The 24-hour shelf-life of cytapheresis platelet concentrates stored in polyvinyl chloride containers should be extended only with caution.
A recent publication suggested that the 24-hour allowable shelf-life of apheresis platelet concentrates collected by open-system techniques be extended to 48 hours because platelets collected in this fashion usually remain sterile for that length of time. The current studies, however, show that the quality of platelet concentrates deteriorates rapidly after storage for more than 24 hours in the relatively small-volume, polyvinyl chloride containers of currently marketed, open-system software, as evidenced by the falling pH, the disintegration of platelets, and the inability of platelets to recover from hypotonic shock. Platelets were markedly defective within 48 hours. Thus, it seems unwise to extend the shelf-life of such platelet concentrates beyond 24 hours solely because they are likely to remain sterile. Collection techniques and software must also be modified to ensure satisfactory platelet quality before the period of storage should be extended.


Diagnosis of primary sclerosing cholangitis in a blood donor with elevated serum alanine aminotransferase.
At routine blood donation, a 37-yr-old man with an elevated serum alanine aminotransferase was found to have primary sclerosing cholangitis. The majority of asymptomatic blood donors with elevated aminotransferase levels are presumed to have fatty liver or chronic non-A, non-B hepatitis. However, a substantial number of blood donors with elevated aminotransferase levels will have other hepatobiliary diseases, including primary sclerosing cholangitis. The implementation of aminotransferase screening of blood donors should result in earlier diagnosis, better understanding of natural history, and occasionally, earlier treatment of a number of hepatobiliary diseases.


Effect of sex steroids on bone formation in an orthopedically expanded suture in rats : An immunohistochemical and computed tomography study.
The purpose of this work was to evaluate the effects of sex steroids on bone formation in response to midpalatal suture expansion by means of histological and immunohistochemical examinations and computed tomography (CT). A total of 32 male and 32 female 12-week-old Wistar rats were divided into four groups per gender. Testosterone was administered to the castrated experimental male rats, estrogen to castrated experimental female rats. Saline solution was given subcutaneously to the male and female control, sham, and castration groups during expansion and retention periods, which lasted 7 and 5 days, respectively. The expansion amount was measured with a digital caliper. The density of the new bone in the expansion area was measured via CT. Histological and CT evaluation revealed that the number of osteoblasts and density of the new bone was higher in male and female experimental groups than in all the other groups. When scores of staining intensity were compared, the experimental groups demonstrated statistically significant greater immunoreactivity in the osteoblasts compared to castrated-only groups. Bone density was higher in the female experimental group than in the others, and higher in the male experimental group than in the others. Expansion amounts in the castrated groups were higher than in the others (p < 0.05). Raising the levels of sex steroids in rats revealed positive effects on bone formation in the midpalatal suture in response to expansion. Increased sex steroid levels can reduce the time needed for retention.


plotsr: visualizing structural similarities and rearrangements between multiple genomes.
Third-generation genome sequencing technologies have led to a sharp increase in the number of high-quality genome assemblies. This allows the comparison of multiple assembled genomes of individual species and demands new tools for visualizing their structural properties. Here, we present plotsr, an efficient tool to visualize structural similarities and rearrangements between genomes. It can be used to compare genomes on chromosome level or to zoom in on any selected region. In addition, plotsr can augment the visualization with regional identifiers (e.g. genes or genomic markers) or histogram tracks for continuous features (e.g. GC content or polymorphism density). plotsr is implemented as a python package and uses the standard matplotlib library for plotting. It is freely available under the MIT license at GitHub (https://github.com/schneebergerlab/plotsr) and bioconda (https://anaconda.org/bioconda/plotsr). Supplementary data are available at Bioinformatics online.


Utility of strain-echocardiography in current clinical practice.
Myocardial strain measurement with two-dimensional speckle-tracking echocardiography (2D-STE) is of paramount importance in the early detection of subclinical left ventricular (LV) systolic dysfunction and the prediction of patient outcomes in various types of heart disease, especially when assessed with global longitudinal strain (GLS). The routine application of myocardial strain parameters requires the definition of normal values and an understanding of their reliabilities. One of the most important potential limitations to widespread clinical application of this technique is inter-vendor differences in normal strain values. Recent clinical reports indicate that the smallest differences were noted in GLS measurements among three orthogonal directions. Because the contribution of circumferential fibers to LV myocardial thickening is greater than that of longitudinal fibers, patients who have a reduced LV ejection fraction can have impaired global circumferential strain (GCS), which reflects more advanced intrinsic myocardial systolic dysfunction and is thus closely related to a poor prognosis. Since STE-derived strain analysis allows us to define the timing of the regional myocardial peak systolic deformation, it permits the assessment of LV mechanical dyssynchrony. The severity of LV mechanical dyssynchrony in the short axis plane, i.e., radial and/or circumferential strain imaging, is favorable for predicting the clinical response to cardiac resynchronization therapy. GLS in the right ventricular (RV) four-chamber view has recently been used as a surrogate for global RV function because longitudinal shortening is the major contributor to overall RV performance. Finally, 2D-STE can be used to quantify and characterize RV mechanical dyssynchrony in various diseases including acute pulmonary thromboembolism and chronic pulmonary hypertension.


Spinous-Process-Splitting Versus Conventional Decompression for Lumbar Spinal Stenosis: Comparative Study with Respect to Short-Term Postoperative Pain and Analgesics Use.
Several microsurgical techniques are available for the decompression of lumbar spinal stenosis (LSS). More recently, a spinous process-splitting laminectomy (SPSL) technique was introduced, with the premise of diminishing paraspinal muscle damage. This study aims to compare the neurologic and functional outcomes, as well as the differences in early postoperative pain and analgesic use during hospitalization after conventional decompression (CD) versus SPSL surgery for LSS. Single-center retrospective analysis of all spinal decompression procedures (CD or SPSL) that were performed or supervised by one consulting spine surgeon, performed for LSS between 2015 and 2020. Preoperative neurologic symptoms, functional outcomes, as well as perioperative analgesic use and reported pain scales during hospitalization were analyzed. From a total of 106 patients, 58 were treated using CD and 48 using SPSL. In both groups, around one-third of the patients were taking opiates preoperatively (38% for CD, 31% for SPSL). Patients submitted to SPSL reported more pain on first postoperative day but significantly less pain in the further postoperative course (day 3 numeric rating scale [NRS] 2.4 vs. 3.4, P = 0.03 and on day 5 NRS 2.5 vs. 3.7, P = 0.009). Equal or less cumulative doses of analgesics were administered postoperatively (significantly less paracetamol on day 5 compared with CD; P = 0.013). Both groups showed a similarly favorable outcome in terms of improved mobility and there were no significant differences between complications and re-stenosis rates between both techniques. Patients treated with SPSL technique for LSS showed an equivalent favorable functional outcome compared to CD. However, SPSL patients showed significantly less subacute postoperative pain while using equal amounts or fewer analgesics postoperatively.


Robotic-assisted laparoscopic prostatectomy: what is the learning curve?
Although equipment for performance of robotic-assisted laparoscopic prostatectomy (RALP) is becoming more widely available, few surgeons have acquired the skill and experience necessary to master RALP. A significant issue has been the requisite training and experience (ie, the "learning curve") necessary for a qualified surgeon to become an expert at RALP. The senior author (J.A.S.) has experience with > 2500 radical retropubic prostatectomy (RRP) and > 350 RALP procedures. He assessed his learning curve in achieving expertise with RALP. Because there are no objective measures to define expertise with RALP, achievement of expert status depends on the surgeon's comfort, experience, and results with alternative approaches. Surgeons with extensive experience with open approaches may "set the bar" higher for the learning curve because of expectations. RALP results comparable to those obtained routinely with RRP were not achieved until after > or = 150 procedures. Surgeon comfort and confidence comparable to that with RRP did not occur until after 250 RALP procedures. Defining the learning curve for RALP as the point at which a surgeon could provide outcomes comparable to those obtainable with alternative surgical approaches means that the point varies, depending on the experience and expertise of the surgeon. Surgeons whose sole or dominant experience is with laparoscopic or robotic approaches may have a different perception of the learning curve compared with an experienced open surgeon.


Erratum to "The response to genetic merit for milk production in dairy cows differs by cow body weight" (JDS Commun. 3:32-37).
[This corrects the article DOI: 10.3168/jdsc.2021-0115.].


The future of functional MRI in clinical medicine.
In the last 20 years or so, functional MRI has matured very rapidly from being an experimental imaging method in the hands of a few labs to being a very widely available and widely used workhorse of cognitive neuroscience and clinical neuroscience research internationally. FMRI studies have had a considerable impact on our understanding of brain system phenotypes of neurological and psychiatric disorders; and some impact already on development of new therapeutics. However, the direct benefit of fMRI to individual patients with brain disorders has so far been minimal. Here I provide a personal perspective on what has already been achieved, and imagine how the further development of fMRI over the medium term might lead to even greater engagement with clinical medicine.


Phosphate metabolism in the red cell of sick prematures.
The effect of different amounts of phosphorus supplementation on phosphate metabolism was studied in two groups of sick preterms (B and C) during the first week of life. Group B included prematures that started formula milk feeding from day 3 and group C neonates on total parenteral nutrition with phosphate supplementation for 7 days. Twelve healthy preterm neonates on formula milk feeding from day 2 (group A) were used as controls. On the 7th day of life all phosphate parameters measured in group C (plasma and red cell inorganic phosphate and erythrocyte ATP and 2,3-diphosphoglycerate) were found significantly lower than in the controls (1.60 +/- 0.07; 0.60 +/- 0.08; 1.45 +/- 0.09 and 4.42 +/- 0.18 vs. 2.05 +/- 0.10; 0.94 +/- 0.11; 1.69 +/- 0.07 and 6.24 +/- 0.42 mmol/l, respectively). The renal tubular reabsorption of phosphate was also lower in this group (86.8 +/- 3.2 vs. 97.3 +/- 1.0%). No significant differences were observed between groups B and A. Higher phosphorus intake that was better achieved through early milk feeding prevented phosphate depletion and the decline of 2,3-diphosphoglycerate in the erythrocytes even of sick neonates which in turn might help to improve tissue oxygenation. The amount of parenteral phosphate supplementation that could have beneficial effects on red cell phosphate parameters needs further investigation.


Diclidophora merlangi (Kuhn, 1829) Krøyer, 1838 (Monogenea: Diclidophoridae) as an indicator of hydrocarbon pollution in the North Sea.
This study presents the results of analyses of data on infections of 2646 whiting Merlangius merlangus with the monogenean Diclidophora merlangi. All fish were caught in the North Sea and off the north coast of Scotland in 1990, 1993 and 1995. The aims were to analyse these data in relation to the locations of whiting sampling stations and oil installations active at that time, and to evaluate the results in terms of D. merlangi as an indicator of hydrocarbon pollution. Mean abundance of D. merlangi increased significantly with increasing proximity to the nearest oil field, with an accelerated rate of increase within approximately 2 km of the oil field. Age of oil field and whiting length showed no significant effect on parasite abundance, but there was a small difference between years. The results support those of previous studies in demonstrating the value of monogeneans as indicators of hydrocarbon pollution.


Premenstrual disorders and gender differences in adolescent mental health.
Gender differences in mental health emerge in adolescence. The timing coincides with the development of premenstrual disorders (PMDs). Here, we examine the association between PMDs and adolescent mental health in the context of gender differences. A cross-sectional analysis comprising 21,239[10,563 (49.7 %) girls] individuals aged 10-19 years from the Santai Youth Mental Health Promotion Cohort in China. Possible PMDs, major depression disorder (MDD), general anxiety disorder (GAD), history of self-injury, and high suicide-risk status were surveyed using standard questionnaires. We used logistic regression to contrast the prevalence of outcomes between girls with and without PMDs, and boys. The prevalence rates of possible MDD and GAD were comparable between girls without PMDs and boys [OR1.03 (0.96-1.11) and 0.99 (0.92-1.07)], whereas a higher burden was observed in girls with PMDs [OR4.76(4.31-5.26) and 3.86(3.50-4.27), respectively]. Moreover, MDD/GAD prevalence among premenarchal girls was comparable to their peer boys. Greater gender differences in self-injury and high suicide-risk status were also found for girls with PMDs [OR 4.70 (4.22-5.24) and 7.49 (6.6-8.5)] than that for girls without PMDs [OR1.45(1.33-1.59) and 1.81 (1.62-2.03)]. Girls with PMDs may have overreported depressive and/or anxiety symptoms due to the overlap of symptomology. The greater gender differences in adolescent mental ill-health among girls with PMDs lend support to the hypothesis that PMDs play an important role in the gender disparities in adolescent mental health, particularly in depression and anxiety.


Cerebral gigantism associated with jaw cyst basal cell naevoid syndrome in two families.
We report 9 subjects from 2 families with the syndrome of cerebral gigantism, seven of the patients also had jaw cyst basal cell naevoid syndrome. Neurological, radiological, somatic and biochemical features of this hitherto unreported association are described. Neurological symptoms included mild hydrocephalus, ventricular malformation, cerebellar syndrome, intracranial calcification, oculomotor disturbances, EEG abnormalities and rarely, mild peripheral nervous disorders. A disturbance of calcium metabolism appears to be a prominent feature of the genetically determined nonprogressive syndrome.


Chromatographic behaviour and comparison of column packed with sub-2 microm stationary phases in liquid chromatography.
In order to reduce the analysis time and maintain good efficiency in liquid chromatography, it is advisable to simultaneously decrease the column length and the particle size of the chromatographic support. Therefore, several manufacturers have developed and commercialized short columns filled with particles that have a diameter smaller than 2 microm. The focus of this work was to check the chromatographic performance of such columns and compare possibilities offered by sub-2 microm supports with conventional columns in terms of analysis time reduction and efficiency improvements. For this purpose, different parameters were discussed namely: separation impedance (E), Knox curves (h,v), and number of plates by time unit (N/t0). Kinetic plots were also drawn. It appeared that sub-2 microm supports were well adapted to improve chromatographic performance and to reduce the analysis time. Furthermore, it was also demonstrated that the best chromatographic performances were reached with high pressure systems (up to 1000 bar).


A Review and Update on Tourette Syndrome: Where Is the Field Headed?
Tourette syndrome (TS) is a childhood onset neurologic disorder with manifestations including multiple motor and phonic tics, and in most cases a variety of behavioral comorbidities such as attention deficit hyperactivity disorder, obsessive compulsive disorder, and other impulse control disorders. Although it is considered a hereditary disorder, likely modified by environmental factors, genetic studies have yet to uncover relevant causative genes and there is no animal model that mimics the broad clinical phenomenology of TS. There has been a marked increase in the number of neurophysiological, neuroimaging, and other studies on TS. The findings from these studies, however, have been difficult to interpret because of small sample sizes, variability of symptoms across patients, and comorbidities. Although anti-dopaminergic drugs are the most widely used medications in the treatment of TS, there has been increasing interest in other drugs, behavioral therapies, and surgical approaches including deep brain stimulation. Herein, we review the current literature and discuss the complexities of TS and the challenges in understanding its pathophysiology and in selecting the most appropriate treatment. We also offer an expert's view of where the field of TS may be headed.


Improvement of the culture stability of non-anchorage-dependent animal cells grown in serum-free media through immobilization.
A murine hybridoma cell line producing a monoclonal antibody against penicillin-G-amidase and a murine transfectoma cell line secreting a monovalent chimeric human/mouse Fab-antibody fragment were cultivated in three different media (serum-containing, low protein serum-free, and iron-rich protein-free) in flask cultures, stirred reactors and a fixed bed reactor. In static batch cultures in flasks both cell lines showed similar good growth in all three media.In suspension in a stirred reactor, the hybridoma cell line could be cultivated satisfactory only in serum-containing medium. In low protein serum-free medium, Pluronic F68 had to be added to protect the hybridoma cells against shear stress. But even with this supplement only batch, not chemostat mode was possible. In iron-rich protein-free medium the hybridoma cells grew also in continuous chemostat mode, but the stability of the culture was low. The transfectoma cell line did not grow in stirred reactors in any of the three media.Good results with both cell lines were obtained in fixed bed experiments, where the cells were immobilized in macroporous Siran(®)-carriers. The media, which were optimized in flask cultures, could be used without any further adaptation in the fixed bed reactor. Immobilization improved the stability and reliability of cultures of non-adherent animal cells in serum-free media tremendously compared to suspension cultures in stirred reactors. The volume-specific glucose uptake rate, an, indicator of the activity of the immobilized cells, was similar in all three media. Deviations in the metabolism of immobilized and suspended cells seem to be mainly due to low oxygen concentrations within the macroporous carriers, where the cells are supplied with oxygen only by diffusion.


Trauma-informed patient and public-engaged research: Development and evaluation of an online training programme.
As patients, members of the public, and professional stakeholders engage in co-producing health-related research, an important issue to consider is trauma. Trauma is very common and associated with a wide range of physical and behavioural health conditions. Thus, it may benefit research partnerships to consider its impact on their stakeholders as well as its relevance to the health condition under study. The aims of this article are to describe the development and evaluation of a training programme that applied principles of trauma-informed care (TIC) to patient- and public-engaged research. A research partnership focused on addressing trauma in primary care patients ('myPATH') explicitly incorporated TIC into its formation, governance document and collaborative processes, and developed and evaluated a free 3-credit continuing education online training. The training was presented by 11 partners (5 professionals, 6 patients) and included academic content and lived experiences. Training participants (N = 46) positively rated achievement of learning objectives and speakers' performance (ranging from 4.39 to 4.74 on a 5-point scale). The most salient themes from open-ended comments were that training was informative (n = 12) and that lived experiences shared by patient partners were impactful (n = 10). Suggestions were primarily technical or logistical. This preliminary evaluation indicates that it is possible to incorporate TIC principles into a research partnership's collaborative processes and training about these topics is well-received. Learning about trauma and TIC may benefit research partnerships that involve patients and public stakeholders studying a wide range of health conditions, potentially improving how stakeholders engage in co-producing research as well as producing research that addresses how trauma relates to their health condition under study. The myPATH Partnership includes 22 individuals with professional and lived experiences related to trauma (https://www.usf.edu/cbcs/mhlp/centers/mypath/); nine partners were engaged due to personal experiences with trauma; other partners are community-based providers and researchers. All partners contributed ideas that led to trauma-informed research strategies and training. Eleven partners (5 professionals, 6 patients) presented the training, and 12 partners (8 professionals, 4 patients) contributed to this article and chose to be named as authors.


Robot-assisted minimally invasive esophagectomy (RAMIE): tips and tricks from the bedside assistant view-expert experiences.
The role of bedside assistants in robot-assisted minimally invasive esophagectomy is important. It includes knowledge of the procedure, knowledge of the da Vinci Surgical System, skills in laparoscopy, and good communicative skills. An experienced bedside assistant will likely improve efficiency and safety of robot-assisted minimally invasive esophagectomy.


Is childhood idiopathic atrophy of the nails due to lichen planus?
Four children with symptomless or 'idiopathic' atrophy of the nails were studied. There were no other cutaneous signs. A longitudinal nail biopsy was performed on each patient and demonstrated active lichen planus in three cases and changes consistent with scarring lichen planus in the fourth.


Synthesis of Heterobactins A and B and Nocardia Heterobactin.
The synthesis of the Rhodococcus erythropolis siderophores heterobactins A and B, and the structurally related Nocardia heterobactin, is described. Two approaches for the assembly of these asymmetric ligand donor chelators are explored. In the first approach, a scheme predicated on the biosynthesis of the Paracoccus denitrificans siderophore, parabactin, is employed. In this approach, the central donor synthon is added last. In the second scheme, the central donor and the terminal 2,3-dihydroxybenzoyl fragment are first fixed to the ligand's D-ornithine backbone. This is followed by condensation with the cyclic ornithine hydroxamate glycine segment. The schemes offer a flexible approach to other heterobactins. Job's plots suggest that heterobactin A and Nocardia heterobactin form 1:1 ligand/metal complexes, while heterobactin B forms a 3:2 ligand/metal complex.


Author Correction: RNA-Seq reveals novel genes and pathways associated with hypoxia duration and tolerance in tomato root.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy.
Paraffin-embedded surgical specimens from 26 infants and children with medulloblastomas treated between 1972 and 1981 were examined for DNA ploidy by flow cytometry (FCM). All patients received a standard treatment (a combination of maximum debulking of medulloblastoma and postoperative craniospinal irradiation with a posterior fossa boost of 5000 rad or more). They were studied to correlate the results of the findings of FCM DNA analysis with their final outcome, DNA ploidy, and extent of tumor resection. All seven patients with totally resected aneuploid medulloblastoma are alive, whereas only one of six patients with subtotally resected diploid medulloblastoma is alive (P = 0.0047). The current study suggests both DNA ploidy and extent of surgical resection are the most important determinant of patients' prognosis. Patients in selected group, particularly those with subtotally resected diploid tumor, are advised to undergo aggressive adjuvant chemotherapy.


The principle of salvage in the context of COVID-19.
The prioritisation of scarce resources has a particular urgency within the context of the COVID-19 pandemic crisis. This paper sets out a hypothetical case of Patient X (who is a nurse) and Patient Y (who is a non-health care worker). They are both in need of a ventilator due to COVID-19 with the same clinical situation and expected outcomes. However, there is only one ventilator available. In addressing the question of who should get priority, the proposal is made that the answer may lie in how the pandemic is metaphorically described using military terms. If nursing is understood to take place at the 'frontline' in the 'battle' against COVID-19, a principle of military medical ethics-namely the principle of salvage-can offer guidance on how to prioritise access to a life-saving resource in such a situation. This principle of salvage purports a moral direction to return wounded soldiers back to duty on the battlefield. Applying this principle to the hypothetical case, this paper proposes that Patient X (who is a nurse) should get priority of access to the ventilator so that he/she can return to the 'frontline' in the fight against COVID-19.


Rapid and reliable identification of waterborne Legionella species by MALDI-TOF mass spectrometry.
Detection and enumeration of Legionella bacteria in drinking water is regulated in Germany by ISO 11731-2. The mandatory method for species identification employs parallel subculturing of suspicious colonies on selective media requiring the handling of a large number of cultivation plates. After changes to the drinking water quality regulation in Germany in 2012 the demand for Legionella contamination testing increased drastically. A more reliable, faster and less laborious method for species identification is therefore desirable. Matrix-assisted laser desorption ionization followed by time of flight detection mass spectrometry (MALDI-TOF MS) promises an accelerated identification of bacteria with high reliability and reduced expenditure. Our study shows that MS-based species identification results are in full concordance with cultural and biochemical detection and differentiation and that valuable additional information can be gained, even though the ISO regulation demands an extended incubation period for primary bacterial cultures that is actually in contrast to the prerequisites of the MALDI Biotyper system. In addition, the established identification algorithm is very economical and improves time-to-result. Based on our findings, the amendment of MALID-TOF MS identification to ISO11731-2 as an alternative identification method should be taken into consideration.


Use of response surface methodology to study the effect of media composition on aflatoxin production by Aspergillus flavus.
Aflatoxins are one of the most important secondary metabolites. These extrolites are produced by a number of Aspergillus fungi. In this study, we demonstrate the effect of media components and enhanced aflatoxin yield shown by A. flavus using response surface methodology in response to different nutrients. Different components of a chemically defined media that influence the aflatoxin production were monitored using Plackett-Burman experimental design and further optimized by Box-Behnken factorial design of response surface methodology in liquid culture. Interactions were studied with five variables, namely sorbitol, fructose, ammonium sulfate, KH(2)PO(4), and MgSO(4).7H(2)O. Maximum aflatoxin production was envisaged in medium containing 4.94 g/l sorbitol, 5.56 g/l fructose, 0.62 g/l ammonium sulfate, 1.33 g/l KH(2)PO(4), and 0.65 g/l MgSO(4)·7H(2)O using response surface plots and the point prediction tool of the DESIGN EXPERT 8.1.0 (Stat-Ease, USA) software. However, a production of 5.25 μg/ml aflatoxin production was obtained, which was in agreement with the prediction observed in verification experiment. The other component (MgSO(4).7H(2)O) was found to be an insignificant variable.


Telemedicine in Pediatric Training: A National Needs Assessment of the Current State of Telemedicine Education in Pediatric Training.
To describe the current state of telemedicine within pediatric training programs to inform development of a national telemedicine training curriculum for pediatric trainees. We conducted an anonymous cross-sectional survey of pediatric residency (Fall 2020) and fellowship program directors (Spring 2021) on their current telemedicine practices in pediatric post-graduate training. Forty-eight US pediatric residency programs (n = 48/198, 24%) and 422 fellowship programs completed the survey (n = 422/872, 48%); combined response rate 44% (n = 470/1070). Pre-COVID-19, 12% (n = 57/470) of programs surveyed reported using telemedicine in their training program, but during the pandemic 71% (n = 334/470) reported telemedicine use with trainees. Over 71% (n = 334/470) agreed that a formalized curriculum is important, yet 69% (n = 262/380) of programs reporting telemedicine use either did not have a curriculum or were unsure if one existed at their program. Respondents who were unsure/not likely to add a telemedicine curriculum and/or indicated that a telemedicine curriculum would not be important (52% n = 243/470), cited "time" (55%, n = 136/243) most frequently as a barrier. Our needs assessment indicates marked increase in use of telemedicine with trainees by respondent pediatric training programs, with fewer than 50% reporting a formalized training curriculum and most agreeing that a curriculum is important.


Acute myocardial infarction after a local anesthetic procedure in a middle-aged patient.
We report a case of acute myocardial infarction (AMI) occurring after a local injection of lidocaine. The patient presented with symptoms of myocardial ischemia, dynamic changes in the ST segment of the electrocardiogram, and significantly elevated levels of cardiac troponin; however, coronary angiography findings were normal. According to the clinical definition of AMI, these features indicated the presence of acute myocardial injury, reflected by abnormal cardiac biomarkers and supported by evidence of acute myocardial ischemia. Coronary artery spasm is an important cause of AMI and can be induced by drug effects. Lidocaine is a local anesthetic and antiarrhythmic drug widely used in clinics. The potential mechanism in this case may be lidocaine-induced coronary artery spasm. The possible serious side effects of lidocaine require the attention and vigilance of clinicians. To our knowledge, this is the first report to describe coronary artery spasm possibly induced directly by lidocaine.


Impact of Abdominal Shape on Short-Term Surgical Outcome of Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer.
Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for gastric cancer. The aim of the present study was to explore the impact of abdominal shape parameters on gastric antrum cancer patients' short-term surgical outcomes of LADG with D2 lymph node dissection in both genders, including the number of lymph nodes retrieved and surgical safety index. This was a retrospective analysis of 177 gastric antrum cancer patients, who underwent LADG between April 2009 and January 2016. The abdominal shape parameters, including abdominal anterior-posterior diameter (APD), transverse diameter (TD), xiphoid process of the sternum-navel distance (XND), and thickness of subcutaneous fat (SCF) at the umbilicus level, were calculated by preoperative abdominal computed tomography (CT) scans. The effects of abdominal shape parameters on the short-term surgical outcomes of LADG were analyzed. In male patients undergoing LADG and D2 lymph node dissection, the number of retrieved lymph nodes was significantly lower in patients with APD ≥17.3 cm (P = 0.005), TD ≥27.4 cm (P = 0.029), SCF ≥1.2 cm (P = 0.014), and BMI ≥22.2 (P = 0.008), whereas in female patients, these were statistically insignificant (P > 0.05). APD, TD, SCF, and BMI were negatively correlated with the number of retrieved lymph nodes in male patients. There was no significant difference in the number of lymph nodes retrieved between high-XND group and low-XND group in either gender. Operation time was significantly shorter in male patients with XND < 17.0 cm (P = 0.044) and in female patients with SCF < 2.15 cm (P = 0.013). Intraoperative blood loss and postoperative complication rate were not significantly different between high- and low-APD groups, high- and low-TD groups, high- and low-XND groups, and high- and low-SCF groups in either gender. Compared with male patients, SCF and TD were significantly higher in female patients. In addition, a higher incidence rate of hypertension was observed in patients of both genders with large APD and SCF, although statistically significant only in male patients. LADG with D2 lymph node dissection can effectively achieve the lymph node dissection requirement of radical distal gastrectomy for patients with various abdominal shapes. It is worth noting that APD, TD, and SCF can impact on lymph node dissection of LADG in male patients. Nevertheless, in female patients, abdominal shape do not impact on lymph node dissection of LADG. Moreover, LADG with D2 lymph node dissection is proved to be safe for various abdominal shape in both genders, even for abdominal obese patients.


International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.
The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.


Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as candidates for tumor markers in patients with pancreatic cancer.
Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the pancreas. Moreover, ADH and ALDH are present in pancreatic cancer cells. The activity of ADH class III isoenzymes is significantly higher in cancerous than in healthy tissues. The expression of these enzymes in cancer cells is reflected by increased enzyme activity in the sera and thus could be helpful for diagnosing pancreatic cancer. The aim of this study was to investigate the potential role of ADH and ALDH as tumor markers for pancreatic carcinoma. Serum samples were taken from 165 patients with pancreatic cancer and 166 healthy controls. Total ADH activity and class III and IV isoenzymes were measured by photometric and ALDH activity, ADH I and II by the fluorometric method. There was a significant increase in the activity of ADH III isoenzyme (14.03 mU/l vs 11.45 mU/l; p < 0.001) and total ADH activity in the sera of pancreatic cancer patients compared to the control. The diagnostic sensitivity for ADH III was 70%, specificity 76%, positive and negative predictive values were 79% and 71% respectively. Area under ROC curve for ADH III was 0.64. The results suggest a potential role for ADH III as a marker of pancreatic cancer.


Foreign protein expression from S phase specific promoters in continuous cultures of recombinant CHO cells.
Foreign protein expression from the commonly used SV40 promoter has been found to be primarily during the S-phase of the cell cycle. Simple mathematical models with this cell cycle phase dependent expression of foreign protein suggest that the specific production rate will be proportional to the cell growth rate, which is particularly disadvantageous in high cell density fed-batch or perfusion bioreactors. In this study we investigate this predicted relationship between the production rate and growth rate by culturing recombinant CHO cells in a continuous suspension bioreactor. One CHO cell line, GS-26, has been stably transfected with the plasmid pSVgal, which contains the E. coli lac Z gene under the control of the SV40 promoter. This GS-26 cell line was grown in suspension cultures over a range of specific growth rates in batch and continuous modes. The intracellular β-galactosidase activity was assayed using a standard spectrophotometric method after breaking the cells open and releasing the enzyme. A strong growth associated relationship is found between the intracellular β-galactosidase content and the specific growth rate in batch and continuous cultures, as predicted.


Adapting without reinforcement.
Our data rule out a broad class of behavioral models in which behavioral change is guided by differential reinforcement. To demonstrate this, we showed that the number of reinforcers missed before the subject shifted its behavior was not sufficient to drive behavioral change. What's more, many subjects shifted their behavior to a more optimal strategy even when they had not yet missed a single reinforcer. Naturally, differential reinforcement cannot be said to drive a process that shifts to accommodate to new conditions so adeptly that it doesn't miss a single reinforcer: it would have no input on which to base this shift.


The salivary gland and salivary enzymes of the giant waterbugs (Heteroptera; Belostomatidae).
The giant waterbugs are predators that utilize extra-oral digestion and are known to capture a wide variety of prey. Herein we describe the differences in salivary enzyme composition between large and small species of giant waterbug (Lethocerus uhleri, Lethocerinae and Belostoma lutarium, Belostomatinae, respectively). The saliva of L. uhleri contains 3 proteolytic enzymes and no amylase, while the salivary gland of B. lutarium produces 2 proteolytic enzymes and amylase. This fundamental difference in salivary enzyme composition correlates with the difference in diet preference between the Lethocerinae and Belostomatinae. Furthermore, we describe the ultrastructure of the salivary gland complex of B. lutarium and present data on the division of labor with respect to compartmentalization of enzyme production. Proteolytic enzymes are produced in the accessory salivary gland and amylase is produced in the main salivary gland lobe. This is the first reported evidence of protease production in the accessory salivary gland in the Heteroptera.


Afforestation impacts microbial biomass and its natural (13)C and (15)N abundance in soil aggregates in central China.
We investigated soil microbial biomass and its natural abundance of δ(13)C and δ(15)N in aggregates (>2000μm, 250-2000μm, 53-250μm and <53μm) of afforested (implementing woodland and shrubland plantations) soils, adjacent croplands and open area (i.e., control) in the Danjiangkou Reservoir area of central China. The afforested soils averaged higher microbial biomass carbon (MBC) and nitrogen (MBN) levels in all aggregates than in open area and cropland, with higher microbial biomass in micro-aggregates (<250μm) than in macro-aggregates (>2000μm). The δ(13)C of soil microbial biomass was more enriched in woodland soils than in other land use types, while δ(15)N of soil microbial biomass was more enriched compared with that of organic soil in all land use types. The δ(13)C and δ(15)N of microbial biomass were positively correlated with the δ(13)C and δ(15)N of organic soil across aggregates and land use types, whereas the (13)C and (15)N enrichment of microbial biomass exhibited linear decreases with the corresponding C:N ratio of organic soil. Our results suggest that shifts in the natural (13)C and (15)N abundance of microbial biomass reflect changes in the stabilization and turnover of soil organic matter (SOM) and thereby imply that afforestation can greatly impact SOM accumulation over the long-term.


Hospitals enter antitrust era.
In the past, the courts tended to rule on antitrust cases in the health care field largely on the basis of motions. Increasingly, however, they are now viewing these cases on their merits. What is more, the Federal Trade Commission has shown an interest in looking more closely at the health care field in terms of antitrust activities.


Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias.
Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.


The N domain of Argonaute drives duplex unwinding during RISC assembly.
Small RNAs, such as microRNAs and small interfering RNAs, act through Argonaute (Ago) proteins as a part of RNA-induced silencing complexes (RISCs). To make RISCs, Ago proteins bind and subsequently unwind small RNA duplexes, finally leaving one strand stably incorporated. Here we identified the N domain of human AGO2 as the initiator of duplex unwinding during RISC assembly. We discovered that a functional N domain is strictly required for small RNA duplex unwinding but not for precedent duplex loading or subsequent target cleavage. We postulate that RISC assembly is tripartite, comprising (i) RISC loading, whereby Ago undergoes conformational opening and loads a small RNA duplex, forming pre-RISC; (ii) wedging, whereby the end of the duplex is pried open through active wedging by the N domain, in preparation for unwinding; and (iii) unwinding, whereby the passenger strand is removed through slicer-dependent or slicer-independent unwinding, forming mature RISC.


Real-time haptic-teleoperated robotic system for motor control analysis.
A versatile teleoperated robotic system was created as an assessment device for testing upper-extremity motor control adaptation using different control strategies. While many systems display output virtually on a computer monitor, this system was designed to output in three-dimensional physical space. The system accepts haptic force and torque input, and outputs robot end-effector displacements and rotations in three spatial dimensions. Benefits of this system include flexibility to conduct a variety of dissimilar tasks and reality of user feedback in physical space. Two separate experiments validated the teleoperated robotic system. The first experiment tested unimanual human motor control and the second tested bimanual motor control. This teleoperated robotic system can be used as an assessment device to study neuromuscular adaptability via a variety of control strategies providing a new and functional approach to human motor control analysis.


[Determination of normal values in the assessment of measurements and side differences in the ultrasonic study of the shoulder joint].
Sonography of the rotator cuff with measurement of relevant soft tissue structures was performed in 120 persons without evidence of shoulder pathology. Although the extension of all structures varied markedly, no significant differences were found on comparing both sides. However, with regard to the variability of side differences, a limited side difference must be accepted as a normal finding. Sex, age and other body-related variables did not correlate well and were not useful in the assessment of the dimension of rotator cuff structures.


Regularized correntropy criterion based semi-supervised ELM.
Along with the explosive growing of data, semi-supervised learning attracts increasing attention in the past years due to its powerful capability in labeling unlabeled data and knowledge mining. As an emerging method, the semi-supervised extreme learning machine (SSELM), that builds on ELM, has been developed for data classification and shown superiorities in learning efficiency and accuracy. However, the optimization of SSELM as well as most of the other ELMs is generally based on the mean square error (MSE) criterion, which has been shown less effective in dealing with non-Gaussian noises. In this paper, a robust regularized correntropy criterion based SSELM (RC-SSELM) is developed. The optimization of the output weight matrix of RC-SSELM is derived by the fixed-point iteration based approach. A convergent analysis of the proposed RC-SSELM is presented based on the half-quadratic optimization technique. Experimental results on 4 synthetic datasets and 13 benchmark UCI datasets are provided to show the superiorities of the proposed RC-SSELM over SSELM and other state-of-the-art methods.


Silicone oil injection after failed primary vitreous surgery in severe ocular trauma.
In 42 cases of complicated retinal detachment following trauma after failed primary vitrectomy, at six months follow-up anatomic retinal reattachment posterior to the scleral buckle was achieved in 20 of 40 eyes (50%). Of the 40 eyes, 11 (28%) had a visual acuity of 5/200 or better. Of the eyes that were completely attached posterior to the buckle at six months, 13 of the 20 (65%) remained attached at the last follow-up examination. Many patients who had visual acuities of 5/200 or better at six months experienced a progressive decrease in visual acuity over three years, primarily because of recurrent retinal detachments and corneal edema. A final visual acuity of 5/200 or better was obtained in only five of the 42 eyes (12%) at the last follow-up examination.


Topical betamethasone 17-valerate is an anticorticosteroid in the rat. 2. Anti-inflammatory and anti-lymphocyte activities.
In the oxazolone-induced delayed hypersensitivity inflammation in the rat ear, betamethasone 17-valerate, in contrast to other topical corticosteroids, is incapable of suppressing oedema. When given in combination with triamcinolone acetonide, betamethasone 17-valerate competitively antagonizes the anti-inflammatory action of the active steroid. When tested in the mouse, betamethasone 17-valerate behaved as an anti-inflammatory agent 15 and 80 times as potent as betamethasone and hydrocortisone respectively. In an in vivo lymphocyte culture system in which preincubation with corticosteroids prevents subsequent phytohaemagglutinin induced DNA synthesis, betamethasone 17-valerate was less active than even hydrocortisone when rat lymph node cells were used, but with human cell preparations it was more potent than either hydrocortisone or betamethasone. Betamethasone 17-valerate behaves uniquely in the rat as an anticorticosteroid; in mouse and in man the compound behaves as a normal corticosteroid.


Rho-dependent termination and concomitant NTPase activity requires a specific, intact RNA region.
We have investigated the specific DNA and RNA requirements for rho-dependent transcription termination in vitro. As a model, we have used templates containing the rho-dependent terminator of the Escherichia coli trp operon, trp t'. Templates containing the trp t' region direct specific rho-dependent termination in vitro, with concomitant stimulation of the rho NTPase activity, and deletion of the trp t' region results in templates that do not induce rho-dependent termination or rho NTPase activity. Addition of ribonuclease T1 to transcription reactions specifically eliminated transcription termination and rho NTPase activity. These results demonstrate the requirement for a specific RNA component within the trp t' transcript necessary for NTPase activation and rho-dependent transcription termination. Active transcription is not a prerequisite for rho NTPase activation; trp t' RNA (rho-terminated transcripts) and read-through transcripts, which contain the trp t' region, activated the rho NTPase when rho was added after inhibition of transcription. As is true for synthetic polynucleotides known to activate the rho NTPase, the trp t' region has few G residues. This reduces the potential for the formation of stable secondary structures in the RNA transcript, and may be one determinant of sites specifying rho-dependent termination of transcription. The implications of this are discussed in the light of the lack of significant sequence homologies between rho-dependent transcription termination sites.


Novel thiazolidinedione derivatives with anti-obesity effects: dual action as PTP1B inhibitors and PPAR-γ activators.
Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC(50) values in a low micromolar range. Compound 18l, the lowest, bore an IC(50) of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.


Keratinophilic fungi from Nigerian soil.
During a survey of keratinophilic fungi in Nigerian soil samples, twelve species of fungi were isolated. These included Chrysosporium keratinophilum, C. tropicum, Curvularia lunata, Microsporum audouinii, M. canis, M. fulvum, M. gypseum, M. vanbreuseghemii, Trichophyton ajelloi, T. mentagrophytes, T. soudanense and T. yaoundei. These keratinophilic fungi had a higher incidence by occurrence of individual species during the rainy season (May-October) than the dry season (November-April).


Onset and end-of-dose levodopa-induced dyskinesias. Possible treatment by increasing the daily doses of levodopa.
Ballistic and dystonic involuntary movements occurring at the beginning and end of the period of levodopa efficacy are described in nine patients exhibiting dyskinesis during long-term levodopa therapy. In contrast to classical abnormal interdose movements, these biphasic dyskinesias were reduced by increasing and fractionating the daily doses of levodopa.


Toward a Partnership in the Transition from Home to a Nursing Home: The TRANSCIT Model.
The transition from home to a nursing home can be stressful and traumatic for both older persons and informal caregivers and is often associated with negative outcomes. Additionally, transitional care interventions often lack a comprehensive approach, possibly leading to fragmented care. To avoid this fragmentation and to optimize transitional care, a comprehensive and theory-based model is fundamental. It should include the needs of both older persons and informal caregivers. Therefore, this study, conducted within the European TRANS-SENIOR research consortium, proposes a model to optimize the transition from home to a nursing home, based on the experiences of older persons and informal caregivers. These experiences were captured by conducting a literature review with relevant literature retrieved from the databases CINAHL and PubMed. Studies were included if older persons and/or informal caregivers identified the experiences, needs, barriers, or facilitators during the transition from home to a nursing home. Subsequently, the data extracted from the included studies were mapped to the different stages of transition (pre-transition, mid-transition, and post-transition), creating the TRANSCIT-model. Finally, results were discussed with an expert panel, leading to a final proposed TRANSCIT model. The TRANSCIT model identified that older people and informal caregivers expressed an overall need for partnership during the transition from home to a nursing home. Moreover, it identified 4 key components throughout the transition trajectory (ie, pre-, mid-, and post-transition): (1) support, (2) communication, (3) information, and (4) time. The TRANSCIT model could advise policy makers, practitioners, and researchers on the development and evaluation of (future) transitional care interventions. It can be a guideline reckoning the needs of older people and their informal caregivers, emphasizing the need for a partnership, consequently reducing fragmentation in transitional care and optimizing the transition from home to a nursing home.


Nutrient budgets drive the changes in shoot N and P concentrations of plants in Inner Mongolia's grasslands over the past 40 years.
The nutrient budgets of grassland ecosystems have been extensively disturbed by human activity. The aims of this study were to quantify nitrogen (N) and phosphorus (P) budgets, and evaluate their contributions to changes in shoot nutrient concentrations of dominant plants in Inner Mongolia's grasslands over the past 40 years. N and P budgets were assessed using a nutrient budget model based on flowing intensity of nutrients in and out of the grassland. Meta-analysis was then conducted to quantify changes in shoot nutrient concentrations. The N budget remained positive and continued to increase throughout the study period, while enhanced N deposition and increased supplementary feeding dominated N input (76% of the total in 2017). In contrast, the P budget was negative until 2003, and became positive thereafter. The P input was mainly attributed to supplementary feeding (88% of the total in 2017). The mean shoot N concentration in 1979-1986 was 2.25%, while an increase to 2.53% was observed in 2006-2016. In contrast, the mean shoot P concentration was 0.17% in 1979-1991, subsequently leveling off at 0.17% in 2006-2016. The mean shoot N: P ratio basically remain unchanged over time from 16.72 to 15.85. The N surplus caused major increases in the shoot N concentration of the grassland plants; also, the increased P budget to compensate for past P deficiency resulted in no significant change of shoot P concentrations. Consequently, the grassland system had been in the joint N and P co-limitation over the past 40 years.


Outwitting the series resistance in scanning spreading resistance microscopy.
The performance of nanoelectronics devices critically depends on the distribution of active dopants inside these structures. For this reason, dopant profiling has been defined as one of the major metrology challenges by the international technology roadmap of semiconductors. Scanning spreading resistance microscopy (SSRM) has evolved as one of the most viable approaches over the last decade due to its excellent spatial resolution, sensitivity and quantification accuracy. However, in case of advanced device architectures like fins and nanowires a proper measurement of the spreading resistance is often hampered by the increasing impact of parasitic series resistances (e.g. bulk series resistance) arising from the confined nature of the aforementioned structures. In order to overcome this limitation we report in this paper the development and implementation of a novel SSRM mode (fast Fourier transform-SSRM: FFT-SSRM) which essentially decouples the spreading resistance from parasitic series resistance components. We show that this can be achieved by a force modulation (leading to a modulated spreading resistance signal) in combination with a lock-in deconvolution concept. In this paper we first introduce the principle of operation of the technique. We discuss in detail the underlying physical mechanisms as well as the technical implementation on a state-of-the-art atomic force microscope (AFM). We demonstrate the performance of FFT-SSRM and its ability to remove substantial series resistance components in practice. Eventually, the possibility of decoupling the spreading resistance from the intrinsic probe resistance will be demonstrated and discussed.


Comprehensive investigation of a structural variant in a bi-specific, N-and C-terminal Fc-fusion molecule, and its monitoring with LC-MS based method.
There is an increasing interest in the generation of Fc-fusion molecules to exploit the effector functions of Fc and the fusion partner, towards improving the therapeutic potential. The Fc-fusion molecules have unique structural and functional attributes that impart various advantages. However, the manufacturing of Fc-fusion molecules possesses certain challenges in the biopharmaceutical development. The fusion of unnaturally occurring two or more domains in a construct can pose problems for proper folding and are prone to aggregation and degradation. Reshuffling of disulfide bridges represents a posttranslational event that affects folding. This can play a critical role in the correct structure of a molecule and leads to structural heterogeneity in biotherapeutics; it may also impact the in vivo biological activities, safety, and efficacy of the biopharmaceutical. Our work presents an investigation case of a doublet band, as observed only in nonreducing sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) for a bi-specific, N- and C-terminal Fc-fusion molecule. Other characterization and orthogonal methods from the analytical panel did not indicate the presence of two distinct species, including the orthogonal CE-SDS (Caliper Lab Chip GXII). Therefore, it was necessary to determine if the phenomenon was an analytical artifact or a real variant of our Fc-fusion molecule. With the comprehensive mass spectrometry-based characterization, we were able to determine that the doublet band was related to the reshuffling of one disulfide bridge in one of the fused domains. Our work illustrates the application of nonreducing peptide mapping by mass spectrometry to characterize and identify disulfide variants in a complex N- and C-terminal Fc-fusion molecule, and further adoption to monitor the disulfide structural variants in the intermediate process samples to drive the manufacturing of a consistent product with the desired quality attributes.


Perceiving while acting: action affects perception.
In two experiments we studied how motor responses affect stimulus encoding when stimuli and responses are functionally unrelated and merely overlap in time. Such R-S effects across S-R assignments have been reported by Schubö, Aschersleben, and Prinz (2001), who found that stimulus encoding was affected by concurrent response execution in the sense of a contrast (i.e., emphasizing differences). The present study aimed at elucidating the mechanisms underlying this effect. Experiment 1 studied the time course of the R-S effect. Contrast was only obtained for short intertrial intervals (ITIs). With long ITIs contrast turned into assimilation (i.e., emphasizing similarities). Experiment 2 excluded an interpretation of the assimilation effect in terms of motor repetition. Our findings support the notion of a shared representational domain for perception and action control, and suggest that contrast between stimulus and response codes emerges when two S-R assignments compete with each other in perception. When perceptual competition is over, assimilation emerges in memory.


The effect of hypergravity, hyperbaric pressure, and hypoxia on osteogenic differentiation of adipose stem cells.
Human adipose stem cells (ASCs) hold great potential for regenerative medicine approaches, including osteogenic regeneration of bone defects, that fail to heal autonomously. Osteogenic differentiation of stem cells is dependent on the stimulation of biophysical factors. In the present study, the effects of hypergravity, hypoxia, and hyperbaric treatment were investigated on adipose stem cell (ASC) metabolic activity, quantified by PrestoBlue conversion, and cell numbers, evaluated by crystal violet staining. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity and cresolphthalein staining of calcium deposition. Differentiation was performed for 12 days, which was accompanied by periodical stimulation. Increasing gravity forces up to 50x g did not affect ASC viability, but it enhanced osteogenic markers with a strongest effect between 20 and 30x g. Hyperbaric stimulation at 3 bar decreased ASC cell numbers but increased ALP activity and calcium deposition. Hypoxia at 8 % atmospheric oxygen did not affect ASC proliferation, while cell numbers were reduced at 3 % oxygen. Furthermore, hypoxic conditions produced opposing results on osteogenic markers, as ALP activity increased whereas cresolphthalein staining decreased upon stimulation. These data demonstrated that intermittent short duration of basal physical or chemical impulses interfere with the osteogenic differentiation of ASCs. Our findings could be of specific relevance in ASC based therapies for regenerative medicine and bone tissue engineering approaches.


Analysis of children with familial short stature: who should be indicated for genetic testing?
Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤-2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader-Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, 4 (11%) a variant affecting GH-insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent's height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent's heights ≤-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent's height and BA are clinical predictors of monogenic FSS.


Atrophoderma vermiculatum. Case reports and review.
Two patients, a father and a daughter, with atrophoderma vermiculatum are presented. The chief characteristics of this rare, benign condition that usually begins in childhood are a symmetric worm-eaten or reticular atrophy of the cheeks that may extend to the ears or forehead. An autosomal dominant mode of inheritance is present in this family. The prominent characteristics, cause, histologic findings, and rare associated medical conditions are reviewed. The prognosis is good, with many instances of spontaneous regression. Primarily a cosmetic problem, therapy for this condition is aimed at reassurance, genetic counseling, and dermabrasion where appropriate.


Large-Scale Implementation of Collaborative Care Management for Depression and Diabetes and/or Cardiovascular Disease.
Collaborative care models have been shown to improve mental and physical health, but their effectiveness varies. Implementation science frameworks identify measures at the structural (eg, sociocultural context, public policies), organizational, provider, innovation, and patient levels that may facilitate or impede collaborative care effectiveness. To describe commonalities and variation in multilevel measures associated with the implementation of Care of Mental, Physical, and Substance-Use Syndromes (COMPASS), a large-scale collaborative care intervention for depression, diabetes, and cardiovascular disease. Qualitative study using semistructured descriptive data obtained from annual site visit reports and supplemental site surveys. COMPASS care teams from 8 health care systems serving 3854 patients with active depression and poorly controlled diabetes and/or cardiovascular disease. COMPASS included weekly case reviews with a consulting physician and psychiatrist, a patient-tracking registry, and monitoring of hospital and emergency department use. Site visit reports were analyzed with Atlas.ti software to qualitatively describe implementation measures and their variation across sites. Nine measures were identified that impacted implementation efforts across health systems: (1) challenges in health systems' organizational environments, (2) prior care coordination experience, (3) physician engagement, (4) care team trust and cohesion, (5) care manager training and experience, (6) patient enrollment length, attainment of clinical targets, and frequency/content of care manager contacts, (7) patient-tracking registries, (8) quality improvement and outcomes monitoring reports, and (9) patients' social needs. Understanding multilevel measures impacting COMPASS implementation could increase the success of future collaborative care implementation efforts.


Oral tripotassium-dicitratobismuthate in gastric and duodenal ulceration. A double-blind controlled trial.
One hundred ambulant outpatients with active, endoscopically proven peptic ulceration entered a double-blind trial of either tripotassium-dicitratobismuthate or placebo. Thirty-four patients had gastric ulceration, 56 had duodenal ulceration, three had both gastric and duodenal ulcers, and two had stomal ulceration. Five patients with gastric ulceration were withdrawn from the trial. Three patients with both gastric and duodenal ulceration and two patients with stomal ulceration were excluded from statistical analysis. After 28 days of tripotassium-dicitratobismuthate 94% of gastric ulcer patients had significant endoscopic healing (P less than 0.01). Although 75% of duodenal ulcers healed after 28 days of tripotassium-dicitratobismuthate, this was not statistically significant because of a 60% rate of healing with placebo. Tripotassium-dicitratobismuthate produced a significantly quicker symptomatic response in duodenal ulcer patients (P less than 0.01). No serious side effects were recorded, and patient acceptability was high. It is concluded that tripotassium-dicitratobismuthate is an effective agent for promoting gastric ulcer healing and for symptomatic relief in duodenal ulceration.


Estimation of the dynamic carotid flow in patients with normal radionuclide cerebral perfusion.
Radioisotope angioscintigraphy following intravenous injection bolus of 99mTc-pertechnetate was performed in 49 patients with cerebrovascular disturbances. The region of interest placement on the sequential analog images of both middle cerebral and internal carotid arteries and time-activity curves were displayed on the video monitor. In 35 cases of this group we have noticed symmetrical cerebral perfusion and a significant difference between right and left internal carotid flow, and in 33 cases of which dynamic studies were made stenosis or occlusion of the extracranial part of the carotid internal artery was revealed by the X-ray angiography.


Progressive patterning precedes somite segmentation in the Mexican axolotl (Ambystoma mexicanum).
Beginning at mid-neurulation, a wave of somite segmentation passes down the axolotl body axis in a cephalocaudal direction. At 20 degrees C a somite forms every 2.57 hr. Fate-mapping of the presomitic mesoderm indicates that the primordia for the next few somites occupy nearly the same space that they will after segmentation, but that the remaining somites are densely packed in tip of the tail bud. Brief heat shocks at 37 and 38.5 degrees C reveal that within the first of these two zones, there is a graded sensitivity to the shock, with the primordia closest to the last-formed somite showing the greatest resistance. However, primordia within the densely packed tip (the packing zone) also appear resistant, or have sufficient time to repair the damage. We propose that once cells have left the packing zone, they undergo progressive patterning which renders them increasingly insensitive to the disruptive effects of heat shock, and culminates in rosette formation.


[MEDIAL SURAL ARTERY PERFORATOR FREE FLAP FOR REPAIR OF DEFECT AFTER TONGUE CANCER ABLATION].
To investigate the effectiveness of medial sural artery perforator free flap (MSAP) for repairing defect after tongue cancer ablation. Between March 2013 and April 2014, the defects after tongue carcinoma resection were repaired with MSAP in 12 patients, including 8 cases of high or medium differentiated squamous cell carcinoma (SCC) and 4 cases of moderately-poor differentiated SCC. There were 7 males and 5 females with a median age of 55 years (range, 45-68 years). The disease duration ranged from 2.0 to 8.5 months (mean, 4.3 months). The tumor located at the tongue edge in 8 cases and at the tongue abdomen in 4 cases (mouth floor infiltration in 1 case). According to TNM stage, 7 cases were rated as T2N0M0, 2 cases as T2N1M0, 2 cases as T3N1M0, and 1 case as T4N1M0. The size of tumor ranged from 3.0 cm x 2.0 cm to 4.5 cm x 3.0 cm. The size of MSAP varied from 4.0 cm x 3.5 cm to 6.5 cm x 6.0 cm. The time of total operation ranged from 5.5 to 8.3 hours (mean, 6.8 hours), and flap harvesting time ranged from 54 to 85 minutes (mean, 65.6 minutes). The other flaps survived except 1 case of vein crisis. All the patients were followed up 6-18 months (mean, 13.7 months). With time passing, the pronunciation got better, and the skin showed mucosa-like change; the patients were capable of normal language exchange at 6 months after operation. No obvious scar on the leg or limitation of limb motion was observed. The MSAP is reliable for repair of defect after tongue cancer ablation, with the advantages of satisfactory recovery of tongue appearance, language function, and less donor site morbidity.


The multifaceted spectrum of liver cirrhosis in older hospitalised patients: analysis of the REPOSI registry.
Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.


Immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics compared with nonalcoholic Native and non-Native controls.
This study was designed to evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics and compare these responses with those in age- and sex-matched nonalcoholic, Native and non-Native control subjects. Native alcoholic patients were recruited from the inpatient medical service and outpatient clinics. Healthy age- and sex-matched Alaska Native and non-Native nonalcoholics were recruited from hospital employees. At the initial visit, a standardized questionnaire, the Alcohol Dependency Scale, was administered to all participants. Participants were examined for liver diseases; blood was drawn for liver function tests and prevaccination pneumococcal antibody levels. Charts of all Native participants were reviewed for alcohol-related diseases. Participants received one dose of the 23-valent pneumococcal vaccine at the time of the initial visit and returned 20 to 55 days after immunization for liver function tests and pneumococcal antibody level measurement. Serotype-specific pneumococcal antibody levels were measured by radioimmunoassay. Logistic regression analysis was used to examine the proportion of persons whose serotype-specific antibody level doubled following vaccination. A model including adjustments for age, sex, and initial antibody level was used to examine the effect of alcohol status and ethnicity on response to the vaccine. Eighty-five persons completed the study. Of these, 41 were chronic alcoholics and 44 were nonalcoholic. Of these, 21 were Alaska Natives and 23 were non-Natives. Before vaccination, the geometric mean titers (GMTs) were similar in all 3 groups but were slightly higher in Native alcoholic participants for 11 of 12 serotypes tested. For 11 or more serotypes tested, 46% of alcoholics and 27% of nonalcoholics had total antibody levels at or above 500 nanograms of antibody nitrogen per milliliter (p = 0.11). After vaccination, the GMTs were higher in nonalcoholic than in alcoholic participants for serotypes 3, 7F, and 19F (p < 0.05). When Natives and non-Natives were compared, non-Natives had higher antibody levels than Native participants for 10 of 12 serotypes. After vaccination, 83% of alcoholics and 91% of nonalcoholics had pneumococcal antibody levels of more than 500 nanograms of antibody nitrogen per milliliter for at least 11 serotypes. When responses consisting of a twofold or greater increase in antibody level were compared, a greater proportion of nonalcoholics than alcoholics responded to serotypes 3, 4, 7F, 8, and 19F. This difference was significant for types 3 and 19F only (p < 0.05). In alcoholics there was a direct correlation between pneumococcal antibody level and age both before and after vaccination. This was significant before vaccination for serotypes 4, 6B, 18C, and 23F, and after vaccination for these types and for types 1 and 19F. In nonalcoholics there was a correlation between age and antibody response, following vaccination, for serotype 9N and 18C. Alcoholic males had antibody levels higher than that in females for most serotypes, but significantly so only for serotype 12F before vaccination, and for type 14 after vaccination. There were no sex differences seen among nonalcoholics, and no differences in response to vaccine could be detected in patients with or without liver dysfunction. In this study of Alaska Natives with chronic alcoholism, Native and non-Native participants responded adequately to immunization with the 23-valent pneumococcal vaccine, although significant differences in some serotypes were evident.


Establishment of Complete Capillary Blood Counts Reference Intervals for Young Children in Local Area, China.
Blood count reference intervals are important to diagnose diseases and assess overall health, especially for young children. Although, in 2021, the National Health Commission of the People's Republic of China issued "Reference intervals of blood cell analysis for children (WS/T 779-2021)", these RIs may not suitable for small children all over the country due to racial, lifestyle, and geographical differences. The aim of this study was to establish and validate locally determined hematological reference intervals among young children in Nantong district and compare them with WS/T 779-2021 and American data. The reference sample consisted of 4,758 apparently healthy small children aged from age 28 days to 3 years according to the EP28-A3c guideline issued by the Clinical and Laboratory Standards Institute (CLSI). Capillary blood samples collected in K2-EDTA anticoagulant tubes analyzed by standard procedures. Statistical analysis was based on the guidelines of the CLSI. Pediatric reference intervals for 18 capillary complete blood count (CCBC) parameters were established for young children. WBC and differentials did not differ by gender in the combined analysis of all data, but showed some variations among different age groups, especially for NE and LYM. RIs of RBC value, MCV, and MCH were established, especially with regard to the difference among different age and gender groups. An overall increasing trend of PLT value was observed in children with no obvious difference between boys and girls. Further validation with 1,136 healthy subjects demonstrated that the verified proportions of our study were within 90.11% - 100%. RIs determined in the present study were more concentrated than WS/T 779-2021, with slight differences in the upper and bottom boundaries. Establishing appropriate region-specific reference intervals for pediatrics is essential. This study offers local reference intervals of CCBC values for young children and could be used as a benchmark for similar populations in the Yangtze River Delta economic region.


Novel mutation in the epithelial sodium channel causing type I pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis.
Cystic fibrosis (CF) is an inherited disorder with a devastating prognosis. Determination of chloride concentration in sweat has been the gold standard test for diagnosing CF for over 50 years and still remains the primary screening test. However, now that the genetic cause is known and can be studied, genetic confirmation is mandatory in every suspected patient. We present a patient who had been clinically diagnosed and whose genetic testing could not confirm CF, leading us to search for other options that may also give a positive sweat test. The patient turned out to suffer type 1 pseudohypoaldosteronism, a condition that may cause severe dehydration, hyponatremia and hyperkalemia episodes if not diagnosed and treated early with sodium supplementation. We found a genetic variation in the epithelial sodium channel gene which has not been reported previously, and we discuss the possibility of it being the cause of our patient's phenotype. this patient clearly illustrates the usefulness of genetic confirmation for CF for the diagnosis and genetic counselling, even when it is clinically oriented, and describes a novel mutation of the amiloride-sensitive epithelial sodium channel possibly causing type 1 pseudohypoaldosteronism.


Extracellular vesicles isolated from hyperuricemia patients might aggravate airway inflammation of COPD via senescence-associated pathway.
Chronic obstructive pulmonary disease (COPD) is a major health issue resulting in significant mortality worldwide. Due to the high heterogeneity and unclear pathogenesis, the management and therapy of COPD are still challenging until now. Elevated serum uric acid(SUA) levels seem to be associated with the inflammatory level in patients with COPD. However, the underlying mechanism is not yet clearly established. In the current research, we aim to elucidate the effect of high SUA levels on airway inflammation among COPD patients. Through bioinformatic analysis, the common potential key genes were determined in both COPD and hyperuricemia (HUA) patients. A total of 68 COPD patients aged 50-75-year were included in the study, and their clinical parameters, including baseline characteristics, lung function test, as well as blood chemistry test were recorded. These parameters were then compared between the COPD patients with and without HUA. Hematoxylin & Eosin (HE), immunofluorescence (IF), and Masson trichrome staining were performed to demonstrate the pathological changes in the lung tissues. Furthermore, we isolated extracellular vesicles (EVs) from plasma, sputum, and bronchoalveolar lavage fluid (BALF) samples and detected the expression of inflammatory factor (Interleukin-6 (IL-6), IL-8 and COPD related proteases (antitrypsin and elastase) between two groups. Additionally, we treated the human bronchial epithelial (HBE) cells with cigarette smoke extract (CSE), and EVs were derived from the plasma in vitro experiments. The critical pathway involving the relationship between COPD and HUA was eventually validated based on the results of RNA sequencing (RNA-seq) and western blot (WB). In the study, the COPD patients co-existing with HUA were found to have more loss of pulmonary function compared with those COPD patients without HUA. The lung tissue samples of patients who had co-existing COPD and HUA indicated greater inflammatory cell infiltration, more severe airway destruction and even fibrosis. Furthermore, the high SUA level could exacerbate the progress of airway inflammation in COPD through the transfer of EVs. In vitro experiments, we determined that EVs isolated from plasma, sputum, and BALF played pivotal roles in the CSE-induced inflammation of HBE. The EVs in HUA patients might exacerbate both systemic inflammation and airway inflammatory response via the senescence-related pathway. The pulmonary function and clinical indicators of COPD patients with HUA were worse than those without HUA, which may be caused by the increased airway inflammatory response through the EVs in the patient's peripheral blood. Moreover, it might mediate the EVs via senescence-related pathways in COPD patients with HUA.


A nomogram constructed using intraoperative ex vivo shear-wave elastography precisely predicts metastasis of sentinel lymph nodes in breast cancer.
To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.


Association between Graves' disease and risk of incident systemic lupus erythematosus: A nationwide population-based cohort study.
Previous case reports have linked Graves' disease to incident systemic lupus erythematosus (SLE). It has also been reported that antithyroid drugs used to treat Graves' disease can induce SLE development. The purpose of this study was to investigate the risk of SLE in patients with Graves' disease. A total of 8779 patients with Graves' disease and 8779 controls (without Graves' disease) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000-2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed SLE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of SLE incidence rate between patients with Graves' disease and unaffected controls. Patients with Graves' disease had a significantly increased risk of SLE than unaffected controls (8.81 vs 2.83 per 10 000 person-years, HR: 5.45, 95% CI: 1.74-17.0) after adjusting for antithyroid therapies (antithyroid drugs, radioactive iodine ablation, and surgery). Diagnostic bias may be present as patients with Graves' disease may seek more help from healthcare providers. After excluding the first 0.5 and 1 year of observation period, similar results were obtained (excluding 0.5 year - HR: 4.30, 95% CI: 2.78-8.57; excluding 1 year - HR: 4.63, 95% CI: 2.33-7.79). This study shows that Graves' disease is associated with an increased risk of incident SLE. Further studies on the underlying pathogenesis linking Graves' disease and SLE are warranted.


Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.
Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation.


Bioaccessibility of PAHs and PAH derivatives in a fuel soot assessed by an in vitro digestive model with absorptive sink: Effects of aging the soot in a soil-water mixture.
Aging soot in soil under neutral aqueous condition for 30days significantly (p<0.05) reduced the apparent gastrointestinal bioaccessibility (Bapp) of polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives (d-PAHs) natively present in a composite fuel soot sample. Bapp was determined under fasting conditions by a previously developed in vitro digestive model that includes silicone sheet as a third phase absorptive sink in the small intestinal stage. Redistribution of contaminants from soot to soil, determined in independent experiments, was too small to affect Bapp. Prior uptake by soot of a commercial humic acid representing dissolved soil organic matter had no impact on Bapp. We identified two causes for the reduction in Bapp by soil and found they were approximately additive. One is an aging time-independent "matrix effect" attributable to competitive sorption by the soil of labile contaminant that is desorbed from the soot during the digestion test. The other is the dissolution of soluble substances from the soot during the aging process that increases soot surface area and nanoporosity. The increased surface area and nanoporosity drive contaminants from labile to nonlabile states in the soot and decrease the desorption into the digestive fluid, the former contributing most to the reduction in Bapp. The present study shows that mixing of raw soot with soil has important effects, both aging and non-aging, on the bioaccessibility of soot-borne contaminants.


Proteomics for identifying mechanisms and biomarkers of drug resistance in cancer.
A major problem in chemotherapy of cancer patients is drug resistance as well as unpredictable response to treatment. During chemotherapy, multiple alterations of genetics and epigenetics that contribute to chemoresistance take place, eventually impacting on disease outcome. A more complex picture of the mechanisms of drug resistance is now emerging through application of high-throughput proteomics technology. We have entered an exciting time where proteomics are being applied to characterize the mechanisms of drug resistance, and to identify biomarkers for predicting response to chemotherapy, thereby leading to personalized therapeutic strategies of cancer patients. Comparative proteomics have identified a large number of differentially expressed proteins associated with chemoresistance. Although roles and mechanisms of such proteins in chemoresistance need to be further proved, at least some of them may be potential biomarkers for predicting chemotherapeutic response. Herein, we review the recent advancements on proteomic investigation of chemoresistance in human cancer, and emphasize putative biomarkers for predicting chemotherapeutic response and possible mechanisms of chemoresistance identified through proteomic approaches. Suggested avenues for future work are discussed.


Relationship of cadmium accumulation to zinc or copper concentration in horse liver and kidney.
The concentrations of Cd, Zn, Cu, and metallothionein (MT) in the liver, renal cortex, and renal medulla were determined in 24 male and 15 female younger thoroughbreds (age 27 to 97 months) and two old male horses (age 154 months and 190 months). High correlations were found between Zn and MT in the liver (partial correlation coefficient 0.836), between Cd and MT in the renal cortex (partial correlation coefficient 0.786), and between Cd and Zn in the renal cortex (partial correlation coefficient 0.675), while the correlation between Cd and MT in the liver was low (partial correlation coefficient 0.124). In the renal medulla, high correlations were found between Cd and Zn (partial correlation coefficient -0.631), between Zn and Cu (partial correlation coefficient 0.881), and between Cd and Cu (partial correlation coefficient 0.785). Therefore, in the liver, the MT concentration is the most highly correlated with the Zn concentration and is not correlated with the CD concentration unless artificially exposed to Cd. In the renal cortex, the MT and Cd concentrations are very highly correlated with each other. The Zn concentration is about 20 micrograms/g when the Cd concentration in the renal cortex is the lowest.


To incinerate or not? - Effects of incineration on the concentrations of heavy metals and leaching efficiency of post-precipitated sewage sludge (RAVITA™).
The major element and heavy metal concentrations of post-precipitated sewage sludge (PPS) and its ash residue (PPA) were determined using microwave digestion followed by inductively coupled plasma optical emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS). To the best of our knowledge, this has not been previously done. In both PPS and PPA the heavy metal concentrations were clearly below the average concentrations than those encountered in sewage sludge in Europe. The leaching efficiency of the metal (Al/ Fe) used as a precipitation agent from post-precipitated sludge and its ash residue with phosphoric acid was also investigated with previously optimized leaching conditions. Tests resulted in leaching efficiencies for Al of 85 ± 1% and 99.5 ± 0.7% for PPS and PPA, respectively which were produced with aluminum as precipitation agent for phosphorus. Sludge, which was produced using iron as a precipitation agent, had a leaching efficiency of Fe 36.6 ± 0.9% and 68.0 ± 1.1%, for PPS and PPA, respectively. The leaching efficiency for P was 94 ± 3% and 96 ± 5% for Al-PPA and Fe-PPA, respectively.


Population dynamics of Steneotarsonemus concavuscutum, a neglected mite pest in coconut fruits (Cocos nucifera).
The meristematic region of Cocos nucifera fruits can be colonized by various species of mites, including Steneotarsonemus concavuscutum, Steneotarsonemus furcatus, and Aceria guerreronis. The consequence of this colonization is the development of necrotic lesions on the fruit, and sometimes its abortion. Losses are commonly attributed to A. guerreronis alone, owing to the similarities in the injuries caused and its predominance in coconut plantations. However, S. concavuscutum may be the predominant pest species in some crops. Despite the possible impact of S. concavuscutum, little is known about its bioecological aspects, such as the influence of biotic and abiotic factors on its population dynamics. Our objective was to document macroclimatic abiotic factors (temperature, relative humidity, and precipitation) and biotic factors (interspecific competition and predation) interfere in the population dynamics of S. concavuscutum. We evaluated the diversity and abundance of mites in the perianth of coconut fruit naturally infested by S. concavuscutum for 1 year. The species found in the fruits of bunch 6 of the plant, which is the fruit age at which the mites commonly reach the highest abundance, were counted every 2 weeks. We found mites from nine families and S. concavuscutum was the predominant species, representing about 92% of the individuals collected. Predators represented approximately 2% of the total collection, with Neoseiulus baraki as the predominant species. Steneotarsonemus concavuscutum population density ranged from 60 to 397 mites/fruit. The highest population densities of S. concavuscutum were observed in the hottest and driest periods of the year. The population densities of S. concavuscutum were negatively associated with the presence of N. baraki, suggesting that this predator may have a role in the biological control of this pest.