The tumour necrosis factor receptor-associated periodic syndrome: current concepts.
The tumour necrosis factor receptor (TNFR)-associated periodic syndrome (TRAPS) is an autosomal dominant, multisystemic, autoinflammatory disorder caused by mutations in the TNFR1 gene ( TNFRSF1A ). Traps seems to be the most common hereditary periodic fever (HPF) syndrome in some western populations, and the second most prevalent HPF worldwide, behind familial mediterranean fever (FMF). The proteins involved in susceptibility to TRAPS (TNFRSF1A) and FMF (pyrin) are both members of the death-domain-fold superfamily. Mutations affecting these proteins might cause dysregulation of innate immune responses, with a propensity to autoinflammation. Most TRAPS patients have reduced blood levels of soluble TNFRSF1A between attacks, with an inappropriately small increase during bouts of fever. The pathogenesis of the 'hyperinflammatory state' in TRAPS has been variously ascribed to a shedding defect of TNFRSF1A from the cell surface resulting in increased TNF inflammatory signalling, or impaired TNF apoptotic signalling. Some low-penetrance TNFRSF1A variants also contribute to the clinical phenotype in individuals carrying other HPF-associated mutations, and have been reported in several disorders such as Behçet's disease and systemic lupus erythematosus. Synthetic anti-TNF agents provide a rational form of therapy for TRAPS, and have been shown to delay or indeed prevent development of systemic amyloidosis (AA type), a life-threatening complication in this condition.


Cancer pain management: what's new?
Decades after the publication of the World Health Organization's analgesic ladder, cancer pain is still a major cause of suffering for patients with cancer and affects millions of people worldwide. Owing to the increasing incidence of cancer, cancer-related pain is a major public health problem worldwide. Unfortunately, current research revealed that available options for the successful treatment of cancer pain is still massively underutilized by physicians, and many patients suffer from insufficiently controlled pain despite available treatment options. This review aims to present a concise update about new data or treatment recommendations from the field of cancer pain management. Therefore, information from guidelines, systematic reviews, and original articles that were published in the year 2012 are presented. Specifically, the publication covers information on tapentadol, fixed oxycodone/naloxone combinations, rapid onset fentanyl, nabiximols, ketamine, denusomab, and specialized psychosocial interventions including early palliative care.


Evaluation of Food-Based Attractants for Drosophila suzukii (Diptera: Drosophilidae).
The Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a highly invasive species attacking a wide range of ripening soft-skinned fruits. A series of laboratory choice tests were conducted to determine whether different levels of rice vinegar affected attraction of Merlot wine to D. suzukii, as well as to compare attractiveness of two common fermentation food baits: wine-vinegar and yeast-sugar water mixtures. The relative attraction of various combinations was used to develop a bait whose effectiveness was tested in the field. In laboratory choice experiments, wine-vinegar (80:20, v:v, hereafter referred to as wine) was more preferred over a yeast-sugar water mixture (hereafter referred to as yeast) by D. suzukii. Combination baits, either a mixture of wine and yeast or a mixture of wine and a supernatant from the yeast (comboS), were significantly more attractive than each product alone. The two combination baits were equally attractive to D. suzukii, so were the yeast and its supernatant, suggesting that yeast supernatant could be used as a replacement for the yeast-sugar mixture currently used for trapping D. suzukii. The additive effect between wine and yeast supernatant in the field was not as profound as observed in the laboratory. In the field trial, numerically more male and female D. suzukii were captured in traps baited with comboS than those baited with the wine or yeast alone; however, significant differences were only found between the comboS and wine or between the comboS and yeast in some weeks over the period of the experiment.


A new genus and two new species of Alysiinae (Hymenoptera: Braconidae) from Papua New Guinea.
Two new species of the genus Leptotrema van Achterberg, 1988 and one new genus of the Alysiinae from Mt Wilhelm, Madang Province, Papua New Guinea are described and illustrated. The distribution of the genus Leptotrema is extended to the Australasian region. Three new combinations are established Idiasta fulmeki (Fischer, 2010) comb. n. (=Microcrasis fulmeki Fischer, 2010), Apiasta postfurcata (Papp, 1966) comb. n. (= Microcrasis postfurcata (Papp, 1966)), and Leptotrema. bovefemora (Bhat, 1979) comb. nov. (=Aspilota bovefemora Bhat, 1979). The status of the genus Apiasta Wharton, 2002 (stat. n.) is reviewed. Keys are provided to enable their identification.


The Glucagon-Like Peptide 1 Receptor Agonist Exenatide Inhibits Small Intestinal Motility, Flow, Transit, and Absorption of Glucose in Healthy Subjects and Patients With Type 2 Diabetes: A Randomized Controlled Trial.
The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 μg) or saline (-30 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq (99m)Tc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia.


After the fire-ball.
A hypothetical aircraft accident scenario is described in which the pilot survives but some of the passengers are fatally injured. Information is provided on the acute situational anxiety that may occur in aircrew after any aviation accident, especially one in which lives are lost. A course of action is discussed which encourages early recognition and treatment of the potentially debilitating phenomenon termed "post-accident anxiety syndrome".


Chromatin-dependent E1A activity modulates NF-kappaB RelA-mediated repression of glucocorticoid receptor-dependent transcription.
The role of chromatin-dependent regulatory mechanisms in the repression of glucocorticoid-dependent transcription from the murine mammary tumor virus (MMTV) promoter by p65 and E1A was investigated by using chromatin and transiently transfected reporters. The p65 RelA subunit of NF-kappaB represses MMTV expression on either transient or integrated reporters. In contrast, the viral oncoprotein E1A represses a transient but not an integrated MMTV. E1A repression is attenuated by chromatin, suggesting p65 but not E1A manipulates chromatin appropriately to inhibit the GR. Coexpression of p65 and E1A additively represses the transient MMTV but restores the transcriptional activation of the chromatin MMTV in response to glucocorticoids. This indicates that E1A has a dominant chromatin-dependent activity that attenuates repression by p65. E1A, p65, and GR bind the MMTV promoter, and chromatin remodeling enhances binding on both repressed and activated promoters. In addition, p65 requires Brg for repression of the integrated MMTV. This suggests that neither p65 repression nor E1A attenuation of repression results from an inhibition of remodeling that prevents transcription factor binding. Furthermore, p300/CBP is also required for both repression and attenuation by p65 and E1A. E1A and p65 mutants that do not bind p300/CBP are inactive, indicative of a requirement for p300/CBP-dependent complex formation for both repression and attenuation with chromatin. These data suggest that both the p65-dependent repression and the E1A-mediated attenuation of repression require the Brg1-dependent chromatin remodeling function and p300/CBP-dependent complex formation at a promoter assembled within chromatin.


Pyridinium-Substituted TetraphenylethyleneEntailing Alkyne Moiety: Enhancement of Photosensitizing Efficiency and Antimicrobial Activity.
Apart from sensing and imaging, luminogens with aggregation-induced emission (AIE) are also interesting for photosensitizing. The photosensitizing behavior and bacteria-killing performance of a pyridinium-substituted tetraphenylethylene with an alkyne group (TPE-A-Py+ ) is reported herein. Interestingly, TPE-A-Py+ exhibits higher photosensitizing efficiency than TPE-Py+ (without alkyne group) when I- was used as a counteranion. This is well explained by the fact that the ΔΕST between the excited singlet state (S1 ) and triplet state (T1 ) was lower for TPE-A-Py+ than for TPE-Py+ , according to theoretical calculations. Moreover, replacement of I- with other anions (PF6- , N(SO2 CF3 )2- and BPh4- ) led to a decrease of photosensitizing efficiency for TPE-A-Py+ . Notably, TPE-A-Py+ could be used as an efficient photosensitizer to photo-inactivate ampicillin-resistant (ampr ) E. coli at low concentration under white-light irradiation very quickly.


Unforced polymer translocation compared to the forced case.
We present results for unforced polymer translocation from simulations using Langevin dynamics in two dimensions (2D) to four dimensions and stochastic rotation dynamics supporting hydrodynamic modes in three dimensions (3D). We compare our results to forced translocation and a simplified model where the polymer escapes from an infinite pore. The simple model shows that the scaling behavior of unforced translocation is independent of the dimension of the side to which the polymer is translocating. We find that, unlike its forced counterpart, unforced translocation dynamics is insensitive to pore design. Hydrodynamics is seen to markedly speed up the unforced translocation process but not to affect the scaling relations. Average mean-squared displacement shows scaling with average transition time in unforced but not in forced translocation. The waiting-time distribution in unforced translocation follows closely Poissonian distribution. Our measured transfer probabilities align well with those obtained from an equilibrium theory in 3D, but somewhat worse in 2D, where a polymer's relaxation toward equilibrium with respect to its translocation time is slower. Consequently, in stark contrast to forced translocation, unforced translocation is seen to remain close to equilibrium and shows clear universality.


Evaluation of IL-12 serum level in patients with recalcitrant multiple common warts, treated by intralesional tuberculin antigen.
No universal consensus about optimal modality for treating the recalcitrant multiple common warts (RMCW). To evaluate the immunological mechanisms and clinical therapeutic effect of using of intralesional purified protein derivative (PPD) in the treatment of RMCW. The study included 40 patients with RMCW. They were randomly assigned to 2 groups: first group (20 patients) received intralesional PPD antigen, and second group (20 patients) received intralesional saline as a control group. In both groups, injections were made into single lesions, or largest wart in case of multiple lesions, at weekly intervals, until complete clearance or for a maximum of six treatments. Blood serum was taken at pre-study and at week 6 to measure IL-12 level. A significant difference was found between the therapeutic responses of RMCW to PPD antigen and saline control group (p < 0.001). In the PPD group, complete response was achieved in 75% after 5.8 ± 0.7 sessions' patients presenting with RMCW. There was a statistically significant increase in IL-12 of PPD group versus saline group. No recurrence was observed in the PPD group. Intralesional immunotherapy by PPD antigen is an effective and a safe treatment for RMCW in previously immunized patients.


Cortical progenitor cells in the developing human telencephalon.
Radial glial (RG) cells have been demonstrated to be a major neural progenitor cell type, but in the human fetal brain, neither their molecular nor their spatiotemporal characteristics are well known. We used glial and neuronal-specific antibodies to determine the antigen characteristics and distribution of RG cells and other neuronal progenitors in the human brain during the first half of intrauterine development. Proliferating RG (4A4+) cells in the ventricular zone (VZ) showed clear caudorostral and ventrodorsal gradients, spreading from the spinal cord to the ventral rhombencephalon, at embryonic stages (4.5-5.5 gestational weeks [gw]). However, in the same embryo, other dividing cells expressed the neuronal marker SMI-31 and were present throughout the entire CNS, including the rostral prosencephalon. At the beginning of cortical neurogenesis (6 gw), proliferating VZ cells labeled either with neuronal markers (SMI-31, MAP2, beta-III-tubulin), double-labeled 4A4(+)/SMI-31+ cells, or cells not labeled with these antibodies, were in close proximity to each other. At midgestation (17-24 gw), RG divisions were less frequent, but were spread throughout the entire cerebral cortex, including the subventricular and intermediate zones and the subpial granular layer. Several subtypes of RG were co-labeled with vimentin and other glial markers (BLBP, GFAP, or GLAST) and quantified in vitro. In conclusion, the diversity of cortical progenitors in the human brain may, in part, explain the unique complexity of the human cerebral cortex.


Injectable Therapeutic Organoids Using Sacrificial Hydrogels.
Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method-by making use of the dynamic nature of hydrogels-could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.


The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents.
Knowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. Analysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. In classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. Second-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted.


[Particle disease--aseptic loosening of the total hip endoprosthesis].
Total hip arthroplasty (THA) improves the ability and quality of life in patients with hip dysfunction due to different causes. Aseptic loosening is the major cause of the late hip endoprosthesis failure. It results from aseptic inflammatory reaction induced by the implant wear debris accumulating at the prosthesis interface, and is mediated by numerous cellular and humoral factors. Due to presence of wear debris we call aseptic loosening of the total hip endoprosthesis as "particle disease". In the most important of factors affecting the risk of aseptic instability include patient's age, sex, body mass index, underlying morbidity (reason for THA), endoprosthetic material and surgeon's skill. However, taken together, all these factors explain only a minor part of variability of this phenomenon. Factors that are decisive for the occurrence of aseptic instability are still largely unknown. The existence of "individual disposition" for development of aseptic instability that is not determined by demographic or biomechanical factors is well recognized.


Self-reported diabetes in Mexican Americans: HHANES 1982-84.
In the Hispanic Health and Nutrition Examination Survey (HHANES) of 3,928 Mexican Americans ages 20-74 years, the age-adjusted prevalence of self-reported diabetes was 6.8 percent among men and 7.6 percent among women. Comparable age-adjusted rates for the US population in a national survey were 2.9 percent in men and 3.8 percent in women. The prevalence of diabetes in Mexican Americans is greater in older age groups, was similar in men and women, and among women only was inversely associated with education.


Conformation of glycopeptides.
The presence of carbohydrate side-chains in native glycoproteins alters a number of biochemical properties of the peptide backbone. One of the most frequently studied questions is the conformation-modifying effect of sugar incorporation into asparagine, serine and threonine residues. When N-glycosylation modifies the conformation, the resulting structures are more ordered than the peptide chain without sugar addition. For O-glycopeptides the final conformations can be either more ordered or less ordered. In any event, only the innermost carbohydrates make contact with the peptide backbone. Through-space structural changes are mostly found downstream of the O-glycosylation site. In the repeat unit of epithelial mucin-1 protein, clustering of the carbohydrates results in an easily observable stabilization of the poly-proline II helix.


Severe renal hemorrhage caused by pyelonephritis in 7 horses: clinical and ultrasonographic evaluation.
Case records of 7 horses diagnosed with pyelonephritis were reviewed to determine common features that might aid in diagnosis, treatment, and prognosis of this disease. All 7 horses had been admitted for evaluation of hematuria. During cystoscopy of 5 horses, hemorrhage was observed from one or both ureters. Renal biopsy of 1 horse, laboratory analysis of ureteral discharge of 2 horses, and renal ultrasonography of all horses indicated that pyelonephritis was the cause of hemorrhage. Sonographic renal changes included decreased length, increased echogenicity, abnormal outline, loss of corticomedullary distinction, pyelectasia, and focal hypoechoic or hyperechoic cortical defects. Renal hemorrhage in all horses eventually resolved but recurred in 4 of 5 horses that were followed long-term.


Effect of Complete Syndesmotic Disruption and Deltoid Injuries and Different Reduction Methods on Ankle Joint Contact Mechanics.
Syndesmotic injuries can be associated with poor patient outcomes and posttraumatic ankle arthritis, particularly in the case of malreduction. However, ankle joint contact mechanics following a syndesmotic injury and reduction remains poorly understood. The purpose of this study was to characterize the effects of a syndesmotic injury and reduction techniques on ankle joint contact mechanics in a biomechanical model. Ten cadaveric whole lower leg specimens with undisturbed proximal tibiofibular joints were prepared and tested in this study. Contact area, contact force, and peak contact pressure were measured in the ankle joint during simulated standing in the intact, injured, and 3 reduction conditions: screw fixation with a clamp, screw fixation without a clamp (thumb technique), and a suture-button construct. Differences in these ankle contact parameters were detected between conditions using repeated-measures analysis of variance. Syndesmotic disruption decreased tibial plafond contact area and force. Syndesmotic reduction did not restore ankle loading mechanics to values measured in the intact condition. Reduction with the thumb technique was able to restore significantly more joint contact area and force than the reduction clamp or suture-button construct. Syndesmotic disruption decreased joint contact area and force. Although the thumb technique performed significantly better than the reduction clamp and suture-button construct, syndesmotic reduction did not restore contact mechanics to intact levels. Decreased contact area and force with disruption imply that other structures are likely receiving more loads (eg, medial and lateral gutters), which may have clinical implications such as the development of posttraumatic arthritis.


Right Upper Abdominal Resections in Advanced Stage Ovarian Cancer.
The right upper abdominal involvement is frequently encountered in patients with advanced stage ovarian cancer. The aim of this paper is to study the safety and efficacy of extended resections at this level as well as to determine the sites of residual disease. Between January 2016 and December 2019, 26 patients submitted to right upper abdominal resections were identified. Peritoneal stripping and full thickness resections were the most commonly performed resections (in 57% and 19% of cases, respectively), followed by capsular liver resection and atypical liver resection (in 30% and 23% of cases, respectively) while the most common sites where resection was incomplete were the liver pedicle and porta hepatis. Exceptionally, one case necessitated performing a pancreatoduodenectomy as part of debulking surgery. Postoperatively, two cases developed serious complications and required reintervention; however, the overall mortality was null. Right upper abdominal resections seem to be feasible and effective in order to maximize the debulking effort with acceptable risks arising from perioperative complications.


MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).
An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.


Effects of intracerebroventricular injection of iron dextran on the iron concentration and divalent metal transporter 1 expression in the caudate putamen and substantia nigra of rats.
The cellular localization of DMT1 and its functional characterization suggest that DMT1 may play an important role in the physiological brain iron transport. But the regulation of DMT1 expression by iron in the brain is still not clearly understood. In this study, both the contents of ferric and ferrous iron as well as DMT1 expression were evaluated in CPu and SN after ICV of 500 microg iron dextran/rat/day for 3 or 7 days. It was found that the iron levels in CPu and SN were not altered obviously until ICV for 7 days. Immunohistochemistry results indicated that the expression of DMT1 (-IRE) in CPu and SN was not altered significantly after 3 days of ICV. Whereas the expression of DMT1 (-IRE) decreased significantly after 7 days of ICV when ferrous iron was increased significantly. Contrary to that of DMT1 (-IRE) in the same regions, there were no significant alterations in DMT1 (+IRE) expression in CPu and SN in spite of the existence of the altered iron levels, compared with that of control groups. The results demonstrate that DMT1 (-IRE) expression was correlated probably with brain iron levels; especially, its regulation was correlated with ferrous iron (not ferric iron) in CPu and SN in adult rats, compared with those of saline-injected control rats. The effect of ferrous iron on the expression of DMT1 (-IRE) in the brain also suggests that it might play a major physiological role in brain iron uptake and transport, but further studies are needed to clarify these issues.


Effects of ovarian stimulation protocols on outcomes of assisted reproductive technology in adenomyosis women: a retrospective cohort study.
To evaluate the effects of different ovarian stimulation protocols on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile women with adenomyosis. We carried out a retrospective cohort study among infertile women with adenomyosis receiving IVF/ICSI treatment, including 257 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles. In fresh ET cycles, ultra-long, long, short, and antagonist protocols were adopted. In FET cycles, patients received long-acting GnRH agonist (GnRHa) pretreatment or not. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes included implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR). In fresh ET cycles, compared with ultra-long and long protocols, IR (49.7%, 52.1% versus 28.2%, P=0.001) and CPR (64.3%, 57.4% versus 35.6%, P=0.004) significantly decreased in the short protocol. Similarly, compared with ultra-long and long protocols, a decreased inclination of IR (49.7%, 52.1% versus 33.3%) and CPR (57.4%, 64.3% versus 38.2%) existed in the antagonist protocol, although no statistical significance was detected because of strict P adjustment of Bonferroni method (Padj=0.008). Compared with long protocol, LBR in short protocol decreased obviously (48.2% versus 20.3%, P<0.001). In FET cycles, no matter which origin of embryos, there were no statistical differences in IR, CPR, and LBR. For women ≥35 years receiving fresh ET, CPR was higher in ultra-long and long protocols (52.1%, 50.0% versus 20.0%, 27.5%, P=0.031) compared to antagonist and short protocols. For women ≥35 years receiving FET, compared with ultra-long and antagonist protocols, cycles with embryos originating from long and short protocols had higher proportions of long-acting GnRHa pretreatment (30.4%,30.00 versus 63.9%, 51.4%, P=0.009). IR (61.1%, 48.6% versus 32.6%, 25.0%, P=0.020) and CPR (58.3%, 48.6% versus 30.4%, 25.0%, P=0.024) in long and short protocols were higher than rates of ultra-long and antagonist protocols, but no statistical differences were supported because of strict Bonferroni method (Padj=0.008). In infertile women with adenomyosis, if a fresh embryo was planned for transfer, an ultra-long or long protocol might be beneficial. If antagonist and short protocols were used, whole embryos frozen followed by FET was recommended. In FET cycles, embryos derived from different protocols had no impact on pregnancy outcomes.


Solvent-assisted multistage nonequilibrium electron transfer in rigid supramolecular systems: Diabatic free energy surfaces and algorithms for numerical simulations.
An approach to the construction of diabatic free energy surfaces (FESs) for ultrafast electron transfer (ET) in a supramolecule with an arbitrary number of electron localization centers (redox sites) is developed, supposing that the reorganization energies for the charge transfers and shifts between all these centers are known. Dimensionality of the coordinate space required for the description of multistage ET in this supramolecular system is shown to be equal to N - 1, where N is the number of the molecular centers involved in the reaction. The proposed algorithm of FES construction employs metric properties of the coordinate space, namely, relation between the solvent reorganization energy and the distance between the two FES minima. In this space, the ET reaction coordinate znn' associated with electron transfer between the nth and n'th centers is calculated through the projection to the direction, connecting the FES minima. The energy-gap reaction coordinates znn' corresponding to different ET processes are not in general orthogonal so that ET between two molecular centers can create nonequilibrium distribution, not only along its own reaction coordinate but along other reaction coordinates too. This results in the influence of the preceding ET steps on the kinetics of the ensuing ET. It is important for the ensuing reaction to be ultrafast to proceed in parallel with relaxation along the ET reaction coordinates. Efficient algorithms for numerical simulation of multistage ET within the stochastic point-transition model are developed. The algorithms are based on the Brownian simulation technique with the recrossing-event detection procedure. The main advantages of the numerical method are (i) its computational complexity is linear with respect to the number of electronic states involved and (ii) calculations can be naturally parallelized up to the level of individual trajectories. The efficiency of the proposed approach is demonstrated for a model supramolecular system involving four redox centers.


Pharmacological properties and underlying mechanisms of aurantio‑obtusin (Review).
Herbal medicine has been widely applied for a range of diseases in China since antiquity. Cassia obtusifolia L. and Cassia tora L. are plants whose seeds have high reported medicinal values and have been documented to function as a laxative, to lower lipid level and to lower blood pressure. The main active ingredient in Cassia seeds is aurantio-obtusin (AO), which is an anthraquinone monomer compound. Currently, AO is listed in China as a quality control index component of Cassia seeds. In clinical practice in China, AO is typically used to treat obesity, diabetes and its complications, non-alcoholic fatty liver disease and allergic reactions. In addition, AO has been reported to confer insecticidal activities and antimalarial effects. Previous studies have even suggested that AO is a potential therapeutic candidate for a variety of diseases with research value. Therefore, the present review summarizes and discuss the existing literature on AO to provide a review of its pharmacological activity and mechanism of action, with the aim of providing a basis for its development and utilization in a clinical setting.


Colonization by Candida in children with cancer, children with cystic fibrosis, and healthy controls.
A longitudinal, prospective study was conducted intermittently in Norway, from 1999 to 2008, to investigate the Candida colonization rates and species distributions in the tonsillopharyngeal and faecal flora in: (i) children with cancer; (ii) children with cystic fibrosis (CF); and (iii) healthy children. The effect of antibiotic treatment on Candida colonization was also studied, and we looked for changes in antifungal susceptibility over time within each child and between the different groups of children. In total, 566 tonsillopharyngeal swabs and 545 faecal samples were collected from 45 children with cancer, 37 children with CF, and 71 healthy, age-matched controls. The overall colonization rate with Candida was not significantly higher in the two groups of children undergoing extensive treatment with broad-spectrum antibiotics than in healthy controls. Approximately one-third of the cancer patients had a total lack of Candida colonization or had only one Candida-positive sample, despite multiple samples being taken, treatment with broad-spectrum antibiotics, long hospital stays, and periods with neutropenia. Children with CF had the highest prevalence of Candida albicans. Amoxycillin, azithromycin, third-generation cephalosporins and oral vancomycin resulted in a significantly increased Candida colonization rate. Phenoxymethylpenicillin, second-generation cephalosporins, metronidazole, trimethoprim-sulphamethoxazole, ciprofloxacin, penicillinase-resistant penicillins and inhaled tobramycin or colistin showed minimal effects on the Candida colonization rate. We found no evidence of development of antifungal resistance over time.


2D Electrets of Ultrathin MoO2 with Apparent Piezoelectricity.
Since graphene, a variety of 2D materials have been fabricated in a quest for a tantalizing combination of properties and desired physiochemical behavior. 2D materials that are piezoelectric, i.e., that allow for a facile conversion of electrical energy into mechanical and vice versa, offer applications for sensors, actuators, energy harvesting, stretchable and flexible electronics, and energy storage, among others. Unfortunately, materials must satisfy stringent symmetry requirements to be classified as piezoelectric. Here, 2D ultrathin single-crystal molybdenum oxide (MoO2 ) flakes that exhibit unexpected piezoelectric-like response are fabricated, as MoO2 is centrosymmetric and should not exhibit intrinsic piezoelectricity. However, it is demonstrated that the apparent piezoelectricity in 2D MoO2 emerges from an electret-like behavior induced by the trapping and stabilization of charges around defects in the material. Arguably, the material represents the first 2D electret material and suggests a route to artificially engineer piezoelectricity in 2D crystals. Specifically, it is found that the maximum out-of-plane piezoresponse is 0.56 pm V-1 , which is as strong as that observed in conventional 2D piezoelectric materials. The charges are found to be highly stable at room temperature with a trapping energy barrier of ≈2 eV.


Effective length calibration method for processing the fluorescence signal detected by charge-coupled device in capillary electrophoresis.
A novel method named effective length calibration method has been developed to process the fluorescence signal detected by charge-coupled device during capillary electrophoresis. The new method treated each pixel as an individual point detector, and effectively binned a large number of pixels into a final electropherogram without losing the narrow detection window defined by a single pixel. Capillary electrophoresis separations of DNA were carried out and detected by charge-coupled device and conventional detector (photomultiplier tube). Detection properties including signal-to-noise ratio, peak width, detection frequency, and tilt of detector were investigated. It was found that the new method achieved much higher signal-to-noise ratio and smaller peak width than the conventional detector did. A Detection width of 0.5 μm was easily achieved.


Successful local and systemic medical treatment of cesarean scar pregnancy and a subsequent term pregnancy after treatment: a case series.
Treatment of cesarean scar pregnancy (CSP) is controversial. The objective of this study was to report our successful experience in the medical treatment of CSP with potassium chloride (KCl) and methotrexate. This is a case series of six patients between 6-12 gestational weeks with the diagnosis of CSP. In five cases the fetus was alive and in one case, despite being at a gestational age of 12 weeks based on CRL, there was no fetal heart activity. In four of these cases, an ultrasound- guided KCl injection in the heart was performed on four living fetuses and then systemic methotrexate was administered. In two other cases, methotrexate was injected into the gestational sac and subsequently the systemic methotrexate was administered. During follow-up, the patients were stable and no complications occurred. Additionally, serum beta human chorionic gonadotropin (β-hCG) was negative between five to 11 weeks later. One of the patients became pregnant one year later. Her pregnancy continued without any complication and she was delivered by cesarean section at the gestational age of 38 weeks. During caesarean section, it was noticed that the appearance of previous cesarean scar was normal and there was no scar. Based on our experience, the combination of systemic Methotrexate with local Methotrexate or KCl is feasible and can be performed as an outpatient procedure and is successful in the treatment of CSP.


MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes.
Calcium/calcineurin signaling is critical for normal cellular physiology. Abnormalities in this pathway cause many diseases, including podocytopathy; therefore, understanding the mechanisms that underlie the regulation of calcium/calcineurin signaling is essential. Here, we showed that critical components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s). We found that these 5 genes are highly expressed as mRNA, but the level of the proteins is low in normal podocytes. Conversely, protein levels were markedly elevated in podocytes from rats treated with puromycin aminonucleoside (PAN) and from patients with focal segmental glomerulosclerosis (FSGS). In both FSGS patients and PAN-treated rats, miR-30s were downregulated in podocytes. In cultured podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and calcineurin activity. Moreover, NFATC3 nuclear translocation, synaptopodin degradation, integrin β3 (ITGB3) activation, and actin fiber loss, which are downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but blocked by the calcineurin inhibitor FK506. Podocyte-specific expression of the miR-30 sponge in mice increased calcium/calcineurin pathway component protein expression and calcineurin activity. The mice developed podocyte foot process effacement and proteinuria, which were prevented by FK506. miR-30s also regulated calcium/calcineurin signaling in cardiomyocytes. Together, our results identify miR-30s as essential regulators of calcium/calcineurin signaling.


Eastern Oysters Crassostrea virginica Produce Plastic Morphological Defenses in Response to Crab Predators Despite Resource Limitation.
Many prey react to predation risk by altering their phenotype to reduce their chances of being consumed but incur reductions in growth and fecundity when reacting to predators. To determine when to produce defenses, prey collect information and evaluate the costs and benefits of defense induction. Resource availability can affect prey ability and willingness to incur defense costs. When resources are scarce, defenses may suffer disproportionate decreases in energy allocation if defenses would further reduce prey access to resources or if resources are needed to maintain metabolic functions. We tested the effects of predation risk and resource availability on plastic defenses in eastern oysters Crassostrea virginica and present novel findings that oysters continued to produce defended shells in response to predators when resources were limited, even though they grew smaller, lighter shells when deprived of food in control conditions. Predation risk affected all three tested shell metrics (area, weight, and strength), but food availability did not. Although low food levels often limit expression of predator defenses, predator cues caused oysters to build shells that were larger and heavier, with a similar trend for shell strength, in treatments with both low and high food levels, suggesting that predation is an important pressure in this system. The differences between predator and control treatments were greater under conditions of low food availability, and thus, resource availability may influence interpretations of plastic responses to predators.


Integration of Alcohol Use Disorder Interventions in General Health Care Settings in Sub-Saharan Africa: A Scoping Review.
Alcohol use disorder (AUD) is among the leading cause of morbidity and mortality in sub-Saharan Africa. Despite this, AUD is often not detected in health care settings, which contributes to a wide treatment gap. Integrating services for mental, neurological, and substance use disorders in general health care settings is among the recommended strategies to narrow this treatment gap. This scoping review aimed to map the available evidence on integration of AUD interventions in general health care settings in sub-Saharan Africa. We searched four databases (PubMed, PsycINFO, CINAHL, and Africa Wide Information) for publications up to December 2020. The search strategy focused on terms for alcohol use, alcohol interventions, and sub-Saharan African countries. Studies that reported AUD interventions in general health care settings in sub-Saharan Africa were eligible for inclusion. Over 3,817 potentially eligible articles were identified. After the removal of duplicates and screening of abstracts, 56 articles were included for full article review. Of these, 24 papers reporting on 22 studies were eligible and included in a narrative review. Of the 24 eligible articles, 19 (80%) described AUD interventions that were being delivered in general health care settings, 3 (12%) described plans or programs for integrating AUD interventions at different levels of care, including in health facilities, and 2 (8%) studies reported on AUD interventions integrated into general health care settings. This review shows that there is limited evidence on the integration of AUD interventions in health care settings in sub-Saharan Africa. There is an urgent need for studies that report systematically on the development, adaptation, implementation, and evaluation of integrated AUD interventions in health care settings in sub-Saharan Africa.


Bivalirudin as an Alternative Anticoagulant for Cardiopulmonary Bypass During Adult Cardiac Surgery-A Change in Practice.
The referral of patients for open heart surgery, presenting with a history of heparin hypersensitivity instigated a multidisciplinary effort to find an alternative anticoagulant to heparin. The various options mentioned in the literature call for changes in the routine practice of open heart surgery on cardiopulmonary bypass. These changes involve mostly the perfusion setup and conduct on bypass and to a lesser extent the anesthetic and surgical practice. Nevertheless, the different professions involved in the cardiac surgical firm discussed the proposed changes in a multidisciplinary effort. A new protocol was drafted, endorsed, and executed. The authors highlight these changes and their successful use in the subsequent case study.


Why we need a theory of suffering, and lots of other theories as well: commentary.
In the first section of his article, "The Role of Suffering and Community in Clinical Ethics," Erich Loewy sketches a theory of suffering. His conviction is that clinical medical ethics is not clearly rooted in theory and is inadequately grounded because of this. While acknowledging the merits of virtue ethics and casuistry, Loewy quickly dispenses with them, as contenders for this theoretical basis. Kantianism and utilitarianism are likewise rejected as "a universally acceptable grounding for ethics." In their place, Loewy proposes that "a deeper and more universal grounding can be found in the capacity of sentient beings to suffer." It is on this capacity to suffer that he builds his hierarchies of moral value, including primary, secondary, and symbolic worth. This theory of suffering should be welcomed. It promises to expand our awareness of clinical experience, and moral life generally, away from autonomy, utility, or virtue orientations toward attention to suffering and our response to it. Such a theory can give us a revitalized language to probe the issues of medical ethics. This should lead us to a careful reading of Loewy's larger work on which this article is based. Yet my enthusiasm is tempered by Loewy's noncritical acceptance of a peculiar, yet pervasive, understanding of the role and use of theory in ethics....


[Cohesion and family adaptability in women with epilepsy: cross-sectional study].
To test the hypothesis that women with epilepsy come from families with poor cohesion and adaptability to the disease, compared with healthy women. Cross-sectional study. A retrospective study was done on 263 women from a neurology outpatient department and a family medicine unit from the Mexican Social Security Institute in Sonora (Mexico) between 2010 and 2011. Were 82 women with epilepsy (cases), and 181 healthy women (control group). Age and area of residence was utilized to pair the sample (1:2,2). Univariate analysis was performed for socio-demographic variables, family type, socio-economic status, level of cohesion and family adaptability based on FACES III. A logistic regression analysis was performed for those variables that were associated with functionality of family in women with and without epilepsy. A family dysfunction were found in 22% of epileptic women (OR = 2.91 [2.17, 3.89], p=.0001). Univariate analysis suggested the presence of epilepsy and of family dysfunction associated with age, disease more than 15 years of evolution, and family type (rural, urban and traditional). The logistic regression model confirmed an association only for presence of epilepsy (OR = 7.30 [4.00, 13.33], p=.0001). The study answers the hypothesis that women with epilepsy live in families with greater psychosocial impairment, manifested by deficiencies in cohesion and adaptability to the disease, compared with healthy women.


Evaluating Machine Learning-Based Automated Personalized Daily Step Goals Delivered Through a Mobile Phone App: Randomized Controlled Trial.
Growing evidence shows that fixed, nonpersonalized daily step goals can discourage individuals, resulting in unchanged or even reduced physical activity. The aim of this randomized controlled trial (RCT) was to evaluate the efficacy of an automated mobile phone-based personalized and adaptive goal-setting intervention using machine learning as compared with an active control with steady daily step goals of 10,000. In this 10-week RCT, 64 participants were recruited via email announcements and were required to attend an initial in-person session. The participants were randomized into either the intervention or active control group with a one-to-one ratio after a run-in period for data collection. A study-developed mobile phone app (which delivers daily step goals using push notifications and allows real-time physical activity monitoring) was installed on each participant's mobile phone, and participants were asked to keep their phone in a pocket throughout the entire day. Through the app, the intervention group received fully automated adaptively personalized daily step goals, and the control group received constant step goals of 10,000 steps per day. Daily step count was objectively measured by the study-developed mobile phone app. The mean (SD) age of participants was 41.1 (11.3) years, and 83% (53/64) of participants were female. The baseline demographics between the 2 groups were similar (P>.05). Participants in the intervention group (n=34) had a decrease in mean (SD) daily step count of 390 (490) steps between run-in and 10 weeks, compared with a decrease of 1350 (420) steps among control participants (n=30; P=.03). The net difference in daily steps between the groups was 960 steps (95% CI 90-1830 steps). Both groups had a decrease in daily step count between run-in and 10 weeks because interventions were also provided during run-in and no natural baseline was collected. The results showed the short-term efficacy of this intervention, which should be formally evaluated in a full-scale RCT with a longer follow-up period. ClinicalTrials.gov: NCT02886871; https://clinicaltrials.gov/ct2/show/NCT02886871 (Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng).


[Surgical treatment of the vertebral column tumors compressing nervous structures].
The results of treatment of 136 patients with primary and metastatic tumors, affecting the vertebra and compressing the spinal cord or its roots were analyzed. The kind and adequacy of access, method of excision of the vertebral column tumor, volume of the tumoral resection, type of used system of the vertebral column stabilization were evaluated. Histological peculiarities of the vertebral column tumors were studied and classified.


Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial-mesenchymal transition-related proteins.
We aimed to investigate the association of the expression levels of five epithelial-mesenchymal transition (EMT)-related proteins (Snail, Twist, E-cadherin, N-cadherin, and Vimentin) with tumorigenesis, pathologic parameters and prognosis in tongue squamous cell carcinoma (TSCC) patients by immunohistochemistry of tissue microarray. The expression levels of Snail, E-cadherin, N-cadherin and Vimentin were significantly different between the tumor adjacent normal and tumor tissues. In tumor tissues, lower E-cadherin and higher N-cadherin levels were associated with a higher grade of cell differentiation, advanced stage of disease, and lymph node metastasis. However, higher Vimentin expression was associated with poor cell differentiation and lymph node metastasis. Patients with low E-cadherin expression had poor disease-specific survival (DSS). Conversely, positive N-cadherin and higher Vimentin expression levels were associated with poor DSS and disease-free survival. Notably, our multivariate Cox regression model indicated that high Vimentin expression was an adverse prognostic factor for DSS in TSCC patients, even after the adjustment for cell differentiation, pathological stage, and expression levels of Snail, Twist, E-cadherin, and N-cadherin. Snail, E-cadherin, N-cadherin, and Vimentin were associated with tumorigenesis and pathological outcomes. Among the five EMT-related proteins, Vimentin was a potential prognostic factor for TSCC patients.


Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation.
We report a method for large-scale absolute protein expression measurements (APEX) and apply it to estimate the relative contributions of transcriptional- and translational-level gene regulation in the yeast and Escherichia coli proteomes. APEX relies upon correcting each protein's mass spectrometry sampling depth (observed peptide count) by learned probabilities for identifying the peptides. APEX abundances agree with measurements from controls, western blotting, flow cytometry and two-dimensional gels, as well as known correlations with mRNA abundances and codon bias, providing absolute protein concentrations across approximately three to four orders of magnitude. Using APEX, we demonstrate that 73% of the variance in yeast protein abundance (47% in E. coli) is explained by mRNA abundance, with the number of proteins per mRNA log-normally distributed about approximately 5,600 ( approximately 540 in E. coli) protein molecules/mRNA. Therefore, levels of both eukaryotic and prokaryotic proteins are set per mRNA molecule and independently of overall protein concentration, with >70% of yeast gene expression regulation occurring through mRNA-directed mechanisms.


Long-term terrestrial carbon dynamics in the Midwestern United States during 1850-2015: Roles of land use and cover change and agricultural management.
To meet the increasing food and biofuel demand, the Midwestern United States has become one of the most intensively human-disturbed hotspots, characterized by widespread cropland expansion and various management practices. However, the role of human activities in the carbon (C) cycling across managed landscape remains far from certain. In this study, based on state- and national census, field experiments, and model simulation, we comprehensively examined long-term carbon storage change in response to land use and cover change (LUCC) and agricultural management in the Midwest from 1850 to 2015. We also quantified estimation uncertainties related to key parameter values. Model estimation showed LUCC led to a reduction of 1.35 Pg (with a range of 1.3-1.4 Pg) in vegetation C pool of the Midwest, yet agricultural management barely affected vegetation C change. In comparison, LUCC reduced SOC by 4.5 Pg (3.1 to 6.2 Pg), while agricultural management practices increased SOC stock by 0.9 Pg. Moreover, we found 45% of the study area was characterized by continuously decreasing SOC caused by LUCC, and SOC in 13% and 31% of the area was fully and partially recovered, respectively, since 1850. Agricultural management was estimated to increase the area of full recovery and partial recovery by 8.5% and 1.1%. Our results imply that LUCC plays an essential role in regional C balance, and more importantly, sustainable land management can be beneficial for strengthening C sequestration of the agroecosystems in the Midwestern US, which may serve as an important contributor to C sinks in the US.


Harms C1-C2 instrumentation technique: anatomo-surgical guide.
Anatomic study. To measure C1 and C2 critical areas related to the screws trajectory, according to Harms technique, in Latin specimens. To investigate vertebral's artery course in cadavers. To our knowledge there are no studies addressing vertebral surface measurements for screw placement, according to Harms C1-C2 instrumentation technique, nor cadaveric measurements of the trajectory of the vertebral artery in Latin specimens. C1 and C2 specimens were measured. C1 measurements: height, width, anteroposterior diameter (intraosseus screw length) and convergence in the axial plane of the lateral mass; length from the posterior border of the posterior C1 arch to the anterior cortex of the articular mass (total screw length). C2 measurements: width, height, convergence and sagittal inclination of the pars interarticularis. Direction of the trajectory of the vertebral artery in the suboccipital region in fresh cadavers. C1: left mass width 14.20 mm, right: 14.32 mm; left intraosseus screw length: 17.17 mm, right 16.9 mm; left total length of the screw: 27.14 mm, right: 26.72 mm; left mass height: 10.22 mm, right: 10.29 mm. Right mass convergence: 24.68°, left: 22.44°. C2: width: left 8.75 mm, right: 8.53 mm; height: left 10 mm, right 9.81 mm; convergence: left 42.15°, right: 38.98°; sagittal inclination: left 35.50°, right 33.07°. Vertebral artery's medial border is between 13 and 22 mm from the middle line of C1 posterior arch. Convergence and inclination of the pars are slightly greater than the suggested by Harms. Individual and/or racial variations must be considered. There is enough space for safe placement of a 3.5 mm screw in the lateral masses of C1 and through the pars of C2. Dissecting the superior face of the posterior arch of C1 laterally more than 10 mm from the posterior tubercule could injure the vertebral artery.


Six-Month Lower Limb Aerobic Exercise Improves Physical Function in Young-Old, Old-Old, and Oldest-Old Adults.
The effect of aerobic exercise on physical function and mental health in various adult age groups (young-old, 65-74; old-old, 75-84; oldest-old, ≥ 85 years) is unclear. The aim of this study was to investigate the effects of the Kohzuki Exercise Program (KEP) on physical function and mental health in these age groups. The KEP consisted of 40-min supervised sessions 3 times per week for 6 months as follows: 5 min of warm-up, 30 min of lower limb aerobic exercise, and 5 min of cool-down. A total of 50 participants (22 young-old, 20 old-old, and 8 oldest-old) who participated in the KEP completed at least 88% of the sessions. In statistical analysis, 3 (group: oldest-old, old-old, young-old) × 2 (time: baseline and after 6 months) analyses of variance were used to determine if there were significant main and interaction effects. Significant interactions were probed using the post-hoc paired t test. The Short Physical Performance Battery (SPPB) score showed significant group × time interactions after 6 months (p = 0.031). In the post-hoc test, oldest-old (p < 0.001), old-old (p < 0.001), and young-old (p < 0.01) groups had significantly better physical function after 6 months. However, none of the mental health measures showed group × time interactions at 6-month. Our results suggest that a 6-month KEP led to improved physical function in oldest-old, old-old, and young-old adults. The KEP was effective for oldest-old adults in particular. The KEP exhibits good adherence, making it suitable for a wide age range in society.


Traffic of proteins and peptides across membranes for immunosurveillance by CD8(+) T lymphocytes: a topological challenge.
Cytotoxic CD8(+) T lymphocytes kill infected cells that display major histocompatibility complex (MHC) class I molecules presenting peptides processed from pathogen proteins. In general, the peptides are proteolytically processed from newly made endogenous antigens in the cytosol and require translocation to the endoplasmic reticulum (ER) for MHC class I loading. This last task is performed by the transporters associated with antigen processing (TAP). Sampling of suspicious pathogen-derived proteins reaches beyond the cytosol, and MHC class I loading can occur in other secretory or endosomal compartments besides the ER. Peptides processed from exogenous antigens can also be presented by MHC class I molecules to CD8(+) T lymphocytes, in this case requiring delivery from the extracellular medium to the processing and MHC class I loading compartments. The endogenous or exogenous antigen can be processed before or after its transport to the site of MHC class I loading. Therefore, mechanisms that allow the full-length protein or processed peptides to cross several subcellular membranes are essential. This review deals with the different intracellular pathways that allow the traffic of antigens to compartments proficient in processing and loading of MHC class I molecules for presentation to CD8(+) T lymphocytes and highlights the need to molecularly identify the transporters involved.


A transgenic mouse line for collecting ribosome-bound mRNA using the tetracycline transactivator system.
Acquiring the gene expression profiles of specific neuronal cell-types is important for understanding their molecular identities. Genome-wide gene expression profiles of genetically defined cell-types can be acquired by collecting and sequencing mRNA that is bound to epitope-tagged ribosomes (TRAP; translating ribosome affinity purification). Here, we introduce a transgenic mouse model that combines the TRAP technique with the tetracycline transactivator (tTA) system by expressing EGFP-tagged ribosomal protein L10a (EGFP-L10a) under control of the tetracycline response element (tetO-TRAP). This allows both spatial control of EGFP-L10a expression through cell-type specific tTA expression, as well as temporal regulation by inhibiting transgene expression through the administration of doxycycline. We show that crossing tetO-TRAP mice with transgenic mice expressing tTA under the Camk2a promoter (Camk2a-tTA) results in offspring with cell-type specific expression of EGFP-L10a in CA1 pyramidal neurons and medium spiny neurons in the striatum. Co-immunoprecipitation confirmed that EGFP-L10a integrates into a functional ribosomal complex. In addition, collection of ribosome-bound mRNA from the hippocampus yielded the expected enrichment of genes expressed in CA1 pyramidal neurons, as well as a depletion of genes expressed in other hippocampal cell-types. Finally, we show that crossing tetO-TRAP mice with transgenic Fos-tTA mice enables the expression of EGFP-L10a in CA1 pyramidal neurons that are activated during a fear conditioning trial. The tetO-TRAP mouse can be combined with other tTA mouse lines to enable gene expression profiling of a variety of different cell-types.


The experience of mothers and fathers in cases of stillbirth in Spain. A qualitative study.
To explore the experience of both the mothers and the fathers regarding the care received during delivery in cases of stillbirth. A hermeneutic phenomenological study based on semi-structured interviews with eleven mothers and fathers who experienced stillbirth. A purposive sample was recruited in Hospital XXX of XX and through a local pregnancy loss support organization. Interviews were recorded and transcribed verbatim and analysed using inductive thematic analysis. Four main categories identified: 1) denial of grief, 2) the life and death paradox, 3) guilt, and 4) go through and overcome the loss. The parents manifested a lack of recognition of their loss and their parenthood. Although the midwife was the highest valued professional, not all the experiences were positive and the parents would have appreciated being accompanied by trained people with good communication skills. They also referred to in-hospital logistic barriers that complicated the process, as well as the fact that these births occurred in the same place where healthy deliveries were attended. Findings highlight the importance of tailoring support systems according to mothers' and fathers' needs. Promoting social and institutional recognition of this kind of loss and training healthcare professionals in the accompaniment of this type of mourning is useful to plan comprehensive care to facilitate the initiation and subsequent evolution of healthy mourning.


An investigation of the actual conditions of use of daily-disposable soft contact lenses and two-week disposable soft contact lenses.
To investigate whether daily-disposable and 2-week disposable soft contact lenses are being used correctly. The number of purchases made and brands selected by the 44,566 consumers who purchased daily-disposable and 2-week disposable soft contact lenses in Okada Eye Clinic institutions between April 1, 2002 and November 1, 2002 were monitored. From the 7,759 respondents to a survey conducted in the clinic between November 1, 2002 and March 31, 2003, the number of purchases made and brands selected by the 1,584 respondents, whose sales records could be traced, were analyzed in further detail. The total number of consumers purchasing daily-disposable soft contact lenses was 14,909, and their annual average purchase was 10.56 boxes. Most purchases were of two boxes followed by purchases of four and then six. Only 6.4% of consumers purchased 24 boxes at a time. Consumers purchasing four or fewer boxes at a time accounted for 37.8%. A total of 25,705 consumers purchased 2-week disposable soft contact lenses, with an annual average purchase of 6.37 boxes per consumer. Nineteen percent of the consumers purchased eight boxes of 2-week disposable soft contact lenses per year. Most consumers tended to purchase their contact lenses in even numbers for daily-disposable and 2-week disposable soft contact lenses. Johnson & Johnson Vision Care (Jacksonville, FL) was the most popular manufacturer. According to the survey, 86.6% of the 2-week disposable soft contact lens wearers followed instructions correctly, whereas 13.4% did not. That is, they exceeded the instructed 14 days of wear. Annual average purchases of daily-disposable and 2-week disposable soft contact lenses tended to be in even numbers and showed differences in their sales depending on contact lens brands. The results obtained from the survey and the actual sales records correlated.


Lung metabolism and systemic organ function.
In the past decade a variety of metabolic events have been described which occur in the lungs. These processes, such as the clearance of serotonin and norepinephrine, the inactivation of bradykinin and the activation of angiotensin II, and the synthesis of prostaglandins, may have a direct impact on systemic organ function. Under certain circumstances the lungs produce prostaglandins that may lead to severe hemodynamic instability and death. Pressure breathing with hyperinflation is a potent pulmonary metabolic stimulus. This commonly used therapeutic maneuver has been shown to increase fibrinolytic activity. The application of end-expiratory pressure will further enhance the fibrinolytic state by virtue of the pulmonary secretion of plasminogen activator. Positive end-expiratory pressure (PEEP) will also cause a lowering of the cardiac output, which is related at least in part to lung metabolism. Circulating factors are released during PEEP that have a negative inotropic effect. It is reasonable to view respiratory failure not only as a defect in gas exchange but also as a derangement in lung metabolism.


Kant on anatomy and the status of the life sciences.
This paper contributes to recent interest in Kant's engagement with the life sciences by focusing on one corner of those sciences that has received comparatively little attention: physical and comparative anatomy. By attending to remarks spread across Kant's writings, we gain some insight into Kant's understanding of the disciplinary limitations but also the methodological sophistication of the study of anatomy and physiology. Insofar as Kant highlights anatomy as a paradigmatic science guided by the principle of teleology in the Critique of the Power of Judgment, a more careful study of Kant's discussions of anatomy promises to illuminate some of the obscurities of that text and of his understanding of the life sciences more generally. In the end, it is argued, Kant's ambivalence with regard to anatomy gives way to a pessimistic conclusion about the possibility that anatomy, natural history, and, by extension, the life sciences more generally might one day become true natural sciences.


Cardiac magnetic resonance imaging in Turner syndrome.
Girls and women with Turner syndrome (TS) have a highly increased morbidity as the result of cardiovascular disease, both congenital and acquired. Increased clinical use of cardiac magnetic resonance imaging (CMR) in patients with TS over recent years has allowed for characterization of disease not always possible with standard imaging modalities, such as echocardiography (echo). In this review, we discuss the current literature regarding CMR in patients with TS and guidelines for its use.


Monoclonal antibodies recognizing different epitopes of cytokeratin No.18.
A comparative study of six mouse monoclonal antibodies against human 45 kDa keratin polypeptide (keratin No. 18) was undertaken using three experimental approaches: immunohistochemistry on normal human tissues, examination of interspecies cross-reactivity and identification of the target polypeptides in 1-D and 2-D immunoblots. The data suggest that at least five different antigenic sites of keratin 18 are recognized by this panel of reagents. The C-04 epitope is keratin 18-specific and widely conserved among mammalian species, while the antibodies DA7 and DC10 also react specifically with the 45 kDa keratin but stain simple epithelia of human origin only. Two antibodies, C-11 and C-66, decorate simple as well as stratified epithelia in human and in all seven animal species tested, but their respective target epitopes are shared by different groups of keratin polypeptides, which indicates their non-identity. In contrast to keratin specificity of the five above mentioned antibodies, the C-08 antibody cross-reacts with a 70 kDa nuclear lamina protein found in human and bovine tissues. The results of the present study provide the necessary basis for future applications of these antibodies in both routine immunodiagnostic work and as probes to study the biology of epithelial cells in general and the significance of keratin intermediate filaments in particular.


A Comparative Study of Five Association Tests Based on CpG Set for Epigenome-Wide Association Studies.
An epigenome-wide association study (EWAS) is a large-scale study of human disease-associated epigenetic variation, specifically variation in DNA methylation. High throughput technologies enable simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. The clustering of correlated DNA methylation at CpGs is reportedly similar to that of linkage-disequilibrium (LD) correlation in genetic single nucleotide polymorphisms (SNP) variation. However, current analysis methods, such as the t-test and rank-sum test, may be underpowered to detect differentially methylated markers. We propose to test the association between the outcome (e.g case or control) and a set of CpG sites jointly. Here, we compared the performance of five CpG set analysis approaches: principal component analysis (PCA), supervised principal component analysis (SPCA), kernel principal component analysis (KPCA), sequence kernel association test (SKAT), and sliced inverse regression (SIR) with Hotelling's T2 test and t-test using Bonferroni correction. The simulation results revealed that the first six methods can control the type I error at the significance level, while the t-test is conservative. SPCA and SKAT performed better than other approaches when the correlation among CpG sites was strong. For illustration, these methods were also applied to a real methylation dataset.


Intake fraction distributions for indoor VOC sources in five European cities.
Distributions of intake fractions for indoor air emissions were estimated for five cities in the EXPOLIS study (Athens, Basel, Helsinki, Oxford, and Prague). Intake fractions are an expression of the mass of a pollutant that reaches a target compared with the mass emitted by a source. They facilitate direct comparisons of the relative impact of different sources on individual or population exposure and dose. The computation of the distributions was obtained through Monte Carlo simulations, based on distributions of residence volume, air exchange rates and time-activity data, calculated from the EXPOLIS database, as well as on distributions from the literature. Some approximations were made that are valid for persistent pollutants and continuous sources, such as emissions from building materials, pesticides, molds, as well as for certain non-continuous sources such as cooking or cleaning products. For these categories of sources, intake fractions are approximately independent of the actual indoor concentrations and irrespective of the source. Intake fractions in the five populations examined followed approximately lognormal distributions. The mean individual intake fractions exhibited some variability across cities, ranging from 1.5x10(-3) in Athens to 4.5x10(-3) in Helsinki. Intake fractions for all the people in a household followed similar distributions, with mean values ranging from 4.6x10(-3) in Athens to 11.8x10(-3) in Helsinki. This modest variability mostly reflects the differences in climates and consequent air-tightness of the buildings. The 95th percentile of the distributions were two to three times the mean values, indicating substantial homogeneity within each population as well. These results compare well with previous estimates for environmental tobacco smoke and cooking, and are two to three orders of magnitude larger than estimates for outdoor sources. Emissions from indoor sources were estimated to be approximately 1000 times more likely to reach a human target than emissions from outdoor sources. Strategies to reduce exposure to indoor sources can only realistically focus on reducing the strength of the emissions.


Could pelvic floor sonography be a standalone method for excluding genuine stress urinary incontinence in women?
Determine whether introital pelvic floor sonography with transvaginal probe (PFS-TV) can be an independent method in the diagnosis of genuine stress urinary incontinence (SUI) and to create a ultrasonographic diagnostic model to objectify diagnostic process. The study involved 315 patients with a history of urinary incontinence problems. Based on the clinical examination and urodynamic examination, the final diagnosis was made. Patients were divided into two groups. Group I included women with SUI and Group II included patients without SUI (OAB and no-UI). Each patient underwent PFS-TV at rest and during straining. The groups were compared in terms of ultrasound parameters. Patients from both groups differed statistically in a significant way (p < 0.05) in terms of mean distance between the lower edge of the pubic symphysis at rest 19 mm vs 22 mm (Group I vs Group II) and during straining (D1 and D2) 22 mm vs 26 mm, the average value of the γ angle (at rest (γ1) 37.5° vs 40° and during straining (γ2) and 66° vs 58.5°, average difference value of angle γ during straining and at rest (γ2-γ1) 29° vs 14°, and frequency of urethral funneling 89% vs 17%. Two parameters studied during PFS-TV were included in the logistic regression model used to exclude the stress component of urinary incontinence. Diagnostic test parameters of model were sensitivity 86.6%, specificity 90.4%, accuracy 93.1%. PFS-TV makes it possible to exclude the stress component of urinary incontinence. The developed logistic regression model allows for the objectification of the results of ultrasound examination in patients with urinary incontinence.


Analysis of pulsed wave Doppler ultrasound spectra obtained from a model intracoronary catheter.
Abnormal arterial blood flow patterns have been implicated in the evolution of various vascular disease processes. Intravascular ultrasound techniques using the pulsed wave Doppler catheter offer the opportunity to characterize these abnormal flow patterns. We have developed a mathematical model that predicts the first two moments of the Doppler spectrum obtained using a Doppler catheter based on the distribution of ultrasonic beam power and velocity profile of fluid flow with an arbitrary distribution of flow disturbances. A scaled-up, in vitro experimental arterial system was used to confirm the validity of the model. Comparison of the predicted first two moments of the Doppler spectrum to the experimental values in this system demonstrated that the distribution of beam power significantly affects the magnitude of the first two moments. Additionally, both velocity gradient and velocity fluctuation broadening effects play prominent roles in determining the magnitude of the second moment. These phenomena must therefore be considered when evaluating in vivo Doppler spectra used for the characterization of abnormal flow patterns.


From an Incidental Finding to an Emergent Treatment: A Case Report of a Hepatic Adenomatosis and Large Ruptured Hepatic Adenoma.
Introduction. Hepatic adenoma is an uncommon benign liver tumor presenting as solitary lesions or even rarely as hepatic adenomatosis. Large lesions carry a risk of rupture, hemorrhage, and malignant transformation. This case report aims to increase awareness about risk factors for hepatic adenomas, considering the increasing prevalence of obesity and the widespread use of oral contraceptive pills. Case Presentation. A 20-year-old obese female who was taking oral contraceptive pills for seven years presented to the emergency department with vomiting and abdominal pain caused by gastroenteritis. On imaging, multiple hepatic adenomas, including two lesions 6 and 9 cm in diameter, were incidentally found. During the hospitalization, the patient suddenly developed acute anemia and rupture of the largest lesion, which was promptly treated with arterial embolization. Discussion. Obesity and exposure to hormones are well-known risk factors for hepatic adenomas. The incidence of hepatic adenomas is steadily increasing because of the prevalence of obesity, especially among females. Lifestyle interventions for weight loss and discontinuation of oral contraceptive pills are considered a conservative treatment of hepatic adenomas. Large lesions possess the risk of malignant transformation and rupture and require surgical excision.


Treatment of children with relapsed soft tissue sarcoma: report of the German CESS/CWS REZ 91 trial.
The present study was performed to evaluate the possibilities of relapse treatment in patients heavily pretreated for a soft tissue sarcoma. Prospective, multicenter study in 44 soft tissue sarcoma (STS) patients with first relapse. Primary diagnosis was embryonal rhabdomyosarcoma (RME) in 17 patients, alveolar rhabdomyosarcoma (RMA) in 13, primitive neuroectodermal tumor (PNET) in 6, and miscellaneous soft tissue sarcomas in 8 patients. Initial chemotherapy consisted of carboplatin/etoposide combination (150 mg/m2 each, days 1 to 4) followed by local therapy including surgical treatment and, whenever possible, radiotherapy. In 11/17 patients without primary tumor resection, CR or PR was achieved following the initial two cycles of chemotherapy (61%). The probability of event-free survival (pEFS) for RME patients was 0.41 +/- 0.12 at 5 years, and 0.25 +/- 0.12 for RMA patients. But, in contrast no PNET patient or patient with another soft-tissue sarcoma achieved long-term remission. Additional local radiotherapy significantly (P = 0.002) improved pEFS (3-year estimates of 0.23 +/- 0.2 vs. 0.1 +/- 0.1 in patients without radiotherapy). In patients with RME, relapse treatment employing a carboplatin/etoposide combination may induce a second remission in approximately 40% of patients. Surgical excision and additional local radiotherapy seem to be essential to maintain a stable remission. In patients with RMA or PNET, however, this treatment strategy is of no long-term benefit.


Leptosphaerulina species isolated from golf turfgrass in China, with description of L. macrospora, sp. nov.
Leptosphaerulina leaf blight occurs on most turfgrasses. Hitherto, Leptosphaerulina species associated with this disease include L. americana, L. argentinensis, L. australis, and L. trifolii. However, following Koch's postulates, L. australis was confirmed as saprobes but not pathogens, and the other three species have not been tested. The pathogenicity of Leptosphaerulina spp. is still questionable. In this study, we isolated 19 Leptosphaerulina strains from diseased golf turfgrasses in China, and they were identified as L. gaeumannii, L. saccharicola, and a new species, L. macrospora, through multilocus (ITS, 28S, rpb2, and tub2) phylogenetic analyses and morphological observations. Pathogenicity test revealed that the three Leptosphaerulina species identified in this study cannot infect live/healthy turfgrass tissues of Poa pratensis and Agrostis stolonifera and only produced pseudothecia on the dead leaves of stressed seedlings. Considering the results of pathogenicity tests in this and previous studies, we speculate that most Leptosphaerulina species isolated from diseased turfgrass are not pathogens but saprobes. Applying proper management practices to prevent severe turfgrass stress is a key measure to reduce or eliminate the effects of Leptosphaerulina on golf turfgrass.


Short-chain fatty acids and other intestinal microflora-associated characteristics in faeces of patients with severe B-cell immunodeficiency.
The intestinal microflora of 18 patients with severe B-cell immunodeficiency was studied by determination of short-chain fatty acids (SCFAs) and other intestinal microflora-associated characteristics in the faeces. Glucose-hydrogen (H2) breath test was also performed. The results were within normal values in most of the patients, indicating no major pathologic changes in the intestinal bacterial microflora. These findings do not indicate any important role of the mucosa-associated B-cell system in the regulation of the composition and metabolic activity of the intestinal microflora.


Bilateral eyelid necrosis as a complication of pseudomonal septicaemia.
We present a case of bilateral eyelid necrosis as a result of Pseudomonas aeruginosa infection. This is a rare condition that occurs only in neutropenic patients. It may be unilateral or bilateral and requires aggressive management with correction of the neutrophil count, local debridement and systemic antibiotic therapy.


Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone.
By using mRNA polymerase chain reaction differential display technique (DDPCR), we have identified one early responsive cDNA fragment, TDD5, from a 5alpha-reductase-deficient T cell hybridoma. The DDPCR profiles of TDD5 suggest that its expression can be repressed by testosterone (T) within 2 hr. More importantly, both DDPCR and Northern blot analysis further demonstrated that the expression of TDD5 was differentially repressed by T and dihydrotestosterone (DHT) at the mRNA level. To our knowledge, this is the first androgen target gene to show a preference in response to T over DHT in cell culture. TDD5 is expressed in several tissues with particular abundance in kidney. Full-length TDD5 cDNA (2,916 bp) encodes a protein with a calculated molecular weight of 42,000. Finally, our animal studies further confirm that TDD5 mRNA levels can be repressed to the basal level 8 hr after DHT administration. The isolation and characterization of the early-responsive androgen target gene TDD5 and the fact that TDD5 mRNA level can be differentially regulated by T and DHT may provide a useful tool to study the molecular mechanism of androgen preference on target gene regulation.


Rapid improvement of acute pulmonary edema with angiotensin converting enzyme inhibitor under hemodialysis in a patient with renovascular disease.
A 71-year-old man with bilateral renovascular disease was admitted to Hamamatsu University hospital because of appetite loss and acute shortness of breath due to acute pulmonary edema (APE) with accelerated hypertension and renal failure. Hypertension and APE were controlled by an angiotensin converting enzyme inhibitor (ACEI) and four sessions of hemodialysis with reduction of 1.8 kg bodyweight. Renal function was later stabilized and the patient required no ACEI or hemodialysis. A trial of right renal angioplasty 1 month after admission failed and renal function deteriorated (serum creatinine 7.1 mg/dL) with accelerated hypertension, gain of bodyweight and APE. Even after four sessions of hemodialysis with adequate reduction of bodyweight, APE was not controlled, but it rapidly improved after administration of an ACEI, without major bodyweight change. As no apparent cardiac dysfunction was evident, APE might have been caused by a direct action of angiotensin II on hyperpermeability in pulmonary capillaries. Blocking of angiotensin II should be considered in such patients even after introduction of hemodialysis.


Amendments suggested for zoo medical research strategies with focus on the D-A-CH region.
Scientific exploration of zoo animals is one of the main missions of modern zoos. As scientific achievements are best reflected within scientific literature, we screened appropriate literature search outcomes from the 5 highest ranked zoos in the D-A-CH region (Germany-Austria-Switzerland) in order to deduce suggestions for optimizations of future research strategies. Literature search was done by entering "Zoo Vienna", "Tiergarten Schönbrunn", "Zoo Berlin", "Tiergarten Berlin", "Tierpark Hellabrunn", "Tierpark Hagenbeck", and "Zoo Zurich" on PubMed and Scopus for the period 2000-2020. These 5 European zoos were chosen due to their broad public recognition and international importance. Inclusion criterion for the literature list was the description/mentioning of analysed animals or samples with a clear affiliation to the respective zoo in the materials and methods or acknowledgements sections. Search hits were then allocated to the following 7 areas: animal nutrition, biology, ethology, infectiology, reproduction, phylogenetics, and clinical medicine. Also, portions of higher animal taxa (and species, if appropriate) were recorded. A total of 142 papers has been published. Mammals, especially large ones, were clearly over-represented in literature with 2 thirds of analysed papers dealing with them. Sauropsids (birds and reptiles) were treated in 28 % and non-amniotic vertebrates (amphibians and fish) as well as invertebrates in only 3 % each. This apportionment is in no relation to the species numbers of the respective higher animal taxa. The predominating research areas (covered by approximately 75 % of papers) were ethological studies, followed by papers on infectious diseases, and finally papers on biology with morphological, physiological, and molecular biological themes. Research on reproductive biology/medicine, which is considered to be of tremendous importance for the establishment of ex-situ populations and thus for the conservation of endangered species, has been covered by only 6 % of papers. Future research should more intensely keep an eye on that discipline, especially in non-mammalian vertebrates.


Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice.
Aluminum trichloride (AlCl3) exposure was proven to encourage some behavioral deficits and eventually induces anxiety and depression in rodents animals. Therefore, this experiment aimed to scout about the effects of pomegranate juice on anxiety- and depression-like behaviors caused by AlCl3 in male mice. Six groups of male mice were administrated orally for 35 days by PJ and AlCl3. The control group (G-I) received tap water, while the PJ groups (G-II and G-III) were treated with 20 % and 40 % PJ, respectively. The AlCl3 group (G-IV) was treated with 400 mg/kg/day of AlCl3, and the last two groups (G-V and G-VI) were treated with AlCl3 and 20 % PJ or 40 % PJ, respectively. Then, the open-field (O-F), elevated plus maze (EPM), tail suspension (TS), forced swimming (FS), and light/dark box (L/DB) tests were applied for anxiety- and depression-like behavior studies. In addition, neurotransmitters and oxidative parameters in the brain were evaluated. The plasma cortisol was measured at the end of the experiment. Behavioral analyses showed that PJ inhibited AlCl3-induced depressive and anxiogenic effects in the O-F, EPM, TS, FS, L/DB tests. In addition, neurochemical results indicated that PJ at 20 % concentration minimized the AlCl3 toxicity on dopamine (DOP), serotonin (SER), and acetylcholinesterase (AChE) levels in the for-brain of male mice. Moreover, PJ moderated the AlCl3 effects by decreasing the level of thiobarbituric acid reactive substances (TBARS), and enhancing catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione (GSH) activities. The plasma cortisol increased in male mice treated with AlCl3 and in a group treated with a high dose of PJ. Our results proposed that the anxiety- and depression-like behaviors induced by AlCl3 exposure in male mice can be ameliorated by PJ treatment, probably through the inhibition of oxidative damage and minimizing the changes in neurotransmitters and hormonal activity.


Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets.
Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups.


Alefacept with methotrexate for treatment of psoriatic arthritis: open-label extension of a randomized, double-blind, placebo-controlled study.
A single course of alefacept intramuscularly in combination with methotrexate (MTX) was effective in treating both psoriasis and psoriatic arthritis (PsA). We sought to determine the efficacy and safety of an additional course of alefacept intramuscularly in combination with MTX in patients with PsA. In this open-label extension study, patients with PsA on stable doses of MTX were treated with an additional 12 weekly intramuscular injections of alefacept followed by 12 weeks of observation. Efficacy of PsA treatment was measured as 20% reduction in American College of Rheumatology criteria (ACR20). At the end of the open-label extension phase, 86 of 160 (54%) patients achieved ACR20, of which 28 of 55 had received placebo plus MTX and 58 of 105 received alefacept plus MTX in the prior double-blind phase. Although there was no increase in the proportion of patients achieving ACR20 after a second course of alefacept plus MTX, those achieving ACR50 and ACR70 increased from 17% and 7%, respectively, in the double-blind phase to 32% and 12%, respectively, in the open-label extension phase. In this open-label extension phase of the study there was no control group and the effect on psoriasis in these patients was not measured. Patients with psoriasis and PsA on stable doses of MTX derive benefit for both conditions from one or more courses of alefacept, with further benefit in PsA apparent after a second course of treatment. No additional toxicity was observed.


[The usefulness of the mandibular kinesiograph (MKG)].
The Jankelson mandibular kinesigraph is intended to reproduce the movements of the mandible electronically. Analyses of the measurements and clinical studies of linearity, reproducibility, and susceptibility to the electromagnetic fields showed that quantitative and qualitative evaluations of the recordings are impossible. The device therefore appears to us to be unsuitable for the clinical diagnosis of abnormal movements of the mandible and disturbances in occlusion.


SRED-ARCE Recommendations for Minimally Invasive Interventions During the COVID-19 Pandemic in Romania.
The Romanian Society of Digestive Endoscopy (SRED) and the Romanian Association of Endoscopic Surgery (ARCE) have decided to establish a joint working group to elaborate specific recommendations for organizing the diagnostic and the minimally invasive interventional procedures, in the context of the COVID-19 pandemic. The recommendations are based on the guidelines of the international societies of endoscopy and gastroenterology (ESGE / BSG / ASGE / ACG / AGA), respectively endoscopic surgery (EAES SAGES) (4-8), on the experience of countries severely affected by the pandemic (Italy, France, Spain, USA, Germany, etc.) and they will be applied within the limits of measures imposed at local and governmental level by the competent authorities. On the other hand, these recommendations should have a dynamic evolution, depending on the upward or downward trend of the COVID-19 pandemic at regional and local level, but also according to the findings of professional and academic societies, requiring regular reviews based on the publica tion of further recommendations or international clinical trials. The objectives of the SRED and ARCE recommendations target the endoscopic and laparoscopic surgery activities, to support their non discriminatory used for diagnostic or therapeutic purposes, pursuing the demonstrated benefits of these procedures, in safe conditions for patients and medical staff.


Quantification of Live Bacterial Sensing for Chemotaxis and Phagocytosis and of Macropinocytosis.
Initial immunological defense mechanisms to pathogen invasion rely on innate pathways of chemotaxis and phagocytosis, original to ancient phagocytes. Although chemotaxis has been well-studied in mammalian and model systems using purified chemoattractants in defined conditions, directed movement toward live bacteria has been more difficult to assess. Dictyostelium discoideum is a professional phagocyte that chemotaxes toward bacteria during growth-phase in a process to locate nutrient sources. Using Dictyostelium as a model, we have developed a system that is able to quantify chemotaxis to very high sensitivity. Here, Dictyostelium can detect various chemoattractants at concentrations <1 nM. Given this exceedingly sensitive signal response, Dictyostelium will migrate directionally toward live gram positive and gram negative bacteria, in a highly quantifiable manner, and dependent upon bacterially-secreted chemoattractants. Additionally, we have developed a real-time, quantitative assay for phagocytosis of live gram positive and gram negative bacteria. To extend the analyses of endocytic functions, we further modified the system to quantify cellular uptake via macropinocytosis of smaller (<100 kDa) molecules. These various approaches provide novel means to dissect potential for identification of novel chemoattractants and mechanistic factors that are essential for chemotaxis, phagocytosis, and/or macropinocytosis and for more detailed understanding in host-pathogen interactive defenses.


K-Means Segmentation of Underwater Image Based on Improved Manta Ray Algorithm.
Image segmentation plays an important role in daily life. The traditional K-means image segmentation has the shortcomings of randomness and is easy to fall into local optimum, which greatly reduces the quality of segmentation. To improve these phenomena, a K-means image segmentation method based on improved manta ray foraging optimization (IMRFO) is proposed. IMRFO uses Lévy flight to improve the flexibility of individual manta rays and then puts forward a random walk learning that prevents the algorithm from falling into the local optimal state. Finally, the learning idea of particle swarm optimization is introduced to enhance the convergence accuracy of the algorithm, which effectively improves the global and local optimization ability of the algorithm simultaneously. With the probability that K-means will fall into local optimum reducing, the optimized K-means hold stronger stability. In the 12 standard test functions, 7 basic algorithms and 4 variant algorithms are compared with IMRFO. The results of the optimization index and statistical test show that IMRFO has better optimization ability. Eight underwater images were selected for the experiment and compared with 11 algorithms. The results show that PSNR, SSIM, and FSIM of IMRFO in each image are better. Meanwhile, the optimized K-means image segmentation performance is better.


[Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin].
To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.