Novel synthesis of fibronectin derived photoluminescent carbon dots for bioimaging applications.
Fibronectin (FN) derived from human plasma has been used for the first time as the carbon precursor in the top-down, microwave-assisted hydrothermal synthesis of nitrogen doped carbon dots (CDs). FN is a large glycoprotein primarily known for its roles in cell adhesion and cell growth. Due to these properties FN can be over expressed in the extracellular matrix (ECM) of some cancers allowing FN to be used as an indicator for the detection of cancerous cells over non-cancerous cells. These FN derived CDs display violet photoluminescence with UV excitation and appear to possess similar functional groups on their surface to their carbon precursor (-COOH and -NH2). This is believed to be due to the self-passivation of the CDs' nitrogen-containing surface functional groups during the heating process. These CDs were then used to stain MCF-7 and MDA-231 breast cancer cells and were observed to interact primarily with the cell membrane rather than intercalating into the cell like the many other types of CDs. This led to the hypothesis that the CDs are selectively binding to the FN overexpressed within the cancer cells' ECM via amide linkages. This is in agreement with the EDX and FTIR spectra of the FN CDs which indicate the presence of -COOH and nitrogen containing surface groups like -NH3. The inherent selectivity of the CDs combined with their ability to photoluminesce enables their use as a fluorophore for bioimaging applications.


Assessment of Confocal Microscopy for the Diagnosis of Polymerase Chain Reaction-Positive Acanthamoeba Keratitis: A Case-Control Study.
To determine in vivo confocal microscopy diagnostic criteria to diagnose Acanthamoeba keratitis (AK) using polymerase chain reaction (PCR) as the reference diagnostic technique. Retrospective case-control study. Data were recorded prospectively and analyzed retrospectively. Fifty patients with PCR-positive AK (study group) and 50 patients with bacterial, fungal, viral, or immune keratitis featuring negative Acanthamoeba PCR results (control group). In vivo confocal microscopy performed at the acute stage of keratitis. Presence of in vivo confocal microscopy images suggestive of AK. Multivariate logistic regression was used to determine the relationship between types of images and presence of PCR-positive AK. The following 4 types of images were associated significantly with PCR-positive AK (P < 0.05): bright spots (round or ovoid hyperreflective objects with no double wall; diameter, <30 μm); target images (hyperreflective objects with hyporeflective halo; diameter, <30 μm); clusters of hyperreflective objects (diameter, <30 μm); and trophozoite-like objects (diameter, >30 μm). Specificity of both target and trophozoite images was 100%. This figure was 98.2% for clusters and 48.2% for bright spots. If the diagnosis of AK was made on presence of target images, clusters or trophozoite images (at least 1 of the 3 features), the positive predictive value of confocal microscopy was 87.5% and the negative predictive value was 58.5%. Acanthamoeba keratitis is a serious vision-threatening disease. In vivo confocal microscopy can help in this challenging diagnosis, especially when PCR is delayed, shows negative results, or is not available. Target images and trophozoite-like images are pathognomonic of AK. Clusters of hyperreflective objects are highly specific of AK. However, the overall sensitivity of in vivo confocal microscopy features of AK is low. In addition to the clinical features, microbiological tests (direct examination and cultures of corneal scrapings), and PCR, in vivo confocal microscopy allows for more rapid diagnosis and treatment initiation, potentially leading to an improved outcome.


Safety of acupuncture by Korean Medicine Doctors: a prospective, practice-based survey of 37,490 consultations.
To evaluate safety of acupuncture treatment by Korean Medicine Doctors (KMDs), a prospective, practice-based survey on adverse events (AEs) associated with acupuncture was conducted. From July 2016 to October 2017, KMDs were invited to participate in an online survey. Frequency was calculated as the number of AEs per 10,000 treatments; severity was assessed with the Common Terminology Criteria for Adverse Events Grading (Severity) Scale; and causality was evaluated using the World Health Organisation-Uppsala Monitoring Centre system for standardised case causality assessment. Associations between AE occurrence and KMDs' type of practice/clinical experience and patient age/gender/current medication(s) were analysed. Data on 37,490 acupuncture treatments were collected from 222 KMDs. At least one AE was reported from 4,518 acupuncture treatments, giving a frequency rate of 1,205 per 10,000 acupuncture treatments; this increased to 4,768 treatments when administrative problems related to defective devices or medical negligence were added, for a rate of 1,272 per 10,000 acupuncture treatments. Commonly reported AEs were bleeding, needle site pain, and bruising. Approximately 72.9% of AEs/administrative problems were assessed as they certainly occurred by acupuncture treatment in causality assessment. Most AEs/administrative problems were considered mild in severity and two life-threatening AEs were resolved with no sequelae. Compared to males, female patients were more likely to experience AEs and KMDs' clinical experience was not associated with reported AE occurrence. Although acupuncture-associated AEs occur commonly, they are largely transient and mild. Acupuncture performed by qualified KMDs may serve as a reliable medical treatment with acceptable safety profiles.


Biomonitoring of thallium availability in two estuaries of southwest England.
Thallium is a highly toxic metal whose biogeochemical behaviour in the marine environment is poorly understood. We measured Tl in sediments, macroalgae (Fucus vesiculosus and Fucus ceranoides) and deposit-feeding invertebrates (Hediste diversicolor, Arenicola marina and Scrobicularia plana) from two estuaries of south west England (Plym and Fal) draining mineralised catchments. In the Plym, and for a given sample type, concentrations of Tl were rather invariant between sample locations and averaged about 500 μg kg(-1) for sediment, 30 μg kg(-1) for macroalgae and 10 μg kg(-1) for the invertebrates. In the Fal, respective concentrations were of a similar order of magnitude but exhibited greater variation between sample locations. Normalisation of Tl concentrations to K, the biogeochemical analogue of Tl(+), revealed bioenrichment of about 20 for all organisms in the Plym and bioenrichment ranging from about 3 (H. diversicolor) to 170 (F. ceranoides) in the Fal. Despite the low bioaccumulation of Tl relative to other metals measured concurrently, it is recommended that Tl be more closely monitored and better studied in the estuarine environment.


Towards Multifractality through an Ernst-Type Potential in Complex Systems Dynamics.
Some possible correspondences between the Scale Relativity Theory and the Space-Time Theory can be established. Since both the multifractal Schrödinger equation from the Scale Relativity Theory and the General Relativity equations for a gravitational field with axial symmetry accept the same SL(2R)-type invariance, an Ernst-type potential (from General Relativity) and also a multi-fractal tensor (from Scale Relativity) are highlighted in the description of complex systems dynamics. In this way, a non-differentiable description of complex systems dynamics can become functional, even in the case of standard theories (General Relativity and Quantum Mechanics).


Developing a predictive model for an emerging epidemic on cassava in sub-Saharan Africa.
The agricultural productivity of smallholder farmers in sub-Saharan Africa (SSA) is severely constrained by pests and pathogens, impacting economic stability and food security. An epidemic of cassava brown streak disease, causing significant yield loss, is spreading rapidly from Uganda into surrounding countries. Based on sparse surveillance data, the epidemic front is reported to be as far west as central DRC, the world's highest per capita consumer, and as far south as Zambia. Future spread threatens production in West Africa including Nigeria, the world's largest producer of cassava. Using innovative methods we develop, parameterise and validate a landscape-scale, stochastic epidemic model capturing the spread of the disease throughout Uganda. The model incorporates real-world management interventions and can be readily extended to make predictions for all 32 major cassava producing countries of SSA, with relevant data, and lays the foundations for a tool capable of informing policy decisions at a national and regional scale.


Successful word retraining, maintenance and transference of practice to everyday activities: A single case experimental design in early onset alcohol-induced brain damage.
Word retraining programs have been shown to improve naming ability post-stroke and in progressive aphasias. Here, we investigated benefits for a 22-year-old Danish man (DJ), whose difficulties followed brain damage from heavy alcohol misuse. Using a multiple baseline-across-behaviours design (target behaviour: retrieval of word list items), DJ completed a 4-week "Look, Listen, Repeat" program on a computer. Ninety personally relevant target words were selected to create three matched lists. List 1 was trained for 10 sessions over 2 weeks, followed by 9 sessions for List 2 over 2 weeks, while the third list remained untrained. Naming performance was evaluated at baseline, during the intervention, and at 1 and 4 months post-training. Naming improved following each intervention block (p < .001), with only one data point overlapping between the baseline and treatment phases for trained items. Untrained words remained unchanged (p = 1.00), with 50% of data points non-overlapping across baseline to treatment phases. Performance was maintained over time, and appeared to generalize, with DJ naming more trained objects in their natural setting (85%) than untrained items (64%). While more evidence is needed, brief (20-minute), intensive (5-day/week) word retraining programs may assist word retrieval for people with brain damage associated with alcohol misuse.


Humanizing bone marrow in immune-deficient mice.
Humanized mice are useful for studying human hematopoietic stem cells (HSCs) and their niche. In particular, clonal study of human HSC enables precise comparison of in vivo behavior between murine and human HSCs. A single HSC is able to reconstitute hematopoiesis even after serial transplantations in mice. While the life span of somatic cells is over that of individual in mice, this is not the case in humans. Clonal studies of human HSCs clearly demonstrated their aging in hosts. Since murine studies have demonstrated that HSCs are protected from aging by their niche in bone marrow, the humanizing niche model will reveal the precise mechanism by which human HSCs are protected from exhaustion in vivo. Direct transplantation of human mesenchymal stem cells into mouse bone marrow results in reconstitution of the functional human hematopoietic microenvironment comprised of pericytes, myofibroblasts, reticular cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells. These humanized mouse models are essential for testing whether the insights on hematopoiesis from mouse studies are applicable to humans before clinical application.


Decellularization optimizes the inhibitory microenvironment of the optic nerve to support neurite growth.
Allogeneic or homologous tissue transplantation is an effective strategy to repair tissue injury. However, the central nervous tissues like the brain, spinal cord, and optic nerve are not ideal materials for nervous tissue regeneration due to the excessive axonal inhibitor cues in their microenvironments. In the present study, we found that decellularization optimizes the function of the adult optic nerve in supporting the oriented outgrowth of dorsal root ganglion (DRG) neurites. The neurites growing on the decellularized optic nerve (DON) showed longer extension distances than those growing on the normal optic nerve (ON). Neurite branching was also significantly increased on the DON compared to on the ON. Decellularization selectively removed some axon-inhibitory molecules such as myelin-associated glycoprotein (basically not detected in DON) and chondroitin sulfate proteoglycans (detected in DON at a level less than 0.3 fold that in ON) and preserved some axon-promoted extracellular matrix (ECM) proteins, including collagen IV and laminin (detected at levels 6.0-fold higher in DON than in ON). Furthermore, collagen IV and laminin were shown to be preserved in DON, and their binding activities with integrin α1 were retained to promote the extension of DRG neurites. Together, the findings provide a feasible way to optimize the axon-inhibited microenvironment of central nervous tissues and establish a theoretical basis for the application of DON scaffolds in repairing central nervous injury.


Degradation of microinjected methylated and unmethylated proteins in hepatoma tissue culture cells.
Radioiodinated proteins were introduced into hepatoma tissue culture (HTC) cells by erythrocyte ghost-mediated microinjection, and their degradation was studied. 125I-bovine serum albumin and 125I-lysozyme were degraded with half-lives of about 7 and 11 h, respectively. The process was ATP-dependent. The breakdown of these proteins was not inhibited by the following inhibitors of lysosomal proteolysis: NH4Cl, methylamine, chloroquine, leupeptin, or antipain. Methylation of 94% of the amino groups of bovine serum albumin or 99% of the amino groups of lysozyme had little effect on the rates of their degradation in HTC cells. In contrast, methylation almost completely inhibited the ATP-dependent proteolysis of both proteins in reticulocyte lysates. Methylated bovine serum albumin was not detectably demethylated in HTC cells. It is concluded that in HTC cells, bovine serum albumin and lysozyme are degraded by a nonlysosomal pathway which differs from the ubiquitin-dependent proteolysis system of reticulocytes in that it does not require free amino groups.


The use of the laryngeal mask airway and Combitube in cardiopulmonary resuscitation; a national survey.
The laryngeal mask airway (LMA) and Combitube have been recommended for use during cardiopulmonary resuscitation (CPR). An overview of current practice was sought by conducting a postal survey of 265 Resuscitation Training Departments, at different hospitals, throughout the UK. One hundred fifty-three (58%) completed questionnaires were returned. Only 38 (25%) hospitals which replied were currently using the LMA in resuscitation while seven (5%) were using the Combitube. The reasons for not using these airway adjuvants included concerns about airway protection, difficulties in training, cost, and the concept that when anaesthetists were available on cardiac arrest teams these devices were unnecessary.


Cost of a group translation of the Diabetes Prevention Program: Healthy Living Partnerships to Prevent Diabetes.
Although numerous studies have translated the Diabetes Prevention Program lifestyle intervention into various settings, no study to date has reported a formal cost analysis. To describe costs associated with the Healthy Living Partnerships to Prevent Diabetes (HELP PD) trial. HELP PD was a 24-month RCT testing the impact of a lifestyle weight-loss intervention administered through a diabetes education program and delivered by community health workers (CHWs) on blood glucose and body weight among prediabetics. In all, 301 participants with prediabetes were randomized in Forsyth County NC. Data reported in these analyses were collected in 2007-2011 and analyzed in 2011-2012. The lifestyle weight-loss group had a 7% weight loss goal achieved and maintained by caloric restriction and increased physical activity. The usual care group received two visits with a registered dietitian and monthly newsletters. Measures are direct medical costs, direct nonmedical costs, and indirect costs over the 2-year study period. Research costs are excluded. The direct medical cost (in 2010 dollars) to identify one participant was $16.85. Direct medical costs per capita for participants in the usual care group were $142 and $850 for lifestyle weight-loss participants. Per capita direct costs of care outside the study were $7454 for the usual care group and $5177 for the lifestyle weight-loss group. Per capita direct nonmedical costs were $12,881 for the usual care group and $13,836 for the lifestyle weight-loss group. The lifestyle weight-loss group in HELP PD cost $850 in direct medical costs for 2 years, compared to $2631 in direct medical costs for the first 2 years of DPP. A community-based translation of the DPP can be delivered effectively and with reduced costs.


Cardiovascular and antiarrhythmic effects of aprindine (AC1802) during partial occlusion of a coronary artery in the pig.
The effect of intravenously administered aprindine (AC1802) as a prophylactic agent against ventricular arrhythmias was studied in pigs. During the first 30 min of ischaemia 5 of the 22 untreated animals died because of ventricular fibrillation against 1 of the 23 animals pretreated with aprindine (P=0.09). Ventricular tachycardias were observed in 10 untreated animals and in none of the aprindine group (P=0.0002). The incidence of other arrhythmias was significantly less in the aprindine group compared with the untreated group (P less than 0.02).


Left-right ventricular interactions in pediatric aortic stenosis: right ventricular myocardial strain before and after aortic valvuloplasty.
Ventricular-ventricular interactions may affect left ventricular (LV) and right ventricular (RV) function but have not been well characterized in chronic LV afterload in children. The aim of this study was to assess RV myocardial strain in children with aortic stenosis before and after aortic balloon valvuloplasty. Two-dimensional echocardiographic images from children aged > 1 month were with aortic stenosis and preserved LV ejection fractions were retrospectively studied using vector velocity imaging. LV and RV strain were compared before and after balloon valvuloplasty and in comparison with normal controls. Twenty-six children were studied. Aortic valve gradient decreased after balloon valvuloplasty. LV ejection fraction, wall thickness, circumferential strain, and basal and mid longitudinal strain were unchanged after valvuloplasty (-18.09 ± 6.97% vs -16.43 ± 6.30%, P = .40, and -14.11 ± 5.011% vs -13.12 ± 5.52%, P = .50, respectively). LV strain tended to be lower than in controls after valvuloplasty (basal, -16.43 ± 6.30% vs -19.77 ± 5.82%, P = .05). RV strain was unchanged at the basal and apical segments but increased at the mid RV segment after valvuloplasty (-21.34 ± 6.55% vs -24.97 ± 8.54%, P = .02). Change in RV strain was not correlated with change in aortic gradient or change in LV strain after valvuloplasty (P = .60). LV and RV strain at baseline and their changes after valvuloplasty were variable between patients. RV strain was normal or reduced in compensated aortic stenosis and was not correlated with LV strain. The change in RV strain was variable among patients after valvuloplasty, with improvement in RV midwall longitudinal strain.


Draft Genome Sequence of Lactobacillus plantarum SF2A35B.
The lactic acid bacterium Lactobacillus plantarum is intensively studied as a model probiotic species. Here, we present the draft genome sequence of the exopolysaccharide-producing strain SF2A35B.


Protein intake in the early recovery period after exhaustive exercise improves performance the following day.
The aim of the present study was to investigate the effect of protein and carbohydrate ingestion during early recovery from exhaustive exercise on performance after 18-h recovery. Eight elite cyclists (V̇o2max: 74.0 ± 1.6 ml·kg-1·min-1) completed two exercise and diet interventions in a double-blinded, randomized, crossover design. Participants cycled first at 73% of V̇o2max (W73%) followed by 1-min intervals at 90% of V̇o2max until exhaustion. During the first 2 h of recovery, participants ingested either 1.2 g carbohydrate·kg-1·h-1 (CHO) or 0.8 g carbohydrate + 0.4 g protein·kg-1·h-1 (CHO + PROT). The diet during the remaining recovery period was similar for both interventions and adjusted to body weight. After an 18-h recovery, cycling performance was assessed with a 10-s sprint test, 30 min of cycling at W73%, and a cycling time trial (TT). The TT was 8.5% faster (41:53 ± 1:51 vs. 45:26 ± 1:32 min; P < 0.03) after CHO + PROT compared with CHO. Mean power output during the sprints was 3.7% higher in CHO + PROT compared with CHO (1,063 ± 54 vs. 1,026 ± 53 W; P = 0.01). Nitrogen balance in the recovery period was negative in CHO and neutral in CHO + PROT (-82.4 ± 11.5 vs. 7.0 ± 15.4 mg/kg; P < 0.01). In conclusion, TT and sprint performances were improved 18 h after exhaustive cycling by CHO + PROT supplementation during the first 2 h of recovery compared with isoenergetic CHO supplementation. Our results indicate that intake of carbohydrate plus protein after exhaustive endurance exercise more rapidly converts the body from a catabolic to an anabolic state than carbohydrate alone, thus speeding recovery and improving subsequent cycling performance.NEW & NOTEWORTHY Prolonged high intensity endurance exercise depends on glycogen utilization and high oxidative capacity. Still, exhaustion develops and effective recovery strategies are required to compete in multiday stage races. We show that coingestion of protein and carbohydrate during the first 2 h of recovery is superior to isoenergetic intake of carbohydrate to stimulate recovery, and improves both endurance time-trial and 10-s sprint performance the following day in elite cyclists.


Intonation in partner accommodation for aphasia: a descriptive single case study.
Previous research has suggested that speaking partners adjust their intonation when conversing with people who are ill or elderly. In the descriptive case study presented in this paper we ask, what adjustments in intonation might be made by the communication partner of an aphasic speaker? A sociolinguistic, semantic analysis of intonation was used to describe the intonation pattern used by the neighbor of an aphasic speaker, during a 15-min natural interaction with the aphasic speaker, his wife, and the first author. The neighbor was found to make more use of two dimensions of intonation that reflected differences in her relationship to the information conveyed, when addressing the aphasic speaker in contrast to when addressing his wife. Firstly, she made proportionally more use of pitch movements associated with referring to shared information, and secondly, she made more use of marked tones (rising-falling, and rising tones). We discuss whether the observed differences may represent an accommodation to speaking to a person with aphasia. The reader will be able: (1) to recognize the role of intonation in discourse as a resource for the exchange of interpersonal meaning, and (2) to identify when speakers are using intonation as part of their speech accommodation for aphasia.


Preliminary Extracellular Vesicle Profiling in Drainage Fluid After Neck Dissection in OSCC.
Lymph node metastasis is related to poor prognosis in oral squamous cell carcinoma (OSCC), and few studies have explored the relevance of postoperative drainage fluid (PDF) in metastasis. Extracellular vesicles (EVs) are nanosized vesicles that can transfer oncogenic molecules to regulate tumorigenesis. However, the proteomic profile of postoperative drainage fluid-derived EVs (PDF-EVs) in OSCC has not been elucidated. Herein, we collected drainage fluid from OSCC patients after neck dissection to investigate the difference in PDF-EVs between patients with metastatic lymph nodes (the LN+ group) and nonmetastatic lymph nodes (the LN- group). The proteomic profile of PDF-EVs from the LN+ and LN- groups was compared using label-free liquid chromatography tandem-mass spectrometry-based protein quantification. The results revealed that PDF-EVs were mainly derived from epithelial cells and immune cells. A total of 2,134 proteins in the PDF-EVs were identified, and 313 were differentially expressed between the LN+ and LN- groups. Metabolic proteins, such as EHD2 and CAVIN1, were expressed at higher levels in the LN+ group than in the LN- group, and the levels of EHD2 and CAVIN1 in the postoperative drainage fluid were positively correlated with lymph node metastasis. Our study revealed previously undocumented postoperative drainage fluid-associated proteins in patients with metastatic OSCC, providing a starting point for understanding their role in metastatic and nonmetastatic OSCC.


Lympho-epithelial thymomas. A retrospective study of 88 resections.
Of 113 lympho-epithelial thymomas retrospectively studied, 56 were epithelial, 20 lymphocytic, 30 mixed and 7 were undefined forms. There were 88 resections (20 stage I, 47 stage II, 13 stage III and 8 stage IV). There were 69 primary resections (followed by radiotherapy in 54 cases) of which 57 were complete and 12 were incomplete. There were 19 secondary resections after radiotherapy: 10 were complete and 9 were incomplete and 25 patients were not operated upon and were treated by radio- and chemotherapy. After primary resection, the actuarial 5-year survival is 64.07% and the 10-year survival is 50.86%. After a secondary resection, the 5 year-survival is 43.74%. After non-surgical treatment, it is 18.67%. After surgery, the prognostic importance of staging is confirmed as more important than the cellular structure. Myasthenic patients are subject to late accidents. Postoperative radiotherapy seems to be justified, but its effect is not statistically significant when resection is complete. Post-radiotherapy surgery is beneficial only in cases of complete resection. The metastatic evolution of thymomas has been underrated and seems to depend upon the local control of the tumour. The use of chemotherapy remains to be defined.


A single phantom, a single statistical method for low-contrast detectability assessment.
The assessment of low-contrast-details is a part of the quality control (QC) program in digital radiology. It generally consists of evaluating the threshold contrast (Cth) detectability details for different-sized inserts, appropriately located in dedicated QC test tools. This work aims to propose a simplified method, based on a statistical model approach for threshold contrast estimation, suitable for different modalities in digital radiology. A home-madelow-contrast phantom, made of a central aluminium insert with a step-wedge, was assembled and tested. The reliability and robustness of the method were investigated for Mammography, Digital Radiography, Fluoroscopy and Angiography. Imageswere analysed using our dedicated software developed on Matlab®. TheCth is expressed in the same unit (mmAl) for all studied modalities. This method allows the collection of Cthinformation from different modalities and equipment by different vendors, and it could be used to define typical values. Results are summarized in detail. For 0.5 diameter detail, Cthresults are in the range of: 0.018-0.023 mmAl for 2D mammography and 0.26-0.34 mmAl DR images. For angiographic images, for 2.5 mm diameter detail, the Cths median values are 0.55, 0.4, 0.06, 0.12 mmAl for low dose fluoroscopy, coronary fluorography, cerebral and abdominal DSA, respectively. The statistical method proposed in this study gives a simple approach for Low-Contrast-Details assessment, and the typical values proposed can be implemented in a QA program for digital radiology modalities.


Migraine: the platelet hypothesis after 10 years.
The proposal that migraine is a blood disorder and caused by a primary abnormality of platelet behaviour was first put forward in 1978. This paper outlines the basis on which the proposal was made and the way in which the platelet hypothesis can account for the many facets of the disorder. It also reports further studies of platelet composition and function which have been undertaken by a large number of independent workers during the past ten years. The results of their investigations provide strong additional support for the platelet hypothesis in migraine.


Outcomes of ventricular assist device implantation in children and young adults: the Melbourne experience.
We evaluated our experience with ventricular assist device (VAD) implantation in children and young adults. A total of 64 patients underwent VAD implantation in two centres. The mean age was 15 ± 7.2 years. Thirty-five (55%) patients were under 18 years of age. Devices implanted included the Thoratec Paracorporeal in 30 (47%) patients, Berlin Heart EXCOR in 11 (17%) and VentrAssist in 14 (22%). The diagnosis was cardiomyopathy in 53, congenital heart disease in 11, and graft failure in four patients. There were 10 (16%) in-hospital deaths. Mortality was higher in patients <18 years of age (26% compared with 3.4% for those ≥18 years, P = 0.02). The use of extracorporeal membrane oxygenation prior to VAD implantation was associated with higher mortality (P = 0.006). Seventeen (27%) patients experienced stroke. Nine patients (14%) required change of VAD because of thrombosis. Transplantation was performed in 44 patients after a mean of 131 ± 141 days on VAD, 11 patients died without transplantation and three patients currently await transplantation. The VAD was explanted in six patients because of recovery. Overall survival from VAD implantation was 69% and 61% at 5 and 10 years, respectively. The 5-year post-transplant survival for those bridged with VAD support was 91% and was comparable with a cohort of patients who did not receive a pre-transplant VAD. Children requiring pre-transplant VAD support have a higher mortality and morbidity compared with young adults. Survival after heart transplantation those supported with VADs was similar to patients of similar age who did not require pre-transplant support.


Cerebral blood flow in systemic lupus erythematosus with or without cerebral complications.
We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.


Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid.
The incidence of valproic acid hepatotoxicity has been reported to increase in patients who are receiving polytherapy. A minor valproic acid metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA), formed by a cytochrome P450-mediated reaction, has been shown to be a potent inducer of microvesicular steatosis in rats. This study tested the hypothesis that formation of 4-ene-VPA would be increased in patients taking valproic acid with carbamazepine or with phenytoin but decreased with coadministration of an inhibitor of cytochrome P450 (the antiepileptic drug stiripentol in 300 to 1200 mg daily doses) in healthy subjects. Blood and urine samples in the studies were collected during a dosing interval at steady state. Valproic acid was assayed in plasma by capillary gas chromatography; valproic acid and 15 metabolites were measured in urine by gas chromatography/mass spectrometry. The formation clearance (CLf) of 4-ene-VPA was increased twofold in the valproic acid-carbamazepine and valproic acid-phenytoin groups. In the valproic acid/stiripentol studies, the CLf of 4-ene-VPA decreased by 32% in the 1200 mg/day stiripentol study. Similar findings were obtained at 600 and 300 mg/day stiripentol. These findings provide evidence supporting a role for cytochrome P450 in the formation of the hepatotoxic metabolite, 4-ene-VPA, in humans. The increased formation of 4-ene-VPA associated with carbamazepine and phenytoin is striking in relation to the epidemiologic finding of increased incidence of valproic acid-related hepatotoxicity during polytherapy with P450 inducers.


Engineering CrtW and CrtZ for improving biosynthesis of astaxanthin in Escherichia coli.
This study engineered β-carotene ketolase CrtW and β-carotene hydroxylase CrtZ to improve biosynthesis of astaxanthin in Escherichia coli. Firstly, crtW was randomly mutated to increase CrtW activities on conversion from β-carotene to astaxanthin. A crtW* mutant with A6T, T105A and L239M mutations has improved 5.35-fold astaxanthin production compared with the wild-type control. Secondly, the expression levels of crtW* and crtZ on chromosomal were balanced by simultaneous modulation RBS regions of their genes using RBS library. The strain RBS54 selected from RBS library, directed the pathway exclusively towards the desired product astaxanthin as predominant carotenoid (99%). Lastly, the number of chromosomal copies of the balanced crtW-crtZ cassette from RBS54 was increased using a Cre-loxP based technique, and a strain with 30 copies of the crtW*-crtZ cassette was selected. This final strain DL-A008 had a 9.8-fold increase of astaxanthin production compared with the wild-type control. Fed-batch fermentation showed that DL-A008 produced astaxanthin as predominant carotenoid (99%) with a specific titer of 0.88 g·L-1 without addition of inducer. In conclusion, through constructing crtW mutation, balancing the expression levels between crtW* and crtZ, and increasing the copy number of the balanced crtW*-crtZ cassette, the activities of β-carotene ketolase and β-carotene hydroxylase were improved for conversion of β-carotene to astaxanthin with higher efficiency. The series of conventional and novel metabolic engineering strategies were designed and applied to construct the astaxanthin hetero-producer strain of E. coli, possibly offering a general approach for the construction of stable hetero-producer strains for other natural products.


The formation and function of the female reproductive tract in flowering plants.
In angiosperms, sexual reproduction requires a sperm cell, contained within a pollen tube, to fertilize the egg cell. The pollen tubes are capable of growth but have a difficult journey, as egg cells are buried within the ovary of the carpel. Several tissues, known collectively as the reproductive tract, develop within the carpel to facilitate the journey of the pollen tube. The genes involved in the formation and function of the reproductive tract have largely remained a mystery but are crucial for successful fertilization. This review summarizes recent advances in our understanding of the genetic control of reproductive tract development.


Opposing functions of glutamatergic inputs between the globus pallidus external segment and substantia nigra pars reticulata.
The indirect pathway of the basal ganglia, including the subthalamic nucleus (STN) and globus pallidus external segment (GPe), is believed to play a crucial role in suppressing involuntary movements. However, recent evidence suggests the STN and GPe also facilitate voluntary movements. This study hypothesized that excitatory inputs from the STN to the GPe contribute to this facilitation, and that excitatory projections to the substantia nigra pars reticulata (SNr) are involved in the inhibition. To disrupt the STN-GPe or STN-SNr projections in monkeys during choice and fixation tasks, glutamate receptor inhibitors were injected into the GPe or SNr, which induced delayed saccade latencies toward good choices in the choice task (GPe) and caused frequent reflexive saccades to objects in the fixation task (SNr). Our findings suggest excitatory inputs to the GPe and SNr work in opposing manners, providing new insights that redefine our understanding of the functions of basal ganglia pathways.


Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes.
Rapid urbanization and unhealthy dietary patterns critically increase the risk of type 2 diabetes (T2D) in middle-aged Indians. However, despite recent evidence of senescence-associated microRNAs (SA-miRNAs) in regulating complex pathways of ageing, their expressions in middle-aged Indians with T2D remain unexplored. Hence we aimed to investigate the changes in expressions of SA-miRNAs miR-34a and miR-126 in middle-aged T2D patients. A total of 30 T2D patients and 30 controls were recruited of age 31-50 years. The expressions of plasma miR-34a and miR-126 were determined by quantitative PCR. Oxidized LDL (OxLDL) and malondialdehyde (MDA) levels were quantified using enzyme-linked immunosorbent assay (ELISA). The effect of different glucose concentrations on miR-34a, miR-126, senescence-associated, and oxidative stress-responsive genes were also studied in an in vitro model of mice pancreatic β-cells. MiR-34a was significantly upregulated, whereas miR-126 was nonsignificantly reduced in T2D patients as compared to controls. T2D patients showed elevated levels of oxidative stress markers than controls. Analysis of cultured mice pancreatic β-cells exposed to high glucose showed significant upregulation of miR-34a, miR-126, p53, and superoxide dismutase 2 (SOD2). We found that circulating miR-34a levels and oxidative stress markers levels were elevated in the middle-aged Indians with T2D as compared to controls. The presence of diabetes may aggravate the normal ageing process in the middle-aged Indians. These SA-miRNAs can also be used to check the cellular dysfunctions and ageing of pancreatic β-cells.


Prevalence of sarcopenia and mortality rate in older adults with hip fracture.
Several international study groups adopted appendicular skeletal muscle mass (ASM) index adjusted by (1) height squared, (2) weight, and (3) body mass index (BMI) in the diagnosis of sarcopenia. However, different prevalence rates of sarcopenia by each index and clinical implications were not well known. The purpose of this study was to compare the differences in (1) the percentage of sarcopenia in hip fracture patients and (2) the relative mortality rate according to the sarcopenia criteria of three ASM indices. Between January 2009 and December 2020, 1003 older adult hip fracture patients at a tertiary institution were eligible and retrospectively reviewed for this study. Based on the ASM measured on dual-energy X-ray absorptiometry, three indices were calculated, and sarcopenia was diagnosed. The proportion of sarcopenia was evaluated according to each index. One, two, and five-year mortality rates were compared between each sarcopenia group and a normal musculature group, based on ASM criteria. The proportion of sarcopenia patients differed according to three ASM indices. The proportion of sarcopenic patients by ASM/height2 index was higher than those of the other two indices in both male and female hip fracture patients. In male patients, 61% were sarcopenic by ASM/height2 index, 37% by ASM/weight index, and 44% by ASM/BMI index. In female patients, 26%, 11%, and 14% were sarcopenic, respectively. Among the three indices, only ASM/height2 had significant correlations with all 1-, 2-, and 5-year mortality rates. The prevalence of sarcopenia in hip fracture patients differed substantially according to ASM indices. Sarcopenic hip fracture patients had a higher mortality rate than those with normal musculature. The 1-year, 2-year, and 5-year mortality rates were discriminated by ASM/height2 criteria in both men and women. Future prospective studies in a larger cohort are warranted.


Longitudinal associations between metabolic score for visceral fat and hyperuricemia in non-obese adults.
The assessment of visceral adiposity is of great significance for the prevention of hyperuricemia (HUA), especially in non-obese individuals. The metabolic score for visceral fat (METS-VF) is a newly proposed surrogate of visceral obesity. We aimed to evaluate the longitudinal associations of METS-VF with the risk of HUA in non-obese adults. A total of 16,058 non-obese adults without HUA were included for this retrospective cohort analyses. The crude incidence rate of HUA in non-obese women and men were 20.9 and 69.6 per 1000 person-years, respectively. The Cox proportional hazards model indicated that METS-VF was significantly associated with the risk of HUA in both genders. Whereas, METS-VF only had the highest HR in women, but not in men. METS-VF, a novel surrogate of visceral adiposity combined biochemical and anthropometric parameters, age, and gender, could be a useful tool for the hierarchical prevention and management of HUA among non-obese women.


Operative treatment and arthroscopic findings in chronic patellar tendinitis.
Patellar tendinitis is a well-described clinical entity that usually responds well to conservative treatment. However, a subset of patients continue with symptoms despite exhaustive nonoperative means. The objective of the study was to review the treatment course and operative results of seven patients (eight knees) with chronic patellar tendinitis treated surgically. Five (70%) of these patients were either professional or collegiate athletes. The average age was 30 years (range, 20 to 45 years). Duration of symptoms averaged 1.4 years (range, 3 months to 4 years) before surgical correction. Operative treatment included knee arthroscopy and open repair consisting of excision of degenerated tissue and stimulation of a healing response of the patellar tendon pathology. Operative findings and pathology reports consistently showed marked fibrotendinous degeneration. Follow-up averaged 3.6 years (range, 4 months to 8.5 years). Outcomes were measured subjectively with SF36 results and objectively with Biodex testing (Biodex, Shirley, NY) and return to previous level of competition. Overall, 86% of patients achieved an excellent result and 14% had a fair result. We recommend operative intervention in a patient with chronic patellar tendinitis who does not improve with well-supervised, comprehensive conservative treatment.


Ethanol treatment a Non-extrusion method for asymmetric liposome size optimization.
siRNA is a new tool for treatment of diseases such as cancer. However, it cannot be used directly due to rapid degradation in body fluid and blood stream; therefore, vectors are necessary for protection of siRNA against RNases and also for its precise delivery to the target cells. Since viral vector causes cancer and immune response in the host, liposomes are more preferable vectors. Liposome size is an important factor for longer circulation time. Extrusion minimizes the liposome size; however, it leads to less liposome encapsulation. Moreover, it changes structure of asymmetric liposomes. Here, ethanol treatment is introduced as a method of liposome size optimization that significantly decreases the liposome size without any effect on liposome encapsulation and its asymmetric structure formulation. For this, after liposome formation while there is some ether in solution, ethanol was added to fresh liposomes (25 and 30 percent of total liposomes volume) and liposomes were incubated at room temperature with mild agitation for 20 minutes. Finally, the extra ethanol and ether were removed by dialysis. Utilizing this method the liposome size was successfully decreased about 100 nm. The size of optimized liposomes (200 nm) is quite suitable for in vivo target delivery.


Endovascular treatment of in-stent occlusion: new technique for recanalization of long superficial femoral artery occlusion (direct stent puncture technique).
In-stent reocclusion is a frequent complication of endovascular treatment and stenting, especially in the superficial femoral artery. Neointimal hyperplasia is the main cause of this problem, but in many cases, it occurs as a result of the presence of stent strut fractures. The two treatment options are endovascular and surgical intervention. The effectiveness of endovascular interventions in patients with critical limb ischemia has been well established, but in some cases, crossing the occluded stent is difficult. We describe a new technique to recanalize long in-stent superficial femoral artery occlusions characterized by direct stent puncture, followed by retrograde-antegrade recanalization after antegrade failures.


Eradication of endotracheal tube biofilm by nebulised gentamicin.
To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm. General intensive care units in two university teaching hospitals. The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation. Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation. Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [ S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23-1.31) mg/l and 0.28 (<0.23-0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34-0.83) mg/l, with trough concentrations of 0.35 (<0.22-0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352-->1250) mg/l and then, before the next dose, were 436 (250-1000) mg/l. Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.


Political repression and its psychological effects on Honduran children.
This paper, based on an exploratory study in Honduras, examines the psychological effects of political disappearance and assassination on surviving child family members. There are few, if any, comparative field studies of non-immigrant, non-refugee or non-clinical populations of children with forcibly disappeared and assassinated parents. In Latin America, violent state power has been exercised in a number of ways, including physical intimidation, jailing, murder and "disappearance". This research compares 16 Honduran children who have experienced the loss of a parent through forced disappearance with 11 Honduran children who suffered a similar loss from a political assassination. Surviving parents or caretakers of these children were also interviewed. Differences between children of the disappeared and assassinated were analyzed using a Rorschach object relations scale, post-traumatic stress and symptom and behavior scales and interviews with the children and the surviving parents. Both groups of children have symptoms of traumatic stress, depression, anxiety and aggressive feelings. Children of both groups remain symptomatic for many years after their loss and children with disappeared parents present more unconscious emotional disturbance in the Rorschach object relations scale than children with assassinated parents. The lack of physical, emotional and legal resolution in forced disappearance appears to impede mourning and a return to age-appropriate concerns.


Introduction and history of the use of electroencephalography in animal drug studies.
A brief review of the development and the state-of-the-art of EEG methods used to study drug effects is presented. Classification systems based on drug effects in animals kept awake artificially, and based on drug effects on the sleep-wake state duration and distribution are discussed. It is concluded that the techniques are there and the time is ripe to develop animal EEG-based drug classification systems with high predictive ability.


Persistence and Safety of Golimumab in Elderly Patients with Rheumatoid Arthritis and Renal Dysfunction in a Real-World Setting.
The efficacy and safety of golimumab in elderly patients with renal dysfunction are not well evaluated due to the exclusion criteria of clinical trials. To assess the persistence and safety of golimumab in elderly rheumatoid arthritis patients with renal dysfunction. In this retrospective observational study, we used Japan's nationwide electronic medical records and claims database to identify patients aged 65 years and older who were newly prescribed golimumab for rheumatoid arthritis between July 2011 and June 2018. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR; high, ≥ 90; moderate, ≥ 60, < 90; low, ≥ 30, < 60), and the persistence of golimumab and adverse events were compared between the groups. A total of 423 patients met the eligibility criteria. At 6 months, the persistence rates of golimumab were 62.4%, 63.7% and 67.0% in the high, moderate and low eGFR groups, respectively. In Cox proportional hazards regression analysis, baseline eGFR was not associated with golimumab persistence or adverse events, but concomitant methotrexate and low baseline C-reactive protein (CRP) were associated with longer golimumab persistence. Reduced renal function was not associated with continuation of golimumab or incidence of adverse events, suggesting that the persistence of golimumab therapy in patients with rheumatoid arthritis is independent of the baseline level of renal function. On the other hand, concomitant use of methotrexate and low baseline CRP levels were suggested as factors that may affect the persistence of golimumab treatment.


Color Doppler tissue imaging for evaluation of right ventricular systolic function in patients with congenital heart disease.
We sought to explore the relationship of color Doppler tissue imaging-derived systolic indices of tricuspid valve annular motion and magnetic resonance imaging-derived right ventricular (RV) ejection fraction in patients with congenital heart disease. Patients with congenital heart disease who underwent echocardiography and magnetic resonance imaging on the same day were included. The tricuspid valve annular color Doppler tissue imaging-derived parameters of peak velocity during isovolumic contraction, myocardial acceleration during isovolumic contraction, peak systolic velocity, and Tei index were compared with magnetic resonance imaging-derived RV ejection fraction. Peak systolic velocity and myocardial acceleration during isovolumic contraction correlated well with RV ejection fraction after adjusting for age, RV dilation, and pressure overload (r = 0.65 and 0.73, respectively). Interobserver and intraobserver reliability were excellent for peak systolic velocity (r = 0.95 and 0.97, respectively) and very good for myocardial acceleration during isovolumic contraction (r = 0.93 and 0.85, respectively). Color Doppler tissue imaging indices of tricuspid valve annular motion are reproducible and provide a potentially useful complementary tool for assessment of RV systolic function in patients with congenital heart disease.


Oxygen uptake kinetics and time to exhaustion in cycling and running: a comparison between trained and untrained subjects.
The objective of the present study was to compare pulmonary gas exchange kinetics (VO2 kinetics) and time to exhaustion (Tlim) between trained and untrained individuals during severe exercise performed on a cycle ergometer and treadmill. Eleven untrained males in running (UR) and cycling (UC), nine endurance cyclists (EC), and seven endurance runners (ER) were submitted to the following tests on separate days: (i) incremental test for determination of maximal oxygen uptake (VO2max) and the intensity associated with the achievement of VO2max (IVO2max) on a mechanical braked cycle ergometer (EC and UC) and on a treadmill (ER and UR); (ii) all-out exercise bout performed at IVO2max to determine the time to exhaustion at IVO2max (Tlim) and the time constant of oxygen uptake kinetics (tau). The tau was significantly faster in trained group, both in cycling (EC = 28.2 +/- 4.7s; UC = 63.8 +/- 25.0s) and in running (ER = 28.5 +/- 8.5s; UR = 59.3 +/- 12.0s). Tlim of untrained was significantly lower in cycling (EC = 384.4 +/- 66.6s vs. UC; 311.1 +/- 105.7 s) and higher in running (ER = 309.2 +/- 176.6 s vs. UR = 439.8 +/- 104.2 s). We conclude that the VO2 kinetic response at the onset of severe exercise, carried out at the same relative intensity is sensitive to endurance training, irrespective of the exercise type. The endurance training seems to differently influence Tlim during exercise at IVO2max in running and cycling.


Contralateral uptake and metastases in sentinel lymph node mapping for recurrent breast cancer.
Sentinel lymph node mapping as a constitutive component in the staging process for invasive breast cancer continues to gain acceptance. We have identified two patients with recurrent invasive breast cancer in whom contralateral sentinel lymph node uptake and metastases, respectively, were detected. Such findings have not been previously reported in our review of the medical literature between 1966 and October 2004. Sentinel lymph node mapping was performed on two patients with recurrent invasive breast cancer at our institution. At the time of their index diagnosis, both had received breast conserving surgery and an axillary lymph node dissection with post-operative radiotherapy (RT). All lymph nodes and margins of resection were without tumor. Both patients remained with no evidence of disease for years until routine serial screening mammography was interpreted as suspicious. Each underwent a stereotactic biopsy of the ipsilateral breast corresponding to the mammographic abnormality. Pathology confirmed invasive ductal carcinoma. Both patients refused the recommended salvage mastectomy. During a second attempt at breast conservation, sentinel lymph node mapping--which is typically contraindicated for patients with prior axillary surgery--revealed contralateral axillary uptake for both patients. The respective contralateral sentinel node was excised with pathology revealing no tumor in one case, and a microscopic focus of metastatic carcinoma in the second case. Some patients may benefit from sentinel lymph node mapping prior to salvage mastectomy. Identifying uptake in a contralateral sentinel lymph node may change the multi-disciplinary management of recurrent invasive breast cancer to include a contralateral axillary dissection, chemotherapy, and/or RT to the contralateral axilla.


[Density of the endotheliocytic layer of the cornea of the eyeball as a function of age].
This article presents the results of measuring the number of corneal endotheliocytes in a unit area of descemet membrane surface in 546 volunteers of different ages. The average values of the density of the corneal posterior epithelium for the age intervals 40-49, 50-59, 60-69, 70-79, 80 years and older are shown, a constant decrease in the number of endotheliocyte cells as the number of years lived increases.


T-shaped toothbrush for plaque removal and gingival health in children: a randomized controlled trial.
To evaluate an experimental T-shaped toothbrush for plaque removal and gingival health when compared to a conventional toothbrush among children. This single blind parallel randomized controlled trial was conducted on 8-10-year-old healthy schoolchildren with no history of recent antibiotic intake, proximal caries or more than 3 missing teeth per quadrant. A computer-generated randomization list allocated child to the 2 groups. Each child received detailed instructions for tooth brushing. Gingival health and plaque scores were recorded in school at baseline, 2 weeks, 1 month and 3 months in a portable dental chair by an examiner who was blind to the allocated toothbrush. A general feedback on the use of the T-shaped toothbrush was obtained at 3 months. Data was analyzed using two-way repeated measure ANOVA, Generalized estimating equation and Bonferroni test. A total of 195 eligible children were invited, 110 parents gave consent and 100 children completed the study; 50 in each group. There were statistically significant reductions in mean gingival and plaque scores at each visit when compared to baseline for both toothbrushes (p < 0.05). There were no statistically significant differences between scores for the two toothbrushes at each visit (p > 0.05). Majority of participants gave positive feedback regarding the T-shaped toothbrush. Both toothbrushes had similar efficacy in removing plaque and improving gingival health among children. The T-shaped toothbrush is an alternative to the conventional toothbrush for oral hygiene in children. Trial registration Retrospectively registered at ClinicalTrials.gov Registry-NCT03989479 18/06/2019.


Correlates of Seroadaptation Strategies Among Black Men Who have Sex with Men (MSM) in 4 US Cities.
We assessed associations of demographic, psychosocial, and substance use factors with seroadaptation strategies among 835 BMSM in four US cities. Seroadaptation strategies were practiced by 59.8 % of men, with 10.5 % practicing 100 % condom use, 26.5 % serosorting, 7.2 % condom serosorting, and 15.6 % seropositioning. In multivariable analyses, compared to men who used no seroadaptation strategies, serosorters were older, were less likely to be HIV infected, had fewer male sex partners, and had higher levels of social support and sexual self-efficacy. Condom serosorters had less psychological distress, were more likely to use methamphetamine, and had higher levels of sexual self-efficacy. Seropositioners were older, were less likely to be HIV infected, to have a main partner, and report alcohol/drug use with sex, while having higher levels of sexual self-efficacy. Seroadaptation practices among BMSM need to be considered to address perceived safer sex strategies and strengthen access to a broader reach of culturally-relevant prevention efforts.


Predictors of baseline peritoneal transport status in Australian and New Zealand peritoneal dialysis patients.
Factors that predict peritoneal transport status in peritoneal dialysis (PD) patients are poorly understood. The aim of the present study is to determine these factors in Australian and New Zealand incident PD patients. The study included all patients on the Australian and New Zealand Dialysis and Transplant Registry who started PD therapy between April 1, 1991, and March 31, 2002, and underwent a peritoneal equilibration test (PET) within the first 6 months. Predictors of peritoneal transport category and dialysate-plasma creatinine ratio at 4 hours (D-P Cr 4h) were assessed by multivariate ordinal logistic regression and multiple linear regression, respectively. A total of 3,188 patients were studied. Mean D-P Cr 4h was 0.69 +/- 0.13. High transport status was associated with older age (adjusted odds ratio [OR], 1.08 for each 10 years; 95% confidence interval [CI], 1.03 to 1.13), Maori and Pacific Islander racial origin (OR, 1.48; 95% CI, 1.13 to 1.94), and normal body mass index (BMI; < 18.5 kg/m2: OR, 0.90; 95% CI, 0.65 to 1.24; BMI of 18.5 to 25 kg/m2: OR, 1 [reference]; BMI of 25 to 30 kg/m2: OR, 0.81; 95% CI, 0.70 to 0.95; BMI > 30 kg/m2: OR, 0.71; 95% CI, 0.58 to 0.86), but was not independently predicted by sex, diabetes, other comorbid diseases, smoking, previous hemodialysis therapy or transplantation, or residual renal function. Similar results were found when peritoneal permeability was modeled as a continuous variable (D-P Cr 4h). In Australian and New Zealand PD patients, higher peritoneal transport status is independently associated with racial origin, older age, and lower BMI. The diversity of peritoneal transport characteristics in different ethnic populations suggests that additional validation of PET measurements in various racial groups and study of their relationship to patient outcomes are warranted.


Grading of CNS neoplasms using continuous arterial spin labeled perfusion MR imaging at 3 Tesla.
To differentiate glioma grade based on blood flow measured using continuous arterial spin labeled (CASL) perfusion MRI, implemented at 3 Tesla for improved signal-to-noise ratio (SNR) and spin labeling effect. CASL perfusion images were obtained preoperatively in 26 patients with brain neoplasms (19 high-grade gliomas (HGGs; WHO grades 3 and 4) and seven low-grade gliomas (LGGs; WHO grades 1 and 2)). The mean and maximum tumor blood flow (TBF and TBFmax) were calculated in the neoplasm, including surrounding infiltrating tumor vs. edema. Measures normalized to global CBF (nTBF and nTBFmax) were also obtained. Normalized measures of TBFmax provided the best distinction between HGG and LGG groups (Wilcoxon rank sum test, P = 0.01). Seventeen of 19 HGGs showed nTBFmax > 1.0, and 15 of 19 showed nTBFmax > 1.3. Four of seven LGGs showed nTBFmax < 1.0, and six of seven showed nTBFmax < 1.3. Absolute TBFmax also differed significantly between the HGG and LGG groups (P = 0.04). TBFmax in 11 of 17 HGGs was >50 mL/100 g/min (mean +/- SD = 94.9 +/- 71.7 mL/100 g/min). All but one LGGs showed TBFmax < or = 50 mL/100 g/min (mean +/- SD = 42.8 +/- 22.0 mL/100 g/min). CASL perfusion MRI provides a quantitative, noninvasive alternative to dynamic susceptibility contrast perfusion MR methods for evaluating gliomas.


Update on the mechanisms of homing of adipose tissue-derived stem cells.
Adipose tissue-derived stem cells (ADSCs), which resemble bone marrow mesenchymal stromal cells (BMSCs), have shown great advantages and promise in the field of regenerative medicine. They can be readily harvested in large numbers with low donor-site morbidity. To date, a great number of preclinical and clinical studies have shown ADSCs' safety and efficacy in regenerative medicine. However, a better understanding of the mechanisms of homing of ADSCs is needed to advance the clinical utility of this therapy. In this review, the reports of the homing of ADSCs were searched using Pubmed and Google Scholar to update our knowledge. ADSCs were proved to interact with endothelial cells by expressing the similar integrins with BMSCs. In addition, ADSCs do not possess the dominant ligand for P-selectin, just like BMSCs. Stromal derived factor-1 (SDF-1)/CXCR4 and CXC ligand-5 (CXCL5)/CXCR2 interactions are the two main axes governing ADSCs extravasation from bone marrow vessels. Some more signaling pathways involved in migration of ADSCs have been investigated, including LPA/LPA1 signaling pathway, MAPK/Erk1/2 signaling pathway, RhoA/Rock signaling pathway and PDGF-BB/PDGFR-β signaling pathway. Status quo of a lack of intensive studies on the details of homing of ADSCs should be improved in the near future before clinical application.


An MHC interaction site maps to the amino-terminal half of the T cell receptor alpha chain variable domain.
We have used cloned T cell receptor (TCR) genes from closely related CD4 T cell lines to probe the interaction of the TCR with several specific major histocompatibility complex (MHC) class II ligands. Complementarity determining region 3 (CDR3) equivalents of both alpha and beta TCR chains are required for antigen-MHC recognition. Our data provide novel information about the rotational orientation of TCR-MHC contacts in that exchange of the amino terminal portion of the TCR alpha chain containing the putative CDR1 and CDR2 regions results in both gain and loss of MHC class II specificity by the resulting receptor. These two TCRs differ primarily in recognition of polymorphisms in the second hypervariable region of the MHC class II alpha chain. These results document the involvement of CDR1 and/or CDR2 of the TCR alpha chain in MHC recognition and suggest a rotational orientation of this TCR to its MHC ligand.


Comparison of four CAD-CAM guides for preparing guiding planes of removable partial dentures.
To evaluate the effect of guiding structure and 3D-printing material of CAD-CAM guides on the accuracy of guiding planes preparation. Four types of computer-aided design and computer-aided manufacturing (CAD-CAM) guides for preparing guiding planes of removable partial denture (RPD) were designed in two types of guiding structures (triple-constraint and single-plane constraint) and were 3D printed using resin and cobalt-chromium (Co-Cr) alloy. Guiding plane preparation of identical resin casts was performed using CAD-CAM guides (resin template, metal template, resin guided device, and metal guide device) in four test groups and by freehand in the control group (n = 22 per group). All prepared casts were then scanned (Test) and aligned to the reference cast with designed guiding planes. 3D compare analysis was performed and root-mean-square (RMS) values were calculated for assessing the 3D trueness and 3D precision of guiding plane preparation. The angle between the prepared guiding plane (Test) and the designed path of placement of RPD (Reference) was measured for evaluating the direction trueness. RMS values of the metal template group for 3D trueness (39.7 ± 14.6 μm) and 3D precision (28.6 ± 6.8 μm) were significantly lower than that of other groups (p < .05). For direction trueness, the metal template group showed the least angle deviation (1.09 ± 0.56°), and the freehand group demonstrated the largest angle deviation (7.03 ± 2.83°). The Co-Cr alloy guides with triple-constraint guiding structure can assist to prepare accurate guiding planes of RPD.


The high prevalence of bipolar II and associated cyclothymic and hyperthymic temperaments in HIV-patients.
Although recent studies have shown high rates of current and lifetime depression in HIV-infected patients, there is little systematic data on the occurrence of bipolarity in these patients. We compared 46 HIV patients with index major depressive episode (MDE) to an equal number of age- and sex-matched seronegative MDE patients, and systematically examined rates of DSM-III-R bipolar subtypes (enriched in accordance with Akiskal's system of classifying soft bipolar disorders). Although HIV and psychiatric clinic patients had comparable background in terms of familial affective loading, HIV patients had significantly higher familial rates for alcohol and substance use. The more important finding was the significantly higher proportion of HIV patients with lifetime bipolar II disorder (78%), and associated cyclothymic (52%) and hyperthymic (35%) temperaments; the findings were the same irrespective of HIV risk status (intravenous drug user vs. homosexual and other risk groups combined). The major methodologic limitation of our study is that clinicians evaluating temperament were not blind to affective diagnoses and family history. The comparison affective group was a sample of convenience drawn from the same tertiary care university facility. The finding of a high rate of bipolar II disorder in HIV patients has treatment implications for seropositive patients presenting with depression. More provocatively, we submit that premorbid impulsive risk-taking traits associated with cyclothymic and hyperthymic temperaments may have played an important role in needle-sharing drug use and/or unprotected sexual behavior, leading ultimately to infection with HIV. Given their public health importance, these clinical findings and insights merit further investigation. In particular, systematic case-control studies, as well as other large scale studies with prospective methodology need to be conducted.


Mortality prediction in pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation: A comparison of scoring systems.
Pediatric postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients have high mortality and morbidity. There are currently three scoring systems available to predict mortality: the Pediatric Extracorporeal Membrane Oxygenation Prediction (PEP) model, Precannulation Pediatric Survival After VA-ECMO (Pedi-SAVE) score, and Postcannulation Pedi-SAVE score. These methods provide risk stratification scores for pediatric patients requiring ECMO for cardiac support. However, comparative validation of these scoring systems remains scarce. We aim to assess the ability of these models to predict outcomes in a cohort of pediatric patients undergoing VA-ECMO after cardiac surgery, and identify predictors of in-hospital mortality. A retrospective analysis of 101 children admitted to Fuwai Hospital who received VA-ECMO from January 1, 2010 to December 31, 2020 was performed. Patients were divided into two groups, survivors (n = 49) and non-survivors (n = 52) according to in-hospital mortality. PEP model and Pedi-SAVE scores were calculated. The primary outcomes were the risk factors of in-hospital mortality, and the ability of the PEP model, Precannulation Pedi-SAVE and Postcannulation Pedi-SAVE scores to predict in-hospital mortality. Postcannulation Pedi-SAVE score accessing the entire ECMO process had the greatest area under receiver operator curve (AUROC), 0.816 [95% confidence interval (CI): 0.733-0.899]. Pre-ECMO PEP model could predict in-hospital mortality [AUROC = 0.691 (95% CI: 0.565-0.817)], and Precannulation Pedi-SAVE score had the poorest prediction [AUROC = 0.582(95% CI: 0.471-0.694)]. Lactate value at ECMO implantation [OR = 1.199 (1.064-1.351), P = 0.003] and infectious complications [OR = 5.169 (1.652-16.172), P = 0.005] were independent risk factors for in-hospital mortality. Pediatric cardiac ECMO scoring systems, including multiple risk factors before and during ECMO, were found to be useful in this cohort. Both the pre-ECMO PEP model and the Postcannulation Pedi-SAVE score were found to have high predictive value for in-hospital mortality in pediatric postcardiotomy VA-ECMO.


Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: IV. The viruses.
Speculations are developed for a mechanism by which oncogenic viruses can induce alterations in cells allowing them to express embryonic genes. It is suggested that if viral deoxyribonucleic acid, directly or via ribonucleic acid directed deoxyribonucleic acid polymerase activity becomes inserted at particular euchromatin - heterochromatin junctions of quasidifferentiated stem-like cells, then deheterochromatization may result, causing in turn derepression of genes for acidic protein phosphokinases. This sets into motion a series of events including altered acid protein repressors of embryonic genes which are repressed by uniquely weak type repressors. This explains how viruses can act as specific embryonic gene-inducing agents similar to chemical inducing agents such as the hepatocarcinogen ethinine.


Fibroblast growth factor 21 attenuates calcification of vascular smooth muscle cells in vitro.
Vascular calcification is a dysfunction of the vasculature. Recent findings indicate that fibroblast growth factor21 (FGF21), a protector of the cardiovascular system, is related to the mineral deposition of bone and enhances the osteogenic activity of bone morphogenic protein (BMP)-2. In this study, we explored whether FGF21 suppresses vascular calcification. A calcifying model was established by culturing primary rat vascular aortic smooth muscle cells (VSMCs) in a beta-glycerophosphate (BGP)-containing calcifying medium for 14 days. In addition, recombinant human FGF21 was applied to protect against VSMC calcification. In the presence of BGP, the expression levels of osteoblastic genes, including alkaline phosphatase (ALP), BMP-2 and runt-related transcription factor (RUNX)-2, were significantly upregulated on day 3, an effect that was maintained through day 14 (P < 0.001). A concomitant increase in ALP protein expression was observed through day 9 (P < 0.05). The incubation of VSMCs with calcifying medium for 14 days increased ALP activity (P < 0.05) and led to the formation of visible calcium nodules over the course of the protocol. β-klotho expression was unaltered in BGP-induced VSMCs for the 14-day culture period. The culturing of VSMCs with calcifying medium led to opposing trends in the expression of FGFRs, namely, an increase in FGFR1 and FGFR4 mRNA levels (P < 0.001) and a decrease in FGFR2 and FGFR3 mRNA levels (P < 0.01). Reduced mineral deposition, in combination with decreased ALP activity (P < 0.001) and ALP protein expression (P < 0.001), was noted in VSMCs treated with varying doses of FGF21 and BGP in a dose-dependent manner. In addition, FGF21 downregulated osteoblastic-promoting gene expression, including ALP (P < 0.001), BMP-2 (P < 0.001) and RUNX-2 (P < 0.001). Furthermore, FGF21 enhanced β-klotho expression (P < 0.05) and increased FGFR1 and FGFR3 mRNA levels (P < 0.001). FGFR-1 inhibitor SU5402 blocked partial inhibition of FGF21 on the expression of BMP-2 (P < 0.001) and RUNX-2 (P < 0.05). Furthermore, FGF21 suppressed the phosphorylation of P38, while P38 inhibitor, SB203580, attenuated the downregulation of RUNX-2 (P < 0.05). These data demonstrate FGF21 attenuates VSMC calcification in vitro via an FGF21/FGFR1/3/β-klotho/P38MAPK/RUNX-2 signalling pathway.


Polyethylene glycol conjugated interleukin-2: clinical and immunologic effects in patients with advanced renal cell carcinoma.
Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20 x 10(6) I.U./m2 day 1 followed by 12 x 10(6) I.U./m2 days 8, 15, 22; and B) 12 x 10(6) I.U./m2 days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A-15/18, B-16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1-15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity (> or = grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carcinoma.


Mediation of spinal nerve injury induced tactile allodynia by descending facilitatory pathways in the dorsolateral funiculus in rats.
Evidence exists to indicate that tactile allodynia arising from peripheral nerve injury is integrated predominately at supraspinal, rather than spinal, sites. In the present experiments, the possibility that disruption of descending pathways through the dorsolateral funiculus (DLF) might alter expression of nerve-injury induced tactile allodynia was explored. Male, Sprague-Dawley rats received L(5)/L(6) spinal nerve ligation (SNL). Lesions to the DLF were made ipsilateral or contralateral to SNL. Tactile allodynia was determined by measuring withdrawal thresholds to probing with von Frey filaments. Rats with DLF lesions presented no apparent motor deficits and did not alter sensory threshold in sham-SNL operated rats. DLF lesions made ipsilateral to SNL completely blocked tactile allodynia in SNL rats. Contralateral DLF lesions and sham surgery did not have any effect on SNL-induced allodynia. These results indicate that tactile allodynia after peripheral nerve injury is dependent upon tonic activation of net descending facilitation from supraspinal sites and support the hypothesis of tonic activation of descending facilitation as a basis for chronic pain.


Challenges and lessons learned from the rapid operationalization of a prospective cohort to study the natural history and neurodevelopmental outcomes of postnatal Zika virus infection among infants and children in rural Guatemala.
During the course of the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas, the emerging virus was recognized as a congenital infection that could damage the developing brain. As the Latin American ZIKV outbreak advanced, the scientific and public health community questioned if this newly recognized neurotropic flavivirus could affect the developing brain of infants and young children infected after birth. We report here the study design, methods and the challenges and lessons learned from the rapid operationalization of a prospective natural history cohort study aimed at evaluating the potential neurological and neurodevelopmental effects of postnatal ZIKV infection in infants and young children, which had become epidemic in Central America. This study enrolled a cohort of 500 mothers and their infants, along with nearly 400 children 1.5-3.5 years of age who were born during the initial phase of the ZIKV epidemic in a rural area of Guatemala. Our solutions and lessons learned while tackling real-life challenges may serve as a guide to other researchers carrying out studies of emerging infectious diseases of public health priority in resource-constrained settings.


The prevalence of depression and anxiety among Chinese adults with cancer: a systematic review and meta-analysis.
A lot of empirical studies have been conducted to evaluate the prevalence of depression and anxiety among Chinese adults with cancer. We aimed to conduct a meta-analysis in order to evaluate the prevalence and odds ratios of depression and anxiety in Chinese adults with cancer compared with those without. The three most comprehensive computerized Chinese academic databases-CNKI, Wangfang and Vip databases-were systematically screened through September 2012. PubMed and Web of Science (SCIE) were also searched from their inception until September 2012 without language restrictions, and an internet search was also used. Case-control studies assessing the prevalence of depression and anxiety among Chinese adults with cancer were analyzed. Study selection and appraisal were conducted independently by three authors. The non-weighted prevalence, pooled random-effects estimates of odds ratio (OR) and 95% confidence intervals (CI) were all calculated. Seventeen eligible studies with a total of 3497 subjects were included. The prevalence of depression and anxiety were significantly higher in adults with cancer compared with those without (Depression: 54.90% vs. 17.50%, OR = 7.85, 95% CI = 5.56-11.07, P = 0.000; Anxiety: 49.69% vs. 18.37%, OR = 6.46, 95% CI = 4.36-9.55, P = 0.000), the same situation was also observed in subgroup of control groups, assessment methods and cancer types. Although no difference of depression was observed in studies utilizing clinical diagnosis compared with self-report, the OR of anxiety in adults with cancer compared with those without was higher in studies utilizing clinical diagnosis (OR = 8.42, 95% CI = 4.83-14.70) than self-reports (OR = 5.83, 95% CI = 3.64-9.34). The ORs of depression and anxiety in cancer patients compared with disease group (Depression: OR = 6.03, 95% CI = 4.23-8.61; Anxiety: OR = 4.40, 95% CI = 3.05-6.36) were lower than in those compared with normal group (Depression: OR = 13.58, 95% CI = 6.26-29.46; Anxiety: OR = 15.47, 95% CI = 10.00-23.95). We identified high prevalence rates of depression and anxiety among Chinese adults with cancer. The findings support that the prevalence of depression and anxiety among adults with cancer should receive more attention in Chinese medical settings.


A case report of Hymenolepis diminuta in Bangkok, Thailand.
A 20-month-old Thai girl was brought to the Phramongkutkao Hospital in Bangkok. The girl's stool was examined and ova of Hymenolepis diminuta were found. She was treated with Niclosamide and magnesium sulphate. Six hours after medication three tapeworms without the scolex were expelled in stool.


Haplotype blocks and linkage disequilibrium in the human genome.
There is great interest in the patterns and extent of linkage disequilibrium (LD) in humans and other species. Characterizing LD is of central importance for gene-mapping studies and can provide insights into the biology of recombination and human demographic history. Here, we review recent developments in this field, including the recently proposed 'haplotype-block' model of LD. We describe some of the recent data in detail and compare the observed patterns to those seen in simulations.


Pichia pastoris Protein Disulfide Isomerase (PDI1) promoter for heterologous protein production and its sequence characterization.
Pichia pastoris (syn. Komagataella phaffii) expression system has been widely used in heterologous protein production. PDI1 is the structural gene for Protein Disulfide Isomerase (PDI) and one of the main proteins in the endoplasmic reticulum (ER). It serves as a chaperone and helps in the formation, restoration and isomerization of disulfide bonds in nascent proteins. Overexpression of chaperone genes like PDI1, is one of the approaches to alleviate unfolded protein response (UPR) in multicopy clones of P. pastoris. However, it is not in a general scheme and these approaches are protein specific. The complete understanding of promoter region of PDI1 can give insights for better regulation of UPR. The aim of our work was to characterize promoter region of PDI1 gene and evaluate the possibility of their use for efficient expression of heterologous proteins. For this purpose, we used a reporter system based on the Candida antarctica lipase B (CalB) gene. The efficiency of PDI1 promoter was also compared with that of inducible promoter, AOX1, and the constitutive promoter, GAP, under different carbon sources like glucose, glycerol and methanol. The results appear that the PDI1 promoter may act as an UPR inducible promoter at high copy numbers of target gene. Therefore, we propose that the PDI1 promoter can be used for moderate expression of heterologous proteins in pathway engineering applications and also for overexpression of molecular chaperones.


Epidemiological control measures and predicted number of infections for SARS-CoV-2 pandemic: case study Serbia march-april 2020.
In this paper, we are studying the response of the Serbian government and health authorities to the SARS-CoV-2 pandemic in the early stage of the local outbreak between Mar. 15th and Apr. 15th, 2020 by predictive numerical models. Such a study should be helpful to access the effectiveness of measures conducted to suppress the pandemic at a local scale. We have performed extrapolation of the number of SARS-CoV-2 infections with the first stable set of data exploiting exponential growth (linear in logarithmic scale). Based on obtained coefficients it is performed prediction of a number of cases until the end of March. After initial exponential growth, we have changed predictive model to the generalized gamma function. Obtained results are compared with the number of infections and the prediction for the remainder of the outbreak is given. We have found that the daily growth rate was above 21.5% at the beginning of the period, increased slightly after the introduction of the State of Emergency and the first set of strict epidemical control measures. It took about 13 days after the first set of strict measures to smooth daily growth. It seems that early government measures had an only moderate impact to reduce growth due to the social behavior of citizens and influx of diaspora returning to Serbia from highly affected areas, i.e., the exponential growth of infected persons is kept but with a reduced slope of about 14-15%. Anyway, it is demonstrated that period required that any measure has effect is up to 15 days after introduction, firstly to exponential growth with a smaller rate and after to smooth function representing the number of infected persons below exponential growth rate. Obtained results are consistent with findings from other countries, i.e., initial exponential growth slows down within the presumed incubation period of 2 weeks after adopting lockdown and other non-pharmaceutical epidemiological measures. However, it is also shown that the exponential growth can continue after this period with a smaller slope. Therefore, quarantine and other social distancing measures should be adopted as soon as possible in a case of any similar outbreak since alternatives mean prolonged epidemical situation and growing costs in human life, pressure on the health system, economy, etc. For modeling the remainder of the outbreak generalized gamma function is used showing accurate results but requiring more samples and pre-processing (data filtering) concerning exponential part of the outbreak. We have estimated the number of infected persons for the remaining part of the outbreak until the end of June.


Gradual decline in performance and changes in biochemical parameters of basketball players while resting after warm-up.
Warm-up is used before every competitive sporting activity as a means to activate the body, reduce the risk of injury and increase performance in subsequent tasks. However, there is little information on how long the effects of warm-up last. This is of particular interest in basketball playing, since no rewarm-up is allowed to players who sit on the bench. Thus, the aim of this study was to examine changes in performance and biochemical parameters of basketball players while resting after warm-up. On each of four consecutive days, 14 elite basketball players (7 male and 7 female) performed a structured warm-up program, after which they had body temperature measured, provided blood samples and performed countermovement jump and 20-m run tests. Then, they rested for either 10, 20, 30 or 40 min in a random, counterbalanced order. Temperature measurement, blood sampling, and performance testing were repeated after each rest interval. Body temperature and countermovement jump decreased gradually during rest (p < 0.05 for linear trend), whereas 10- and 20-m run times increased gradually (p < 0.05 for linear trend). Serum glucose decreased during rest (p = 0.028) independent of interval duration. We conclude that there is a relatively fast decline in jumping and running performance when basketball players remain inactive after warm-up. Our study highlights the need to address the rapid drop in performance after warm-up for the basketball players who do not participate in a game from the start.


Spatial distribution and viability of nitrifying, denitrifying and ANAMMOX bacteria in biofilms of sponge media retrieved from a full-scale biological nutrient removal plant.
The spatial distribution and activities of nitrifying and denitrifying bacteria in sponge media were investigated using diverse tools, because understanding of in situ microbial condition of sponge phase is critical for the successful design and operation of sponge media process. The bacterial consortia within the media was composed of diverse groups including a 14.5% Nitrosomonas spp.-like ammonia oxidizing bacteria (AOB), 12.5% Nitrobacter spp.-like nitrite oxidizing bacteria (NOB), 2.0% anaerobic ammonium-oxidizing (ANAMMOX) bacteria and 71.0% other bacteria. The biofilm appeared to be most dense in the relatively outer region of the media and gradually decreased with depth, but bacterial viabilities showed space-independent feature. The fluorescent in situ hybridization results revealed that AOB and NOB co-existed in similar quantities on the side fragments of the media, which was reasonably supported by the microelectrode measurements showing the concomitant oxidation of NH(4) (+) and production of NO(3) (-) in this zone. However, a significantly higher fraction of AOB was observed in the center than side fragment. As with the overall biofilm density profile, the denitrifying bacteria were also more abundant on the side than in the center fragments. ANAMMOX bacteria detected throughout the entire depth offer another advantage for the removal of nitrogen by simultaneously converting NH(4) (+) and NO(2) (-) to nitrogen gas.


Impact of CALGB 9343 Trial and Sociodemographic Variation on Patterns of Adjuvant Radiation Therapy Practice for Elderly Women (≥70 Years) with Stage I, Estrogen Receptor-positive Breast Cancer: Analysis of the National Cancer Data Base.
The Cancer and Leukemia Group B (CALGB) 9343 trial demonstrated that adjuvant radiation therapy (RT) can be omitted in women 70 years or older, with small (≤2 cm), negative lymph nodes, estrogen receptor (ER)-positive breast cancer. We examined whether RT usage following the CALGB publication had decreased over time and evaluated sociodemographic and clinical factors associated with RT omission. From the National Cancer Data Base, we analyzed a cohort of 120,308 women aged 70 years or older with stage I, ER-positive breast cancer who underwent lumpectomy. Patients were classified into two groups based on the time of CALGB 9343 publication: (i) pre-CALGB (up to 2004), and (ii) post-CALGB (2005-2012). Clinicopathological and sociodemographic variables were compared between pre- and post-CALGB groups. Chi-square and multivariable logistic regression were employed, with the omission of adjuvant RT as the primary outcome in the regression analysis. Radiation therapy usage decreased by 4.1% after CALGB publication (on average 71.6% pre-CALGB vs. 67.5% post-CALGB; p<0.0001). Almost one-third of women aged ≥85 years received RT in the post-CALGB group. In a multivariable model, the variables significantly associated with increased odds for omission of RT in the post-CALGB group were: advanced age, African-American, increased great circle distance, therapy under academic research program, residents of East South-Central region, living in a rural population <2,500 not adjacent to a metropolitan area, low income level, Medicaid recipients, high comorbidity index, small tumor, well-differentiated histology, residual tumor, and lack of receipt of chemotherapy and anti-hormonal therapy. During the study period, the CALGB trial publication had a minimal impact on the rate of adjuvant RT use among elderly women with small, ER-positive breast cancers. Significant variation in RT usage existed across sociodemographic strata.


Inhibition of fatty acid biosynthesis by bezafibrate in different rat cells.
Bezafibrate is one of the main drugs used in the treatment of human hyperlipemic diseases. Its action on the biosynthesis of fatty acids has been studied and the following conclusions have been drawn: (1) Lipogenesis from glucose is inhibited in hepatocytes and adipocytes isolated from "refed" rats previously treated with bezafibrate. (2) Lipogenesis from glucose is inhibited by bezafibrate in hepatocytes and adipocytes isolated from "refed" rats. (3) Lipogenesis from glucose is also inhibited by bezafibrate in acini isolated from lactating rats. These results show that bezafibrate is an inhibitor of fatty acid synthesis.


Multiresidue analysis of 24 Water Framework Directive priority substances by on-line solid phase extraction-liquid chromatography tandem mass spectrometry in environmental waters.
This paper reports the development of a fully multiresidue and automated on-line solid phase extraction (SPE) - liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of 24 priority substances (PS) belonging to different classes (pesticides, hormones or pharmaceuticals) included in the Directive 2013/39/UE and the recent Watch List (Decision 2015/495) in water samples (drinking water, surface water, and effluent wastewaters). LC-MS/MS conditions and on-line SPE parameters such as sorbent type, sample and wash volumes were optimized. The developed method is highly sensitive (limits of detection between 0.1 and 1.4ngL-1) and precise (relative standard deviations lower than 8%). As part of the method validation studies, linearity, accuracy and matrix effects were assessed. The main advantage of this method over traditional off-line procedures is the minimization of tedious sample preparation increasing productivity and sample throughput. The optimized method was applied to the analysis of water samples and the results revealed the presence of 16 PS in river water and effluent water of wastewater treatment plants.


Mechanism of synergism between sympathetic and parasympathetic autonomic nervous systems in the regulation of motility of the stomach and sphincter of Oddi.
The mechanisms of stimulatory effect of the sympathetic trunk on gastric motor activity and vagal inhibitory effect on electromotor activity of the sphincter of Oddi were studied. Gastric contractions were augmented by preganglionic serotoninergic fibers related synaptically to serotoninergic neurons, while inhibition of electromotor activity of the sphincter of Oddi was elicited by activation of alpha- and beta-adrenoceptors.


Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.
We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress.


Functional potential of sewage sludge digestate microbes to degrade aliphatic hydrocarbons during bioremediation of a petroleum hydrocarbons contaminated soil.
Sewage sludge digestate is a valuable organic waste which can be used as fertilizer in soil bioremediation. Sewage sludge digestate is not only a good source of nutrients but is also rich in bacteria carrying alkB genes, which are involved in aliphatic hydrocarbons metabolism. Increase of alkB genes ratio in polluted soils has been observed to improve bioremediation efficiency. In this study, for the first time, the genetic potential of indigenous microorganisms of digestate to degrade petroleum products was assessed. The objectives were to study petroleum hydrocarbons (PHCs) removal together with shifts in soil taxa and changes in the concentration of alkB genes after digestate application. Initial alkB genes concentration in contaminated soils and digestate was 1.5% and 4.5%, respectively. During soil incubation with digestate, alkB genes percentage increased up to 11.5% and after the addition of bacteria immobilized onto biochar this value increased up to 60%. Application of digestate positively affected soil respiration and bacterial density, which was concomitant with enhanced PHCs degradation. Incubation of soil amended with digestate resulted in 74% PHCs decrease in 2 months, while extra addition of bacteria immobilized onto biochar increased this value up to 95%. The use of digestate affected the microbial community profiles by increasing initial bacterial density and diversity, including taxa containing recognized PHCs degraders. This study reveals the great potential of digestate as a soil amendment which additionally improves the abundance of alkB genes in petroleum contaminated soils.


Are temporal features crucial acoustic cues in dog vocal recognition?
To investigate the perceptual mechanisms underlying conspecific vocal recognition in canine species, eighteen dogs were presented with playbacks of normal and reversed versions of typical dog vocalizations. Auditory perception was analysed using the head-turn paradigm, a non-invasive technique extensively employed to study hemispheric specializations for processing conspecific vocalizations in primates. The results revealed that dogs usually turn their heads with the right ear leading (left hemisphere activation) in response to the forward version of their typical calls, and with either no bias and the left ear leading (right hemisphere activation) in response to the reversed call versions. Overall, our findings suggest that temporal features are determinant auditory cues for call sound recognition in dogs, and support earlier findings of the role of the left hemisphere in the analyses of intraspecific communication.