/Ave). Seven interventions were identified and proposed by stakeholders. Training and sensitisation by peers were unanimously preferred. The lowest I-CVI for the content was 86%, with an S-CVI/Ave of 98%. This indicates that the intervention package was highly relevant to the target community. The stakeholder workshop enabled a participatory approach to identify the most appropriate intervention. All the proposed interventions fell under one of the intervention functions of the BCW. The intervention should be evaluated for its effectiveness in improving lifejacket wear among occupational boaters.


Reducing the genetic redundancy of Arabidopsis PHOSPHATE TRANSPORTER1 transporters to study phosphate uptake and signaling.
Arabidopsis (Arabidopsis thaliana) absorbs inorganic phosphate (Pi) from the soil through an active transport process mediated by the nine members of the PHOSPHATE TRANSPORTER1 (PHT1) family. These proteins share a high level of similarity (greater than 61%), with overlapping expression patterns. The resulting genetic and functional redundancy prevents the analysis of their specific roles. To overcome this difficulty, our approach combined several mutations with gene silencing to inactivate multiple members of the PHT1 family, including a cluster of genes localized on chromosome 5 (PHT1;1, PHT1;2, and PHT1;3). Physiological analyses of these lines established that these three genes, along with PHT1;4, are the main contributors to Pi uptake. Furthermore, PHT1;1 plays an important role in translocation from roots to leaves in high phosphate conditions. These genetic tools also revealed that some PHT1 transporters likely exhibit a dual affinity for phosphate, suggesting that their activity is posttranslationally controlled. These lines display significant phosphate deficiency-related phenotypes (e.g. biomass and yield) due to a massive (80%-96%) reduction in phosphate uptake activities. These defects limited the amount of internal Pi pool, inducing compensatory mechanisms triggered by the systemic Pi starvation response. Such reactions have been uncoupled from PHT1 activity, suggesting that systemic Pi sensing is most probably acting downstream of PHT1.


'The formula that killed Wall Street': the Gaussian copula and modelling practices in investment banking.
Drawing on documentary sources and 114 interviews with market participants, this and a companion article discuss the development and use in finance of the Gaussian copula family of models, which are employed to estimate the probability distribution of losses on a pool of loans or bonds, and which were centrally involved in the credit crisis. This article, which explores how and why the Gaussian copula family developed in the way it did, employs the concept of 'evaluation culture', a set of practices, preferences and beliefs concerning how to determine the economic value of financial instruments that is shared by members of multiple organizations. We identify an evaluation culture, dominant within the derivatives departments of investment banks, which we call the 'culture of no-arbitrage modelling', and explore its relation to the development of Gaussian copula models. The article suggests that two themes from the science and technology studies literature on models (modelling as 'impure' bricolage, and modelling as articulating with heterogeneous objectives and constraints) help elucidate the history of Gaussian copula models in finance.


The Future of Periodontal-Systemic Associations: Raising the Standards.
Periodontal medicine recognizes a "bidirectional" interaction between periodontitis and systemic conditions. Unfortunately, the facile ability to publish a periodontal-systemic association, regardless of biologic plausibility or rigorous scientific scrutiny, continues without abate. The increasing number of periodontal-systemic associations corrupts the ability of dentists to distinguish which of the associations are spurious and which are valid. The use of a Disease Association Checklist creates a register for rational assessment of current disease associations. However, to diminish the publication of spurious periodontal-systemic observational associations, editors must demand that authors follow Bradford-Hill criteria and the STROBE Statement to ensure a stringent pathway to publication.


Morphometric analysis of mouse airways after chronic allergen challenge.
Understanding the mechanisms of airway remodeling in chronic allergic conditions such as asthma is increasingly dependent on the use of animal models. Techniques for quantifying structural changes are required that are reproducible and responsive and that can be applied to different staining techniques in both human and animal airway tissues. Here, we characterize a morphometric technique to quantify changes in extracellular matrix and contractile tissue as two indices of airway remodeling in mice. Specific aims were to establish the optimum projection beneath the epithelium to assess remodeling changes and to determine whether such changes are reproducible within different areas of the lung. Finally, based on the variance within measurements, we calculated sample size requirements for research applications of this technique. BALB/c mice were sensitized to ovalbumin and studied after chronic allergen challenge. Lungs were formalin fixed and sectioned were then assayed for extracellular matrix or contractile tissue using morphometric/colorimetric techniques. In this model, the optimum projected distance to measure changes in extracellular matrix or contractile tissue was 20 micro m beneath the epithelium; projecting beyond this depth resulted in decreased ability to detect allergen-induced changes (signal) because of increased irrelevant staining of surrounding parenchymal tissue (noise). The technique was responsive, because an allergen-induced signal was detected in all airway sections and all lung regions studied (p < 0.05). The power of this analysis was such that allergen-induced changes can be reliably (>80% power) detected using 8 to 10 mice. This morphometric technique provides a valid and objective method to assess structural changes in the airways of mice after chronic allergen exposure.


In vitro glucuronidation of xanthohumol, a flavonoid in hop and beer, by rat and human liver microsomes.
Xanthohumol (XN) is the major prenylated flavonoid of hop plants and has been detected in beer. Previous studies suggest a variety of potential cancer chemopreventive effects for XN, but there is no information on its metabolism. The aim of this study was to investigate in vitro glucuronidation of XN by rat and human liver microsomes. Using high-performance liquid chromatography, two major glucuronides of XN were found with either rat or human liver microsomes. Release of the aglycone by enzymatic hydrolysis with beta-glucuronidase followed by liquid chromatography/mass spectrometry and nuclear magnetic resonance analysis revealed that these were C-4' and C-4 monoglucuronides of XN.


The ricinosomes of senescing plant tissue bud from the endoplasmic reticulum.
The ricinosome (synonym, precursor protease vesicle) is a novel organelle, found so far exclusively in plant cells. Electron microscopic studies suggest that it buds off from the endoplasmic reticulum in senescing tissues. Biochemical support for this unusual origin now comes from the composition of the purified organelle, which contains large amounts of a 45-kDa cysteine endoprotease precursor with a C-terminal KDEL motif and the endoplasmic reticulum lumen residents BiP (binding protein) and protein disulfide isomerase. Western blot analysis, peptide sequencing, and mass spectrometry demonstrate retention of KDEL in the protease proform. Acidification of isolated ricinosomes causes castor bean cysteine endopeptidase activation, with cleavage of the N-terminal propeptide and the C-terminal KDEL motif. We propose that ricinosomes accumulate during senescence by programmed cell death and are activated by release of protons from acidic vacuoles.


Has intraoperative cholangiography during laparoscopic cholecystectomy become obsolete in the era of preoperative endoscopic retrograde and magnetic resonance cholangiopancreatography?
Preoperative ERCP, magnetic resonance cholangiopancreatography (MRCP), and intraoperative cholangiography (IOC) are standard procedures in evaluating patients with suspected choledocholithiasis. This study evaluates the changing practice patterns over time of these 3 procedures in a large cohort of patients undergoing laparoscopic cholecystectomy (LC) at a single tertiary care center. Data from all patients undergoing an LC with or without preoperative ERCP, MRCP, or an IOC from January 1, 2004 to December 31, 2013 were retrospectively reviewed from billing data obtained by CPT code and analyzed by chi-square testing. During 10 years, 7,427 patients underwent successful LC. The number of patients undergoing successful IOC (11.9% to 7.6%) or preoperative ERCP (7.2% to 1.5%) decreased significantly during that time interval (p < 0.01). In the last 6 years, 4,506 patients underwent successful LC. The number of patients from this group undergoing a preoperative MRCP (0.9% to 8.6%) or MRCP and ERCP (0.4% to 3.6%) increased significantly (p < 0.001). Despite a shift from IOC and preoperative ERCP to preoperative MRCP alone or with ERCP, a significant percentage (7.6%) of patients still underwent IOC in 2013. Use of IOC during LC has decreased but is not considered obsolete, rather, it remains a valuable tool for the evaluation of bile duct anatomy, bile duct injury, or suspected choledocholithiasis. Intraoperative cholangiography during uncomplicated LC should be emphasized in teaching programs to insure general surgery resident competency with the procedure.


HLA-A, B (Class I) and HLA-DR, DQ (Class II) antigens in Turkish patients with recurrent aphthous ulceration and Behçet's disease.
The aims of the present study were to typify the human leukocyte antigen system (HLA)-A, B (class I) and HLA-DR, DQ (class II) antigens and to assess the frequency of the presence of these antigens in the Turkish population with recurrent aphthous ulceration (RAU) and Behçet's disease (BD) compared to healthy subjects. Thirty patients with RAU, 30 with BD, and 15 healthy subjects were included in the study. HLA typing was performed by serology with commercial kits for HLA class I and II (One Lambda, Canoga Park, Calif., USA). The HLA-A23 frequency was 26.7% in the RAU patients, which was significantly higher than the 3.3% frequency in the patients with BD (p < 0.05). The HLA-A24 frequency was 33.3% in the RAU patient group, which was significantly higher (p < 0.05) than the frequency in the healthy subjects (6.7%). Significantly higher frequencies (46.7%) of HLA-A30 were found in the healthy subjects compared to the BD (13.3%) and RAU (3.3%) patients (p < 0.05 and p < 0.01, respectively). A higher frequency of HLA-B13 was observed in the RAU (23.3%) patients compared to the BD (0%) patients (p < 0.01). A decrease was observed in HLA-DR10 and HLA-DR17 in the RAU patients (p < 0.05), while a higher frequency of HLA-DR10 was observed in the BD patients compared to the RAU patients (p < 0.01). These results showed that RAU and BD were not in the same spectrum and the involvement of other genetic and/or environmental factors might be responsible for the development of these diseases and/or disease progression.


Towards reproducible metabarcoding data: Lessons from an international cross-laboratory experiment.
Advances in high-throughput sequencing (HTS) are revolutionizing monitoring in marine environments by enabling rapid, accurate and holistic detection of species within complex biological samples. Research institutions worldwide increasingly employ HTS methods for biodiversity assessments. However, variance in laboratory procedures, analytical workflows and bioinformatic pipelines impede the transferability and comparability of results across research groups. An international experiment was conducted to assess the consistency of metabarcoding results derived from identical samples and primer sets using varying laboratory procedures. Homogenized biofouling samples collected from four coastal locations (Australia, Canada, New Zealand and the USA) were distributed to 12 independent laboratories. Participants were asked to follow one of two HTS library preparation workflows. While DNA extraction, primers and bioinformatic analyses were purposefully standardized to allow comparison, many other technical variables were allowed to vary among laboratories (amplification protocols, type of instrument used, etc.). Despite substantial variation observed in raw results, the primary signal in the data was consistent, with the samples grouping strongly by geographical origin for all data sets. Simple post hoc data clean-up by removing low-quality samples gave the best improvement in sample classification for nuclear 18S rRNA gene data, with an overall 92.81% correct group attribution. For mitochondrial COI gene data, the best classification result (95.58%) was achieved after correction for contamination errors. The identified critical methodological factors that introduced the greatest variability (preservation buffer, sample defrosting, template concentration, DNA polymerase, PCR enhancer) should be of great assistance in standardizing future biodiversity studies using metabarcoding.


Infarct size estimation from serial CK MB determinations: peak activity and predictability.
In 198 patients with acute myocardial infarction serial measurements of plasma creatine kinase isoenzyme MB (CK MB) were performed at four hour intervals. In every patient, maximal CK MB activity (peak activity) was compared with calculated total release per litre plasma. In 28 patients (group 1) sufficient plasma samples were available for calculation of the apparent first order inactivation constant kd. Mean apparent kd in group 1 patients was 0 . 085 +/- 0 . 018 h-1 (mean +/- SD). Total release in group 1 was calculated with individual apparent kd values (Q) and with the mean kd value (Q*). In the remaining 170 patients (group 2), Q* only was calculated. A linear relation between peak activity P and total release (both Q and Q*) was found, extending over the whole range of CK MB peak activities that are routinely observed (4-216 U/l). It was immaterial whether a one or a two compartment model was used: both yielded a close linear relation. Though the mean ratio between Q* and peak activity depends on the value of kd chosen for calculation of total release (the ratio increasing with increasing kd), linearity between peak activity and Q* was found for any value of kd up to 0 . 4 h-1. In group 1, shapes of calculated CK MB release curves Q*(t), expressed relative to maximal release Q(40), were sufficiently similar so as to be superimposable; the section of the release curves extending from 12 hours before until two hours after peak time could be tentatively described by a linear time course with a slope of 4 . 2 +/- 0 . 5% per hour (mean +/- SD). We conclude that peak activity of CK MB is a reliable estimate of cumulative CK MB release and may be clinically more practicable than calculation of Q(40). Both the similarity and the large apparently linear section of the calculated enzyme release curves possibly permit early prediction of Q(40), with acceptable precision.


Comparative effectiveness of adalimumab and etanercept for rheumatoid arthritis in the Brazilian Public Health System.
Biological disease-modifying antirheumatic drugs (bDMARDs) are used to treat rheumatoid arthritis (RA) with adalimumab and etanercept the most used bDMARDs in Brazil. This open prospective cohort study evaluated their effectiveness and safety among RA patients in the Brazilian Public Health System given their costs. The Clinical Disease Activity Index was primarily used to assess their effectiveness after 6 and 12 months of follow-up. The Health Assessment Questionnaire and EuroQol-5D were also used. A total of 266 RA patients started treatment with adalimumab or etanercept. Adalimumab was the most widely used bDMARD (70%). In total, 46% achieved remission or low-disease activity at 12 months with no difference in effectiveness between them (p = 0.306). bDMARDs were more effective in patients who had better functionality at treatment onset and had spent longer in education. This real-world study demonstrated that adalimumab and etanercept are equal alternatives for RA treatment and both were well tolerated.


[Population pathology--a new trend in pathology research].
An advanced type of population studies is now epidemiological studies of non-infectious diseases. Population pathology allows studying the whole spectrum of the disease development (predisease, early preclinical and overt stages) and the disease risk factors. Epidemiological studies of atherosclerosis provided information on the disease evolution within 25-year period in male population of 9 cities, a peculiar type of fibrous plaque formation in the aorta and coronary arteries is described and some features of lipid spots in the aorta in various populations are observed.


Spastic muscle properties are affected by length changes of adjacent structures.
Recent animal experiments have shown that up to 37% of muscle force may be transmitted to adjacent structures rather than reach the insertion of the muscle's tendon, and that the extent of such force transmission depends on the length and relative position of these structures. We tested whether the force-length characteristics of the distally tenotomized human flexor carpi ulnaris muscle (FCU) of nine patients with cerebral palsy varied with the change of relative length of adjacent structures induced by a change of wrist position. In four patients, the FCU exerted up to 40% more active force in a flexed wrist position at short FCU length, whereas the active force was not significantly higher in the other five. In the same manner, passive force-length characteristics of the spastic FCU changed upon changes in wrist position. Variability in myofascial force transmission may partly explain the variability in success of the FCU-transfer.


Short bowel syndrome in infancy: recent advances and practical management.
Short bowel syndrome (SBS) is a rare condition characterised by extensive loss of intestinal mass secondary to congenital or acquired disease. The outcomes are determined by dependency on parenteral nutrition (PN), its possible complications and factors that influence intestinal adaptation. In order to achieve the best results, patients should be managed by a specialised multidisciplinary team with the aims of promoting growth and development, stimulating intestinal adaptation and preventing possible complications. This involves timely surgical management aimed at rescuing maximum bowel length and eventually re-establishing intestinal continuity where appropriate. A combination of enteral and parenteral nutrition needs to be targeted towards maintaining a balance between fulfilling the nutritional and metabolic needs of the child while preventing or at least minimising potential complications. Enteral nutrition and establishment of oral feeding play a fundamental role in stimulating bowel adaptation and promoting enteral autonomy. Other measures to promote enteral autonomy include the chyme recycling in patients where bowel is not in continuity, autologous gastrointestinal reconstruction and pharmacological treatments, including promising new therapies like teduglutide. Strategies such as lipid reduction, changing the type of lipid emulsion and cycling PN are associated with a reduction in the rates of intestinal failure-associated liver disease. Even though vast improvements have been made in the surgical and medical management of SBS, there is still lack of consensus in many aspects and collaboration is essential.


The Influence of Binocular Vision Symptoms on Computerized Neurocognitive Testing of Adolescents With Concussion.
Binocular vision disorders are commonly found postconcussion and associated with high symptom burden. We investigated the relationship between binocular vision symptoms and neurocognitive test performance. Thirty-four adolescents with concussion and 18 without concussion were assessed for cognitive performance using the CogState Brief Battery. Binocular vision disorders were determined using clinical examination and vision symptoms with the Convergence Insufficiency Symptoms Survey (CISS). A cutoff CISS score of 13 had high predictive accuracy for identifying individuals with a binocular vision disorder. CogState scores for processing speed and attention were significantly lower in the concussion group compared with the control group. Within the concussion group, scores for attention, learning, and working memory were significantly lower in those with vision symptoms. The presence of vision symptoms did not significantly affect CogState scores within the control group. The presence of vision symptoms in individuals with concussion is associated with significantly reduced scores on individual components of the CogState.