Murine model for non-invasive imaging to detect and monitor ovarian cancer recurrence.
Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer.


Heterogeneity of the breakpoint in the ABL gene in cases with BCR/ABL transcript lacking ABL exon a2.
We report cases with a variant BCR/ABL mRNA expression lacking ABL exon a2 sequences. Two of these cases showed major breakpoint cluster region (BCR) exon 3 (b3) and ABL exon 3 (a3) junction (b3/a3), while the other case showed minor BCR exon 1 (e1) and a3 junction (e1/a3). One of the two cases with b3/a3 junction and the case with e1/a3 junction were diagnosed as acute lymphoblastic leukemia, and the remaining case with b3/a3 junction was chronic myeloid leukemia. Two of these cases, however, were found to have a breakpoint in the ABL gene outside of the intron between exons a2 and a3, probably 5' upstream of exon a2, suggesting that the BCR exon was spliced to ABL exon a3. These findings differ from those previously reported, in which the breakpoints in the ABL gene were between exons a2 and a3, and indicate a novel mechanism for the deletion of ABL exon a2 sequences in the formation of a variant BCR/ABL fusion transcript. The significance of the finding that a part of the SH3 region of ABL protein is missing in some Philadelphia chromosome-positive leukemias is discussed in reference to the cases reported previously.


Spindle epithelial tumor with thymus-like differentiation of the thyroid.
Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid is a rare tumor that occurs habitually in children and young adults. To date, about 20 cases of SETTLE have been reported in the English medical literature. It is considered to be a tumor of low malignancy with a favorable outcome, but delayed blood-borne metastases have been reported (sometimes over 20 years after initial treatment). In the current report, the authors describe an interesting case of SETTLE in a young woman. Double phase Tc-99m tetrofosmin scintigraphy showed accumulation of the tracer in the thyroid mass.


Embedded-explicit emergent literacy intervention II: goal selection and implementation in the early childhood classroom.
This article, the second in a two-part series, provides guidance to speech-language pathologists (SLPs) for implementing the explicit component of the embedded-explicit emergent literacy intervention model for at-risk preschool and kindergarten children. The explicit component refers to the provision of regular structured therapeutic interactions that intentionally target critical emergent literacy goals. This article describes fundamental principles of explicit literacy instruction, identifies literacy domains targeted as part of explicit literacy instruction, and presents examples of how early childhood classrooms can be organized to implement the embedded-explicit model.


Curative pelvic exenteration: initial experience and clinical outcome.
in patients with advanced primary or recurrent gynecologic, urologic, or rectal cancers without metastatic disease, extensive aggressive surgery such as pelvic exenteration may be necessary for curative intent treatment. This study aims to present the initial experience and clinical outcome of curative pelvic exenteration procedures for advanced or recurrent pelvic cancer in our center. a retrospective cross-sectional study was conducted at the colorectal unit at King Hussein Medical Center in Amman, Jordan, between March 2014 and December 2021. All patients who underwent pelvic exenteration procedures were included in this study. Demographic characteristics, type of procedure, completeness of excision, postoperative complications, morbidity, and mortality were analyzed. a total of 30 patients underwent thirty-one operations. There were 22 females and eight males with a median age of 55 (range 25-86) years. Twenty-six surgeries were for advanced primary and 5 for recurrent malignancies. Twenty-nine operations were performed for colorectal and 2 for gynecological tumors. There were 19 posterior pelvic exenterations, 2 posterior pelvic exenterations with sacrectomy, and ten total pelvic exenterations. Completeness of tumor excision R0 was observed in 21 specimens, incomplete (R1/R2) in 6 specimens. The overall complication rate was 67.7% and 30-day mortality was 16.7%. Ten (33.3%) patients are disease free at a median follow-up of 22 months. in our study, pelvic exenteration provides above 40% overall survival at a median follow-up of two years. Gaining experience in this type of procedure, a multidisciplinary approach, careful patients' selection, and preoperative counseling will reduce postoperative morbidity and mortality.


Conformational properties of semirigid antipsychotic drugs: the pharmacophore for dopamine D-2 antagonist activity.
Conformational energy calculations using the MM2-87 program have been performed on the tetracyclic spiro amines 1 (A23887) and 2 (A31472) which have previously been shown to have considerable affinity for dopamine D-2 receptors. These compounds are important for defining the pharmacophore for D-2 antagonist activity due to their limited conformational freedom. Possible foldings of the multicyclic structure were energy minimized and the barriers for inversion and for rotation of the ammonium group were computed. The conformational properties of 1 and 2 are consistent with a pharmacophore recently proposed by Liljefors and Bøgesø. The greater affinity of (S)-octoclothepin for D-2 receptors as compared with its enantiomer was attributed to the latter having an incorrect orientation of the ammonium hydrogen despite the correct folding of the tricyclic structure. Other D-2 antagonists with limited conformational freedom such as butaclamol, isobutaclamol, loxapine, clozapine, and resolved cyproheptadine analogues were also found to be consistent with the pharmacophore. In addition, 1, 2, and their enantiomers were tested on radioligand binding assays for dopamine D-1, dopamine D-2, noradrenergic alpha-1, serotonergic 5-HT2, muscarinic, and sigma receptors. 1 and 2 have greater affinities than their enantiomers in the D-1, D-2, alpha-1, and 5-HT2 assays though there was little difference between 2 and its enantiomer in the latter two assays. In the muscarinic assays, 2 and its enantiomer, which were approximately equipotent, had greater affinity than 1 and its enantiomer. None of the compounds had substantial affinity for sigma receptors. Since the same enantiomers of 1, 2, butaclamol, and the resolved cyproheptadine analogues also have greater affinities for D-1 receptors, the conformational requirements of D-1 ligands appear to be quite similar to those of D-2 ligands.


Spemann organizer transcriptome induction by early beta-catenin, Wnt, Nodal, and Siamois signals in Xenopus laevis.
The earliest event in Xenopus development is the dorsal accumulation of nuclear β-catenin under the influence of cytoplasmic determinants displaced by fertilization. In this study, a genome-wide approach was used to examine transcription of the 43,673 genes annotated in the Xenopus laevis genome under a variety of conditions that inhibit or promote formation of the Spemann organizer signaling center. Loss of function of β-catenin with antisense morpholinos reproducibly reduced the expression of 247 mRNAs at gastrula stage. Interestingly, only 123 β-catenin targets were enriched on the dorsal side and defined an early dorsal β-catenin gene signature. These genes included several previously unrecognized Spemann organizer components. Surprisingly, only 3 of these 123 genes overlapped with the late Wnt signature recently defined by two other groups using inhibition by Dkk1 mRNA or Wnt8 morpholinos, which indicates that the effects of β-catenin/Wnt signaling in early development are exquisitely regulated by stage-dependent mechanisms. We analyzed transcriptome responses to a number of treatments in a total of 46 RNA-seq libraries. These treatments included, in addition to β-catenin depletion, regenerating dorsal and ventral half-embryos, lithium chloride treatment, and the overexpression of Wnt8, Siamois, and Cerberus mRNAs. Only some of the early dorsal β-catenin signature genes were activated at blastula whereas others required the induction of endomesoderm, as indicated by their inhibition by Cerberus overexpression. These comprehensive data provide a rich resource for analyzing how the dorsal and ventral regions of the embryo communicate with each other in a self-organizing vertebrate model embryo.


Is visual metacognition associated with autistic traits? A regression analysis shows no link between visual metacognition and Autism-Spectrum Quotient scores.
Metacognition -the human ability to recognize correct decisions- is a key cognitive process linked to learning and development. Several recent studies investigated the relationship between metacognition and autism. However, the evidence is still inconsistent. While some studies reported autistic people having lower levels of metacognitive sensitivity, others did not. Leveraging the fact that autistic traits are present in the general population, our study investigated the relationship between visual metacognition and autistic traits in a sample of 360 neurotypical participants. We measured metacognition as the correspondence between confidence and accuracy in a visual two alternative forced choice task. Autistic-traits were assessed through the Autism-spectrum Quotient (AQ) score. A regression analysis revealed no statistically significant association between autistic traits and metacognition or confidence. Furthermore, we found no link between AQ sub-scales and metacognition. We do not find support for the hypothesis that autistic traits are associated with metacognition in the general population.


Estimates of genetic parameters for linear body measurements and prediction of body weight in goat.
The objective of this study is to estimate genetic parameters for linear body measurements along with their correlation to live weight with a focus on devising a scale to predict live weights from body measurement. A total of 142,564 records on body measures and live weights were collected from 8701 Jamunapari goats. Genetic parameters were obtained for body length (L), height at withers (H) and heart girth (G) from birth to adult stage by univariate and multivariate analysis using the average information restricted maximum likelihood method. The best model for body measures at birth included the additive effect of animal and dam along with their covariance and maternal environment, whereas for traits measured later in life, the maternal environment was not significant. After accounting for the direct maternal correlation (ram ), the total heritability estimates for linear body measurements (L,H and G) at the preweaning and postweaning stages of growth ranged from 0.14 to 0.20. Significant genetic variability implies further scope for selection. The genetic correlations of live weight at birth, 3, 6, 9 and 12 months with corresponding L,H and G were high in magnitude indicating scope to select animals for higher weight using morphometric measurements. When weighing scales are unavailable in the field, prediction of weight using L and G was recommended [live weight = (0.291 × L) + (0.306 × G) - 16.8]. We recommend the use of body measurements in the Jamunapari goat breeding program owing to their high genetic correlation with corresponding live weights.


Comparison of Septic Shock Due to Multidrug-Resistant Acinetobacter baumannii or Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Intensive Care Unit Patients.
A significant cause of mortality in the intensive care unit (ICU) is multidrug-resistant (MDR) Gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). The aim of the present study was to compare the clinical features, therapy, and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. We retrospectively analyzed patients admitted to the ICU of a teaching hospital from November 2010 to December 2015 who developed septic shock due to MDR-AB or KPC-Kp infection. Data from 220 patients were analyzed: 128 patients (58.2%) were diagnosed with septic shock due to KPC-Kp, and 92 patients (41.8%) were diagnosed with septic shock due to MDR-AB. The 30-day mortality rate was significantly higher for the MDR-AB group than the KPC-Kp group (84.8% versus 44.5%, respectively; P < 0.001). Steroid exposure and pneumonia were associated with MDR-AB infection, whereas hospitalization in the previous 90 days, primary bacteremia, and KPC-Kp colonization were associated with KPC-Kp infection. For patients with KPC-Kp infections, the use of ≥2 in vitro-active antibiotics as empirical or definitive therapy was associated with higher 30-day survival, while isolation of colistin-resistant strains was linked to mortality. Patients with MDR-AB infections, age >60 years, and a simplified acute physiology score II (SAPS II) of >45 points were associated with increased mortality rates. We concluded that septic shock due to MDR-AB infection is associated with very high mortality rates compared to those with septic shock due to KPC-Kp. Analysis of the clinical features of these critically ill patients might help physicians in choosing appropriate empirical antimicrobial therapy.


Hypothalamic cavernous angioma associated with memory and behavior disturbance attacks: role of imaging in diagnosis.
Deep seated cavernous angioma (CA) is a very rare entity, those occurring in the hypothalamus are still less common. We present a case of a 52-year-old man who presented with behavior and memory disturbance attacks. He had a CA of the hypothalamus as revealed by magnetic resonance imaging (MRI). We will discuss the role and importance of imaging in such scenario and also the differential diagnoses of this rare entity.


The relationship between chronic rhinosinusitis and metabolic syndrome.
This study aimed to investigate the correlation between metabolic syndrome and chronic rhinosinusitis (CRS), with related risk factors for CRS according to data from the Korean National Health and Nutrition Examination Survey (KNHANES). The KNHANES surveyed individuals >19 years of age from January 2010 to December 2011. CRS encompassed "symptom-based CRS" as defined by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Metabolic syndrome was diagnosed according to the American Heart Association/National Heart Lung and Blood Institute criteria. A χ2 analysis, univariate analysis, and multivariate analysis were conducted. A total of 12,015 individuals were analyzed in this study. The prevalence of CRS in the patients with metabolic syndrome (high triglyceride level, reduced high-density lipoprotein level, and elevated blood pressure) was significantly higher than that in patients without metabolic syndrome (14.15 versus 10.16%) (p < 0.05). Allergic rhinitis was the only significant risk factor for CRS found to be associated with metabolic syndrome (p < 0.05). CRS was more prevalent in patients with metabolic syndrome, especially those with allergic rhinitis, than in patients without metabolic syndrome. Accordingly, CRS should be considered in patients with metabolic syndrome and allergic rhinitis.


A censored quantile regression approach for relative survival analysis: Relative survival quantile regression.
We propose a censored quantile regression model for the analysis of relative survival data. We create a hybrid data set consisting of the study observations and counterpart randomly sampled pseudopopulation observations imputed from population life tables that adjust for expected mortality. We then fit a censored quantile regression model to the hybrid data incorporating demographic variables (e.g., age, biologic sex, calendar time) corresponding to the population life tables of demographically-similar individuals, a population versus study covariate, and its interactions with the variables of interest. These latter variables can be interpreted as relative survival parameters that depict the differences in failure quantiles between the study participants and their population counterparts.


Neuroepidemiology of human T-lymphotrophic virus type-I-associated tropical spastic paraparesis.
Tropical spastic paraparesis (TSP) is a chronic neurological syndrome of gradual onset involving the pyramidal tracts and upper motor neurons, resulting in weakness and stiffness of the lower extremities, hyperactive tendon reflexes, spasticity, low back pain, and urinary disturbances. Clusters of endemic TSP have been noted in Africa, the Seychelles Islands, Colombia, and the Caribbean. Recently, studies have linked human T-lymphotrophic virus type-I (HTLV-I) with the endemic form of the disease. In Japan a very similar clinical syndrome has been identified as HTLV-I-associated myelopathy and may be a non-tropical version of the same disease. The purpose of the present review is to examine the role HTLV-I may play in the pathogenesis of these myelopathies from a neuroepidemiological point of view.


Molecular uncoupling of C-C chemokine receptor 5-induced chemotaxis and signal transduction from HIV-1 coreceptor activity.
The C-C chemokine receptor 5 (CCR5) plays a crucial role in facilitating the entry of macrophage-tropic strains of the HIV-1 into cells, but the mechanism of this phenomenon is completely unknown. To explore the role of CCR5-derived signal transduction in viral entry, we introduced mutations into two cytoplasmic domains of CCR5 involved in receptor-mediated function. Truncation of the terminal carboxyl-tail to eight amino acids or mutation of the highly conserved aspartate-arginine-tyrosine, or DRY, sequence in the second cytoplasmic loop of CCR5 effectively blocked chemokine-dependent activation of classic second messengers, intracellular calcium fluxes, and the cellular response of chemotaxis. In contrast, none of the mutations altered the ability of CCR5 to act as an HIV-1 coreceptor. We conclude that the initiation of signal transduction, the prototypic function of G protein coupled receptors, is not required for CCR5 to act as a coreceptor for HIV-1 entry into cells.


Mitral-aortic intervalvular fibrosa pseudoaneurysm causing compression of superior vena cava and right atrium.
The mitral-aortic intervalvular fibrosa (MAIVF) is a fibrous, avascular region between the anterior leaflet of the mitral valve and noncoronary cusp of the aortic valve. This makes MAIVF vulnerable to injury and infection; thus pseudoaneurysm may develop. The pseudoaneurysm can cause compression to coronary arteries which causes angina or pulmonary artery resulting in pulmonary hypertension. We presented the pseudoaneurysm of MAIVF causing compression of superior vena cava and right atrium which was visualized by two- and three-dimensional transesophageal echocardiography and cardiac computed tomography.


Insulin Sensitivity To Trace Metals (Chromium, Manganese) In Type 2 Diabetic Patients And Non Diabetic Individuals.
Diabetes mellitus constitutes one of the most important problems in developing and non-developing countries. The purpose of the study to estimate the concentrations of Chromium and Manganese in diabetic and non-diabetic population of Hazara division. The cross sectional comparative study was carried out on one hundred blood samples of Type 2 Diabetic patients collected non-randomly from Ayub Teaching Hospital and one hundred normal healthy controls from Women Medical College Abbottabad from September 2014 to April 2015. The study included two hundred subjects. Among them 100 were diabetic and 100 non diabetic respectively. The blood samples were collected from Ayub Medical College, Abbottabad. The serum Chromium and Manganese levels were determined by Atomic Absorption spectrophotometer. Serum Chromium and Manganese levels were decreased in diabetic and increased in non-diabetic patients. Low serum level of Chromium and manganese were found in diabetic patients as compare to non-diabetic individuals.


Relationship between the transport and toxicity of cephalosporins in the kidney.
Large doses of cephaloridine cause acute necrosis of the proximal renal tubule that can be prevented by probenecid and other organic anions. Although there is little or no net secretion of cephaloridine by the mammalian kidney, the degree of cephaloridine uptake by the cortex of the rabbit kidney is substantial; this uptake is also prevented by probenecid and other organic anions. Cortical concentrations of cephaloridine were measured in control and probenecid-treated animals of different mammalian species. Evidence of cephaloridine trnsport was found in the guinea pig and the rat as well as in the rabbit. The degree of reduction of cortex-to-serum ratios by probenecid (control cortex-to-serum minus probenecid-treated cortex-to-serum ratios) correlated with the sensitivity to the nephrotoxicity of the drug. This degree or reduction was greatest in the rabbit, intermediate in the guinea pig, and least in the rat. In addition, the newborn rabbit, which is more resistant to the toxicity of cephaloridine than the adult, also had significantly lower cortical concentrations of cephaloridine. Finally, the acute tubular necrosis produced by extremely large doses of cefazolin in the adult rabbit was prevented by probenecid. It was concluded (1) that the nephrotoxicity of cephaloridine is related to its renal cortical transport with high intracellular concentrations of drug; and (2) that this relationship between transport and toxicity exists for cefazolin as well, although the toxicity is of a different order of magnitude. The unusual mechanism of cephaloridine transport in the proximal tubule was contrasted with that of the other cephalosporins in an attempt to explain its greater degree of nephrotoxicity.


COVID-19 pandemic: Evaluating its psychological impact and individuals' depression, anxiety, and stress levels.
The COVID-19 pandemic is a global public health problem affecting mental health, and basic data are required for evidence-based mental health interventions. This study aimed to identify the prevalence of psychological impacts, anxiety, depression, stress, and any associated risk factors in individuals living in Turkey during the COVID-19 pandemic. The population of this descriptive study consisted of individuals over the age of 18 living in Turkey. The data were collected between July-September 2020 using the snowball sampling method. The study was completed with 1733 participants. The data were collected using the Impact of Events Scale-Revised and the Depression Anxiety Stress Scale. Statistical analyses included percentage, mean, standard deviation, a Chi-square test, a Mann Whitney U test, Kruskal Wallis and Tamhane's T2 post hoc, and Spearman's correlation. P < 0.05 was considered statistically significant. 45.1% had moderate or severe psychological effects; 42.7% had a moderate or severe depression, 31.7% had moderate or severe anxiety, and 28.5% had moderate or severe stress levels. Being a woman, being single, unemployment, smoking, the presence of chronic diseases, being young (<35), being a university graduate, having a household size of 5 or more, a low income, having poor health, and being underweight were significantly correlated with some psychological impact, depression, anxiety, and stress levels of people. During the pandemic period, almost half of the respondents were found to experience some psychological impact of the pandemic and have negative moderate to severe mental health levels. Risk groups for mental health were identified.


Redox states of dinitrogen coordinated to a molybdenum atom.
Chemical structures bearing a molybdenum atom have been suggested for the catalytic reduction of N2 at ambient conditions. Previous computational studies on gas-phase MoN and MoN2 species have focused only on neutral structures. Here, an ab initio electronic structure study on the redox states of small clusters composed of nitrogen and molybdenum is presented. The complete-active space self-consistent field method and its extension via second-order perturbative complement have been applied on [MoN]n and [MoN2]n species (n = 0, 1±, 2±). Three different coordination modes (end-on, side-on, and linear NMoN) have been considered for the triatomic [MoN2]n. Our results demonstrate that the reduced states of such systems lead to a greater degree of N2 activation, which can be the starting point of different reaction channels.


[Recurrence of varicosities in the femoral canal following surgery of the internal saphenous vein].
Perforating veins in the femoral canal, which establish a communication, on the medial aspect of the thigh, between the deep venous system and: either the trunk of the long saphenous vein, single or double, or one or several separate trunks, follow three anatomical patterns which clinical examination, phlebography and, now, echo-doppler, can identify clearly. When they are incompetent, they increase the natural progress of the varicose disease, after surgery of the long saphenous vein. Often, they are associated with a redux at the level of the saphenofemoral junction and also, sometimes, with an incompetence, primary or recurrent, at the short sapheno-popliteal junction, or, furthermore, with an incompetence of the medial gastrocnemial veins and their accompanying perforators, within the popliteal venous complex. Anastomotic networks between the different superficial venous territories in the inguino-genital region, the femoral canal and the supero-medial aspect of the leg, explain the cross-evolution between different systems. Sclerotherapy is effective when the perforators are not too large and their reflux not too important. If it fails, it is necessary to operate after precise localization of the sites of reflux through good imaging. A good picture is obtained with B mode ultrasound examination and hemodynamic studies with pulsed doppler and, even more reliably, with color Doppler. Thus, in recurrences in the femoral region, color Doppler will show up certain perforators which, despite being dilated, are nevertheless competent and do not need to be dealt with.


Dental caries and sugar consumption into the 21st century.
New trends towards the effect and role of sugar consumption in the etiology of dental caries into the 21st century are presented, analyzed and discussed. Many factors such as the amount of sugar consumed, the frequency of sugar intake and the kind of sugars ingested have to be taken into consideration. Over the years, the relative importance of these factors has changed. For a very long time, sugar has been "blamed" as a primary etiological factor in the development of dental caries. However, a number of recent reports have attributed a much less important role to carbohydrates. Sugar consumption only does not affect caries prevalence as much as it used to. It is obvious that the role of sugar in the etiology of caries must be reviewed. Additional factors like overall nutrition, the number of meals and snacks per day, education and motivation, fluoride (in tablets or drops, in mouthwashes, toothpastes, baby foods, formulas, beverages, milk, vitamin supplements and/or fluoridated water ingested), socioeconomic group, ethnicity, oral hygiene status, use of preventive methods and sweeteners other than sucrose are presented.


Structural differences among guinea pig Fc gamma 1/gamma 2 receptors on macrophages, polymorphonuclear cells, and lymphocytes.
Using the cDNA, D-3, coding for Fc gamma 1/gamma 2 receptor of guinea pig macrophages that binds IgG1 and IgG2 (Fc gamma 1/gamma 2R), we examined the cell distribution of this receptor by RNA blot analysis. The Fc gamma 1/gamma 2R mRNA was expressed in polymorphonuclear cells and B cells as well as in macrophages, but not at the detectable level in T cells. The cDNA amplified from RNA of polymorphonuclear cells in the polymerase chain reaction was the same as D-3. The cDNA of B cells was found to have about 140 bp cDNA segment inserted to the cytoplasmic tail of D-3. We found that the cDNA amplified from T cell RNA differed in signal peptide and extracellular domain sequence from cDNAs of other cell types. This cDNA does not seem to be amplified from the mRNAs of contaminating other cell types.


Upcoming Challenges in Multidisciplinary Heart Failure Management: Active Role of Future Clinical Pharmacists.
In their article "Role and Value of Clinical Pharmacy in Heart Failure Management" Stough and Patterson discuss the potential benefits that clinical pharmacists could bring to heart failure management. They mostly focused on chronic stable heart failure. The objective of this commentary is to provide future perspectives for clinical pharmacist involvement in multidisciplinary heart failure team in the management of patients admitted in emergency for decompensation of their heart condition.


Headache in the writings of Moses Maimonides and other Hebrew sages.
In the history of philosophy, theology, and medicine, Maimonides shares the limelight with Arabic scholars such as Ibn Rushd, Ibn Sinna and Ibn Zuhr, chronologically between the great intellectuals of classical Greece and Rome and those of the later Middle Ages and early Renaissance. Maimonides was a very great philosopher and theologian, usually underrated by the historians. He was also an outstanding medical practitioner and teacher. Moses Maimonides had an incredible literary ability and an encyclopedic knowledge. He wrote extensively in the fields of theology, mathematics, law, philosophy, astronomy, ethics, and, of course, medicine. His medical writings are varied, comprising extracts from Greek medicine, a series of monographs on health in general and several diseases in particular, and a pharmacopoiea. The present essay extracts, primarily from Maimonides' medical writings, his pronouncements dealing with headache. Since most of Maimonides' pronouncements about headache in his Medical Aphorisms were derived from Graeco-Roman medical writers such as Hippocrates, and especially Galen, in regard to these statements Maimonides was merely a compiler--not an innovator. Some of his concepts about the causes of headaches being related to a dysequilibrium of the body humors are clearly medieval in origin. Other statements demonstrate this concern with preventive medicine and the maintenance of a healthy regimen of daily living. Medications to treat illness should only be used if non-medicinal means such as diet and exercise are not effective. The heritage of Maimonides' writings is being more and more appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)


An Experimental Model for Simultaneous Study of Migration of Cell Fragments, Single Cells, and Cell Sheets.
Recent studies have demonstrated distinctive motility and responses to extracellular cues of cells in isolation, cells collectively in groups, and cell fragments. Here we provide a protocol for generating cell sheets, isolated cells, and cell fragments of keratocytes from zebrafish scales. The protocol starts with a comprehensive fish preparation, followed by critical steps for scale processing and subsequent cell sheet generation, single cell isolation, and cell fragment induction, which can be accomplished in just 3 days including a 36-48 h incubation time. Compared to other approaches that usually produce single cells only or together with either fragments or cell groups, this facile and reliable methodology allows generation of all three motile forms simultaneously. With the powerful genetics in zebrafish our model system offers a useful tool for comparison of the mechanisms by which cell sheets, single cells, and cell fragments respond to extracellular stimuli.


Reproducibility and Sensitivity of the 6-Minute Stepper Test in Patients with COPD.
The aims of this study were to test the reproducibility of the 6-minute stepper test (6MST), and evaluate its accuracy in detecting improved functional capacity after pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). Thirty-five COPD outpatients performed two 6MSTs in the same session, before (6MST1 and 6MST2) and after (6MST3 and 6MST4) PR. The performance, perceived exertion, heart rate and arterial oxygen saturation were measured during each 6MST. The performance was higher during the second 6MST of the same session (before PR: 514 strokes during the 6MST2 > 471 strokes during the 6MST1, and after PR: 559 strokes during the 6MST4 > 508 strokes during the 6MST3; p = 0.04). After PR, 6MST performance was higher than before PR (6MST3 > 6MST1 and 6MST4 > 6MST2; P < 0.01). The bias (the difference in the number of strokes) between the two 6MSTs from the same session (before PR: 6MST2-6MST1 = 42 strokes vs after PR: 6MST4-6MST3 = 52 strokes) was not different (P = 0.34). However, both bias were greater than 0 (P < 0.001). The mean performances for the two 6MSTs of the same session (before PR: 6MST1 and 6MST2 and after PR: 6MST3 and 6MST4) were correlated with the bias between these performances (P < 0.01; r = 0.32). The perceived exertions were lower after PR (P < 0.02). The systematic improvement of performance (8-10%) during the second 6MST of the each session may be explained from the warming of hydraulic jacks of the stepper and/or learning effect. On the other hand, the 6MST seems sufficiently sensitive to detect functional capacity improvements after PR in patients with COPD.


[The effect of the fused gene of SP-TAT-Apoptin transfected by lentivirus on HepG2 cells].
To Package the recombinant lentivirus containing the fused gene of SP-TAT-Apoptin to infect HepG2 cell and measure the efficiency of apoptosis. The eukaryotic expression vector of SP-TAT-Apoptin fused gene and other packaging plasmids were transfected into 293FT cells by Lipofectamine(TM);2000 reagent. The supernatant of the cultured 293FT cells was harvested and virus titration was determined by real time PCR. The expression of the fused gene of SP-TAT-Apoptin in 293FT cells infected by the recombinant lentivirus was examined by immunofluorescence histochemistry method. At the same time, the apoptosis rates of the HepG2 cells infected by the recombinant lentivirus were determined by using flow cytometer. The 293FT cells infected by the recombinant lentivirus could express the fused protein SP-TAT-Apoptin. Anexin-V PI assay showed that SP-TAT-Apoptin carried by the recombinant lentivirus could cause the HepG2 cell apoptosis, and its apoptosis rate was significantly more than paired control group and SP-TAT-Apoptin carried by liposomes only. The recombinant lentivirus of SP-TAT-Apoptin is successfully packaged and it can induce HepG2 cells to apoptosis.


Tinea corporis due to Trichophyton violaceum: A report of two cases.
Dermatophytes are Fungi which infect keratinized tissues, that is, skin epidermis, hair and nails. Trichophyton violaceum is an anthropophilic, cosmopolitan dermatophyte. It primarily causes tinea capitis and less commonly tinea corporis and tinea unguium. We present a report of two cases of tinea corporis due to T. violaceum in children. Infections due to T. violaceum are important because of its transmissibility within families and community and its potential to spread and establish in new geographical areas.


Sexual and intimacy health of Roman Catholic priests.
This study explores the sexual experiences and sexual health of Roman Catholic priests. The qualitative research design looked at priests' responses to the question, "Please share one or more sexual experiences in your lifetime." The qualitative responses were analyzed and categorized into seven groupings: (a) Childhood and adolescent homosexual experiences; (b) Childhood and adolescent heterosexual experiences; (c) Both homosexual and heterosexual childhood and adolescent experiences; (d) Adult sexual experiences before ordination to the priesthood; (e) Adult sexual experiences since ordination to the priesthood; (f) Masturbation; and (g) Other sexual experiences. The data were analyzed by frequency of responses and percentages within each of the seven categories. The results indicate the need for early intervention and education during seminary, ongoing education after ordination, and psychotherapy support for priests.


Analysis of the Effectiveness of Nursing Interventions in Critically Ill Patients in Respiratory Medicine.
To enhance and analyze the clinical effectiveness of implementing quality nursing interventions in the clinical care of critically ill patients in respiratory medicine. Clinical data of respiratory medicine patients treated in our hospital over the years were collected and 96 patients who met the requirements of the purpose of this study and the sample inclusion criteria were selected as the study subjects from the patients treated between April 2019 and January 2020. According to the care methods received by the patients in our hospital, 48 of them who implemented conventional care were used as the control group, and another 48 patients who were given quality care interventions were used as the observation group. The data were statistically recorded and comparatively analyzed for the indicators such as nursing oxygen index, heart rate, and clinical treatment efficiency of patients in both groups. Compared with the control group, patients in the observation group who received quality nursing intervention had more significant improvement in blood oxygen index and heart rate after nursing care; the clinical treatment efficiency of patients in the observation group was significantly higher than that of the control group (95.83% vs. 81.25%). The data comparison between the groups showed a significant difference, P < 0.05, which was statistically significant. Adding quality nursing interventions to the implementation of conventional care for patients with respiratory diseases can better improve patients' clinical symptoms, accelerate their clinical recovery, improve and enhance prognosis, and further improve clinical outcomes.


CH3 NH3 PbBr3 Perovskite Nanocrystals as Efficient Light-Harvesting Antenna for Fluorescence Resonance Energy Transfer.
Hybrid perovskites have created enormous research interest as a low-cost material for high-performance photovoltaic devices, light-emitting diodes, photodetectors, memory devices and sensors. Perovskite materials in nanocrystal form that display intense luminescence due to the quantum confinement effect were found to be particularly suitable for most of these applications. However, the potential use of perovskite nanocrystals as a light-harvesting antenna for possible applications in artificial photosynthesis systems is not yet explored. In the present work, we study the light-harvesting antenna properties of luminescent methylammonium lead bromide (CH3 NH3 PbBr3 )-based perovskite nanocrystals using fluorescent dyes (rhodamine B, rhodamine 101, and nile red) as energy acceptors. Our studies revealed that CH3 NH3 PbBr3 nanocrystals are an excellent light-harvesting antenna, and efficient fluorescence resonance energy transfer occurs from the nanocrystals to fluorescent dyes. Further, the energy transfer efficiency is found to be highly dependent on the number of anchoring groups and binding ability of the dyes to the surface of the nanocrystals. These observations may have significant implications for perovskite-based light-harvesting devices and their possible use in artificial photosynthesis systems.


The presence of sporogonic stages of Tetracapsuloides bryosalmonae in Icelandic salmonids detected using in situ hybridisation.
Proliferative kidney disease (PKD) is a widespread temperature-dependent disease in salmonids caused by the myxozoan parasite, Tetracapsuloides bryosalmonae (Canning, Curry, Feist, Longshaw et Okamura, 1999) (Tb). Tb has a two-host life cycle, involving fish as an intermediate host and freshwater bryozoans as the definitive host. Although salmonids are acknowledged as hosts for the parasite, it is less clear which fish species are active hosts in the life cycle of Tb. Differences in infection dynamics have been observed between some fish species, which are thought to be related to the existence of two main Tb-strains, the American and European. Iceland, having three species of indigenous salmonids and positioned geographically between Europe and North America, is an ideal location to study the natural development of Tb in wild fish. The main aim of this study was to determine the genetic origin of Tb in Iceland and confirm whether mature spores are produced in Icelandic salmonids. In this study, Icelandic salmonids were infected with the European Tb-strain. In situ hybridisation revealed that intraluminal sporogonic stages, including mature spores, were commonly observed in all three salmonid species. The presence of intraluminal stages has previously been confirmed in brown trout Salmo trutta Linnaeus and Atlantic salmon S. salar Linnaeus in Europe, but they have only been observed in Arctic charr Salvelinus alpinus (Linnaeus) in North America, infected by the local strain. This is, therefore, the first time that sporogonic stages have been observed in Arctic charr in Europe, where fish are infected with the European Tb-strain. Our data strongly suggest that all the three salmonid species inhabiting Icelandic waters serve as active hosts in the life cycle of Tb. However, for full confirmation, transmission trials are needed.


Electromagnetic resonance analysis of asymmetric carbon nanotube dimers for sensing applications.
In this work, we study the electromagnetic scattering characteristics of asymmetric carbon nanotube (CNT) dimers with rigorous computational experiments. We show that the configurational asymmetry in the CNT dimer assembly creates a unique field distribution in the vicinity of the dimer, which in turn generates two distinct resonances representing the bonding and anti-bonding modes. The sensitivity of these two modes towards CNT lengths, orientations, and shapes, is studied. We also show the ability of asymmetric CNT dimer for the contactless detection of nanoparticles (NP). The presence of a NP in the vicinity of the CNT dimer perturbs the dimer's field distribution and causes unequal shifts in the bonding and anti-bonding resonances depending on the NP location, material, size and shape. By studying the differences in these resonance shifts, we show that the relative location and orientation of the NP can be reconstructed. The computational experiments performed in this work have the potential to guide the use of asymmetric CNT dimers for novel sensing applications.


Antigenicity of the carboxyl terminus of insulin: isolation of human insulin-specific monoclonal antibodies.
Monoclonal technology was used to isolate antibodies binding the B30 (carboxy) terminal residue in the polyclonal-provoked immune response to human insulin. Although both spleen and lymph node cell fusions were carried out, only the latter were successful in isolating monoclonal antibodies that bound the carboxy terminal of human insulin. The binding of such antibodies was abolished or diminished by substitutions of the B30 residue. Studies with insulin species variants showed that the molecular binding between antibody and insulin may be critically determined by a subresidue feature, e.g. presence or absence of a single methyl group, as shown by the binding of the monoclonal antibody D10 to human insulin (threonine at B30) but not to rabbit insulin (serine at B30). Such studies are of interest in the study of the molecular basis of antibody-antigen interaction.


Rapid conventional scheme for biochemical identification of antibiotic resistant enterobacteriaceae isolates from urine.
Six conventional biochemical tests were combined to produce an identification scheme. These tests included decarboxylation of lysine and ornithine, fermentation of glucose and cellobiose, indole production and urease production. Three hundred antibiotic resistant coliforms from urine specimens were tested by this scheme and also by the API 20E for comparison. Two hundred and seventy nine (93%) of organisms were correctly identified using the six tests, 17 (5.7%) were referred for further study, and four (1.3%) were misidentified. It is concluded that this combination of tests provides an inexpensive, accurate, and rapid tool for identification.


PA3225 Is a Transcriptional Repressor of Antibiotic Resistance Mechanisms in Pseudomonas aeruginosa.
The tssABC1 locus is part of the Hcp secretion island I (HSI-I) type VI secretion system (T6SS) in Pseudomonas aeruginosa Previous work implicated the tssC1 gene in P. aeruginosa biofilm-specific antibiotic resistance, and tssC1 is preferentially expressed in biofilms compared to planktonic cells. Using a DNA-dependent protein pulldown approach, we discovered that PA3225, an uncharacterized LysR-type transcriptional regulator, specifically bound to the tssABC1 upstream regulatory region. The deletion of PA3225 led to a 2-fold decrease in tssA1 expression levels in planktonic cells compared to the wild type, and tssA1 expression was slightly reduced in ΔPA3225 biofilms compared to wild-type biofilms. Intriguingly, further investigations revealed that the ΔPA3225 mutant was less susceptible to multiple, structurally unrelated antibiotics with various mechanisms of action when grown planktonically. The ΔPA3225 mutant was additionally more resistant to ciprofloxacin when grown in a biofilm. The decreased antibiotic susceptibility of the ΔPA3225 strain was linked to the transcriptional upregulation of the MexAB-OprM efflux pump. By using transcriptome sequencing (RNA-seq), other PA3225-regulated genes were identified, and the products of these genes, such as the putative ABC transporter PA3228, may also contribute to antibiotic resistance.


Natural computing and biological evolution: a new paradigm.
After a brief outline of the available hypotheses on the mechanism of biological evolution, attention is called on the global nature of the variations leading to the generation of new species. Integrated changes may hardly be attributed to beneficial random mutations of single traits even if assisted by a phylogenetic elimination of poorly adapted individuals. Rather, integrated variations are likely to reflect the outcome of cybernetic algorithms (natural computing) operating on organism's resources and impending environmental changes. As all organisms are endowed with computing capacities that modulate and integrate ontogenetic development and maintenance of biological functions, structures, and behaviors, these capacities are assumed to have moulded the evolutionary variations of organisms, and their transfer to the progeny.


Changes of gastric mucus glycoproteins with aspirin administration in rats.
The qualitative changes of gastric mucus glycoproteins occurring after aspirin dosing in rats were further investigated. Mucus glycoprotein contents of test animals were 55 and 53% of the control value at 3 and 7 h after dosing, respectively. The glycoproteins were further fractionated by CM-Sepharose CL-6B chromatography. 5 fractions were separated, 1 unadsorbed (fraction 1) and 4 adsorbed (fractions 2-5). Ratios of the major fractions 1:2:4 were 36:47:17 for control, 40:35:25 3 h after aspirin dosing, and 47:33:20 7 h after aspirin administration. Fractions 1, 2, and 4 corresponded to sulfomucin and sialomucin (relatively high content of sialic acid), sialomucin, and neutral mucin, respectively. While the absolute amount of each mucus glycoprotein fraction decreased with aspirin administration, the diminution of fraction 2 was distinct.


Low magnitude high frequency vibration promotes adipogenic differentiation of bone marrow stem cells via P38 MAPK signal.
Low magnitude high frequency vibration (LMHFV) has been mainly reported for its influence on the musculoskeletal system, particularly the bone tissue. In the bone structure, osteogenic activity is the main focus of study with regards to LMHFV. However, adipogenesis, another important mode of differentiation in the bone marrow cavity that might be affected by LMHFV, is much less researched. Furthermore, the molecular mechanism of how LMHFV influences adipogenesis still needs to be understood. Here, we tested the effect of LMHFV (0.3g, 40 Hz, amplitude: 50μm), 15min/d, on multipotent stem cells (MSCs), which are the common progenitors of osteogenic, chondrogenic, adipogenic and myogenic cells. It is previously shown that LMHFV promotes osteogenesis of MSCs. In this study, we further revealed its effect on adipo-differentiation of bone marrow stem cells (BMSCs) and studied the underlying signaling pathway. We found that when treated with LMHFV, the cells showed a higher expression of PPARγ, C/EBPα, adiponectin and showed more oil droplets. After vibration, the protein expression of PPARγ increased, and the phosphorylation of p38 MAPK was enhanced. After treating cells with SB203580, a specific p38 inhibitor, both the protein level of PPARγ illustrated by immunofluorescent staining and the oil droplets number, were decreased. Altogether, this indicates that p38 MAPK is activated during adipogenesis of BMSCs, and this is promoted by LMHFV. Our results demonstrating that specific parameters of LMHFV promotes adipogenesis of MSCs and enhances osteogenesis, highlights an unbeneficial side effect of vibration therapy used for preventing obesity and osteoporosis.


Refractory Takayasu's Arteritis with Severe Coronary Involvement-Case Report and Literature Review.
This report presents the case of a female patient diagnosed with Takayasu arteritis from childhood, with severe, refractory coronary involvement, leading to two acute coronary syndromes and multiple anginous episodes. Consequently, the patient suffered aorto-bicarotid bypass two times, multiple interventional procedures with stent implantation, balloon angioplasty, and up to ten repeated in-stent restenosis that required reinterventions, despite being on maximal immunosuppressive treatment. In recent years, various studies have been reported that aim to best characterize this particular type of vascular damage and to indicate optimal therapeutic options for treatment. The latter should be based on the activity of the underlying disease; however, no reliable markers are available in TA. The management of TA patients with coronary involvement continues to be a challenge and requires both drug and interventional techniques to avoid life-threatening events.


Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn.
Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns. The turn mimetic was assembled from three types of building blocks: an azido epoxide, an alpha-bromo acid, and a protected beta-amino alcohol. The oxytocin analogue did not induce contractions of the uterus nor did it inhibit oxytocin-induced contractions. It is suggested that the loss of bioactivity is mainly due to the presence of a psi[CH(2)O] isostere instead of an amide bond between residues i and i + 1 in the turn mimetic.


Using neutral beams as a light ion beam probe (invited).
By arranging the particle first banana orbits to pass near a distant detector, the light ion beam probe (LIBP) utilizes orbital deflection to probe internal fields and field fluctuations. The LIBP technique takes advantage of (1) the in situ, known source of fast ions created by beam-injected neutral particles that naturally ionize near the plasma edge and (2) various commonly available diagnostics as its detector. These born trapped particles can traverse the plasma core on their inner banana leg before returning to the plasma edge. Orbital displacements (the forces on fast ions) caused by internal instabilities or edge perturbing fields appear as modulated signal at an edge detector. Adjustments in the q-profile and plasma shape that determine the first orbit, as well as the relative position of the source and detector, enable studies under a wide variety of plasma conditions. This diagnostic technique can be used to probe the impact on fast ions of various instabilities, e.g., Alfvén eigenmodes (AEs) and neoclassical tearing modes, and of externally imposed 3D fields, e.g., magnetic perturbations. To date, displacements by AEs and by externally applied resonant magnetic perturbation fields have been measured using a fast ion loss detector. Comparisons with simulations are shown. In addition, nonlinear interactions between fast ions and independent AE waves are revealed by this technique.


Investigations into Recycling Zinc from Used Metal Oxide Varistors via pH Selective Leaching: Characterization, Leaching, and Residue Analysis.
Metal oxide varistors (MOVs) are a type of resistor with significantly nonlinear current-voltage characteristics commonly used in power lines to protect against overvoltages. If a proper recycling plan is developed MOVs can be an excellent source of secondary zinc because they contain over 90 weight percent zinc oxide. The oxides of antimony, bismuth, and to a lesser degree cobalt, manganese, and nickel are also present in varistors. Characterization of the MOV showed that cobalt, nickel, and manganese were not present in the varistor material at concentrations greater than one weight percent. This investigation determined whether a pH selective dissolution (leaching) process can be utilized as a starting point for hydrometallurgical recycling of the zinc in MOVs. This investigation showed it was possible to selectively leach zinc from the MOV without coleaching of bismuth and antimony by selecting a suitable pH, mainly higher than 3 for acids investigated. It was not possible to leach zinc without coleaching of manganese, cobalt, and nickel. It can be concluded from results obtained with the acids used, acetic, hydrochloric, nitric, and sulfuric, that sulfate leaching produced the most desirable results with respect to zinc leaching and it is also used extensively in industrial zinc production.


A Reliable von Willebrand factor: ristocetin cofactor enzyme-linked immunosorbent assay to differentiate between type 1 and type 2 von Willebrand disease.
von Willebrand disease (vWD) is the most common hereditary bleeding disorder due to either a qualitative or a quantitative defect in von Willebrand factor (vWF). vWF is a multimeric plasma protein that plays an important role in (1) primary hemostasis, by sustaining indirect platelet adhesion especially at high shear rates, and in (2) secondary hemostasis, by protecting factor VIIIc (FVIIIc) from degradation. A correct diagnosis of vWD is based on the accurate identification of one of the six different subtypes (type 1, 2A, 2B, 2M, 2N, 3). To do this, different laboratory tests are available. One aspect of the identification is the discrimination between type 1 and type 2 (2A, 2B, and 2M) vWD. In type 1 vWD, both vWF levels (vWF:Ag) and vWF activity (vWF:RCof) are decreased; in type 2, the vWF:Ag level is normal or decreased and vWF:RCof is decreased. Thus, ratios of vWF:Ag to vWF:RiCof above 1 allow identifation of type 2 vWD patients. The currently used vWF:RCof test is an agglutination test in which patients' plasma is added to washed fixed control platelets in the presence of ristocetin and the extent of agglutination is measured. This test suffers from high interlaboratory and intralaboratory variability. We have recently shown that the same vWF:RCof can also be measured in an enzyme-linked immunosorbent assay (ELISA) with a low interassay and intraassay variability and can be used to identify patients suffering from vWD. We here show that our test allows the discrimination between type 1 and type 2 vWD patients.


Development of serum hexosaminidase activity in infants.
Serum activity of hexosaminidases A and B has been measured to identify patients with Tay-Sachs and Sandhoff diseases, and may also be influenced by other clinical conditions including neonatal necrotizing enterocolitis. We have characterized the normal developmental pattern of hexosaminidase activity in serum by measuring this enzyme activity in 61 neonates of 27-40 weeks gestation who were followed from birth to age 4-8 weeks. Total serum hexosaminidase activity significantly increased with postnatal and gestational age, and with initiation of enteral feeding. We conclude that serum hexosaminidase activity in infants with clinical conditions that may influence serum activity of this enzyme must be compared to that in normal infants of similar gestational and postnatal ages.


[The influence of Beijing TCM society on the development of TCM in Beijing].
Being a medical institution with the longest history and most influential TCM academic group, Beijing TCM Learned Society had a 3-stage history in Beijing area. in the Republican period of China in the 1920s, it was set up and organized by the imperial physicians and compiled History of Imperial Physicians in the Qing Dynasty and Yi Tong Zheng Mai (Orthodox Medical Heritage). In the 1930s, the number of its members and achievements reach its zenith. It started to publish China Medical Monthly, compiled many TCM books and extended its influence nationwide. In the 1940s, it was renamed China Medicine Research Association, then joined the International Science Organization. After that it held many academic activities and exchanged many valuable articles. These three phases promoted the development of TCM in Beijing in varying degrees.


A close association between alteration in growth kinetics by neoadjuvant chemotherapy and survival outcome in primary breast cancer.
Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.


Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area.
Fabry disease (FD) is a lysosomal storage disorder characterized by pervasive renal involvement. However, this disease is underdiagnosed in patient with chronic kidney disease (CKD), including those with end stage renal disease (ESRD), so their investigation represents an unexploited opportunity for early diagnosis of the disease and for its identification in relatives of affected patients. We investigated Fabry disease in a clinical and biological database including ESRD patients of unknown cause in a geographical area with 2 million residents. The study was based on state of art GLA gene sequencing and was extended to relatives of affected ESRD patients. Among ESRD patients qualified for enrollment into this study, a previously undiagnosed young man harboring the mutation p.I91T was identified. The study of the proband's family led to the identification of 8 additional cases. In another ESRD male patient, we identified the functional polymorphism p.D313Y. Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of uncertain functional relevance in the non-coding regions of the GLA gene. A comprehensive survey of ESRD patients in a geographical area of 2 million residents identified one undiagnosed case of Fabry disease and led to the identification of 8 additional cases among his relatives. Screening protocols starting from the dialysis population and upstream extended to families of affected individuals may be an effective strategy to maximize the early identification of subjects with Fabry disease.


Atypical haemolytic uremic syndrome from multiple missenses to a full-blown disease.
A 72-year-old woman was admitted to the hospital because of dorsal, lumbar and lower abdomen pain that had started 4 days before. She had a history of age-related macular degeneration (treated with intraocular bevacizumab). Blood tests showed anaemia, thrombocytopaenia, acute kidney injury, elevated liver enzymes and total bilirubin (mainly because of the indirect fraction). Viral serologies and ADAMTS13 activity levels were normal, and stool testing was negative for Escherichia coli-producing Shiga toxins. E. coli was isolated in urine. Atypical haemolytic uremic syndrome triggered by a urinary tract infection or by the vascular endothelial growth factor-inhibitor bevacizumab were the most likely hypothesis. The patient started urgent plasmapheresis and dialysis that lasted for a total of 18 days. There was complete remission and recovery of kidney function allowing for treatment discontinuation, and she was discharged home. After 6 months of follow-up, she shows no signs of relapse.


Vestibular disease unmasked by hyperventilation.
Hyperventilation-induced dizziness is often thought to be psychogenic, but its effects in the presence of known vestibular disease have not been adequately examined. In this study hyperventilation was tested in two models of vestibular disease. These were, first, patients with profound unilateral vestibular deficit (prior translabyrinthine acoustic neuroma resection [postsurgery group]) and, second, patients with variable unilateral vestibular deficit (unoperated unilateral acoustic neuroma [presurgery group]). Patients were hyperventilated for 90 seconds. Using infrared videonystagmography, 100% of the 32 postsurgery patients and 82% of the 28 presurgery patients developed nystagmus with hyperventilation. Hyperventilation was more sensitive than head shake for eliciting nystagmus in these models. The false-positive rate for nystagmus in 29 normal volunteers was 3.5% for hyperventilation and 10% for head shake. Our results show that hyperventilation can unmask underlying vestibular disease.


Rex1p deficiency leads to accumulation of precursor initiator tRNAMet and polyadenylation of substrate RNAs in Saccharomyces cerevisiae.
A synthetic genetic array was used to identify lethal and slow-growth phenotypes produced when a mutation in TRM6, which encodes a tRNA modification enzyme subunit, was combined with the deletion of any non-essential gene in Saccharomyces cerevisiae. We found that deletion of the REX1 gene resulted in a slow-growth phenotype in the trm6-504 strain. Previously, REX1 was shown to be involved in processing the 3' ends of 5S rRNA and the dimeric tRNA(Arg)-tRNA(Asp). In this study, we have discovered a requirement for Rex1p in processing the 3' end of tRNA(i)(Met) precursors and show that precursor tRNA(i)(Met) accumulates in a trm6-504 rex1Delta strain. Loss of Rex1p results in polyadenylation of its substrates, including tRNA(i)(Met), suggesting that defects in 3' end processing can activate the nuclear surveillance pathway. Finally, purified Rex1p displays Mg(2+)-dependent ribonuclease activity in vitro, and the enzyme is inactivated by mutation of two highly conserved amino acids.


Single-stage synthesis and characterization of reflective and conductive silver-polyimide films prepared from silver(I) complexes with ODPA/4,4'-ODA.
Reflective and surface conductive polyimide films were prepared by the incorporation of silver(I) acetate and trifluoroacetylacetone into a dimethylacetamide solution of the poly(amic acid) formed 3,3',4,4'-oxidiphthalic dianhydride (ODPA) and 4,4'-oxidianiline (4,4'-ODA). Thermal curing of (trifluoroacetylacetonato)silver(I)-poly(amic acid) films led to cycloimidization with concomitant silver(I) reduction, which yielded a reflective and conductive silver surface at selected silver concentrations if the film was cured to a final temperature of 300 degrees C for several hours. The metallized ODPA/4,4'-ODA films retain the essential mechanical properties of an undoped film and have good thermal stability, particularly under a nitrogen atmosphere. The bulk of the composite film was not electrically conductive. The use of (hexafluoroacetylacetonato)silver(I) and silver(I) tetrafluoroborate as sources of silver(I) with ODPA/4,4'-ODA yielded modestly reflective films that never developed conductivity. The silvered films prepared with (trifluoroacetylacetonato)silver(I) can be patterned using mask-etch techniques. Comparisons are made among four similar silver-polyimide systems, with the polyimides being ODPA/4,4'-ODA, BTDA/4,4'-ODA, BPDA/4,4'-ODA, and 6FDA/4-BDAF.


[Genetic diversity of DNA microsatellite for Tibetan Yak].
To assess the genetic diversity and relationship of the Tibetan yak breeds. The genetic diversity and phylogenies of a total of 480 individual from 11 Tibetan yak groups were analyzed using PCR and multiplex gel electrophoresis of silver staining technology with eight pairs of microsatellite markers.The result showed that these markers were highly polymorphic loci with rich genetic diversity in the Tibetan yak populations.The average polymorphic information content (PIC) in 11 groups of yak were higher than 0.5. The highest HEL13 was 0.8496, and the lowest TGLA57 was 0.7349. Among them, the PICof Dingqing yak was minimum (0.7505), indicating that the group is relatively pure.Sangri Yak had the highest PIC value (0.7949) indicating greater genetic variationwithinthe groups. Among the 11 groups examined, the order of heterozygosity size wasSangri(0.8193)>Jiangda(0.8190)>Sangsang(0.8157)>Baqing(0.8150)>Kangbu(0.8123)> Jiali(0.8087)>Gongbujiangda(0.8054)>Sibu(0.8041)>Leiwuqi(0.8033)>Pali(0.8031)>Dingqing(0.7831). The groups from eastern Tibet had grater genetic diversity than those from Western Tibet, which indicate that Tibet may be one of the cradles of the yak.According to the genetic distance, the cluster relationship constructed with UPGMA and NJ methods showed that 11 yak groups in Tibet could be divided into three forms. In summary,Tibet yak has abundant genetic diversity and the selected microsatellite markers can be used to evaluategenetic diversity of Tibetan yak.


HER2 overexpression and activation, and tamoxifen efficacy in receptor-positive early breast cancer.
Tamoxifen is a partial ER antagonist that is highly effective in the treatment of receptor positive breast cancer. It significantly reduces recurrence and improves survival in both pre- and postmenopausal women. Unfortunately, many ER+ positive tumors progress despite tamoxifen treatment and until now, no possibility exists to prospectively identify tamoxifen-resistant tumors. It has been suggested that that in HER2 over-expressing tumors, cross-talk via activated HER2 receptors is a key mechanisms by which tumors become tamoxifen-resistant. We have therefore used immunohistochemistry to analyze the expression of HER2 and activated ptyr-1248 HER2 in 408 women of ER+, early breast cancer who had received at least 2 years of adjuvant tamoxifen. We then analyzed possible associations between HER2 and pHER2 expression, and prognostic parameters, and evaluated the effect of HER2 expression and survival. With HER2 being positive in 12 of 208 (2.9%) of ER+ positive tumors, HER2 overexpression was found to be considerably less common in ER+ tumors than what has been thought previously. The majority of HER2 overexpressing tumors, however, also expressed the activated receptor form (r = 0.664; P < 0.0001). Both HER2 and pHER2 are moderately correlated with Grading (r = 0.138; P = 0.0052 and r = 0.118; P = 0.0241, respectively) and nodal involvement (r = 0.163; P = 0.0018 and r = 0.134; P = 0.016, respectively), but neither HER2 nor its activated form are significant predictors of RFS, DFS, or OS. Taken together, we have demonstrated that in ER+ breast cancer, the HER2 receptor is commonly activated, but its low prevalence in ER+ tumors does not render it a useful prognostic parameter in tamoxifen-treated patients.


Current Status of Fear of Disease Progression in Patients with Advanced Cancer and Usefulness of Dignity Therapy Intervention.
With changes in lifestyle and an increase in bad health habits, cancer has become a noncommunicable and frequently occurring disease that poses a serious threat to human life. Cancer is associated with high rates of morbidity and mortality worldwide. As a major negative life event, advanced malignancies lead to strong mood swings in most patients. Furthermore, various internal and external factors can have a huge impact on patients' physical and mental health and put them in a stressful situation, causing a series of psychological stress responses. To explore the degree of fear of disease progression in patients with advanced cancer and the usefulness of dignity therapy. Overall, 120 patients with advanced malignant tumors admitted to Shijiazhuang No. 1 hospital between January 2019 and January 2020 were enrolled. The selected patients were divided into the test and control groups (60 people per group) using a random number table. All patients received basic treatment. Patients in the trial group also received dignity therapy. The intervention period was 4 weeks. Simplified scales were used for assessing disease progression (FoP-Q-SF) and quality of life (QLQ-C30) before and after the intervention, and the scores were compared between the groups. After the intervention, the degree of fear in the experimental group was lower than that of the control group. Cognitive function, emotional function, and the scores of the overall health status of the experimental group were higher than those of the control group. Additionally, the scores of fatigue, insomnia, loss of appetite, and diarrhea in the experimental group were lower than those of the control group (P < 0.05). The social support level scale scores, depression scores, hospital anxiety and depression scale scores, and patient dignity inventory scores of the experimental group were lower than those of the control group (P < 0.05). Patients with advanced malignant tumors have fear, anxiety, and depression related to disease progression. Dignity therapy is useful for improving the patients' quality of life, increasing dignity, and enhancing social support.


In vitro antioxidant studies of Sphaeranthus indicus (Linn).
The free radical scavenging potential of the plant S. indicus was studied by using different antioxidant models of screening. The ethanolic extract at 1000 microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS) observed upto 41.99% followed by the scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (33.27%), superoxide dismutase (25.14%) and nitric oxide radical (22.36%) at the same concentration. However, the extract showed only moderate scavenging activity of iron chelation (14.2%). Total antioxidant capacity of the extract was found to be 160.85 nmol/g ascorbic acid. The results justify the therapeutic applications of the plant in the indigenous system of medicine, augmenting its therapeutic value.


[Effects on cervical spondylosis of neck type treated with Hegu needling and Shu needling techniques at the positive reaction points].
To observe the clinical effects on cervical spondylosis of neck type treated with the combined therapy of Hegu needling and Shu needling techniques at the positive reaction points as compared with the conventional acupuncture. A total of 90 patients of cervical spondylosis of neck type were randomized into an observation group and a control group, 45 cases in each one. In the observation group, the combined therapy of Hegu needling and Shu needling techniques at the positive reaction points was adopted. The positive reaction points were selected in the neck, shoulder and back regions. In the control group, the conventional acupuncture therapy was provided. The main acupoints were Tianzhu (BL 10), Fengchi (GB 20), Quchi (LI 11), Waiguan (TE 5), Neck-Jiaji (EX-B 2) of C4 to C6 and ashi points. The supplementary acupoints were Yinxi (HT 6) and Geshu (BL 17). The treatment was given once every two days, 10 treatments as one course in the two groups. Separately, before treatment, after the 1st treatment and at the end of one course of treatment, the scores of symptoms and physical signs and the scores of visual analogous scale (VAS) were observed in the two groups. The comprehensive clinical effects were compared between the two groups at the end of treatment. After the 1st treatment and at the end of treatment, the scores of symptoms and physical signs and VAS scores were reduced obviously as compared with those before treatment in the two groups (all P<0.05). After the 1st treatment, the scores of symptoms and physical signs and VAS scores were not different significantly between the two groups (both P>0.05). At the end of treatment, the scores of symptoms and physical signs and VAS scores in the observation group were reduced more obviously as compared with the control group (both P<0.05). The curative and remarkably effective rate was 84.1% (37/44) in the observation group, better than 65.1% (28/43) in the control group (P<0.05). Either the combined therapy of Hegu needling and Shu needling techniques at the positive reaction points or the conventional acupuncture is effective in the treatment of cervical spondylosis of neck type. The combined therapy of Hegu needling and Shu needling techniques at the positive reaction points achieves the superior effects as compared with the conventional acupuncture.


Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.
The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.


Hereditary nonspherocytic hemolytic disease associated with an altered phospholipid composition of the erythrocytes.
A hemolytic disorder with mild hyperbilirubinemia and reticulocytosis of 6 to 15% was documented in eight members of a large family from the Dominican Republic and was presumed to be present in eight other members. The disorder appeared to be inherited as an autosomal dominant characteristic. Analysis of phospholipids by quantitative thinlayer chromatography revealed a distinct increase in phosphatidyl choline (lecithin) to 35.5 +/- SD 1.3% of the total (normal: 28.2 +/- 1.4%) in erythrocytes of affected members of the family, but not in the cells of unaffected relatives. The alteration appeared to constitute an absolute increase in lecithin content, rather than a decrease in other phospholipids. Erythrocytes from patients with other varieties of hereditary hemolytic disorders and comparable levels of reticulocytosis had normal phospholipid compositions. Plasma lipids of six affected members of the family were not unusual with respect to total lipid weight, total phospholipid, and cholesterol. Three patients with liver disease and jaundice were found to have marked increases in the lecithin content of the erythrocytes, but they also had extremely high plasma levels of total lipid, phospholipids, and cholesterol. Osmotic fragility of the erythrocytes of affected patients was decreased and the increase in fragility after incubation for 24 hr was less than that observed with normal erythrocytes. Autohemolysis after 48 hr was slightly increased and was corrected to nearly normal by the addition of glucose. The activities of 15 enzymes of the erythrocytes of the propositus were normal or elevated and the adenosine triphosphate content was normal. An abnormal hemoglobin could not be demonstrated. The life span of isologous erythrocytes in the propositus was reduced, but homologous erythrocytes survived normally.A causal relationship between the altered phospholipid composition and the hemolytic disorder has not been established.


Evaluation of Chitosan-Based Films Containing Gelatin, Chondroitin 4-Sulfate and ZnO for Wound Healing.
In this work, chitosan-based films containing gelatin and chondroitin-4-sulfate (C4S) with and without ZnO particles were produced and tested in vitro to investigate their potential wound healing properties. Chitosans were produced from shrimp-head processing waste by alkaline deacetylation of chitin to obtain chitosans differing in molecular weight and degree of deacetylation (80 ± 0.5%). The film-forming solutions (chitosan, C4S and gelatin) and ZnO suspension showed no toxicity towards fibroblasts or keratinocytes. Chitosan was able to agglutinate red blood cells, and film-forming solutions induced no hemolysis. Film components were released into solution when incubated in PBS as demonstrated by protein and sugar determination. These data suggest that a stable, chitosan-based film with low toxicity and an ability to release components would be able to establish a biocompatible microenvironment for cell growth. Chitosan-based films significantly increased the percentage of wound healing (wound contraction from 65 to 86%) in skin with full-thickness excision when compared with control (51%), after 6 days. Moreover, histological analysis showed increased granulation tissue in chitosan and chitosan/gelatin/C4S/ZnO films. Chitosan-based biopolymer composites could be used for improved biomedical applications such as wound dressings, giving them enhanced properties.


A critical assessment of the utility of protein-free splicing systems.
U2 and U6 snRNAs form part of the catalytic spliceosome and represent strong candidates for components of its active site. Over the past decade it has become clear that these snRNAs are capable of catalyzing several different chemical reactions, leading to the widespread conclusion that the spliceosome is a ribozyme. Here, we discuss the advances in both protein-free and fully spliceosomal systems that would be required to conclude that the reactions observed to be catalyzed by protein-free snRNAs are related to splicing and question the reliability of snRNA-only systems as tools for mechanistic splicing research.


Enhancing UAV Detection in Surveillance Camera Videos through Spatiotemporal Information and Optical Flow.
The growing intelligence and prevalence of drones have led to an increase in their disorderly and illicit usage, posing substantial risks to aviation and public safety. This paper focuses on addressing the issue of drone detection through surveillance cameras. Drone targets in images possess distinctive characteristics, including small size, weak energy, low contrast, and limited and varying features, rendering precise detection a challenging task. To overcome these challenges, we propose a novel detection method that extends the input of YOLOv5s to a continuous sequence of images and inter-frame optical flow, emulating the visual mechanisms employed by humans. By incorporating the image sequence as input, our model can leverage both temporal and spatial information, extracting more features of small and weak targets through the integration of spatiotemporal data. This integration augments the accuracy and robustness of drone detection. Furthermore, the inclusion of optical flow enables the model to directly perceive the motion information of drone targets across consecutive frames, enhancing its ability to extract and utilize features from dynamic objects. Comparative experiments demonstrate that our proposed method of extended input significantly enhances the network's capability to detect small moving targets, showcasing competitive performance in terms of accuracy and speed. Specifically, our method achieves a final average precision of 86.87%, representing a noteworthy 11.49% improvement over the baseline, and the speed remains above 30 frames per second. Additionally, our approach is adaptable to other detection models with different backbones, providing valuable insights for domains such as Urban Air Mobility and autonomous driving.


Variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2.
CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia (CAH) cases, a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provide critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Here, we analyzed the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of CYP21A2. SNVs of CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. All SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy of between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). From our analysis, we identified four predictors of CYP21A2 variant pathogenicity with good performance, CADD, ConSurf, DANN, and PolyPhen2. These results can be used for future analysis to infer the impact of uncharacterized SNVs in CYP21A2.


Identification and RNA Interference of the Pheromone Biosynthesis Activating Neuropeptide (PBAN) in the Common Cutworm Moth Spodoptera litura (Lepidoptera: Noctuidae).
Spodoptera litura F. is one of the most destructive insect pests of many agricultural crops and notorious for developing insecticide resistance. Developing environmental friendly control methods such as novel pheromone and RNAi-related control strategies is imperative to control this pest. In the present study, the full-length cDNA encoding the diapause hormone and pheromone biosynthesis activating neuropeptide (DH-PBAN) was identified and characterized in S. litura. This 809-bp transcript contains a 573-nucleotide ORF encoding a 191-amino acid protein, from which five putative neuropeptides, including PBAN, DH, and α-, β-, and γ-subesophageal ganglion neuropeptides, were derived. Phylogenetic analysis showed that both the whole protein and each of the five neuropeptides have high similarities to those of DH-PBANs from other insect orders particularly Lepidoptera. Females treated with TKYFSPRLamide (the active core fragment of PBAN) produced significantly more four types of pheromone compounds (A; B; C; D) than controls. RNA interference by injection of PBAN dsRNA significantly reduced the relative expression levels of this gene in adult females (approximately reduced by 60%). As a consequence, females treated with PBAN dsRNA produced significantly less four types of pheromone compounds (A; B; C; D) than controls. These results suggest that PBAN function in activating sex pheromone biosynthesis and the RNAi of DH-PBAN gene can be induced by the injection of dsRNA into the body cavity in S. litura. This study suggests the possibility of novel pheromone-related pest control strategies based on RNAi techniques.


Nonlinear modulation of interacting between COMT and depression on brain function.
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.


Molecular conformations of dumbbell-shaped polymers in good solvent.
We study conformational properties of diluted dumbbell polymers composed of two rings attached to both ends of a linear spacer segment. Our investigation involves analytical methods of field theory and bead-spring coarse-grained molecular dynamics simulations. We focus on the influence of the relative length of the spacer segment to the length of side rings on the shape and the relative size of dumbbells as compared to linear polymers of equal mass. We find that dumbbells with short spacers exhibit a significantly more compact structure than linear polymers. Conversely, as the spacer length increases, the influence of the side rings on the size of the dumbbells becomes negligible. Consequently, dumbbell molecules with long spacers attain a size comparable to corresponding linear chains. Our analytical theory accurately predicts a quantitative conformational crossover between the behaviors of short-spacer and long-spacer dumbbells, which is further confirmed by our numerical simulations.


Methicillin-resistant Staphylococcus aureus otorrhea after tympanostomy tube placement.
To compare a retrospective cohort of nonhospitalized children with methicillin-resistant Staphylococcus aureus (MRSA) otorrhea with those with methicillin-sensitive S aureus (MSSA) otorrhea to determine the risk factors predisposing to MRSA otorrhea and the treatments used. Retrospective case-controlled series. Tertiary pediatric care facility. Seventeen children with MRSA otorrhea after bilateral myringotomy with tympanostomy tube insertion (BM&T) and 19 age- and sex-matched control subjects who demonstrated MSSA otorrhea. The average age at culture in MRSA patients was 52 months; in MSSA patients, 54 months. There were 8 boys and 3 girls in the MRSA group and 8 boys and 4 girls in the MSSA group. Oral, topical, and intravenous antimicrobial agents. Antibiotic exposure and history of otitis media and routine antibiotic administration (topical, oral, or intravenous). The following findings were statistically significant (P < or = .06, Mann-Whitney test): (1) longer duration of antibiotic treatment after BM&T for patients with MRSA vs those with MSSA; (2) increased number of episodes of acute otitis media before BM&T in patients with MRSA vs those with MSSA; and (3) increased number of courses of antibiotics after BM&T in patients with MRSA vs those with MSSA. Methicillin-resistant S aureus otorrhea is commonly seen as a community-acquired infection in otherwise healthy pediatric outpatients. Risk factors for development of MRSA otorrhea include the number of episodes of acute otitis media before BM&T and number of treatment courses and duration of antibiotic therapy after BM&T.


Testosterone replacement therapy for a man with prostate cancer.
A 52-year-old male with elevated serum prostate-specific antigen (PSA) level, moderate lower urinary tract symptoms (LUTS), and negative family history of prostate cancer is found to have adenocarcinoma of the prostate with negative bone scan. Following radical retropubic prostatectomy and satisfactory postoperative recovery, heretofore undetectable serum PSA level rose 35 months later. Digital rectal examination (DRE) and bone scan were negative. Adjuvant external beam radiation preceded by a 3-month injection of goserelin was initiated. Radiation was well tolerated, although the patient reported significant loss of libido, hot flashes, and depression warranting antidepressant medication. Failure to respond to this intervention led to initiation of supplemental testosterone; 1 month later, the patient reported significant relief of symptoms. The patient is currently successfully tapering use of supplemental testosterone in order to decrease andropause symptoms and to permit restoration of intrinsic testosterone.


Nonequilibrium interfacial properties of chemically driven fluids.
Chemically driven fluids can demix to form condensed droplets that exhibit phase behaviors not observed at equilibrium. In particular, nonequilibrium interfacial properties can emerge when the chemical reactions are driven differentially between the interior and exterior of the phase-separated droplets. Here, we use a minimal model to study changes in the interfacial tension between coexisting phases away from equilibrium. Simulations of both droplet nucleation and interface roughness indicate that the nonequilibrium interfacial tension can either be increased or decreased relative to its equilibrium value, depending on whether the driven chemical reactions are accelerated or decelerated within the droplets. Finally, we show that these observations can be understood using a predictive theory based on an effective thermodynamic equilibrium.


Phosphorylation of the transcription factor Ets-1 by ERK2: rapid dissociation of ADP and phospho-Ets-1.
ERK2, a major effector of the BRAF oncogene, is a promiscuous protein kinase that has a strong preference for phosphorylating substrates on Ser-Pro or Thr-Pro motifs. As part of a program to understand the fundamental basis for ERK2 substrate recognition and catalysis, we have studied the mechanism by which ERK2 phosphorylates the transcription factor Ets-1 at Thr-38. A feature of the mechanism in the forward direction is a partially rate-limiting product release step (koff = 59 +/- 6 s(-1)), which is significant because to approach maximum efficiency substrates for ERK2 may evolve to ensure that ADP dissociation is rate-limiting. To improve our understanding of the mechanism of product release, the binding of the products to ERK2 was assessed and the reaction was examined in the reverse direction. These studies demonstrated that phospho-Ets-1 (p-Ets) binds >20-fold more tightly to ERK2 than ADP (Kd = 7.3 and 165 microM, respectively) and revealed that the products exhibit little interaction energetically while bound to ERK2 and that they can dissociate ERK2 in a random order. The overall equilibrium for the reaction in solution (Keq = 250 M(-1)) was found to be similar to that with the substrate bound to the enzyme (Kint = 525 M(-1)). To determine what limits koff, several pre-steady-state experiments were performed. A catalytic trapping approach furnished a rate constant (k-ADPa) of 61 +/- 12 s(-1) for the dissociation of ADP from the abortive ternary complex, ERK2.Ets.ADP. To examine p-Ets dissociation, the binding of a fluorescent derivative (p-Ets-F), which binds ERK2 with an affinity similar to that of p-Ets, was examined by stopped-flow kinetics. Using this approach, p-Ets-F was found to bind through a single-step mechanism, with the following parameters: k-p-Ets-F = 121 +/- 3.8 s(-1), and kp-Ets-F = (9.4 +/- 0.3) X 10(6) M(-1) s(-1). Similar results were found in the presence of a saturating ADP concentration. These data suggest that koff may be limited by the dissociation of both products and are consistent with the notion that Ets-1 has evolved to be an efficient substrate for ERK2, where ADP release is, at least, partially rate-limiting. A molecular mechanics model of the complex formed between ERK2 and residues 28-138 of Ets-1 provides insight into the role of substrate docking interactions.


One-Dimensional Carrier Confinement in "Giant" CdS/CdSe Excitonic Nanoshells.
The emerging generation of quantum dot optoelectronic devices offers an appealing prospect of a size-tunable band gap. The confinement-enabled control over electronic properties, however, requires nanoparticles to be sufficiently small, which leads to a large area of interparticle boundaries in a film. Such interfaces lead to a high density of surface traps which ultimately increase the electrical resistance of a solid. To address this issue, we have developed an inverse energy-gradient core/shell architecture supporting the quantum confinement in nanoparticles larger than the exciton Bohr radius. The assembly of such nanostructures exhibits a relatively low surface-to-volume ratio, which was manifested in this work through the enhanced conductance of solution-processed films. The reported core/shell geometry was realized by growing a narrow gap semiconductor layer (CdSe) on the surface of a wide-gap core material (CdS) promoting the localization of excitons in the shell domain, as was confirmed by ultrafast transient absorption and emission lifetime measurements. The band gap emission of fabricated nanoshells, ranging from 15 to 30 nm in diameter, has revealed a characteristic size-dependent behavior tunable via the shell thickness with associated quantum yields in the 4.4-16.0% range.


Protection of Arabidopsis Blunt-Ended Telomeres Is Mediated by a Physical Association with the Ku Heterodimer.
Telomeres form specialized chromatin that protects natural chromosome termini from being recognized as DNA double-strand breaks. Plants possess unusual blunt-ended telomeres that are unable to form t-loops or complex with single-strand DNA binding proteins, raising the question of the mechanism behind their protection. We have previously suggested that blunt-ended telomeres in Arabidopsis thaliana are protected by Ku, a DNA repair factor with a high affinity for DNA ends. In nonhomologous end joining, Ku loads onto broken DNA via a channel consisting of positively charged amino acids. Here, we demonstrate that while association of Ku with plant telomeres also depends on this channel, Ku's requirements for DNA binding differ between DNA repair and telomere protection. We show that a Ku complex proficient in DNA loading but impaired in translocation along DNA is able to protect blunt-ended telomeres but is deficient in DNA repair. This suggests that Ku physically sequesters blunt-ended telomeres within its DNA binding channel, shielding them from other DNA repair machineries.