PORT (Programme of Recognition and Therapy): the first Polish recognition and treatment programme for patients with an at-risk mental state.
To present the activities of the first early intervention centre in Poland and the Programme of Recognition and Therapy (PORT) run by the centre. An overview of the admission process, diagnostic procedures and therapeutic interventions offered to individuals with an at-risk mental state. The PORT programme, developed in 2010, included 81 individuals, aged 15-29 years so far. The diagnostic procedures consists of evaluation of symptoms with the use of the Comprehensive Assessment of At-Risk Mental State (CAARMS), assessment of premorbid and current personality traits and the evaluation of cognitive functions. Therapeutic interventions include cognitive behavioural therapy, diet supplementation with omega-3 fatty acids and pharmacological treatment. Overall rate of conversion into psychosis within the years 2010-2103 was 18.5%. The programme has also been a source of research in the field of early psychosis. The PORT programme enables young people with an ARMS an easy access to the specialized service offering treatment tailored to their specific needs.


The complete mitochondrial genome of Hemigrapsus sinensis (Brachyura, Grapsoidea, Varunidae) and its phylogenetic position within Grapsoidea.
In this study, the complete mitogenome of Hemigrapsus sinensis was the first identified and analyzed. The complete mitochondrial genome of Hemigrapsus sinensis (Brachyura, Grapsoidea, Varunidae) and its phylogenetic position within Grapsoidea. The sample of Hemigrapsus sinensis was collected and DNA was extracted. After sequencing, NOVOPlasty was used for sequence assembly. Annotate sequences with MITOS WebServer, tRNAscan-SE2.0, and NCBI database. MEGA was used for sequence analysis and Phylosuite was used for phylogenetic tree construction. DnaSP was used to calculate Ka/Ks. This mitochondrial genome shows that it was 15,900 bp and encoded 13 PCGs, 22 tRNA genes, two rRNA genes, and one control region. The genome composition tends to A + T (74.34%) and presents a negative GC-skew (- 0.22) and AT-skew (- 0.03). The PCGs initiation codon was the typical ATN and termination codon was the typical TAN, incomplete T or missing. The ML and BI trees showed that H. sinensis was most closely related to Hemigrapsus and clustered together with the Varunidae. And our phylogenetic trees provide proof that Ocypodoidea and Grapsoidea may be of common origin. Meanwhile, in the phylogenetic tree, parallel mixing of Chiromantes and Orisarma raised doubts over the traditional classification system. Besides, Incomplete Lineage sorting (ILS) was observed in Varunidae. In the subsequent analysis of evolution rate, we found that all of the PCGs (NAD4 was not calculated) had undergone negative selections, indicating the conservation of mitochondrial genes of H. sinensis during the evolution. Therefore, researching the complete mitogenome of H. sinensis would be contributing to molecular taxonomy, phylogenetic relationship, and breeding optimization within the Grapsoidea superfamily.


A three-dimensional graphic reconstruction method of the vertebral column from CT scans.
The method of graphic reconstruction using the oblique view technique was applied on the transverse CT scans of the vertebral column. In the scanning procedure the low-dose thin-slice technique was used. The method proved valuable for the construction of three-dimensional models as reliable reproduction of the original. The results are useful for preoperative evaluation of the deformed spine as well as for anatomic research.


Characterization of polyion complex micelles designed to address the challenges of oligonucleotide delivery.
To optimize oligonucleotide (ODN)-based polyion complex micelles (PICMs) by studying the effects of polymer composition and length on their properties. Atom transfer radical polymerization was used to synthesize copolymers with increasing hydrophilic nonionic and cationic block lengths. PICMs were prepared by mixing the copolymers and ODN at various nitrogen-to-phosphate (N/P) ratios and characterized by gel electrophoresis and dynamic light scattering. The stability of the complexes towards dissociation was tested using a competitive assay with heparin. Finally, protection of the incorporated ODN against DNAse I degradation was evaluated. A library of copolymers composed of poly(ethylene glycol) (PEG) and poly(aminoethyl methacrylate) (PAEMA) and/or poly((dimethylamino)ethylmethacrylate) (PDMAEMA) was synthesized. All polymers efficiently interacted with the ODN at N/P ratios approaching 1.5. Narrowly distributed but easily dissociable PICMs were obtained using PEG 5000 and short DMAEMA chains. Shortening the PEG block to 2000, increasing the number of cationic units and using AEMA produced more stable complexes but at the cost of colloidal properties. All polymers were able to protect the ODN from nuclease degradation. PEG 3000-based PICMs possess good colloidal properties, intermediate stability towards dissociation and adjustable buffering capacity, making them potentially useful for the delivery of nucleic acid drugs.


Concurrent chemoradiotherapy using cisplatin plus S-1, an oral fluoropyrimidine, followed by surgery for selected patients with stage III non-small cell lung cancer: a single-center feasibility study.
This single-institutional study was designed to determine whether S-1, an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible as an induction treatment for locally advanced non-small cell lung cancer (NSCLC). Eighteen patients were analyzed in this study from July 2005 to March 2008. The patients received 40 mg/m(2) S-1 orally twice per day on days 1 through 14 and 22 through 35, and cisplatin (60 mg/m(2)) was injected intravenously on days 8 and 29. The patients also underwent radiotherapy, and received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical resection was performed from 3 to 6 weeks after completing the induction treatment. Nine (50%) of the 18 patients who received the induction treatment achieved a partial response. One patient refused to undergo surgery. The remaining 17 patients underwent a complete surgical resection. There were no deaths nor any major morbidities during the perioperative period. The recurrence-free survival and overall survival rate at 2 years for the patients who underwent resection were 63.3% and 88.2%, respectively. Induction treatment using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for selected patients with stage III NSCLC is a feasible and promising new treatment modality.


Outcome of treatment after failed endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: results from the International Infant Hydrocephalus Study (IIHS).
After an endoscopic third ventriculostomy (ETV) fails, it is unclear how well subsequent treatment fares, especially in comparison to shunts inserted as primary treatment. In this study, we present a further analysis of the infants enrolled a prospective multicentre study who failed ETV and describe the outcome of their subsequent treatment, comparing this to those who received shunt as their primary treatment. This was a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicentre study of infants with hydrocephalus from aqueductal stenosis who received either an ETV or shunt. In the current analysis, we compared the results of the 38 infants who failed ETV and the 43 infants who received primary shunt. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. There were a total of 81 patients: 43 primary shunts, 34 shunt post-ETV, and 4 repeat ETV. The median time between the primary ETV and the second intervention was 29 days (IQR 14-69), with no significant difference between repeat ETV and shunt post-ETV. Median length of available follow-up was 800 days (IQR 266-1651), during which time, failure was noted in 3 (75.0%) repeat ETV patients, 10 (29.4%) shunt post-ETV patients, and 9 (20.9%) primary shunt patients. In an adjusted Cox regression model, the risk of failure was higher for repeat ETV compared to primary shunt, but there was no significant difference between primary shunt and shunt post-ETV. No other variable showed statistical significance. In our prospective study of infants with aqueductal stenosis, there was no significant difference in failure outcome of shunts inserted after a failed ETV and primary shunts. Therefore, our data do not support the notion that previous ETV confers either a protective or negative effect on subsequently-placed shunts. Larger studies, in a wider ranging population, are required to establish how widely these data apply. NCT00652470.


Spatiotemporal regularity and spillover effects of carbon emission intensity in China's Bohai Economic Rim.
The Bohai Economic Rim (BER) is a momentous economic growth district with rapid development in northern China, but the environmental problems there have also become prominent. In 2017 the BER's carbon emission intensity outclassed the national average, the emission reduction situation was also grim. For clarifying the influence mechanism of the economy on carbon emission intensity, this paper explores the spatiotemporal regularity, the spatial correlation, and the spillover effect in carbon emission intensity employing the Moran index and the spatial Durbin model. The results indicate that the carbon emission intensity in the BER decreased year-by-year from 2006 to 2017. Shanxi and Inner Mongolia were emission hot spots, whereas Beijing and Tianjin were emission cold spots. And the Moran's I values all passed the significance test, which verified the spatial correlation of the carbon emission intensity in the BER is significant. Urbanization, energy intensity, population density, and industry structure have a biggish impact on such spatial distribution of the carbon emission intensity. The direct effect coefficient of the energy intensity is the highest, and the spillover effect of the industry structure is the most significant. Finally, this paper puts forward suggestions on the formulation of regional coordinated carbon reduction programs in the BER.


Substantially Elevated Atherosclerotic Risks in Japanese Severe Familial Hypercholesterolemia Defined by the International Atherosclerosis Society.
The International Atherosclerosis Society (IAS) has proposed "severe familial hypercholesterolemia" (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown. This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH. This study analyzed 380 clinically diagnosed subjects with heterozygous FH without any history of atherosclerotic cardiovascular diseases. Severe FH was defined as untreated low-density lipoprotein cholesterol >400 mg/dL, >310 mg/dL plus 1 high-risk feature, or >190 mg/dL plus 2 high-risk features according to IAS-proposed statement. The occurrence of first and subsequent composite outcomes (cardiac [cardiac death + coronary artery disease + coronary revascularization] and noncardiac events [stroke + peripheral artery disease] was compared between subjects with severe (n = 135) and non-severe (n = 227) FH. Severe FH was identified in 40.3% of study population. They had higher low-density lipoprotein cholesterol (P < 0.001) and lipoprotein(a) (P = 0.03) levels. Moreover, they more frequently received high-intensity statin (P < 0.001), PCSK9 inhibitor (P < 0.001), and lipoprotein apheresis (P = 0.01) than nonsevere FH subjects did, which resulted in a lower on-treatment low-density lipoprotein cholesterol level of subjects with severe FH (113 ± 47.2 vs 130 ± 53.9 mg/dL; P = 0.007). However, during the 7.4-year observational period, subjects with severe FH exhibited a 9.3-, 15.4-, and 5.9-fold greater risk for first composite (P < 0.001), cardiac (P < 0.001), and noncardiac outcomes (P = 0.02), respectively. Multivariate Cox proportional hazard model consistently revealed the 7.8- and 7.9-fold elevated risks of first (P < 0.001) and of subsequent (P < 0.001) composite outcomes in subjects with severe FH. Japanese subjects with severe FH present profound risks of both first and subsequent atherosclerotic cardiovascular diseases in the primary prevention settings. These findings support the clinical applicability of IAS-defined severe FH in Japanese patients, which identifies those who require further stringent antiatherosclerotic management.


Purely endoscopic and endoscope-assisted approaches to lesions of the third ventricle in pediatric age-a technical collection.
One of the main difficulties in third ventricle surgery is its deep and central location within the brain, surrounded by many eloquent neurovascular structures. Such anatomical environment obviously makes it very hard to safely approach and excise lesions in there. The introduction of the surgical microscope into the neurosurgical field undoubtedly played an important and pivotal role in improving the surgical results and increasing the safety of operations in and around the third ventricle. Although the surgical microscope remained the gold standard of intraoperative visualization for many decades, the advent of endoscopes revolutionized surgery of the third ventricle. Neuroendoscopic procedures for lesions of the third ventricle encompass a greatly variable array of endochannel, endoscope-assisted and endoscope-controlled techniques. In this collection on purely endoscopic and endoscope-assisted approaches to lesions of the third ventricle in pediatric age, the readership is presented with a selected group of these operations performed by experts in the field, shedding light mainly on their technical aspects and surgical pearls. The text description in each article is supplemented by a surgical video.


[Intraoperative chemotherapy after radical pleurectomy or extrapleural pneumonectomy].
Trimodality treatment including induction and/or adjuvant chemotherapy, surgical resection and in some cases radiotherapy offers a curative intention in selected patients with pleural malignancies (malignant pleural mesothelioma, thymoma with pleural spread). Nevertheless, locoregional tumor recurrence mainly limits the outcome and the quality of life. A few years ago an additional intraoperative chemotherapy perfusion was developed in order to improve local tumor control and prognosis after surgical resection in a multimodality treatment setting. Cytoreductive surgery with the purpose of a macroscopic complete resection could be achieved by radical pleurectomy or extrapleural pneumonectomy. The concept, techniques and perioperative management of this additional treatment option are presented along with a detailed review of the recent literature.


Development of whole body adiposity in preterm infants.
The long-term effects of prematurity, early diet and catch-up growth on metabolic risk and body adiposity are of increasing interest to Neonatologists. Poor growth is known to be associated with poorer neuro-developmental outcome but concern exists that increased rates of "catch-up" (or "recovery") growth may be associated with increased adiposity and the later development of metabolic syndrome. In this manuscript we review the published data on body composition in preterm infants, and present new analyses of body adiposity in preterm infants during the 12-15 months of life, and the effect of growth rate (weight gain) on body adiposity. We conclude that although preterm infants have increased adiposity at term corrected age, they generally have lower body fat than their term peers during the rest of the 12-15 months of life. Although more rapid "catch-up" growth in preterm infants during the first year of life is associated with greater body fatness than slower rates of growth, these higher rates of growth lead to body composition more similar to that of the term-born infant, than do slower rates of growth. Although more studies are needed to determine whether these short-term increases or the longer-term decreases in adiposity modify the risk on chronic diseases such as diabetes mellitus, hypertension or other components of the metabolic syndrome, the widely held concern that preterm babies have greater adiposity than their term peers, and that this is worsened by greater amounts of catch-up growth, are not supported by the available evidence.


Psychophysical study of image orientation perception.
The experiment reported here investigates the perception of orientation of color photographic images. A collection of 1000 images (mix of professional photos and consumer snapshots) was used in this study. Each image was examined by at least five observers and shown at varying resolutions. At each resolution, observers were asked to indicate the image orientation, the level of confidence, and the cues they used to make the decision. The results show that for typical images, accuracy is close to 98% when using all available semantic cues from high-resolution images, and 84% when using only low-level vision features and coarse semantics from thumbnails. The accuracy by human observers suggests an upper bound for the performance of an automatic system. In addition, the use of a large, carefully chosen image set that spans the 'photo space' (in terms of occasions and subject matter) and extensive interaction with the human observers reveals cues used by humans at various image resolutions: sky and people are the most useful and reliable among a number of important semantic cues.


Extracorporeal membrane oxygenation in lung transplantation.
The use of extracorporeal techniques in cardiopulmonary support has spread in the last 20 years. ECMO (extracorporeal membrane oxygenation) devices are the most commonly employed option, and have been used for years in lung transplant programs. Nevertheless, few articles on the results of ECMO involving large numbers of cases have been published to date. The use of ECMO in respiratory failure affords immediate oxygen support in patients with severe hypoxia and/or acidosis, and moreover provides pulmonary protection, since it allows an instantaneous decrease in the ventilator pressure and FiO2 needs. The complications of ECMO have been minimized thanks to the technological improvements found in the latest devices, though renal failure, infections, bleeding, and vascular and mechanical complications are still reported in many studies. At present there is less controversy regarding the use of cardiorespiratory assists with ECMO as an alternative in decompensated patients who are on the waiting list, referred to the intra- and postoperative periods of lung transplantation.


Qualitative detection of N-nitrosodiethanolamine in cosmetic products.
A relatively quick and simple procedure is described for the detection of N-nitrosodiethanolamine in various cosmetic products. The procedure is based on the irreversible formation of p-nitroso-N,N-dimethylaniline which has a bright yellow colour in basic solution. The compound is formed following extraction of the cosmetic, photolysis of the aqueous extract and the addition of N,N-dimethylaniline to photolysed extract.


Repeated [131I]metaiodobenzylguanidine therapy in two patients with malignant pheochromocytoma.
Approximately 10% of pheochromocytomas are malignant with a 5-yr survival rate of less than 40%. Promising results have been published on single high-dosage [131I]metaiodobenzylguanidine ([131I]MIBG) treatment for malignant pheochromocytoma. We present our experience with multiple intermediate-dosage [131I]MIBG therapy instead of single high-dosage therapy. The study took place at University Medical Centers and included two patients (one male, 36 yr of age, and one female, 43 yr of age) with widely spread metastatic pheochromocytoma and bad prognosis because of liver and lung metastases. Instead of a single high dosage, these two patients were treated with multiple intermediate dosages of [131I]MIBG. The first patient received 37 GBq (1 Ci) [131I]MIBG in five sessions [7400 MBq (200 mCi) each; interval range, 2-11 months]; the second patient received 66.6 GBq (1.8 Ci) [131I]MIBG in 12 sessions [5550 MBq (150 mCi) each; interval range, 2-14 months]. We measured efficacy, toxicity, and survival. Both patients had a complete symptomatic response and a partial tumor volume response. The first patient had a partial biochemical response, the second a complete biochemical response. In both cases, toxicity has been confined to nausea during treatment. Hematological toxicity was minimal, and both patients stayed euthyroid. The survival (so far) of these patients was 5 yr (clinical case 1) and 16 yr (clinical case 2) after initial diagnosis. Repeated intermediate-dosage [131I]MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant pheochromocytoma, providing longstanding palliation and prolonged survival.


Axillary skin crease incision versus conventional posterolateral incision in open repair of patent ductus arteriosus for extremely low birth weight infants: a retrospective study.
Thoracotomy with posterolateral incision (PLI) is commonly used for surgical repair of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Some reports have described thoracotomy for PDA using an axillary skin crease incision (ASCI) in consideration of cosmetic problems such as surgical wounds and thoracic deformities, but the details remain unclear. In this study, we performed clipping ligation by thoracotomy with ASCI for ELBW infants with PDA from 2011 to 2015 for the purpose of improving cosmetic results, and retrospectively compared the results with those for conventional PLI cases performed from 2016 to 2020. ASCI was found to be associated with serious surgical complications and showed a significant difference in outcome parameters only for surgery time, suggesting a safety problem for ASCI. Considering these results, PLI allows clipping of the nearby PDA from the thoracotomy wound while looking straight ahead, whereas the PDA in ASCI is positioned deep and oblique to the thoracotomy wound, so the clipping angle is limited and accurate completion of the procedure is difficult. Regarding PDA repair in ELBW infants, ASCI shows a high risk of serious surgical complications. Conventional PLI remains preferable for safe and accurate results.


Effects of crop residue incorporation and properties on combined soil gaseous N2O, NO, and NH3 emissions-A laboratory-based measurement approach.
Crop residues may serve as a significant source of soil emissions of N2O and other trace gases. According to the emission factors (EFs) set by the Intergovernmental Panel on Climate Change (IPCC), N2O emission is proportional to the amount of N added by residues to the soil. However, the effects of crop residues on the source and sink strength of agroecosystems for trace gases are regulated by their properties, such as the C and N content; C/N ratio; lignin, cellulose, and soluble fractions; and residue humidity. In the present study, an automated dynamic chamber method was used in combination with soil mesocosms to simultaneously measure the effects of nine different crop residues (oilseed rape, winter wheat, field pea, maize, potato, mustard, red clover, sugar beet, and ryegrass) on soil respiration (CO2) and reactive N fluxes (N2O, NO, and NH3) at a high temporal resolution. Specifically, crop residues were incorporated in the 0-4 cm topsoil layer and incubated for 60 days at a constant temperature (15 °C) and water-filled pore space (60% WFPS). Residue incorporation immediately and sharply increased soil N2O and CO2 emissions, but these were short-lived and returned to background levels within respectively 10 and 30 days. The magnitude of increase in soil NO flux following residue incorporation was lower than that in CO2 and N2O fluxes, with peak emissions observed around day 20. Overall, the N content or C/N ratio of the applied residue could not sufficiently explain the variation in soil N2O and NO emissions. The range of the calculated N2O EFs over a 60-day period was -0.17 to +4.5, being wider than that proposed by the IPCC (+0.01 to +1.1). Therefore, the residue maturity stage may be used as a simple proxy to estimate the N2O + NO emissions from incorporated residue.


A concise route to benzofused macrolactones via ynolides: cycloproparadicicol.
A new facile synthesis has been developed for nanomolar Hsp90 inhibitor, cycloproparadicicol (2). Our approach relied on cobalt-complexation promoted RCM, in combination with tandem Diels-Alder/retro-Diels-Alder reactions to assemble the resorcycinylic macrolactone.


Omega-3 fatty acids: mechanisms underlying 'protective effects' in atherosclerosis.
This article provides an updated review on mechanistic and molecular studies relating to the effects of n-3 fatty acids (FA) on inhibiting atherogenesis. The effects of n-3 FA on modulating arterial lipoprotein lipase levels link to changes in lipid deposition in the arterial wall. Lipoprotein lipase expression in the arterial wall also relates to local macrophage-mediated inflammatory processes. Increasing evidence suggests that n-3 FA ameliorate inflammation, another key component in the development of atherosclerosis, including decreases in proinflammatory cytokine production. n-3 FA inhibit atherogenic signaling pathways and modulate the phenotypes of inflammatory leukocytes and their recruitment in the arterial wall. New mechanistic insights into the antiatherogenic action of n-3 FA have emerged. These studies may contribute to future therapeutic advances in preventing mortality and morbidity associated with atherosclerosis.


[Hemoptysis during concomitant treatment with rivaroxaban and amiodarone in a patient with a history of pulmonary disease].
Rivaroxaban, a selective inhibitor of active factor X, is metabolized by cytochrom P450 3A4 (CYP3A4) and is a substrate for transporter protein--P-glycoprotein (P-gp). Amiodarone, an antiarrhytmic agent, is classified as moderate CYP3A4 and P-gp inhibitor. A 75-year-old male, who underwent lobectomy for bronchiectasis many years ago, is presented. For one year the patient was treated with rivaroxaban (20 mg/d) due to venous thromboembolism and recurrent episodes of atrial fibrillation. Two weeks after amiodarone initiation (200 mg/d) hemoptysis occurred and computed tomography revealed unilateral pulmonary infiltrates with ground-glass opacities limited to the lower lobe of the left lung. The symptoms disappeared following discontinuation of the two medications and did not recur while rivaroxaban was reintroduced in a dose of 15 mg/d; measurement of anti-Xa activity confirmed it as a therapeutic dose. Amiodarone, that had been used for a short time and well tolerated a few years before, was definitely withdrawn. The authors suggest, that the concomitant use of rivaroxaban and amiodarone should be very careful in patients with a history of pulmonary disease.


Impact of different dimethyl sulphoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells.
The procedure of autologous hematopoietic stem/progenitor cell transplantation requires cryopreservation. Addition of DMSO is necessary to secure the viability of such cells, but this solvent is potentially toxic to stem cells' recipient. 10% DMSO solution is used by the majority of transplant centres. The aim of our study was to test if DMSO concentration might be reduced without negative impact on cell recovery and clonogenicity. Samples were prospectively collected from 20 patients. Small volumes of leukapheresis products were frozen with different cryoprotective mixtures, containing 10%, 7·5%, 5% and 2·5% DMSO, respectively. The quality of cryoprotective mixtures was evaluated based on recovery, viability and clonogenic potential of hematopoietic stem cells after defreezing. Reduction in DMSO concentration to 7·5% or lower was associated with decreased recovery of nucleated cells. In contrast, the number of colonies was highest for 7·5% DMSO with significant differences when compared to 10% DMSO solution. Reduction in DMSO concentration from 10% to 7·5% may have favourable impact on hematopoietic recovery after autologous transplantation. The findings require confirmation in a clinical setting.


Head and body movements evoked electrically from the caudal superior colliculus of rats: pulse frequency effects.
The effects of pulse frequency and current intensity on circling elicited from the caudal superior colliculus (SC) of rats were studied. The displacement of the head with respect to the body were measured for different levels of frequency (20, 29, and 50 Hz) and current (200 or 500 microA) at a pulse duration of 0.1 ms. The rate of circling increased monotonically with frequency and current. The rate at which the head was displaced laterally varied as a function of frequency. It is postulated that lateral head and body movements are affected by the firing frequency of SC output neurons.


Range extension of the vulnerable dwarf marmoset, Callibella humilis (Roosmalen et al. 1998), and first analysis of its long call structure.
We present two new records for the vulnerable dwarf marmoset, Callibella humilis. The first record, based on observed and photographed individuals, is from a campinarana area on the left (west) bank of the Rio Madeirinha, a left (west)-bank tributary of the Rio Roosevelt in the state of Amazonas, municipality of Novo Aripuanã and extends the distribution of the species ~270 km southwards, to the left (west) bank of the rio Roosevelt. The second record is based on an individual collected from the mouth of the Rio Roosevelt, at less than 10 km from the type locality of Mico marcai. This indicates that the species occurs sympatrically with M. marcai and probably Mico melanurus. We also present the first sonogram analysis of its long call structure, which shows some similarities, in the note duration and frequency, with Cebuella pygmaea and Mico argentatus.


Evaluation of several flocculants for flocculating microalgae.
Flocculation of microalgae with chitosan, polyacrylamide, Al2(SO4)3, NaOH and HNO3 was evaluated. Their flocculation efficiencies and optimal dosages were discussed. The effects of the flocculants on cells viability were also investigated and the cells were found to be intact during the flocculation process. Moreover, the effects of flocculants on the extractions were evaluated. Lipid content after flocculants treatments showed no significant differences. Carbohydrate content was lower but protein content was higher after NaOH treatment than those after other treatments. Furthermore, the five flocculated media maintained approximate growth yields to that of the fresh medium in microalgal cultivation, indicating the five flocculated media could be recycled, thereby reducing the cost of biodiesel production from microalgae. Finally, economic comparison of the flocculants was made and the cost of using HNO3, including flocculating cells and recycling medium, was found to be the lowest.


Minimally-Invasive Plate Osteosynthesis for Clavicle Fractures.
Objective To analyze the radiological, clinical, and functional outcomes of clavicle fractures treated with the minimally-invasive plate osteosynthesis (MIPO) technique. Methods From June 2018 to July 2019, 17 cases of clavicular fractures were managed using the MIPO technique under C-arm fluoroscopy. The functional outcomes were assessed using the Constant-Murley score and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. The clinical results of union, the complications, the operative time, the hospital stay, as well as infection, were analyzed. Results The mean follow-up time was of 10.41 ± 1.75 months (range: 8 to 14 months). There were 11 male and 6 female patients, with a mean age of 39.05 ± 10.76 years (range: 22 to 57 years). All fractures united on the mean time of 15.35 ± 3.08 weeks (range: 12 to 20 weeks). The mean operative time was of 98.11 ± 13.83 minutes (range: 70 to 130 minutes), and the mean length of the hospital stay was of 4.7 ± 1.12 days (range: 3 to 7 days). The mean Constant-Murley score was of 74.82 ± 6.36 in 4 th postoperstive month, and of 92.35 ± 5.48 in the 8 th postoperative month, which was statistically significant. The mean DASH score was of 9.94 ± 1.55 in the 4 th postoperative month, and of 5.29 ± 1.85 in the 8 th postoperative month, which was also statistically significant. One patient had superficial skin infection at the site of the incision. Conclusions The MIPO technique is an alternative method for the fixation of clavicle fractures, but it is technically more demanding, and requires well-equipped operating room facilities.


A study of the anatomy of the anterior communicating artery with the aid of the operating microscope.
The anatomy of the Anterior Communicating Artery complex is studied with the aid of the Zeiss operating microscope in 75 human brains removed at autopsy. The variations in the structure of the Anterior Communicating Artery and the A1 and A2 segments of the Anterior Cerebral Artery are reported. Special attention is given to the site of origin and number of branches from the Anterior Communicating Artery and the site of origin of Heubner's arteries. The necessity of using the operating microscope during surgical treatment of aneurysms of the Anterior Communicating Artery complex is stressed.


Uveitic macular edema.
Macular edema (ME) may complicate anterior, intermediate, and posterior uveitis, which may be because of various infectious, neoplastic or autoimmune etiologies. BRB breakdown is involved in the pathogenesis of Uveitic ME (UME). Optical coherence tomography has become a standard tool to confirm the diagnosis of macular thickening, due to its non-invasive, reproducible, and sensitive features. Retinal fluorescein and indocyanine green angiography is helpful to study the macula and screen for associated vasculitis, detect ischemic areas and preretinal, prepapillary or choroidal neovascular complications, and it may provide information about the etiology and be needed to assess the therapeutic response. UME due to an infection or neoplastic infiltration may require a specific treatment. If it remains persistent or occurs in other etiologies, immunomodulatory treatments may be needed. Intravitreal, subconjunctival, or subtenon corticosteroids are widely used. Their local use is contraindicated in glaucoma patients and limited by their short-lasting action. In case of bilateral sight-threatening chronic posterior uveitis, systemic treatments are usually needed, and corticosteroids are used as the standard first-line therapy. In order to reduce the daily steroid dose, immunosuppressive or immunomodulatory agents may be added, some of them being now available intravitreally. Ongoing prospective studies are assessing biotherapies and immunomodulators to determine their safety and efficacy in this indication.


Longitudinal and vertical distribution of microplastics in various pipe scales in an operating drinking water distribution system.
Microplastics (MPs) are ingested by humans through the daily consumption of drinking water. Pipe scales are recognized as important sites of MPs occurrence in the drinking water distribution system (DWDS). Despite extensive research on drinking water, no study has been conducted to investigate the distribution of MPs in pipe scales within an operational DWDS. The underground placement of DWDSs brings challenges for sampling pipe scales. In this study, 5 tap water and 16 pipe scales samples were collected from a typical DWDS. The analysis of MPs abundance in these 21 samples filled the data gap in the distribution of MPs in both pipe scales and tap water along the DWDSs. MPs were detected in all water samples (1.74-20.88 MPs/L) and pipe scales samples (0.03-3.48 MPs/cm2). In tap water, MPs abundance increased abruptly in the stagnant-slow flow region and reached the maximum value (20.88 MPs/L), even surpassing the abundance in raw water (6.42 MPs/L). In the pipe scales, MPs abundance decreased from the upstream to downstream of DWDS and was associated with the heavy metal concentration. MPs smaller than 150 µm accounted for 91.6% of the tap water (21-971 µm) and pipe scales (20-2055 µm). The abundance of MPs showed a logarithmic increase as the size decreased. The proportion of MPs fibers in tap water was lower than that in pipe scales. A total of 35 MPs polymers were detected, with 34 polymers in pipe scales and 26 polymers in tap water. In terms of abundance, polyethylene terephthalate (50.0%) was the dominant polymer in pipe scales, while polyamide (70.3%) was the dominant polymer in tap water. Regarding detection rate, polyamide was detected in all 21 samples, followed by polyurethane in 19 samples. The distribution of MPs along the longitudinal direction of the DWDS was correlated with heavy metal. While the distribution of MPs in the vertical direction of large diameter pipe scales was dependent on their sizes, and densities. The greatest abundance, size and density of MPs were detected at the bottom 120-degree.


Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.
Sézary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate antitumor immunity in certain cancer patients. In this study, we determined whether mRNAs from Sézary cells could be used for loading DCs and stimulating antitumor immunity. Autologous DCs were generated from monocytes of the peripheral blood from 10 patients with SzS. Total RNA was extracted from Sézary cells and amplified by T7 in vitro transcription. The induction of antitumor IFN-gamma and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays. We found that IFN-gamma was required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed in total RNA from Sézary cells and the paired amplified mRNAs. RNA-transfected DCs induced antitumor IFN-gamma-producing CTLs in 7 of 10 subjects and GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells. These data support the concept of using tumor mRNA for a vaccine strategy that requires small amounts of tumor cells without need for specific antigens in patients with SzS.


Familial occurrence of classical and idiopathic trigeminal neuralgia.
Trigeminal neuralgia (TN) is a severe facial pain disease with unknown pathogenesis. It has been thought that the familial form of TN is rare with a prevalence of about 1-2% among affected individuals, but emerging evidence suggests a role of genetic factors. This study examined the occurrence of familial TN among patients with classical or idiopathic TN. Patients with TN recruited from a hospital registry received an informed consent form with a questionnaire, and individuals reporting other family members with TN underwent a structured phone-interview. For affected family members, type of TN, available clinical, imaging, management results and available hospital patient records were studied. Pedigrees for all affected families were established. This study included 268 patients with either classical or idiopathic TN. The familial form of TN was present in 41/268 (15.3%) patients, that is, 37/244 (15.2%) patients with classical TN and in 4/24 (16.7%) with idiopathic TN. Total 38 families were identified, with two affected members in 32/38 families (84.2%), three affected family members in 5/38 (13.2%) and four family members in 1/38 (2.6%) families. Comparing the 41 familial TN cases with the 227 sporadic TN patients showed significantly earlier onset of TN and a significantly higher occurrence of right-sided pain in familial cases, while there was no difference in gender distribution, occurrence of arterial hypertension or trigeminal branch involved. Among patients with classical or idiopathic TN, the occurrence of the familial form of the disease is more frequent than traditionally assumed.


The Effect of Intramedullary vs Extramedullary Tibial Guides on the Alignment of Lower Extremity and Functional Outcomes Following Total Knee Arthroplasty: A Randomized Clinical Trial.
Total knee arthroplasty (TKA) has been known as a definitive treatment for advanced knee osteoarthritis. Both intramedullary (IM) and extramedullary (EM) tibial guides have been used to restore the desired extremity alignment. However, controversy exists regarding the superiority of either technique We aimed to compare the functional outcomes and accuracy of IM and EM tibial guides in providing neutral alignment after TKA. In a randomized, double-blinded clinical trial, we studied 98 patients undergoing primary TKA in two groups of IM and EM. We measured the medial proximal tibial angle (MPTA), varus angle (VA), and joint-line convergence angle with normal ranges of 90°±3°, 0-2°, and 0±3°, respectively, on a three-joint alignment view after three months. We also assessed the functional outcomes at the last follow-up. Finally, we compared these outcomes between the two groups. Eighty-four patients (IM=42, EM=42) were included in the final analysis (16 males, 68 females, mean age: 63.9±8.6 years, mean follow-up: 13±2.9 months). The mean postoperative (post-op) alignment angles showed no significant difference, although MPTA outliers were significantly more frequent in the EM group (26.2% vs. 9.5% in IM, P=0.04). None of the functional outcomes showed a significant difference between the two groups. However, the mean increase in knee range of motion (ROM) was significantly higher in the knees with VAs within ±3° of neutral than those outside this range (30.8 vs. 27.4, respectively, P=0.039). We conclude that both techniques were not different regarding the mean alignment angles and functional outcomes. However, fewer MPTA outliers can be seen with the IM technique. A post-op mechanical axis within ±3° of neutral can result in a more ROM increase after one year.


Dynamic regulation of DNA methylation coupled transcriptional repression: BDNF regulation by MeCP2.
A recurrent theme in eukaryotic genome regulation stipulates that the properties of DNA are strongly influenced by the nucleoprotein complex into which it is assembled. Methylation of cytosine residues in vertebrate genomes has been implicated in influencing the assembly of locally repressive chromatin architecture. Current models suggest that covalent modification of DNA results in heritable, long-term transcriptional silencing. In October of 2003, two manuscripts were published that challenge important aspects of this model, suggesting that modulation of both DNA methylation itself, as well as the machinery implicated in its interpretation, are involved in acute gene regulation.


Ghost chest tube after talc pleurodesis.
After the talc pleurodesis, CT showed the tract made from the chest tube even after its removal. The unexpanded thoracic space might also contribute to it; thus, gathering specific medical history is important to understand this rare phenomenon.


In silico design of high-affinity ligands for the immobilization of inulinase.
Using computer modeling, virtual screening of high-affinity ligands for immobilization of inulinase - an enzyme that cleaves inulin and fructose-containing polymers to fructose - has been performed. The inulinase molecule from Aspergillus ficuum (pdb: 3SC7) taken from the database of protein structures was used as a protein model and the target for flexible docking. The set of ligands studied included simple sugars (activators, inhibitors, products of enzymatic catalysis), as well as high-molecular weight compounds (polycation and polyanion exchange resins, glycoproteins, phenylalanine-proline peptide, polylactate, and caffeine). Based on the comparative analysis of the values of the total energy and the localization of ligand binding sites, we made several assumptions concerning the mechanisms of interaction of the suggested matrices for the immobilization of enzyme molecules and the structural features of such complexes. It was also assumed that the candidates for immobilization agents meeting the industrial requirements may be glycoproteins, for which we propose an additional incorporation of cysteine residues into their structure, aimed to create disulfide «anchors» to the surface.


Practical guide to undertaking scoping reviews for pharmacy clinicians, researchers and policymakers.
Scoping reviews are a valuable evidence synthesis methodology. They can be used to map the evidence related to any topic to allow examination of practice, methods, policy and where (and how) future research could be undertaken. As such, they are a useful form of evidence synthesis for pharmacy clinicians, researchers and policymakers to review a broad range of evidence sources. This commentary presents the most comprehensive and up to date methodology for scoping reviews published by Joanna Briggs Institute (JBI). This approach builds upon two older approaches by Arksey and O'Malley, and Levac. To assist reviewers working in the field of pharmacy with planning and conducting scoping reviews, this paper describes how to undertake scoping reviews from inception to publication with specific examples related to pharmacy topics. The JBI scoping review methodology is a valuable evidence synthesis approach to the field of pharmacy and therapeutics. This approach can assist pharmacy clinicians, researchers and policymakers to gain an understanding of the extant literature, to identify gaps, to explore concepts, characteristics and to examine current practice.


Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum.
Pulmonary atresia with intact ventricular septum can be complicated by the presence of large ventriculo-coronary arterial communications which disturb normal myocardial perfusion. In the selection of patients for surgery the presence of these communications provides an additional problem. On the basis of previous cineangiocardiographic study, we performed a histopathological study of 16 cases. Twelve presented with ventriculo-coronary arterial communications and four only showed myocardial sinusoids. A tripartite right ventricle was seen in the latter group but not exclusively. It is shown that subepicardial coronary arterial pathology is exclusively present in cases with ventriculo-coronary arterial communications although not solely at a connection site between a communication and an artery. The affected coronary artery is itself focally abnormal and hypoplastic and can be blocked or even absent. The interruption of such an artery can also occur after birth and not necessarily at a site of connection with a communication. This implies that infants with communications either already have a coronary circulation partly or completely dependent on ventriculo-coronary arterial communications at birth or can develop such a condition in time. This hazard to myocardial perfusion, often compromised by a large "steal" from the aorta to the right ventricle, limits the choice of surgical procedures.


Cloning of a trans-spliced glyceraldehyde-3-phosphate-dehydrogenase gene from the potato cyst nematode Globodera rostochiensis and expression of its putative promoter region in Caenorhabditis elegans.
Reverse genetics to determine the relative importance of individual pathogenicity factors of the potato cyst nematode Globodera rostochiensis depends, apart from an efficient transformation protocol for this obligatory plant parasite, on the availability of an efficient promoter. PCR-based cloning was used to isolate a cDNA encoding glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, a crucial enzyme in glycolysis and gluconeogenesis; this gene was designated gpd) and its 5'-flanking region. The cDNA includes 1047 nucleotides encoding an open reading frame that shows high homology with GAPDHs from Caenorhabditis elegans and other species. Analysis of the 745 bp 5'-flanking region of the gpd gene showed no homology with a similar region in C. elegans. In this region several eukaryotic promoter elements are present. 5' Rapid amplification of cDNA ends revealed this gene was trans-spliced with a SL1 spliced leader. The 5'-flanking region of the gpd gene was fused to green fluorescent protein reporter gene and microinjected into the gonads of C. elegans. Green fluorescent protein expression, under the transcriptional control of the 5'-flanking region of gpd, was mainly observed in body wall muscles of transgenic animals. This putative promoter region of GAPDH could be a valuable tool to drive gene expression in transgenic G. rostochiensis and other related plant-parasitic nematode species.


[Methods of treatment of preschool children used in the orthodontics department, Institute of Stomatology, Medical Academy in Warsaw].
The reported analysis was based on 288 clinical cards of patients aged 2 to 6 years, admitted for treatment in the years 1980-1985. The greatest group was that of children aged 3 years (28%), followed by those aged 6 years (25%). Abnormalities from the group of distocclusion prevailed (28%), followed by teeth abnormalities (26%), and cross-bite (16%). In 165 cases functional apparatus was used initially, in 66 cases Schwarz or Adams plates, in 31 cases dental prostheses, and in 22 cases chin sling. Four cases were observed after removal of malocclusion cause. Besides treatment with removable devices myotherapy and spatula exercises were used.


Surgical resection of stage IV colorectal cancer and prognosis.
Colorectal cancer (CRC) harbors accumulated genetic alterations with cancer progression, which results in uncontrollable disease. To regulate the most malignant CRC, we have to know the most dismal phenotype of stage IV disease. A retrospective review of the Kitasato University Hospital was performed (from 1990 to 2001) to extract the 162 resected stage IV CRC. Clinical variables were tested for their relationship to survival in a multivariate prognostic analysis and revealed the interaction of the prognostic factors. In stage IV CRC with noncurable resection, the most robust univariate predictors for poor prognosis were preoperative high value of CA19-9, peritoneal dissemination, depth of invasion, age, extent of liver metastases, pathologic lymph node metastasis status, and gender as tumor factors, and postoperative therapy, perioperative transfusion, and lymph node dissection extent as treatment factors. Among these factors, postoperative therapy (p < 0.0001), perioperative transfusion (0.0002), CA19-9 (0.001), extent of liver metastases (0.004), and peritoneal dissemination (0.02) were identified as independent prognostic factors by multivariate analysis. Interestingly, among the independent prognostic factors, treatment factors did not depend upon tumor factors and the combination of the three tumor factors (CA19-9, extent of liver metastases, and peritoneal dissemination) can clearly classify the patients into the definite prognostic groups. Our results suggested that the most dismal CRC harbors three definite vectors that may represent the strongest phenotype of putative systemic immune (CA19-9), distant metastasis (extent of liver metastases), and local progression (peritoneal dissemination).


Myotomy for reflux-induced cricopharyngeal dysphagia. Five-year review.
This report describes 25 patients with reflux-induced cricopharyngeal dysphagia ultimately requiring surgical management. Eighteen patients underwent cricopharyngeal myotomy alone and seven patients required cricopharyngeal myotomy after an antireflux operation failed to correct this symptom. Cricopharyngeal incoordination was demonstrated at manometry in over 90% of patients. Treatment included cricopharyngeal myotomy, which was extended proximally to the pharynx and distally to the intrathoracic esophagus. Results were excellent to satisfactory in 24 of 25 patients. Pathologic examination of the cricopharyngeal muscle demonstrated a wide variety of myopathic degenerative changes. We stress that cricopharyngeal myotomy may be performed even in the presence of reflux without fear of subsequent aspiration.


Calcineurin inhibitor-free immunosuppression in renal transplantation.
To describe our initial results using a calcineurin inhibitor-free immunosuppression protocol in renal transplants. Between October 2001 and June 2003, 56 recipients of a renal allografts were started on an immunosuppression protocol without calcineurin inhibitors, consisting of basiliximab, sirolimus, mycophenolate mofetil, and steroids. We analyzed patient and graft survival, acute rejection episodes, and renal function. The mean follow-up was 19.6 months. Actuarial patient survival at 1 and 2 years was 98.1% and 95.3%, respectively. Actuarial graft survival at 1 and 2 years was 92.9% and 87.6%, respectively. Acute rejection occurred in 27.8% of the patients, usually Banff 1 (73.3%). There was stable renal function with mean serum creatinine of 1.3, 1.4, 1.3, and 1.3 mg/dL at 1, 6, 12, and 24 months after transplant. The use of immunosuppression free of calcineurin inhibitors is effective and safe. Further follow-up is needed to evaluate the impact on long-term results.


[New methods of coagulation analysis using chromogenic substrates].
The available assay systems for the determination of coagulation factors based on clotting methods are unsatisfactory, despite efforts to stabilize and to standardize them. Analysis by means of chromogenic peptide substrates offers new possiblities for routine diagnostics, and for fundamental research. The development of these new methods, however, is at an early stage.


On the genus Limnocassis Spaeth, with description of two new species from South Africa (Coleoptera: Chrysomelidae: Cassidinae).
Limnocassis compacta sp. nov. and L. regularis sp. nov. are described from South Africa. They are well distinguished from Limnocassis pumilio (Boheman, 1854), the only known species in the genus, in fine and mostly regular elytral punctation. Colour photographs of all species and new distribution data for L. pumilio are given.


Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer.
Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA2 -AA-COX-2-PGE2 pathway by inhibiting the expression of iPLA2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.


Acute renal outcomes with sodium-glucose co-transporter-2 inhibitors: Real-world data analysis.
To assess the possible risk of acute kidney injury (AKI) with the use of sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a real-world setting. Included in this historical cohort study were patients with type 2 diabetes in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i) during 1 April 2015 to 30 June 2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, hospitalization with AKI, any hospitalization and all-cause mortality. Overall 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence interval [CI]) for ≥30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30 to 45 and ≥90 mL/min/1.73 m2 , respectively. Risks of AKI (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i versus DPP-4i. This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised.


In silico study on Penicillin derivatives and Cephalosporins for upper respiratory tract bacterial pathogens.
Upper respiratory tract infection (URTI) is an acute infection which involves the upper respiratory tract: nose, sinuses, tonsils and pharynx. URT infections are caused mainly by pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Conventionally, β-lactam antibiotics are used to treat URT infections. Penicillin binding proteins (PBPs) catalyze the cell wall synthesis in bacteria. β-Lactam antibiotics like Penicillin, Cephalosporins, Carbapenems and Monobactams inhibit bacterial cell wall synthesis by binding with PBPs. Pathogenic bacteria have efficiently evolved to resist these β-lactam antibiotics. New generation antibiotics are capable of inhibiting the action of PBP due to its new and peculiar structure. New generation antibiotics and Penicillin derivatives are selected in this study and virtually compared on the basis of interaction studies. 3-Dimensional (3D) interaction studies between Lactivicin, Cefuroxime, Cefadroxil, Ceftaroline, Ceftobiprole and Penicillin derivatives with PBPs of the above-mentioned bacteria are carried out. The aim of this study was to suggest a potent new generation molecule for further modification to increase the efficacy of the drug for the URTI.


A single amino acid determinant of the membrane localization of lipoproteins in E. coli.
When beta-lactamase was fused with the signal peptide plus the amino-terminal 9 amino acid residues of the major outer membrane lipoprotein, the resultant lipo-beta-lactamase (LL-1) was shown to be localized to the outer membrane. However, when the 9 residue sequence was replaced with the amino-terminal 12 residue sequence of lipoprotein-28, an inner membrane protein, the resultant lipo-beta-lactamase (LL-2) was found exclusively in the inner membrane. The localization of LL-2 was shifted to the outer membrane simply by substituting the second amino acid residue (Asp) of LL-2 with Ser. Conversely, the alteration of the second residue (Ser) of LL-1 to Asp resulted in the localization of LL-1 to the inner membrane. These results suggest that the second amino acid residue of the lipoproteins plays a crucial role in determining their final locations in the E. coli envelope.


Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes.
We investigated the action of macrolide antibiotics, which are considered to have anti-inflammatory activity, on lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 synthesis and the expression of mRNAs for cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 in human leukocytes. The production of LPS-stimulated PGE2 was significantly increased in peripheral polymorphonuclear leukocytes (PMNLs) and in mononuclear leukocytes (MNLs). Amounts of mRNAs for COX-2 and cPLA2, but not for COX-1, were enhanced by LPS in PMNLs and MNLs. The LPS-enhanced PGE2 synthesis and the expression of cPLA2 and COX-2 mRNAs were inhibited by clarithromycin, azithromycin and dexamethasone in PMNLs and MNLs. The mRNA expression of COX-1 in PMNLs was decreased by clarithromycin and azithromycin. Macrolide antibiotics inhibited PGE2 synthesis in human leukocytes by suppressing cPLA2, COX-1, and COX-2 mRNA expression. These data indicate one mechanism of macrolide anti-inflammatory activity.


Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients.
The clinical presentation of the disease and the results of treatment in 42 patients with malignant peripheral neuroectodermal tumors (MPNT) entered into the Cooperative Ewing's, soft tissue, and neuroblastoma trials of the German Society of Pediatric Oncology were retrospectively analyzed. Within the Ewing's sarcoma trial, patients with chest wall lesions were particularly analysed for MPNT features. The period of observation ranged from 15 to 86 months; the median relapse-free time was 24 months. There were 28 male and 14 female patients, the median age of patients was 15 years (range, 9 months-23 years). Thirty-two patients had localized disease (M0), and ten patients presented with primary metastases (M1). The predominant location of the tumors was the thoracopulmonary region, followed by the extremities, the abdominal/pelvic, and head and neck region. Thirty-one of 42 tumors involved the adjacent bone. The disease-free survival according to Kaplan-Meier life-table analysis was 56% +/- 11% for Stage M0 patients at 3 years. Nine of ten patients with M1 disease showed progression of their disease. Most patients had combined modality treatment with surgery, chemotherapy and radiation therapy. Best results were obtained with extensive surgery. Radiation doses ranged from 20 to 60 Gy and could not be correlated with the outcome of the disease. Most recurrences occurred at the site of the primary tumor. In patients with primary chemotherapy after biopsy-proven diagnosis, the responsiveness of this disease to chemotherapy could be demonstrated. Combination chemotherapy containing anthracyclines and high doses of alkylating agents appeared superior.


Distribution of the functional MDR1 C3435T polymorphism in the Han population of China.
3435C>T, a single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, is linked to the variability of P-gp expression and function among different individuals. It was found that ethnic differences exist in the polymorphism of the MDR1(C3435T) gene. However, the distribution of 3435C>T genotypes in the Chinese Han population is not clear up till now. In this study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess 3435C>T genotypes in 265 healthy individuals of the Han population of China. The genotype frequencies were: CC 32% (n = 85), CT 48% (n = 127) and TT 20% (n = 53). C and T allele frequencies were 0.56 and 0.44 respectively. The C allelic frequency for female was 56.5% (T: 43.5%), and 55.9% (T: 44.1%) for male. There was no significant difference between females and males (p = 0.92, OR = 1.02, 95%CI: 0.67-1.57) in the present study. The frequency of C-allele was similar to that of some populations in Asia/Europe and was lower than that of populations in Africa. When compared with the study on Singapore-Chinese, some differences were found. The results of this study would be useful for individualised therapy of some diseases, and could have a prognostic implication for the Chinese Han population.


Spectratype analysis of clonal T cell expansion in murine experimental stroke.
T lymphocytes are major contributors to post-ischemic neuroinflammation following ischemic stroke. However, the mode of postischemic T cell activation remains a controversial issue. Therefore, this study aimed to directly investigate antigen-dependent clonal T cell expansion after experimental brain ischemia using spectratype/immunoscope analysis. We detected clonal T cell expansion in ischemic brains and to a lesser extent in secondary lymphatic organs and characterized its time course. This is the first study presenting direct evidence of clonal T cell expansion after stroke - however, with delayed kinetics that make antigen-dependent mechanisms unlikely in acute post-ischemic neuroinflammation.


Inhibitory effect of clonidine on cholinergic transmission.
Equilibrium geometry and electronic structure of three local anesthetic molecules and clonidine were computed. It was shown that clonidine molecule could incorporate into local anesthetic binding centers in potential-operated Na+ channels and in ionic channels coupled to nicotinic cholinergic receptors. The modulatory effect of clonidine on contractile responses of skeletal muscle showed that blockade of Na+ channels and nicotinic cholinergic receptors is a part of its analgesic action.


Measurement of Th1, Th2 cytokines and white cell count in childhood haemoglobinopathies with uncomplicated malaria infection.
The relative balance between Th1 and Th2 cytokines appears crucial in the outcome of infections. We assayed the levels of some proinflammatory Th1 cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and anti-inflammatory Th2 cytokines, IL-4 and IL-10 in homozygous haemoglobin (Hb) AA, heterozygous HbAS-genotyped and sickle cell (HbSS) individuals with uncomplicated Plasmodium falciparum malaria. Levels of Th1 and Th2 cytokines of 111 children aged 1-5 years with uncomplicated malaria and 89 healthy controls were determined by enzyme linked immunosorbent assay and haematological parameters were estimated using the automated Swelab counter (Boule Medical, Stockholm, Sweden). Th1 and Th2 cytokine levels were significantly higher in HbAA and HbAS-genotyped patients compared to their respective healthy controls (P<0·05). IFN-gamma, IL-2, and IL-10 were significantly elevated in HbAA compared to HbAS and HbSS subjects (P<0·05). The mean haematological parameters (total white cell count and monocytes) of HbSS-infected children were significantly higher compared to those of HbAA and HbAS subjects (P<0·05); however, their mean packed cell volume was significantly lower compared to others (P<0·05). Our results showed a stronger Th1 cytokine response in HbAA than HbAS and HbSS individuals; this may suggest an immunocompetence of the HbAA individuals in early infection.


Intersectionality and reflexivity-decolonizing methodologies for the data science process.
Using intersectionality as a methodology illuminated the shortcomings of the data science process when analyzing the viral #metoo movement and simultaneously allowed me to reflect on my role in that process. The key is to implement intersectionality to its fullest potential, to expose nuances and inequities, alter our approaches from the standard perfunctory tasks, reflect how we aid and abide by systems and structures of power, and begin to break the habit of recolonizing ourselves as data scientists.


Validation of a new duplex derived haemodynamic effectiveness score, the saphenous treatment score, in quantifying varicose vein treatments.
To evaluate a duplex-derived score for varicose vein treatments using numerical values of haemodynamic effectiveness. The saphenous treatment score (STS) was developed prospectively to compare the effect of endovenous treatments on reflux within saphenous segments. Sixty-six patients were randomised to endovenous laser ablation (EVLA) or ultrasound-guided foam sclerotherapy (UGFS) to the great saphenous vein (GSV). Assessments included the Aberdeen varicose vein severity score (AVVSS), the venous clinical severity score (VCSS), the venous filling index (VFI) and the STS. A mean STS of 5.70 decreased to 3.30, P < .0005, post-treatment. The median (IQR) AVVSS, VCSS and VFI (ml/sec) decreased from 21.52(15.48) to 18.86(11.27), P = .14, from 6(4) to 3(4), P < .0005 and from 7.1(6.9) to 1.9(.9) P < .0005, respectively. In 15 patients requiring additional UGFS the mean STS values decreased from 5.8 to 4.13 and then to 2.6 P < .0005, respectively. The individual above and below knee mean treatment differences in STS on 38 EVLA and 28 UGFS patients were 1.92 and .87 (EVLA) compared to 1.57 and .29 (UGFS) P = .001, respectively. The STS has been shown to grade the haemodynamic effects of different treatments as well as ongoing treatments on the GSV.


Bipolaroxin, a selective phytotoxin produced by Bipolaris cynodontis.
Two sesquiterpenes have been isolated from the fungal pathogen of Bermuda grass Bipolaris cynodontis. Chemical, spectral, and x-ray diffraction studies have led to the characterization of these as bipolaroxin and dihydrobipolaroxin, highly oxygenated members of the eremophilane family. Bipolaroxin is phytotoxic to some but not all of the plants tested. To our knowledge, a phytotoxin with host selectivity isolated from a weed pathogen has not been reported previously.


Two Japanese cases of pigmentary glaucoma followed for 15 and 16 years following laser peripheral iridotomy.
To report two Japanese cases of pigmentary glaucoma (PG) treated with laser peripheral iridotomy (LPI) that were followed for 15 and 16 years, respectively. The medical records of two patients with PG who were successfully treated with LPI were reviewed. Changes in the intraocular pressure (IOP) were followed. Case 1 was that of a 35-year-old man with LPI who underwent argon laser trabeculoplasty twice. He required ocular hypotensive drugs to maintain the IOP at normal levels. Case 2 involved a 36-year-old man with LPI who required ocular hypotensive drugs to maintain his IOP at the low-teen level. The IOP of both patients was unstable during the first 6-8 years following the LPI, but showed a decrease at each annual follow-up examination up to the age of 50 years. Although only two cases were followed, we conclude that the long-term effects of LPI may play a role, at least partly, in stabilizing the IOP at the low-teen level. Both patients were relatively young at the time of the LPI, and age may have been a factor in the stabilization process. Our findings confirm similar findings in Western countries.


SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer.
ORF8 is an accessory protein encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consensus regarding the biological functions of ORF8 is lacking, largely because the fundamental characteristics of this protein in cells have not been determined. To clarify these features, we herein established an ORF8 expression system in 293T cells. Using this system, approximately 41% of the ORF8 expressed in 293T cells were secreted extracellularly as a glycoprotein homodimer with inter/intramolecular disulfide bonds. Intracellular ORF8 was sensitive to the glycosidase Endo H, whereas the secreted portion was Endo-H-resistant, suggesting that secretion occurs via a conventional pathway. Additionally, immunoblotting analysis showed that the total amounts of the major histocompatibility complex class Ι (MHC-I), angiotensin-converting enzyme 2 (ACE2), and SARS-CoV-2 spike (CoV-2 S) proteins coexpressed in cells were not changed by the increased ORF8 expression, although FACS analysis revealed that the expression of the cell surface MHC-I protein, but not that of ACE2 and CoV-2 S proteins, was reduced by ORF8 expression. Finally, we demonstrate by RNA-seq analysis that ORF8 had no significant stimulatory effects in human primary monocyte-derived macrophages (MDMs). Taken together, our results provide fundamental evidence that the ORF8 glycoprotein acts as a secreted homodimer, and its functions are likely associated with the intracellular transport and/or extracellular signaling in SARS-CoV-2 infection.


Special types of muscle anomalies associated with Graves' disease.
This paper discusses two cases of superior oblique paresis, two cases of cyclic hypertropias, and ten cases of large angle esotropia with high myopia. The association with Graves' disease, the treatment, and favorable prognosis in all cases is presented.


Chemotherapy Refractory Spindle-Cell Rhabdomyosarcoma of the Bladder Treated With Consolidative Ovarian-Sparing Radical Surgery.
We present a case of chemotherapy refractory spindle cell rhabdomyosarcoma of the lower urinary tract in a 15-month-old female that ultimately required consolidative surgery with cystectomy, urethrectomy, ovarian-sparing hysterectomy, bilateral salpingectomy, anterior vaginal wall resection, and bilateral pelvic lymph node dissection. Genitourinary reconstruction was performed by ileal conduit creation and vaginoplasty. After completion of her maintenance postoperative chemotherapy regimen, the patient has remained disease-free for approximately 27 months.


Long-term effects of a communication intervention for Spanish-dominant Latinas.
Few studies compare the influence of different types of dietary interventions on the dietary practices of Latinas in the short and long term. The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber. Three-group randomized controlled trial: (1) personalized dietary counseling via lay heath advisors (promotoras) plus tailored print materials delivered via the mail, (2) tailored mailed print materials only, and (3) targeted mailed "off-the-shelf" materials. A total of 357 Latinas were randomly assigned to the three aforementioned conditions. Promotora and tailored print materials. Fat intake (total grams of fat and percent calories from dietary fat) and number of grams of dietary fiber. Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams, and lower levels of energy intake, total saturated fat, total carbohydrates, glucose, and fructose than the targeted group. However, the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved. The high interactivity (i.e., calls, visits) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring, making this type of intervention more effective than the comparison groups in the short term. Further research should explore whether booster sessions involving promotoras help to maintain the impact over time.


Preconsultation exchange for ambulatory hepatology consultations.
Preconsultation exchange is an emerging model of specialty care proposed by the American College of Physicians that seeks to answer a clinical question without a formal patient visit to the specialty clinic. This form of specialty care has been little studied. We sought to determine the appropriateness of preconsultation exchange for ambulatory hepatology consultations within our urban health care system. Retrospective study of referrals for ambulatory hepatology consultation in the safety net health care system of San Francisco, Calif from January 2007 through April 2010. Of the 500 referrals reviewed, 87 were excluded as repeat requests. The most common reasons for referral were hepatitis B (34.9%) and hepatitis C (32.0%). Fifty-six referrals (13.6%) were appropriate for preconsultation exchange, and 190 (46.0%) were inappropriate for preconsultation exchange. One hundred sixty-seven (40.4%) referrals did not include enough information to determine appropriateness for preconsultation exchange. Most of these (83.8%) were made for hepatitis B or hepatitis C, despite the presence of explicit referral guidelines. Midlevel providers were more likely than physicians to provide enough information to determine appropriateness for preconsultation exchange. In our urban health care system, preconsultation exchange appears to be an appropriate form of specialty care for some ambulatory hepatology consultations. Communication between primary care provider and specialist appears to be an important barrier to broader implementation of preconsultation exchange. Optimizing the preconsultation exchange is critical to improve the primary-specialty care interface, and to build a true Patient-Centered Medical Home Neighborhood.


Nested graft for chronic ulcer in scar tissue after heroin extravasation in a drug addict.
Nested graft is a surgical technique that allows to manage difficult-to-treat medical conditions such as chronic cutaneous ulcers, thanks to the high efficacy it has in reverting the fibroblasts senescence. Because of its peculiar regenerative property, nested graft is a surgical technique suitable also for the treatment of cutaneous ulcers developing on fibrotic scar tissue. We reported the case of a 45-year-old man, drug-addict, with a large ulcer on the back of the right forearm in the context of scar fibrotic tissue. This lesion resulted from a previous heroin extravasation treated with a dermo-epidermal skin graft, that was accidentally scratched away by mechanical trauma. After several therapeutic failures with topical medications, we decided to treat the ulcer performing a skin graft using the nested graft technique. No adverse events were reported by the patient during or after the surgery. At the clinical evaluation performed three years later the wound was completely healed. Nested graft represents a safe and easy-to-use technique that can be successfully used to treat ulcers on scar tissue, ensuring the achievement and the long-term maintenance of optimal resistance and aesthetic results.


[Coronary heart disease in childhood in familial hypercholesteremia. Maximum therapy with LDL apheresis].
In children with familial hypercholesterolemia, coronary heart disease requires both medical theraphy and LDL apheresis. We report a case of verified occlusion of the anterior descending branch of the left coronary artery in a 10-year-old patient. The pathological findings revealed by ergometry established the diagnosis. The goal was to achieve the greatest possible reduction of lipid parameters and fibrinogen by lowering plasma viscosity employing LDL apheresis. It is astonishing that this treatment is also well tolerated by children. The basic vascular approaches suffice and shunt operations are not absolutely necessary. The efficacy of this method became vividly apparent by the changes in the skin lesions. Additional angiographic follow-up and further clinical course wil provide information on the usefulness of this treatment strategy with maximum lipid theraphy and the expected improvement in prognosis.


Scanning electron microscopy of Dalkon Shield tails.
Scanning electron micrographs of Dalkon Shield tails removed from asymptomatic patients show a variety of microbes and debris throughout their entire length. Apparently, even in undamaged tails, bacterial flora thrive in the protein-rich environment within the multifilament tail. The presence of microbes in the portion of the tail beyond the double knot indicates that an alternative mechanism of microbial transport can occur. Since transient endometritis often occurs immediately after insertion of intrauterine devices, microbes may come in contact with both exposed ends of the multifilament tail and be drawn into the tail by capillary action from the uterine environment down the tail toward the double knot as well as upward from the vagina. Such microorganisms could serve as an inoculum for infection.


Corneal ulcer of the side port after phacoemulsification induced by Acinetobacter baumannii.
A 75-year-old man had clear corneal phacoemulsification using a temporal approach in the left eye. Two months after surgery, a focal corneal epithelial defect developed with infiltration near the lower limbus on the site of the side-port incision. The culture of corneal scrapping grew Acinetobacter baumannii, which is resistant to most ordinary antibiotics in sensitivity tests. After appropriate antibiotic treatment, the ulcer healed gradually with vessel ingrowth. Acinetobacter baumannii is usually found in nosocomial infection of immune-compromised patients in the intensive care unit. It is a rare pathogen of infectious keratitis. Our case, with its unusual infection site, may point to potential risk factors for this pathogen.


A promising immunosuppressive strategy of cyclosporine alternately combined with levamisole is highly effective for moderate aplastic anemia.
The appropriate management of patients with moderate aplastic anemia (mAA) remains to be unclear and controversial. A cohort of 118 patients with mAA received a novel immunosuppressive strategy of cyclosporine alternately combined with levamisole (CSA and LMS regimen), which included 42 newly diagnosed and 76 chronic (disease duration >6 months) cases. CSA and LMS regimen was orally administrated with the initial dose of CSA 3 mg/kg per day in adults or 5 mg/kg per day in children, and LMS 150 mg per day in adults or 2.5 mg/kg per day in children, continued for 12 more months after achieving maximal hematologic response, followed by a slow tapering. The overall response rates were of 100 and 86.8 % for newly diagnosed and chronic group, respectively. The 24-month progression-free survival were 95.2 % (95 % confidence intervals [CI], 85.9-100 %) and 93.6 % (95 % CI, 86.9-100 %) for newly diagnosed and chronic group, respectively (P = 0.50). The 2-year event-free survival for the patients in newly diagnosed group (86.6 %; 95 % CI, 70.4-100 %) was superior to that in chronic group (57.0 %; 95 % CI, 43.5-70.4 %, P = 0.001). To date, 11 patients relapsed and no patients evolved to clonal disorders. Thus, CSA and LMS regimen represents a promising immunosuppressive strategy for mAA.


Selective peroxisome proliferator-activated receptor-α modulator K-877 regulates the expression of ATP-binding cassette transporter A1 in pancreatic beta cells.
ATP-binding cassette transporter A1 (ABCA1) protein is a pivotal regulator of cholesterol and phospholipid efflux from cells to high-density lipoprotein (HDL) particles. Pancreatic ABCA1 functions in beta cell cholesterol homeostasis and affects insulin secretion. We investigated the effect of pemafibrate (K-877), a novel selective PPARα modulator (SPPARMα), on pancreatic ABCA1 expression. In vivo experiment, mice were divided into four treatment groups, namely, normal food plus placebo, high fat diet (HFD) plus placebo, normal food plus K-877 (0.3 mg/kg/day), or HFD plus K-877 (0.3 mg/kg/day), and treated for eight weeks. The results in vitro experiment indicate that K-877 treatment increased levels of ABCA1 mRNA, as well as protein, subsequently reduced the cellular cholesterol content in INS-1 cells. PPARα specific antagonist GW6471 attenuate K-877 induced ABCA1 expression in INS-1 cells. ABCA1 promoter activity increased with K-877 treatment at concentration 1 μM and 10 μM. Glucose-stimulated insulin secretion was ameliorated by K-877 treatment in INS-1 cells and isolated mouse islets. Although the expression of ABCA1 was reduced in mice with HFD treatment, both ABCA1 protein and mRNA levels were increased in mice with K-877 treatment. K-877 treatment improved glucose intolerance induced by HFD in mice. These findings raise the possibility that K-877 may affect insulin secretion by controlling ABCA1 expression in pancreatic beta cells.


Proteus syndrome: what the anesthetist should know.
Proteus syndrome (PS), a rare hamartomatous disorder, manifests itself in asymmetric and disproportionate overgrowth of multiple body tissues. Because of complexity of the disorder, the anesthetic problems encountered during patients' perioperative management are very varied. We discuss the case of a 14-year-old adolescent boy diagnosed with PS who underwent corrective osteotomy of right knee joint under subarachnoid block. The salient points the anesthetists need to be aware of while caring for patients with PS are highlighted.


Divergence function, duality, and convex analysis.
From a smooth, strictly convex function phi: Rn --> R, a parametric family of divergence function Dphi(alpha) may be introduced: [ equation: see text] for x, y epsilon int dom (Phi) subset Rn, and for alpha in R, with Dphi(+/-1) defined through taking the limit of alpha. Each member is shown to induce an alpha-independent Riemannian metric, as well as a pair of dual alpha-connections, which are generally nonflat, except for alpha = +/-1. In the latter case, Dphi(+/-1) reduces to the (nonparametric) Bregman divergence, which is representable using phi and its convex conjugate phi* and becomes the canonical divergence for dually flat spaces (Amari, 1982, 1985; Amari & Nagaoka, 2000). This formulation based on convex analysis naturally extends the informationgeometric interpretation of divergence functions (Eguchi, 1983) to allow the distinction between two different kinds of duality: referential duality (alpha <--> -alpha) and representational duality (phi <--> phi*). When applied to (not necessarily normalized) probability densities, the concept of conjugated representations of densities is introduced, so that +/-alpha-connections defined on probability densities embody both referential and representational duality and are hence themselves bidual. When restricted to a finite-dimensional affine submanifold, the natural parameters of a certain representation of densities and the expectation parameters under its conjugate representation form biorthogonal coordinates. The alpha representation (indexed by beta now, beta epsilon [-1, 1]) is shown to be the only measure-invariant representation. The resulting two-parameter family of divergence functionals D(alpha,beta), (alpha, beta) epsilon [-1, 1] x [-1, 1] induces identical Fisher information but bidual alpha-connection pairs; it reduces in form to Amari's alpha-divergence family when alpha = +/-1 or when beta = 1, but to the family of Jensen difference (Rao, 1987) when beta = -1.


Risk factors and trajectories of opioid use following total knee replacement.
Opioids are commonly used to manage orthopedic pain in those undergoing total knee arthroplasty (TKA). There are limited studies assessing patterns of perioperative opioid use and risk factors for chronic use in patients undergoing TKA. This is a retrospective longitudinal cohort study of Medicaid enrollees undergoing TKA between 2014 and 2017 using de-identified medical and pharmacy claims. The primary outcome was chronic opioid use (opioid prescription filled 90-270 days following TKA). Trajectory group membership was determined by identifying distinct groups of patients with similar patterns of daily morphine milligram equivalent (MME) values during the postsurgery follow-up period. In total, 1666 TKA surgeries performed in 1507 patients were included; 69% of patients were classified as chronic opioid users. Multivariable analyses identified prior opioid use, high opioid doses during the month after TKA, concomitant mood therapies and benzodiazepines, and comorbid conditions as important risk factors. Group-based trajectory analysis identified five distinct post-TKA surgery opioid use phenotypes with several key characteristics predicting group membership. This large-scale analysis demonstrated that chronic opioid use was common after TKA surgery and established several important risk factors for chronic use following TKA. Novel analysis revealed five distinct opioid use trajectories and identified key characteristics to help guide clinicians when determining perioperative opioid use. Results demonstrate that interventional studies attempting to reduce opioids after TKA are needed if reductions in long-term use are to be realized in this high-risk patient population.


Brief communication: factors affecting rehospitalisation in psychiatric patients in Singapore.
To study the patterns of readmission in Singapore using a cohort of first admission schizophrenia patients to the state mental health institute. A retrospective analysis of case records was done of first admission schizophrenia patients to the hospital from April 1993 to March 1994. Patients who had only one admission in the five years of follow up were compared to 'revolving door patients'. The cohort comprised 133 males (56.8%) and 101 females (43.2%). Seventy-eight patients (33.3%) had one admission to the hospital while 56 (23.9%) fulfilled the revolving door criteria. On performing a logistic regression we found sex (p = 0.02), shorter duration of illness (p = 0.01) and CPN referral (0.006) were significantly associated with revolving door phenomena. Our study has identified male gender, history of self-harm and a short duration of illness to be risk factors for 'revolving door' phenomena.


Clinical results of ab interno trabeculotomy using the Trabectome in patients with pigmentary glaucoma compared to primary open angle glaucoma.
To evaluate outcomes of Trabectome on pigmentary glaucoma (PG) patients compared to matched controls with primary open angle glaucoma (POAG). Prospective comparison study PARTICIPANTS: A total of 101 POAG cases were matched with 101 PG cases. Data of the patients diagnosed with PG or POAG was obtained from Trabectome Study Group Database. A one-to-one exact matching was performed between POAG and pigmentary cases based on type of surgery, baseline IOP and baseline number of glaucoma medications. IOP and number of glaucoma medications were compared between groups by Wilcoxon test. Success was defined as IOP ≤ 21 mmHg, at least 20% IOP reduction from baseline for two consecutive visits after 3 months and no secondary surgery. Success rate after Trabectome surgery in PG patients. Baseline IOP for PG is 24.4 ± 7.7 mmHg and 24.2 ± 7.5 mmHg for POAG (P = 1.0), while baseline number of glaucoma medications was 2.8 ± 1.2 mmHg for PG and 2.8 ± 1.2 mmHg for POAG (P = 1.0). Postoperative IOP values at 12 months were 17.1 ± 5.0 for PG cases and 15.9 ± 4.2 mmHg for POAG cases. Postoperative number of glaucoma medications at 12 month was 2.1 ± 1.4 in PG cases and 2.4 ± 1.3 in POAG cases. There was no statistically significant difference between groups in IOP or number of medications at any time point. Survival rate at 12 months was 92% and 86% in PG and POAG, respectively (P = 0.47). Six PG cases and nine POAG cases required secondary surgery. Trabectome provides similar outcomes to PG patients and POAG patients.


Metabolizable Energy of Soybean Meal and Canola Meal as Influenced by the Reference Diet Used and Assay Method.
A 21-day experiment was conducted to study the effect of reference diet type and assay method on apparent metabolizable energy (AME) and nitrogen-corrected (AMEn) of soybean meal (SBM) and canola meal (CM). Broilers (n = 240) were allocated to 10 treatments with eight replicates/treatment and three birds/replicate. Treatments included corn-SBM or corn-CM reference diets (RD). To each RD, 300 or 450 g/kg of SBM or CM were added to make a total of eight test diets. For the difference method, AME of SBM and CM substituted at 300 g/kg in corn-CM RD gave greater AME values compared to inclusion in the corn-SBM RD. The AMEn of SBM increased with increase in inclusion level in the corn-CM RD but AMEn of CM decreased with increased inclusion level of CM in the corn-SBM RD. For the regression method, AME and AMEn of the test feedstuffs were greater with corn-CM RD compared with corn-SBM RD. The AME of SBM was not affected by assay method, whereas AME of CM was lower when determined using the regression method. In conclusion, both the reference diet type and assay method influenced assayed AME and AMEn value of test protein feedstuffs and should be considered in cross-studies comparisons.


Antigenic sites of the nicotinic acetylcholine receptor cannot be predicted from the hydrophilicity profile.
The amino acid sequences of the polypeptide chains of the acetylcholine receptor have recently been published. From the hydrophilicity profiles, it has been proposed that residues 161-166 of the alpha-chain might be an important antigenic site. We have synthesised a peptide containing this sequence and raised antisera to it. Here we report that this peptide does not represent an important antigenic site on the molecule, and that this region is probably inaccessible to antibodies. Based on the known DNA sequences and hydrophilicity profiles of the receptor chains, we suggest that many regions of high hydrophilicity may represent inter-domain regions of proteins.


Outcomes of video training on smoking cessation counseling for nurses.
Lack of smoking cessation education hinders nurses in providing adequate tobacco cessation counseling. Video training on smoking cessation counseling for nurses was developed and assessed for its short-term outcomes on knowledge and self-efficacy. A quasi-experimental study using pretest-posttest design was conducted with nurses in Thailand in 2020. A total of 126 nurses received online video training. Patient-nurse role-playing was used to demonstrate cessation counseling for smokers who are in the contemplation and preparation stage. Motivational interviewing techniques were emphasized throughout the video. Knowledge and self-efficacy in smoking cessation counseling were assessed pre and post training by a questionnaire. Comparisons of the pre and post training, mean score of knowledge (10.75 ± 2.39 vs 13.01 ± 2.86, t=7.716, p<0.001) and self-efficacy in smoking cessation counseling (3.70 ± 0.83 vs 4.36 ± 0.58, t=11.187, p<0.001) were significantly increased. These positive learning outcomes were found in nurses with experience and no experience in cessation counseling (p<0.001). This study shows that video training can improve nurses' knowledge and confidence in smoking cessation counseling. It could therefore be included in nursing continuing education to improve nurses' knowledge and confidence in smoking cessation services.


Placental abnormalities associated with post-natal mortality in sheep somatic cell clones.
We report on cloning experiments designed to explore the causes of peri- and post-natal mortality of cloned lambs. A total of 93 blastocysts obtained by nuclear transfer of somatic cells (granulosa cells) were transferred into 41 recipient ewes, and pregnancies were monitored by ultrasound scanning. In vitro derived, fertilized embryos (IVF, n=123) were also transferred to assess oocyte competence, and naturally mated ewes (n=120) were analysed as well. Cloned embryos developed to the blastocyst stage and implanted at the same rate as IVF embryos. After day 30 of gestation, however, dramatic losses occurred, and only 12 out of 93 (13%) clones reached full-term development, compared to 51 out of 123 (41.6%) lambs born from the IVF control embryos. Three full-term lamb clones were delivered stillborn, as a result of placental degeneration. A further five clone recipients developed hydroallantois. Their lambs died within 24h following delivery by caesarian section, and displayed degenerative lesions in liver and kidney resulting from the severe hydroallantois. One set of twins was delivered by assisted parturition at day 150, but died 24h later due to respiratory distress syndrome. The remaining two clone recipients underwent caesarian section, and the corresponding two lambs displayed signs of respiratory dysfunction and died at approximately 1 month of age due to a bacterial complication. Blood samples collected from the cloned lambs after birth revealed a wide range of abnormalities indicative of kidney and liver dysfunction. Macroscopical and histopathological examination of the placentae revealed a marked reduction in vascularization, particularly at the apex of the villous processes, as well as a loss of differentiation of the trophoblastic epithelium. Our results strongly suggest that post-mortality in cloned lambs is mainly caused by placental abnormalities.


Rotavirus infection stimulates the Cl- reabsorption process across the intestinal brush-border membrane of young rabbits.
Rotavirus is a major cause of infantile gastroenteritis worldwide. However, the mechanisms underlying fluid and electrolyte secretion associated with diarrhea remain largely unknown. We investigated the hypothesis that loss of Cl(-) into the luminal contents during rotavirus infection may be caused by a dysfunction in the chloride absorptive capacity across the intestinal brush-border membrane (BBM). The luminal Cl(-) concentrations in the entire small intestine of young rabbits infected with lapine rotavirus decreased at 1 and 2 days postinfection (dpi), indicating net Cl(-) absorption. At 7 dpi, luminal Cl(-) concentrations were slightly increased, indicating a moderate net Cl(-) secretion. By using a rapid filtration technique, (36)Cl uptake across BBM was quantified by modulating the alkali-metal ion, electrical, chloride, and/or proton gradients. Rotavirus infection caused an identical, 127% +/- 24% increase in all Cl(-) uptake activities (Cl(-)/H(+) symport, Cl(-) conductance, and Cl(-)/anion exchange) observed across the intestinal BBM. The rotavirus activating effects on the symporter started at 1 dpi and persisted up to 7 dpi. Kinetic analyses revealed that rotavirus selectively affected the capacity parameter characterizing the symporter. We report the novel observation that rotavirus infection stimulated the Cl(-) reabsorption process across the intestinal BBM. We propose that the massive Cl(-) reabsorption in villi could partly overwhelm chloride secretion in crypt cells, which possibly increases during rotavirus diarrhea, the resulting imbalance leading to a moderate net chloride secretion.