Insulin and C-peptide secretion from B cells in human subjects stimulated with glucose.
Two groups of immunoreactive insulin in human sera were reported by Kakita et al. (4), using gel chromatography after acid-alcohol extraction. These analogs were noted not only in circulating human sera but also in incubation medium and incubated human pancreas. The release of these insulin analogs was discussed in a previous report (5). The circulating C-peptide immunoreactivity was separated into two groups on a Bio-Gel column, and the early peak should not be proinsulin but an associated C peptide (6). These analogs of insulin were separated by the methods of ion-exchange chromatography, isoelectric focusing, gel electrophoresis, and gel chromatography. Immunoreactive insulin was also separated into two major bands by standard polyacrylamide gel electrophoresis. The fast migrating band corresponds to the rat insulin II position, and the slower corresponds to rat insulin I, which has one more basic amino acid residue in comparison with rat insulin II. Further studies have been performed in five healthy adults in order to elucidate the physiological relationship between analogs of insulin and C-peptide peak substances in human serum; the results are reported in this paper with a consideration of the mechanism of insulin secretion.


Secretion in the rat coagulating gland (anterior prostate) after copulation.
The effect of copulation on the rat coagulating gland (anterior prostate) was studied. At 4 to 6 h after the beginning of copulation the coagulating glands of rats that had produced copulatory plugs were nearly empty of secretion. Ultrastructurally, the coagulating gland has large cisternae of rough endoplasmic reticulum (RER) and few condensing vacuoles or secretion granules. After copulation the number of secretion granules and the frequency of their expulsion into the lumen increased. Also in the lumen were "fragmentation" vesicles (50-100 nm diameter) that were bounded by a unit membrane and appeared to arise from microvilli. At 4, 6, and 7h after the beginning of copulation there was an increase in apical blebbing. Blebbing was found in both perfusion and immersion-fixed tissue. Also, after copulation there was an increase in "light cells" that were characterized by reduced RER cisternae, an electron lucent cytoplasm, and atrophic Golgi apparatus. The luminal ground substance, secretion granules, and some Golgi elements, contained polysaccharides as seen with the periodic acid-thiocarbohydrazide-silver proteinate method.


Plasmon mediated super-absorber flexible nanocomposites for metamaterials.
A flexible host has been selected to achieve, for the first time, functional nanocomposites based on CdSe@ZnS core-shell type quantum dots (QDs) and Au nanoparticles (NPs), simultaneously dispersed in a polymer matrix. Coherent interactions between QDs and plasmonic Au NPs embedded in PDMS films have been demonstrated to lead to a relevant enhancement of the absorption cross-section of the QDs, remarkably modifying the optical response of the entire system. Optical and time resolved spectroscopy studies revealed an active gain-plasmon feedback behind the super-absorbing overall effect.


New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones.
An effective one-pot strategy was developed for the synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones from pyrazolo[3,4-b]pyridin-6-ones, obtained by reacting 5-aminopyrazoles with 4-arylidene-2-phenyloxazol-5(4H)-ones (azlactones) under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium (t-BuOK/DMSO). The fluorescent properties of the synthesized compounds were studied. 4-Arylpyrazolo[3,4-b]pyridin-6-ones luminesce in the region of 409-440 nm with a quantum yield of 0.09-0.23 when irradiated with UV light.


The scope and significance of anger in the experience of chronic pain.
This paper is divided into 3 sections. The first provides the conceptual framework by introducing definitions of anger and related constructs and highlighting pertinent aspects of the concept of pain. The second section examines the evidence for anger as a feature of chronic pain. The available research indicates that chronic pain patients experience anger but this may be underestimated because of denial. In fact, anger stands out as one of the most salient emotional correlates of pain, even though past research has been largely confined to the study of depression and anxiety. the third section explores the significance of anger in chronic pain, in terms of its compounding effects on pain, depression and psychosocial functioning, as well as its consequences for physical health and health habits. The impact of anger among chronic pain patients for treatment outcome is discussed. Finally, the information from these sections is integrated into a model depicting the antecedents and consequences of anger as specifically associated with the chronic pain experience.


Nucleation of nuclear bodies.
The nucleus is a complex organelle containing numerous highly dynamic, structurally stable domains and bodies, harboring functions that have only begun to be defined. However, the molecular mechanisms for their formation are still poorly understood. Recently it has been shown that a nuclear body can form de novo by self-organization. But little is known regarding what triggers the formation of a nuclear body and how subsequent assembly steps are orchestrated. Nuclear bodies are frequently associated with specific active gene loci that directly contribute to their formation. Both coding and noncoding RNAs can initiate the assembly of nuclear bodies with which they are physiologically associated. Thus, the formation of nuclear bodies occurs via recruitment and consequent accumulation of resident proteins in the nuclear bodies by nucleating RNA acting as a seeder. In this chapter I describe how to set up an experimental cell system to probe de novo biogenesis of a nuclear body by nucleating RNA and nuclear body components tethered on chromatin.


Facial reanimation of patients with neurofibromatosis type 2.
Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome defined by bilateral vestibular schwannomas. Facial paralysis, from either tumor growth or surgical intervention, is a devastating complication of this disorder and can contribute to disfigurement and corneal keratopathy. Historically, physicians have not attempted to treat facial paralysis in these patients. To review our clinical experience with free gracilis muscle transfer for the purpose of facial reanimation in patients with NF2. Five patients with NF2 and complete unilateral facial paralysis were referred to the facial nerve center at our institution. Charts and operative reports were reviewed; treatment details and functional outcomes are reported. Patients were treated between 2006 and 2009. Three patients were men and 2 were women. The age of presentation of debilitating facial paralysis ranged from 12 to 50 years. All patients were treated with a single-stage free gracilis muscle transfer for smile reanimation. Each obturator nerve of the gracilis was coapted to the masseteric branch of the trigeminal nerve. Measurement of oral commissure excursions at rest and with smile preoperatively and postoperatively revealed an improved and nearly symmetric smile in all cases. Management of facial paralysis is often times overlooked when defining a care plan for NF2 patients who typically have multiple brain and spine tumors. The paralyzed smile may be treated successfully with single-stage free gracilis muscle transfer in the motivated patient.


Detection and quantification of laryngotracheopulmonary aspiration with scintigraphy.
Aspiration is analyzed by a new scintigraphic technique and standard videofluoroscopy in 78 patients with head and neck pathology and neurologic disorders. When both methods are compared to clinical aspiration and a positive x-ray film of pneumonia, they appear to complement each other and provide a very accurate evaluation. Scintigraphy is a more sensitive method for detecting aspiration below the vocal cords and also provides for flow dynamics and a method of quantifying the amount of aspirated material. Videofluoroscopy shows more clearly the mechanism of the swallowing disorder and how the bolus enters the tracheobronchial tree. Studies in patients following head and neck surgery demonstrate a high incidence of dysphagia, aspiration, and pneumonia.


Application of 1.5 T magnetic resonance imaging in endometrial cancer.
To determine the diagnostic accuracy, sensitivity and specificity of magnetic resonance imaging (MRI) in detecting myometrial invasion, cervical involvement and disease stage in endometrial cancer. 168 consecutive patients with endometrial carcinoma underwent preoperative MRI. We classified myometrial invasion as no invasion, ≤50% invasion or >50% invasion and cervical involvement as positive or negative. The preoperative MRI findings and stagings were compared with final surgical and histological staging; the latter was taken as the gold standard. Standard statistical calculations were used. The sensitivity, specificity, and accuracy of MRI for the detection of myometrial invasion >50% were 64.7, 92.5, and 86.9%, respectively. Positive and negative predictive values were 68.8 and 91.2%, respectively. The sensitivity, specificity, and accuracy of MRI for the detection of cervical invasion were 52.63, 93.08, and 83.93%, respectively. Positive and negative predictive values were 68.97 and 87.05%, respectively. 102 cases were classified as stage IA (early disease) by histology. MRI accurately predicted the degree of invasion in 88 cases and overestimated in 14, giving a sensitivity of 86.3% and specificity of 69.1%. However, MRI showed reduced sensitivity for predicting stage IB and advanced endometrial cancer (stages III and IV) at 33.3 and 30.3%, respectively, but was found to be specific for predicting these stages; the specificity were 94.7 and 85.1%, respectively. MRI also showed good accuracy for predicting stage IA, IB, II and advanced endometrial cancer at 80.4, 86.9, 91.7, and 83.9, respectively. MRI assists in planning the surgical treatment of endometrial cancer with good accuracy and specificity, although sensitivity is suboptimal.


Enhancement of the structure, solar cells and vibrational studies of undoped CuCr2O4 and La-doped CuCr2O4 semiconductor compounds.
In the present paper, we report the successful synthesis of spinel-type of CuCr2O4 and La doped CuCr2O4 semiconductor nanoparticles by a microwave method. Starting with the precursor complex, this technique includes the creation of homogenous solid intermediates, which reduces atomic diffusion pathways during the microwave process. CuCr2O4 and La doped CuCr2O4 were characterized by the following analytical methods for instance X-ray diffraction (XRD), transmission electron microscopy (TEM), Ultraviolet-visible (UV-Vis) spectroscopy and Fourier transform infrared spectroscopy (FTIR). The results demonstrated that modifying the precursor had a significant impact on the size, solar cell size, as well as reaction period of synthesizing CuCr2O4 and La doped CuCr2O4. The impacts of precursors on the morphological and structural characteristics of CuCr2O4 and La doped CuCr2O4 were examined for the first time in this publication.


Large cross-sectional area of the umbilical cord as a predictor of fetal macrosomia.
To determine whether a large cross-sectional area of the umbilical cord is a predictor of fetal macrosomia. Consecutive patients of > 34 weeks' gestation, who presented for sonographic examination and who delivered within 4 weeks of the examination, were included in the study. The sonographic cross-sectional areas of the umbilical cord, the umbilical vessels and the Wharton's jelly were measured in a free loop of the umbilical cord. Logistic regression analysis was used to determine significant predictors of macrosomia (actual birth weight > 4000 g and > 4500 g). Fetal biometric parameters (biparietal diameter, abdominal circumference and femur length), sonographic estimated fetal weight and umbilical cord area > 95(th) centile for gestational age were used as covariates. During the study period, 1026 patients were enrolled. Fifty-three (5.2%) newborns had a birth weight > 4000 g, and 22 (2.1%) weighed > 4500 g. The proportion of cases with a large umbilical cord was significantly higher in the group of macrosomic compared with non-macrosomic infants (54.7% vs. 8.7%, P < 0.0001). Multiple regression models demonstrated an independent contribution of the large cord in the prediction of birth weight > 4000 g and > 4500 g (odds ratio (95% CI), 20.6 (9.2-45.9) and 4.2 (1.2-17.7), respectively). The sensitivity, specificity and positive and negative predictive values of a sonographic large umbilical cord were 54.7%, 91.3%, 25.4%, and 97.4%, respectively. The combination of abdominal circumference > 95(th) centile and large cord predicted 100% of macrosomic infants. The proportion of umbilical cords with a Wharton's jelly area > 95(th) centile for gestation was significantly higher in macrosomic fetuses of diabetic compared with non-diabetic mothers. Sonographic assessment of umbilical cord area may improve the prediction of fetal macrosomia.


[Mesenteric venous thrombosis. A retrospective study of 23 cases].
Mesenteric venous thrombosis is uncommon. Diagnosis is difficult and much remains to be learned about clinical aspects, etiology and treatment options. We conducted a retrospective study over 5 years concerning patients with isolated mesenteric venous thrombosis or with extension to the portal vein. Twenty-three patients (12 women), mean age 55 years, were included. Abdominal pain (96%), bowel obstruction (35%), fever (26%), diarrhea (17%), gastrointestinal bleeding (13%) were the most common symptoms at presentation. In 78% of patients, at least one underlying condition was identified: thrombophilia, oral contraceptive, cancer, paroxysmal nocturnal hemoglobinuria, essential thrombocythemia, intra-abdominal processes. CT scan and ultrasound diagnostic sensitivity were 89% and 57% respectively. Outcome was favorable for the 18 patients treated with anticoagulants (associated with surgery in 4 patients). Three patients with neoplasm died early. Mesenteric venous thrombosis must be kept in mind as a possible diagnosis in patients with abdominal pain. Predisposing factors are frequently associated and should be searched for. Early diagnosis, using CT scan or ultrasound, enables immediate anticoagulation and seems to improve outcome.


Ultrastructural investigation of DNA in megakaryoblastic leukemia by using osmium-ammine-B: comparison with several types of leukemia.
Using DNA staining with highly stable osmium-ammine-B, the blasts of AMKL were observed under an electron microscope, in comparison with AML, ALL, CML-MK crisis and TMD. The DNA within the nucleus of the megakaryoblasts was observed as a high electron-density substance and tended to be uniformly dispersed within the nucleus. DNA, associated with nucleoli, could be roughly divided in four types based on the presence or absence of peri-nucleolar clumps and intra-nucleolar clumps. In cases of AMKL, we often observed a type that did not have peri-nucleolar DNA clumps but did have DNA flecks within the nucleoli. By analytical evaluation there were no differences among cells from several subtypes of megakaryocytic leukemia, such as AMKL in children with Down's syndrome, AMKL in children without Down's syndrome, AMKL in adults, and CML-MK crisis. The DNA distribution of TMD blasts, which were self-limited and not malignant, resembled that of AMKL blasts.


Non-transferrin bound iron.
Non-transferrin-bound iron (NTBI) is an important biomarker related to the iron loading status of patients with certain diseases. NTBI is a highly toxic form of iron capable of generating free radicals and can lead to oxidative damage of various tissues. It is critical to quantify NTBI in blood to ensure personalised patient chelation management and to prevent high iron concentrations that can lead to toxicity and organ failure. Different analytical methods for the direct quantification of NTBI are described in the literature, but none have been translated for use in clinical laboratories. This review provides a critical discussion on the recent breakthroughs and remaining challenges for the direct quantification of NTBI. Most of the developed methods involve lengthy and complex sample preparation, use of expensive reagents and equipment while lacking the required accuracy and reproducibility. Collectively, these factors have limited the clinical translation of the developed methods, and therefore, the need for a reliable and widely accepted analytical method to quantify NTBI remains. Finally, this review explores the potential of rapid and accurate electrochemical techniques that have been demonstrated for environmental samples but are yet to be applied to detect NTBI in human blood plasma/serum and translation to widespread routine clinical use.


Imaging features of lower limb malformations above the foot.
Lower limb malformations are generally isolated or sporadic events. However, they are sometimes associated with other anomalies of the bones and/or viscera in patients with constitutional syndromes or disorders of the skeleton. This paper reviews the main imaging features of these abnormalities, which generally exhibit a broad spectrum. This paper focuses on several different bone malformations: proximal focal femoral deficiency, congenital short femur and femoral duplication for the femur, tibial hemimelia (aplasia/hypoplasia of the tibia) and congenital bowing for the tibia, fibular hemimelia (aplasia/hypoplasia) for the fibula, and aplasia, hypoplasia and congenital dislocation for the patella.


Biological mechanisms in posttraumatic stress disorder. Relevance for substance abuse.
Recent studies suggest a significant biological contribution to posttraumatic stress disorder (PTSD). In particular, central catecholamine and endogenous opioid systems have been implicated both in this syndrome and in substance abuse. We review relevant animal and human studies that support these hypotheses and suggest that this overlap may contribute to the incidence of substance abuse in PTSD. The animal studies have primarily employed the learned helpless and conditioned emotional response models and have included assessments of brain catecholamines, locus ceruleus activity, and behavioral correlates in rodents and nonhuman primates. Human studies have used only indirect measures to assess these variables. However, both therapeutic approaches and attempts at self-medication for PTSD have supported this hypothesis.


Predicting termination of atrial fibrillation based on the structure and quantification of the recurrence plot.
Predicting the spontaneous termination of the atrial fibrillation (AF) leads to not only better understanding of mechanisms of the arrhythmia but also the improved treatment of the sustained AF. A novel method is proposed to characterize the AF based on structure and the quantification of the recurrence plot (RP) to predict the termination of the AF. The RP of the electrocardiogram (ECG) signal is firstly obtained and eleven features are extracted to characterize its three basic patterns. Then the sequential forward search (SFS) algorithm and Davies-Bouldin criterion are utilized to select the feature subset which can predict the AF termination effectively. Finally, the multilayer perceptron (MLP) neural network is applied to predict the AF termination. An AF database which includes one training set and two testing sets (A and B) of Holter ECG recordings is studied. Experiment results show that 97% of testing set A and 95% of testing set B are correctly classified. It demonstrates that this algorithm has the ability to predict the spontaneous termination of the AF effectively.


All-cause mortality and suicide mortality in autistic individuals: An entire population longitudinal study in Taiwan.
Our study was the first population-based study in an Asian country to investigate the mortality rates among autistic individuals. Among the entire Taiwanese population (N = 29,253,529), between 2003 and 2017, 45,398 autistic individuals were identified and 1:4 age-/sex-matched to 181,592 non-autistic individuals. We found that autistic individuals had increased risks of all-cause mortality, natural-cause mortality, and suicide mortality compared with non-autistic individuals. Furthermore, autistic males were more likely to die by suicide, and autistic females were more likely to die of accident compared with the non-autistic individuals.


Quality of end-of-life care for patients with metastatic non-small-cell lung cancer in general wards and palliative care units in Japan.
Patients with lung cancer in Japan often receive aggressive care near the end of life and die in an acute care hospital. We describe the differences in end-of-life care for metastatic non-small-cell lung cancer (NSCLC) patients between general wards and a palliative care unit (PCU). A retrospective analysis was conducted using data from patients who received at least second-line chemotherapy between 2002 and 2007 in a single institute. Among 72 eligible patients, we categorised patients into two groups, those who died in general wards (n = 57) and those who died in the PCU (n = 15), and examined end-of-life care including chemotherapy, do-not-resuscitate (DNR) decision making and treatment in the last 48 h of life. Mean number of days between the last chemotherapy and death was shorter in general wards than in the PCU (P = 0.019). Furthermore, 25% of patients in general wards received chemotherapy within the last 2 weeks of life. Rates of multiple hospitalisations in the last month of life appeared higher in general wards than in the PCU. Mean number of days between documentation of DNR and death was shorter in general wards than in the PCU (P = 0.0010). Patients in general wards received a greater volume of hydration than those in the PCU (P < 0.001). Patients with metastatic NSCLC in general wards receive inappropriate care near the end of life. Further studies are needed to develop interventions for making decisions regarding end-of-life care.


Methods in drug abuse models: comparison of different models of methamphetamine paradigms.
Methamphetamine (METH) is a widely abused psychomotor stimulant. Investigating the effects of METH use on the brain has been applied in different animal models, including rats, mice, and nonhuman primates. Human abuse of METH occurs in different paradigms ranging from episodes of binge abuse to chronic abuse over years; different animal models have been established to replicate these various patterns of human behavior. In this chapter, we discuss the different models of METH abuse, including the acute model which assesses the immediate effects of METH on the brain and chronic exposure model which simulates the more common long-term use observed in humans; additionally, two other relevant models, escalating dose paradigm and METH self-administration, are examined. In comparing the models, this chapter briefly considers the METH-induced neurotoxic effects associated with each METH administration paradigm and the behavioral changes observed.


Contribution of endermology to improving indurations and panniculitis/lipoatrophy at glatiramer acetate injection site.
Endermology is a mechanical massage therapy that enables fat mobilization and body contouring. The authors' aim was to assess the effect of endermology on indurations and panniculitis/lipoatrophy associated with subcutaneous administration of glatiramer acetate in patients with multiple sclerosis (MS). This was a multicenter pilot experience carried out in patients with MS treated with glatiramer acetate who showed indurations and/ or panniculitis/lipoatrophy at the injection site. Patients underwent endermology and glatiramer acetate treatment according to clinical practice. The primary endpoint was the change in indurations and/or panniculitis/lipoatrophy after 12 endermology sessions. Between April and July 2011, a total of 13 evaluable patients were included (mean age, 40.7±3.1 years; female, 100%; white, 100%; mean MS duration, 10.1±2.3 years; previous MS treatment, 46.2%; mean glatiramer acetate treatment duration, 27.3±9.5 months). Eleven patients (84.6%) showed local indurations (mean diameter, 3.4±0.5 cm; mean number, 9.0±1.0) and six patients (46.2%) areas of panniculitis/ lipoatrophy (mean number, 5.0±1.1). After 12 endermology sessions, patients with indurations reported having experienced a reduction in size (10 patients [90.9%]; mean diameter, 0.1±0.05 cm; P<0.001) and number of indurations (nine patients [81.8%]; mean number, 2.3±1.1; P<0.005). These indurations completely disappeared from arms, thighs, buttocks, and abdomen in six (75.0%), six (75.0%), two (50.0%), and three (42.9%) patients, respectively. Three of these patients (27.3%) recovered from all indurations. Although panniculitis/lipoatrophy did not completely disappear, all patients reported improvements. Most patients with indurations (63.6%) felt very satisfied and considered endermology very useful for reducing indurations. All patients with panniculitis/lipoatrophy were satisfied and considered to be endermology useful in improving it. In addition, endermology enabled glatiramer acetate tolerance to be improved in most patients (60.0%). Endermology may contribute to improving indurations and panniculitis/ lipoatrophy at the site of subcutaneous injection of glatiramer acetate in patients with MS, enabling areas of injection to recover, and treatment tolerance to increase.


Massive infantile myofibromatosis of the upper lip causing airway distress in a newborn.
Infantile myofibromatosis is a rare condition characterized by benign spindle cell tumors most commonly involving the head, neck, and chest. An infant female with a prenatal diagnosis of a large facial mass was delivered via Cesarean at 34 weeks. Sparse prenatal care was received. Following delivery, the neonate was found to have an 8 cm ulcerative mass involving the upper lip and philtrum. Respiratory distress developed, and mask ventilation was difficult secondary to the size of the mass. The patient was successfully intubated after numerous attempts and then transferred to the children's hospital. Additional imaging demonstrated similar masses within bilateral iliopsoas and gluteal muscles, and her right gastrocnemius. A biopsy confirmed infantile myofibromatosis. At two weeks of life, she underwent resection with bilateral myocutaneous advancement flaps and successful extubation. She received adjuvant vinblastine and methotrexate for her pelvic and extremity disease with excellent response. We present the first case of airway distress secondary to myocutaneous myofibromatosis.


Biofunctional nanosystems based on dendritic polymers.
Among the various polymeric architectures, dendritic polymers have received a substantial scientific focus for their highly branched, multifunctional, and well-defined structures. Dendritic scaffolds have found many applications for designing nanoscale drug/gene delivery carriers and constructing diagnostic and biosensor devices, and protein-resistant surfaces. A significant number of research groups across Europe share the common objective, yet in conspicuously individual ways, of utilizing such polymers for devising innovative biomedical tools and techniques. This review describes the European effort of finding the application of dendritic polymers as advanced generation therapeutics within the purview of nanomedicine.


Anion Substitution in Porous Aromatic Frameworks: Boosting Molecular Permeability and Selectivity for Membrane Acetylene Separation.
Precise tailoring of pore chemistry is indispensable for efficient membrane gas separation, particularly for the challenging acetylene system. Here, a strategy called "anion substitution" is reported, to strengthen the interaction between anions and acetylene within the pores, for radically improving gas selectivity and permeability. The anions F- and OH- are infixed in iPAF-1 to replace the original Cl- ion. Their small anionic radii allow retention of the original high porosity of iPAF-1-Cl in iPAF-1-F and iPAF-1-OH. Highly basic F- and OH- confined in the pores attract acidic acetylene strongly and preferentially. Nanoparticles of iPAF-1 are processed to form mixed matrix membranes, represented by iPAF-1-OH/6FDA-ODA. The prepared membranes exhibit remarkable performance in separating acetylene from ethylene and ethane. Transplantation of porous and functional iPAF-1-OH into 6FDA-ODA significantly enhances both acetylene permeability (sevenfold) and permselectivity (fivefold) for acetylene over ethylene and ethane, which is crucial for membrane acetylene gas separation.


Diuretic effect and metabolism of bumetanide in man.
Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.


Three is not a crowd: efficient sensitization of TiO2 by a bulky trichromic trisheteroleptic cycloruthenated dye.
A cyclometalated Ru dye bearing two triphenylamine groups to augment light absorption exhibits a power conversion efficiency (PCE) in excess of 7% in the dye-sensitized solar cell despite having a large molecular footprint on TiO(2).


Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting in the Setting of Acute Coronary Syndrome.
After acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) is the standard of care for both invasive management with percutaneous intervention and noninvasive (medical) management. Conversely, studies using dual antiplatelet in the population of patients presenting with ACS who undergo coronary artery bypass grafting (CABG) are conflicting. The appropriate antiplatelet regimen after CABG remains an area of controversy. Plaque stability, prevention of graft closure, and secondary thrombosis form the basis for using a second antiplatelet drug, whereas the additional risk of bleeding and lack of conclusive evidence should also be considered. After an extensive literature search, 12 clinical trials with efficacy outcomes were identified. Most of the studies are retrospective, nonrandomized single-center trials. A few large patient populations have been examined using database information. To date, there is only 1 prospective, multicenter, randomized trial published. Recommendations from national guidelines differ, proposing single antiplatelet therapy with aspirin or DAPT with the combination of aspirin and clopidogrel. The purpose of this report is to review the available clinical trial data and provide guidance to practitioners when caring for this patient population. In conclusion, there is no clear consensus regarding the use of DAPT in patients after CABG. If not contraindicated, it is reasonable to use DAPT, starting in the postoperative period, in patients presenting with ACS. Large, multicenter, randomized clinical trials are needed to definitively investigate the role of DAPT in patients with ACS after CABG.


Biomechanical analysis of the shear behaviour adjacent to an axially loaded implant.
Good mechanical fixation of an implant to the surrounding bone is important for its longevity, and is influenced by both biological and mechanical factors. This study parametrically evaluates the mechanics of the interface with a computationally efficient analytic structural model of the shear stress field and global shear stiffness of an axially loaded implant. The utility of the analytic model was first established by validating its assumptions with a case-specific finite element model. We then used the analytic model for a sensitivity analysis of the relationship between the pattern of tissue growth and shear properties of the interface for our previously reported loaded in vivo experimental micromotion device. The bone located directly at the implant surface was found to be the most effective site for increasing interface stiffness. This suggests that the implant surface is the most desirable site for bone growth, yet is also the most mechanically challenging environment due to its maximal shear stresses. Thus, these findings support the further investigation of osteo-conductive coatings and other biological stimuli to overcome the challenging mechanics, and to promote bone growth directly at the implant surface. The model also demonstrated that the mechanical contribution to the global implant shear stiffness of a commonly observed isolated sclerotic bone rim is very limited. The results of this sensitivity analysis agree with experimental studies with the micromotion device, and with clinical studies reporting good results with osteo-conductive coatings.


Characterization of the expression profile of CRBP1 and CRBP3 gene in chicken.
In this study, we quantified the expression of CRBP1 and CRBP3 in Roman layer (R) and Erlang mountainous chickens (SD02 and SD03), to discern the tissue, breed and age-related expression patterns in order to discover potential involvement in egg production and other related reproduction traits. Real-time quantitative PCR assays were developed for accurate measurement of CRBP1 and CRBP3 mRNA levels in different tissues from chickens at four ages (12, 20, 32 and 45 weeks). We found that the CRBP1 and CRBP3 were expressed in all six tissues examined in all three breeds of chicken at 32 weeks. CRBP1 mRNA levels in SD02 kidneys were slightly higher than those in SD03 and R at 12 weeks, whereas, at the other three time points, the expression levels of CRBP1 in SD03 were higher than those in SD02 and R. In addition, there was higher hepatic expression of CRBP3 mRNA in layers (R) compared to broilers (SD02 and SD03) at 20 and 32 weeks. An age-related expression pattern of CRBP1 gene was evident in liver (P < 0.01), but not in pituitary (P > 0.05). Overall, the expression level of CRBP1 gene in kidney, ovary and oviduct at the different ages had a "decline-rise-decline" trend in all three breeds. In contrast, in pituitary, hypothalamus, liver and kidney CRBP3 mRNA expression levels were significantly different at various ages (P < 0.05) and exhibited a "rise-decline-rise" pattern in all three breeds. Our results show that the expression of CRBP1 and CRBP3 in chicken tissues exhibit specific developmental changes and age-related patterns.


Effect of kidney replacement therapy modality after first kidney graft failure on second kidney transplantation outcomes.
There is a lack of information regarding which is the best dialysis technique after kidney transplant (KT) failure. The aim of this study is to compare the effect of kidney replacement therapy modality-peritoneal dialysis (TX-PD-TX), haemodialysis (TX-HD-TX) and preemptive deceased donor retransplantation (TX-TX) on patient survival and second KT outcomes. A retrospective observational study from the Catalan Renal Registry was carried out. We included adult patients with failing of their first KT from 2000 to 2018. Among 2045 patients, 1829 started on HD (89.4%), 168 on PD (8.2%) and 48 (2.4%) received a preemptive KT. Non-inclusion on the KT waiting list and HD were associated with worse patient survival. For patients included on the waiting list, the probability of human leucocyte antigens (HLA) sensitization and to receive a second KT was similar in HD and PD. A total of 776 patients received a second KT (38%), 656 in TX-HD-TX, 72 in TX-PD-TX and 48 in TX-TX groups. Adjusted mortality after second KT was higher in TX-HD-TX patients compared with TX-TX and TX-PD-TX groups, without differences between TX-TX and TX-PD-TX groups. Death-censored second graft survival was similar in all three groups. Our results suggest that after first KT failure, PD is superior to HD in reducing mortality in candidates for a second KT without options for preemptive retransplantation.


In vitro siRNA-mediated GPX4 and AKT1 silencing in oxaliplatin resistance cancer cells induces ferroptosis and apoptosis.
Oxaliplatin is a member of platinum-based chemotherapy drugs frequently used in colorectal cancer (CRC). However, resistance to oxaliplatin causes tumor progression and metastasis. Akt1 and Gpx4 are essential regulator genes of apoptosis and ferroptosis pathways. Inhibition of these genes might eradicate oxaliplatin resistance in resistant CRC cells. We compared two cell death strategies to reverse drug resistance in Caco-2 and HT-29 oxaliplatin-resistant cell lines. We used the AKT1-specific siRNA to induce apoptosis. Also, GPX4-specific siRNA and FIN56 were utilized to generate ferroptosis. The effect of these treatments was assessed by reactive oxygen species (ROS) formation, cell viability, and protein expression level assays. Besides, the expression of GPX4, CoQ10, and NRF2 was assessed in both cell lines after treatments. Correctly measuring the expression of these responsible genes and proteins confirms the occurrence of different types of cell death. In addition, the ability of Akt1/ GPX4 siRNA in resensitizing HT-29 and Caco-2 oxaliplatin resistance cells was evaluated. Our finding showed that the upregulation of GPX4/siRNA caused a reduction in GPX4 and CoQ10 expressions in both cell lines. However, the expression level of NRF2 showed the same level in our cell lines, so we observed a downregulation of NRF2 in resistant CRC cell lines. Cell viability assay indicated that induction of ferroptosis by GPX4/siRNA or FIN56 and apoptosis by Akt1/siRNA in resistant cell lines could reverse the oxaliplatin resistance. We concluded that downregulation of Akt1 or Gpx4 could increase the efficacy of oxaliplatin to overcome the resistance compared to FIN56.


Two 5S rDNA arrays in neotropical fish species: is it a general rule for fishes?
In this paper we describe Southern blot hybridization results probed with 5S rRNA genes for several Neotropical fish species representing different taxonomic groups. All the studied species showed a general trend with the 5S rDNA tandem repeats organized in two distinct size-classes. At the same time, data on 5S rDNA organization in fish genome were summarized. Previous information on the organization and evolution of 5S rRNA gene arrays in the genome of this vertebrate group are in agreement with the Southern results here presented. Sequences obtained for several fish species have revealed the occurrence of two distinct 5S rDNA classes characterized by distinct nontranscribed spacer sequences, which are clustered in different chromosomes in some species. Moreover, the 5S rDNA loci are generally distributed in an interstitial position in the chromosomes and they are usually not syntenic to the 45S rDNA. The presence of two classes of 5S rDNA in several non-related fish species suggests that this could be a common condition for the 5S rRNA gene organization in the fish genome.


Expanded Milan criteria on pathological examination after liver transplantation: analysis of preoperative data.
We sought to evaluate the accuracy of imaging techniques related to the Milan criteria (MC) compared with the explant histology and the survival of these patients. Between 1997 and 2006, we selected 45 cirrhotic patients with hepatocellular carcinoma distributed into two groups according to explant histology: MC and Expanded Milan Criteria (EMC). Age, gender, preoperative imaging (ultrasound [US] and/or computed tomography [CT]), maximal tumor dimension, number of tumors, explanted histology, histology degree, alpha-fetoprotein (AFP) level and vascular invasion were compared among the patients to evaluate the value of these prognostic factors for survival after liver transplantation. By histology 42.2% explants were identified as EMC. The mean AFP level was 204.5 ng/mL. Vascular invasion was detected in 31.5% of explants and 68.4% showed incidental tumors. The survival rates after 10 years were 47.4% whereas MC patients showed 57.77%. The mean AFP level among MC patients was 150.2 ng/mL with vascular invasion detected in 7.7% of explants, and 47.4% with incidental tumors. The overall sensitivity of the imaging techniques was 83.3% for CT and 75% for US. The specificity was 96% for CT and 80.1% for US. Scan examinations in the preoperative evaluation underestimated about 42.2% of tumors. Those patients had vascular invasion but the survival after 10 years was similar between the ECM and MC groups.


Choline diet improves serum lipid parameters and alters egg composition in breeder ducks.
Choline is an important nutrient, playing key roles in numerous metabolic pathways relevant to animal health. The objective of this study was to evaluate the effect of dietary choline on the lipid parameters, cardiovascular health (CVH), and levels of egg trimethylamine (TMA) and cholesterol in breeder ducks during the late laying period. A total of 60 Jingjiang ducks were randomly separated into six replicates of 10 ducks each. After peak production until 65 weeks of age, the birds were fed a control basal diet. The same ducks served as the control group until 65 weeks of age, when the same ducks served as the choline-supplemented group, after 15 days of dietary choline supplementation at 2955 mg/kg choline above and over the basal diet initially provided. The 15 days of choline supplementation included an initial 5-day acclimatisation period. Dietary choline supplementation increased serum TMA (p < 0.01), high-density lipoprotein cholesterol, very low-density lipoprotein, and triglyceride levels in older breeder ducks. However, it did not change the levels of trimethylamine N-oxide but decreased the atherosclerosis index compared with those of the control group (p < 0.01). Moreover, it increased (p < 0.01) the egg yolk TMA levels but did not change the concentrations of cholesterol in egg yolk. Dietary choline supplementation had a beneficial effect on lipid parameters and CVH in older breeder ducks, although it increased the serum and egg yolk TMA levels.


On Plasmon Polariton Propagation Along Metallic Nano-Chain.
The collective wave type plasmon polariton self-modes in the metallic (Au, Ag) nano-chain were determined and analyzed with respect to the nano-sphere size and chain separation parameters. At some regions for parameters, the undamped modes were identified when the interaction had been assumed as the near-field-zone dipole coupling. These modes were found on the rim of stability of the linear theory, which indicates artifact of the model of near-field coupling. Inclusion of the medium- and far-field zone contributions to dipole interaction removes, however, instability and allows for fully analytical demonstration of quenching of irradiation losses of plasmon polaritons in the chain to the level of only ohmic attenuation. The plasmon polariton dispersion and the group velocity of plasmon polariton wave packets were examined with respect to nano-sphere and chain parameters and mode polarization. Previous numerical results related to long-range plasmon polariton propagation in the chain are transparently interpreted within the analytical approach.


Initial Post-Operative Visit Absenteeism is Associated With Worse Amputation-Free Survival after Tibial Angioplasty.
Tibial revascularization is often performed in the setting of critical limb ischemia and tissue loss requiring close patient monitoring in the early post-operative period for worsening gangrene and/or ischemia. Multiple studies have shown loss to follow-up is an independent risk factor for poor outcomes in several vascular procedures. Therefore, we evaluated the risk factors relating to loss to follow up against outcomes in patients undergoing tibial endovascular procedures with the hypothesis that poor post-operative visit compliance is associated with decreased amputation-free survival rates. We performed a single-institution retrospective chart review of patients who underwent therapeutic endovascular tibial revascularization between 2014-2018. Patient follow-up and outcomes of death or major amputation (trans-tibial/trans-femoral) were followed up to 36-months post-operatively. Patients who had undergone previous infra-geniculate interventions or reached mortality/major amputation within 30-days post-operatively were excluded from analysis. We identified 89 patients who met inclusion criteria. The overall rate of attendance at less than <1 month, 1-6 months, 6-15 months and 15-36 months post-operatively were 60%, 64%, 60 and 40% respectively. 16% of patients had complete loss to follow-up. Patients without tissue loss (≤ Rutherford 4) were less likely to attend early <1 month and 1-6 month follow-up intervals. Notably, absenteeism from the first immediate post-operative visit was a significant risk factor for further absenteeism at 1-6 months (51% vs. 26%; P = 0.01) and at greater than 6-month follow-up (48% vs. 31%; P = 0.05). Compared to the cohort of all patients, failure to follow-up within 1 month was associated with a decrease in attendance from 64% to 26% at 1-6 months and 63-31% at more than 6 months. Missing the first post-operative visit was also associated with decreased amputation-free survival (P = 0.04). Absenteeism from the first post-operative visit is associated with worse amputation-free survival and a significant risk factor for further absenteeism from post-operative care. Given these results, ensuring close immediate post-operative follow up is essential to improving outcomes in patients undergoing tibial revascularization.


The MS Choices Survey: findings of a study assessing physician and patient perspectives on living with and managing multiple sclerosis.
Treatment of multiple sclerosis (MS) with disease-modifying drugs (DMDs) can reduce relapse frequency and delay disability progression. Although adherence to DMDs is difficult to measure accurately, evidence suggests that poor adherence is common and can compromise treatment success. There are likely to be multiple factors underlying poor adherence. To better understand these factors, the global MS Choices Survey investigated patient and physician perspectives regarding key aspects of MS diagnosis, treatment adherence and persistence, and disease management. The survey was conducted in seven countries and involved patients with MS (age 18-60 years; MS diagnosis for ≥1 year; current treatment with a DMD) and physicians (neurologist for 3-30 years; treating ≥15 patients with MS per average month; >60% of time spent in clinical practice). Separate questionnaires were used for physicians and patients, each containing approximately 30 questions. Questionnaires were completed by 331 patients and 280 physicians. Several differences were observed between the responses of patients and physicians, particularly for questions relating to treatment adherence. Overall, the proportion of patients reporting taking a treatment break (31%) was almost twice that estimated by physicians (on average 17%). The reasons cited for poor adherence also differed between patients and physicians. For example, more physicians cited side effects as the main reason for poor patient adherence (82%), than responding patients (42%). Physicians may underestimate the scale of poor adherence to DMDs, which could impact on their assessment of treatment efficacy and result in inappropriate treatment escalation. In addition, disparities were identified between patient and physician responses regarding the underlying reasons for poor adherence. Improvements in the dialog between patients and neurologists may increase adherence to DMDs.


Surgical Outcomes in High-risk Prostate Cancer and Salvage Radical Prostatectomy.
Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered. To describe our experience with surgery of high-risk patients and SRP. This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes. Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed. Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.


Proof-of-concept for the detection of early osteoarthritis pathology by clinically applicable endomicroscopy and quantitative AI-supported optical biopsy.
Clinical trials for osteoarthritis (OA), the leading cause of global disability, are unable to pinpoint the early, potentially reversible disease with clinical technology. Hence, disease-modifying drug candidates cannot be tested early in the disease. To overcome this obstacle, we asked whether early OA-pathology detection is possible with current clinical technology. We determined the relationship between two sensitive early OA markers, atomic force microscopy (AFM)-measured human articular cartilage (AC) surface stiffness, and location-matched superficial zone chondrocyte spatial organizations (SCSOs), asking whether a significant loss of surface stiffness can be detected in early OA SCSO stages. We then tested whether current clinical technology can visualize and accurately diagnose the SCSOs using an approved probe-based confocal laser-endomicroscope and a random forest (RF) model. We demonstrated a correlation between AC surface stiffness and the SCSO (rrm = -0.91; 95%CI: -0.97, -0.73), and an extensive loss of surface stiffness specifically in those ACs with early OA-typical SCSO (95%CIs: string SCSO: 269-173 kPa, double string SCSO: 77-46 kPa). This established the SCSO as a visualizable, functionally relevant surrogate marker of early OA AC surface pathology. Moreover, SCSO-based stiffness discrimination worked well in each patient's AC. We then demonstrated feasibility of visualizing the SCSO by clinical laser-endomicroscopy and, importantly, accurate SCSO diagnosis using RF. We present the proof-of-concept of early OA-pathology detection with available clinical technology, introducing a future-oriented, AI-supported, non-destructive quantitative optical biopsy for early disease detection. Operationalizing SCSO recognition, this approach allows testing for correlations between local tissue architectures with other experimental and clinical read-outs, but needs clinical validation and a larger sample size for defining diagnostic thresholds.


A case of Takayasu arteritis causing subclavian steal and presenting as syncope.
The American Heart Association website defines syncope as "temporary loss of consciousness and posture." Syncope is a common presentation to the Emergency Department (ED). Although case reports of subclavian steal syndrome (SSS) from Takayasu arteritis (TA) and of TA causing syncope have been rarely reported in the literature, our MEDLINE search revealed no published description of the three entities of SSS, TA, and syncope presenting simultaneously. We then describe a case of a 48-year-old woman who presented to our ED with syncope and was found to have SSS. We describe the patient's hospital course leading to the diagnosis of TA, which is a rare form of vasculitis. Finally, we briefly discuss TA, explain the mechanism of SSS in TA, and outline the diagnostic criteria established by the American College of Rheumatology for TA.


Incorporation of nucleic acid and protein precursors in enriched populations of proliferating normal and leukemic cells.
Nucleic acid and protein synthesis was determined in immature myeloid cells isolated from seven normal bone marrow samples and compared to blasts from nine patients with fullblown acute non-lymphocytic leukemia. Samples obtained from normal bone marrow contained a mean of 82% immature myeloid cells with 29.9% S-phase cells. These cells incorporated [3H]thymidine with a mean of 17,500 counts/min [3H]uridine with a mean of 24,000 counts/min and [3H]leucine with a mean of 2100 counts/min per 0.2 x 10(6) cells. Leukemic bone marrow cells could be separated in fractions with different proliferative activities. Leukemic samples with a mean of 3.6% S-phase cells incorporated [3H]thymidine with a mean of 1100 counts/min, [3H]uridine with a mean of 15,700 counts/min and ]3H]leucine with a mean of 2600 counts/min per 0.2 x 10(6) cells. For leukemic samples with a mean of 30.6% S-phase cells these values were: [3H]thymidine 22,200 counts/min, [3H]uridine 49,700 counts/min and [3H]leucine 6700 counts min per 0.2 x 10(6) cells. The incorporation studies were carried out for the first time in normal and leukemic cells with a comparable proliferative activity. Non-lymphocytic leukemic blastic cells showed a two-fold increase in RNA synthesis and a three-fold increase in protein synthesis compared to enriched samples of normal early myeloid cells with the same proliferative activity.


Innovations. DNA detectives.
To understand the many potential causes and resulting consequences of DNA damage, scientists first need methods to detect it. Canadian scientists X. Chris Le and Michael Weinfeld, with help from U.S. molecular biologist Steven Leadon, developed a selective, sensitive technique for measuring DNA damage. The scientists combined a thymine glycol antibody with thymine glycol to selectively tag a specific type of DNA damage. They then added a second antibody with fluorescing properties, and used laser-induced fluorescence to identify the damaged portion of the tagged DNA. The fluorescence can be quantified, with higher levels of fluorescence indicating higher DNA damage. The technique was shown to find 1 damaged base in 1 billion normal bases. This level of sensitivity could allow the measurement of DNA damage resulting from clinical levels of radiation, and may allow scientists to establish a day-to-day baseline for DNA damage. From this baseline, it would be possible to ascertain the levels of damage that a cell can tolerate, as well as how much damaged it is capable of repairing on a daily basis.


Neuropsychological testing in skilled nursing facilities: the failure to confirm diagnoses of dementia.
To investigate to what degree dementia diagnoses of record in skilled nursing facilities (SNFs) are supported by objective neuropsychological testing data. Retrospective analysis of ongoing neuropsychological testing data Nursing facilities in New York state (n = 11) Nursing home residents (n = 73) Neuropsychological testing Standardized neuropsychological testing instruments that included the Cognistat neurobehavioral status examination, the Dementia Rating Scale-2 (DRS-2), the Wechsler Abbreviated Scale of Intelligence (WASI), and the battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD battery). A total of 41 males and 32 females were examined. Of those tested, 10 residents were not suspected of having dementia, but required testing to ascertain the nature of certain cognitive complaints presented. Of the remaining residents, 44 had an established diagnosis of dementia in their medical records, and 19 were referred because of a suspicion of dementia, but with no established diagnosis in the record. Based on data from the testing studies, of those with established diagnoses, only 17 (38.6%) met criteria for dementia, while with those with "suspected" dementia, only 3 of the 19 referred (15.7%) met criteria. Of those that did not meet criteria but had an established dementia diagnosis in the record, about half met criteria for "Mild Cognitive Impairment" (MCI), a possible "predementia" condition that involves memory disturbance, but no other cognitive disability. The remaining half met criteria for an Axis I diagnosis, which, in this sample, included mostly depressive disorder, but also cases of anxiety and noncompliance. For those with "suspected" dementia, the overwhelming majority (84.2%) did not meet criteria for a dementia diagnosis, with 75% of those residents meeting criteria for an Axis I diagnosis and 25% meeting criteria for MCI. Only 3 of the 19 "suspected" cases (15.7%) actually met criteria for dementia, according to DSM-IV criteria. Dementia diagnoses may be inaccurate for many nursing home residents. Using objective measurement of cognitive functioning provided by neuropsychological testing could result in greater diagnostic accuracy and help provide for more accurate and appropriate treatment planning.


Congenital adrenal hyperplasia in females with virilized genitalia: the problem of delayed diagnosis.
Six girls with the non-salt-losing form of congenital adrenal hyperplasia are described. Diagnosis was delayed in five, the range of ages of diagnosis being 19 months-7 years. In the sixth, despite early diagnosis and medical treatment, surgery was delayed electively until she was 3 years old. The five in whom diagnosis was delayed were all virilized with a markedly advanced bone age and reduced adult height prognosis. Diagnosis was delayed for a variety of reasons: misinterpretation of laboratory data (one), lack of availability of medical assistance (one), language problems (one), maternal inexperience (one), and failure of the doctor to recognize an obvious clinical abnormality (one). All six children came from immigrant families, and all except one was born in a major centre. None was born before 1979.


Freeze-fracture for scanning electron microscopy.
Two different freeze-fracture methods are explored for preparation of biological material for scanning electron microscopy. In the simpler method the tissues are first fixed and dehydrated. They are then frozen and fractured, and after thawing, critical-point dried. This method has already been used in a number of studies of animal tissues (heart, liver, kidney). It is applied here to the examination of plant material (leaf mesophyll cells). In the second method tissues, or cells, are first infiltrated with cryoprotectant (dimethylsulphoxide) then frozen and fractured, and not fixed until after thawing. The fixed tissues are finally dehydrated and critical-point dried. This method also has previously been used in the study of animal tissues, and is applied here to carrot protoplasts, chicken erythrocytes, and leaf mesophyll cells.


Kallikrein and amylase contents in tissues from a mutant mouse model for human cystic fibrosis.
Kallikrein and amylase activities are decreased in the pancreas and salivary glands from cri/cri homozygote mutant mice. Kallikrein is decreased in the cri/cri kidney too. With reference to nucleic acid concentrations there is no difference between control and mutant mice. The previously described electrolyte abnormalities of the cribriform degeneration (cri) mutant mouse, could be due to the abnormal activity of the kallikrein-kinin system on the transport mechanism of tubular cells in the organs mentioned. These findings represent a new step on our efforts to develop a useful animal model for human cystic fibrosis research.


Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis.
Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, lung ILC2s are hypothesized to coordinate epithelial responses to the external environment; however, how barrier surveillance is linked to ILC2 activation remains unclear. Here, we demonstrate that alveolar type II cells are the main source of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) generated in response to chitin or migratory helminths. IL-33 and TSLP synergistically induce an interferon regulatory factor 4 (IRF4)-IL-9 program in ILC2s, and autocrine IL-9 promotes rapid IL-5 and IL-13 production required for optimal epithelial responses in the conducting airways. Thus, ILC2s link alveolar function to regulation of airway flow, revealing a key interaction between resident lymphoid and structural cells that might underlie similar organizational hierarchies in other organs.


A method for simple identification of signature peptides derived from polyUb-K48 and K63 by MALDI-TOF MS and chemically assisted MS/MS fragmentation.
A simple method is described to identify signature peptides derived from polyubiquitin (polyUb) chains. The method is based on MALDI-TOF MS/MS analysis after chemically assisted fragmentation, and works on peptides isolated from polyacrylamide gels. PolyUb chains branched at K48 and K63 were chosen as models for Ub-protein conjugates. They were resolved by SDS-PAGE, and their tryptic peptides (in-gel-trypsinolysis) derivatized with 3-sulfopropinic acid NHSester to obtain chemically assisted fragmentation during the MS/MS analysis. PolyUb-K63 produced a single peptide identified as (55)TLSDYNIQK(63) (GG)ESTLHLVLR(72). PolyUb-K48 produced two branched signature peptides identified as (43)LIFAGK(48)(GG)QLEDGR(54) and (43)LIFAGK(48)(LRGG)QLEDGR(54). The recovery of signature peptide with LRGG as branched chain underscores the need to take limited proteolysis into account in the search for detection of ubiquitinated peptides in proteomics studies. In conclusion, a simple method has been described allowing the identification of signature peptides, which are diagnostic markers of the majority of polyUb-conjugated proteins. In principle, the method should be applicable also for other more rare signature peptides.


Central neurocytoma responsive to topotecan, ifosfamide, carboplatin.
A 5-year-old male presented with spinal cord drop metastasis from a recurrent neurocytoma. Topotecan (0.5 mg/m(2)) and carboplatin (250 mg/m(2)) were administered on days 1-3 and ifosfamide (1,800 mg/m(2)) on days 1-5, every 21 days, for three cycles and resulted in complete response without severe complications. A literature review yielded 20 patients with central neurocytoma but no complete responses. The complete response of central neurocytoma to chemotherapy only reported here should be helpful to those caring for patients with this rare tumor.


Outpatient laparoscopic appendectomy.
Laparoscopy has allowed surgeons the ability to perform procedures which result in less postoperative discomfort, earlier return to daily activities, and better cosmesis. For example, laparoscopic cholecystectomy has virtually replaced open cholecystectomy, and many of these operations are performed in the outpatient setting. The role of laparoscopic appendectomy is yet to be defined, however. Over an 18-month period from February 1992 to July 1993, 75 laparoscopic appendectomies were performed at Kaiser Permanente Medical Center in Los Angeles. Thirty-five of the patients undergoing this procedure were outpatients. While there were a total of three complications, including two intraabdominal abscesses, there were no complications in the outpatient appendectomy group. Laparoscopic appendectomy may be safely performed in the outpatient setting in patients with acute nonperforated appendicitis.


Hypoglycaemic effect of Helicteres isora bark extract in rats.
The hypoglycaemic effect of the aqueous extract of the bark of Helicteres isora L. (Sterculiaceae) was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the bark of Helicteres isora L. (100 and 200 mg/kg/p.o.) significantly (P<0.001) reduced the blood glucose levels from 64.5-48.5 and 67-47 mg% 2h after oral administration of bark extract and also significantly lowered the blood glucose in STZ diabetic rats from 68-105 and 66-85.5 mg% 21 days after daily oral administration of the extract (P<0.001). The results suggested that the aqueous extract of bark of Helicteres isora L. possesses a potential hypoglycaemic effect in diabetic rats.


Rigid motion-resolved B1+ prediction using deep learning for real-time parallel-transmission pulse design.
Tailored parallel-transmit (pTx) pulses produce uniform excitation profiles at 7 T, but are sensitive to head motion. A potential solution is real-time pulse redesign. A deep learning framework is proposed to estimate pTx B1+ distributions following within-slice motion, which can then be used for tailored pTx pulse redesign. Using simulated data, conditional generative adversarial networks were trained to predict B1+ distributions in the head following a displacement. Predictions were made for two virtual body models that were not included in training. Predicted maps were compared with ground-truth (simulated, following motion) B1 maps. Tailored pTx pulses were designed using B1 maps at the original position (simulated, no motion) and evaluated using simulated B1 maps at displaced position (ground-truth maps) to quantify motion-related excitation error. A second pulse was designed using predicted maps (also evaluated on ground-truth maps) to investigate improvement offered by the proposed method. Predicted B1+ maps corresponded well with ground-truth maps. Error in predicted maps was lower than motion-related error in 99% and 67% of magnitude and phase evaluations, respectively. Worst-case flip-angle normalized RMS error due to motion (76% of target flip angle) was reduced by 59% when pulses were redesigned using predicted maps. We propose a framework for predicting B1+ maps online with deep neural networks. Predicted maps can then be used for real-time tailored pulse redesign, helping to overcome head motion-related error in pTx.


Medical retrieval of pregnant women in labour: A scoping review.
Remote Australian women in labour often rely on retrieval services to allow birthing in specialist obstetric centres. However, there is currently debate over when not to transfer a woman in labour, for risk of an in-transit birth, associated with worse neonatal outcomes. A scoping review methodology was undertaken, to define the scope of published literature on the topic and identify gaps in the current knowledge. A total of seven full texts were deemed suitable for synthesis, which were all retrospective observational studies. Four themes from the studies' findings were identified: population features, predicting time-to-birth, use of tocolysis and birth during medical evacuation. The evidence identified in this review was of low methodological quality and heterogenous. The key findings were that births in-flight are rare, despite geographical distances and long transport times, with a knowledge gap on predictors of time-to-birth.


Effect of the change of mechanical ventilation mode on cerebral oxygen saturation level in neonates.
This study aimed to apply near-infrared spectroscopy (NIRS) to monitor cerebral oxygen saturation (SrO2) level in neonates before and after the change of mechanical ventilation mode, and thus, the effects of the change of mechanical ventilator mode on SrO2 level in neonates were assessed. This trial was designed as an observational study .A total of 70 neonates who were admitted to the Department of Neonatology of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China) between September 2019 and October 2021 and required respiratory support were included. The variations of SrO2 level before and after the change of mechanical ventilation mode, including changing from Synchronized intermittent mandatory ventilation (SIMV) to noninvasive ventilation (NIV, group 1), and from NIV to oxygen inhalation (group 2), were monitored by Enginmed EGOS-600 A. The changes of SrO2 level at 30 min before and 1 h after the change of ventilation mode were compared between the two groups. The SrO2 level in the group 1 30 min before, as well as 10 min, 30 min, and 1 h after the change of ventilation mode was 62.54 ± 3.36%, 65.43 ± 3.98%, 64.38 ± 4.23%, and 64.63 ± 3.71%, respectively. The SrO2 level at all the points after the change of ventilation mode increased compared with 30 min before the change (P < 0.05). The SrO2 level in the group 2 at each time point was 62.67 ± 4.69%, 64.61 ± 5.00%, 64.04 ± 4.48%, and 64.55 ± 4.32%, respectively. Compared with 30 min before ventilator weaning, the SrO2 level at all the points after ventilator weaning increased (P < 0.05). Peak inspiratory pressure (PIP) excluding Nasal Continuous Positive Airway Pressure (NCPAP)) in group 1 was lower than that before extubation, and the difference was statistically significant (P = 0) (Table 7). SrO2 level showed an increasing trend after the change of ventilation mode, and the increase of SrO2 level at 10 min after the change of ventilation mode was the most prominent. From SIMV to NIV, increased SrO2 levels may be associated with decreased PIP.


Synthesis of 2-((2-(Benzo[d]oxazol-2-yl)-2H-imidazol-4-yl)amino)-phenols from 2-((5H-1,2,3-Dithiazol-5-ylidene)amino)phenols through Unprecedented Formation of Imidazole Ring from Two Methanimino Groups.
A new synthetic pathway to four substituted imidazoles from readily available 2-((4-aryl(thienyl)-5H-1,2,3-dithiazol-5-ylidene)amino)phenols has been developed. Benzo[d]oxazol-2-yl(aryl(thienyl))methanimines were proved as key intermediates in their synthesis. The formation of an imidazole ring from two methanimine derivatives likely includes the opening of one benzoxazole ring followed by ring closure by intermolecular nucleophilic attack of the N-methanimine atom to a carbon atom of another methanimine.


Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair.
Submucosal collagen is paramount for colonic anastomotic integrity. Matrix metalloproteinases (MMPs) mediate collagen degradation that increases the risk of wound dehiscence. Although broad-spectrum MMP inhibitors are beneficial for anastomotic strength, they can cause adverse reactions. Knowledge of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic repair. Left-sided colonic anastomoses were made in male Sprague-Dawley rats. After 3 days when biomechanical strength is lowest, MMP mRNA and protein levels were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays and gelatin zymography. The effects of the MMP-8, MMP-9 and MMP-12 synthetic inhibitor AZD3342 was also studied. MMP-8, MMP-9 and MMP-12 gene and protein expression increased profoundly (p < 0.01), and MMP-13 mRNA and MMP-2 mRNA and protein modestly (p < 0.001) in the anastomoses. MMP-3 mRNA levels were not up-regulated significantly compared with adjacent uninjured colon. Increased anastomotic MMP-12 levels paralleled macrophage infiltration by immunohistochemical analyses. AZD3342 (50 mg/kg) treatment increased the anastomotic breaking strength by 29% (p = 0.015) day 3 compared with vehicle. Improved anastomotic strength was not accompanied with alterations of type I or type III procollagen mRNA but was possibly due to inhibition of the concerted digestive action on the existent submucosal collagens by the targeted MMPs. The present findings justify the concept of selective MMP inhibition to enhance anastomotic strength in colon.


New cytotoxic flavonoids from Thelypteris torresiana.
During our search for anti-tumor agents from pteridophytes, three new flavonoids, protoapigenone (1), 5',6'-dihydro-6'-methoxyprotoapigenone (2), and protoapigenin (3), along with four known compounds, protoapigenin 4'- O-beta- D-glucoside (4), apigenin 4'- O-beta- D-glucoside (5), kaempferol 3- O-alpha- L-rhamnopyranoside (6), kaempferol 3,7-di- O-alpha- L-rhamnopyranoside (7), were isolated from Thelypteris torresiana using bioactivity-guided fractionation methods . The structures of the new isolates were elucidated by 1D- and 2D-NMR spectral analysis. Among the 7 compounds, protoapigenone (1) exhibited significant anti-tumor activities toward Hep G2, Hep 3B, MCF-7, A549, and MDA-MB-231 with IC50 values of 1.60, 0.23, 0.78, 3.88 and 0.27 microg/mL, respectively.


Natural and synthetic modulators of SK (K(ca)2) potassium channels inhibit magnesium-dependent activity of the kinase-coupled cation channel TRPM7.
Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a bifunctional protein comprising a TRP ion channel segment linked to an α-type protein kinase domain. TRPM7 is essential for proliferation and cell growth. Up-regulation of TRPM7 function is involved in anoxic neuronal death, cardiac fibrosis and tumour cell proliferation. The goal of this work was to identify non-toxic inhibitors of the TRPM7 channel and to assess the effect of blocking endogenous TRPM7 currents on the phenotype of living cells. We developed an aequorin bioluminescence-based assay of TRPM7 channel activity and performed a hypothesis-driven screen for inhibitors of the channel. The candidates identified were further assessed electrophysiologically and in cell biological experiments. TRPM7 currents were inhibited by modulators of small conductance Ca²⁺ -activated K⁺ channels (K(Ca)2.1-2.3; SK) channels, including the antimalarial plant alkaloid quinine, CyPPA, dequalinium, NS8593, SKA31 and UCL 1684. The most potent compound NS8593 (IC₅₀ 1.6 µM) specifically targeted TRPM7 as compared with other TRP channels, interfered with Mg²⁺ -dependent regulation of TRPM7 channel and inhibited the motility of cultured cells. NS8593 exhibited full and reversible block of native TRPM7-like currents in HEK 293 cells, freshly isolated smooth muscle cells, primary podocytes and ventricular myocytes. This study reveals a tight overlap in the pharmacological profiles of TRPM7 and K(Ca)2.1-2.3 channels. NS8593 acts as a negative gating modulator of TRPM7 and is well-suited to study functional features and cellular roles of endogenous TRPM7.


Anti-hyperlipidemic constituents from the bark of Shorea roxburghii.
The methanol extract from the bark of Shorea roxburghii (Dipterocarpaceae, "Phayom" in Thai) was found to suppress plasma triglyceride elevation in olive oil-treated mice, and also to inhibit pancreatic lipase activity (IC(50) = 31.6 μg/ml). From the extract, two new 3-acetyl-4-phenyl-3,4-dihydroisocoumarins, phayomphenols A(1) (1) and A(2) (2) were isolated, together with 22 known compounds. The structures of 1 and 2 were elucidated on the basis of chemical and spectroscopic evidence, including X-ray crystallographic analysis. Among the isolates, several oligostilbenoids, including (-)-hopeaphenol (3) and (+)-isohopeaphenol (4), showed inhibitory effects on plasma triglyceride elevation at a dose of 200 mg/kg p.o. and pancreatic lipase inhibitory activity (IC(50) = 32.9 and 26.5 μM, respectively).


Selective effects of apomorphine on dorsal raphe neurons: a cytofluorimetric study.
Using a quantitative cytofluorimetric method to detect changes in the intracellular levels of serotonin (5-HT) in individual neurons in rat brain, we have found that the dopaminergic agonist apomorphine increases 5-HT content of dorsal raphe cell bodies without affecting cells in the median raphe nucleus. Liquid chromatographic studies revealed that apomorphine also elevated the concentrations of both 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in striatum, the projection site for dorsal raphe neurons. Conversely, the dopaminergic antagonist haloperidol, at a dose of 0.8 mg/kg, decreased 5-HT levels in dorsal raphe cells. A lower dose of haloperidol (0.4 mg/kg), which had no significant effect alone, completely blocked the effect of apomorphine in the dorsal raphe. These results support the hypothesis that the effects of apomorphine on serotonergic neurons are secondary to dopamine receptor stimulation.


Neutrophil priming, caused by cell membranes and microvesicles in packed red blood cell units, is abrogated by leukocyte depletion at collection.
BACKGROUND AND OBJECTS: Lipids with platelet activating factor (PAF)-like activity in supernatant of packed red blood cells (PRBC) cause priming of the neutrophil respiratory burst. This effect increases with length of storage. Washing of PRBC has been considered as a means to eliminate this effect; however, the role of the cellular component was not evaluated independently of the supernatant. The source of the inflammatory lipids of the supernatant is likely to be cell membranes altered during ageing in storage and therefore, washing will not eliminate neutrophil priming caused by transfusion of aged PRBC units. The ability of washed PRBC to prime mononuclear cells for another known effect of PAF, the production of IL-8, and the probability that this lipid activity is present on microparticles in PRBC supernatant were also investigated. At collection 10 units of whole blood were split into two equal aliquots one filtered and one unfiltered. PRBC were prepared and stored at 4 degrees C in CPD-AS5. Each week, fresh neutrophils were incubated with samples of washed PRBC and fixed. Change in CD11b, a marker known to increase on the surface of primed neutrophils, was determined by flow cytometry. To determine whether neutrophil priming ability of PRBC supernatant is contained on microvesicles, centrifuged and uncentrifuged supernatant samples were incubated with fresh neutrophils and change in CD11b expression was determined. Plasma IL-8 levels were also measured after exposure of monocytes from fresh whole blood to filtered and unfiltered washed PRBC with and without the addition of fMLP. Washed PRBC caused a 50-116% increase in CD11b neutrophil surface expression over baseline expression. Filtration of whole blood at collection reduced this CD11b up-regulation by 25-34%. Reduction of priming ability by filtration began on the day of collection and persisted for the storage life of the units. Centrifugation resulted in a reduction of CD11b up-regulation of 11-28% compared with unspun supernatant. Incubation of unfiltered PRBC resulted in priming of mononuclear leukocytes for IL-8 production with a 73-109% increase over baseline, but no increase over baseline was seen for incubation with filtered blood. Washing does not eliminate the ability of PRBC units to prime neutrophils and mononuclear cells, because the cellular component of PRBC, in addition to the supernatant, induces priming. Leukodepletion filters significantly reduce these effects compared with unfiltered PRBC. The in vitro beneficial effect of filtration lasts for the shelf life of 42 day units. The ability of PRBC supernatant to prime neutrophils is present on microvesicles.


Uncoupling of blood flow and metabolism in focal epilepsy.
Interictal measurements of cerebral blood flow are less helpful in localizing epileptic foci than are measurements of brain metabolism. This may be related to an uncoupling of blood flow and metabolism. In this study, brain metabolism and blood flow were compared in an acute experimental model of focal interictal epilepsy. Interictal epileptic foci were induced by an epicortical application of penicillin in rats. After 1 h, stereotyped interictal activity was initiated, lasting until the end of the experiment. Brain metabolism was determined with [14C]deoxyglucose, and cerebral blood flow with [14C]iodoan-tipyrine autoradiography. In control experiments, metabolism and blood flow were coupled. In animals with focal interictal epileptic activity, the metabolism was strongly increased in the focus and reduced in areas lateral to the focus. In contralateral brain areas, blood flow and metabolism varied in a parallel fashion. Ipsilateral to the focus, however, blood flow and metabolism were altered disproportionately. In the focus, the increase of blood flow was less marked than the increase of metabolism, and the area with increased blood flow was larger than the area with increased metabolism. Lateral to the focus, in the area with a hypometabolism, blood flow was not concomitantly reduced. The experiments show that blood flow and metabolism in focal epilepsy may be uncoupled in widespread regions. This is due neither to structural abnormalities nor to the duration or discharge pattern of epileptic activity. The results explain why interictal metabolic investigations have a higher predictive value in presurgical epilepsy evaluation than do interictal measurements of blood flow.


Intracellular Lipid Levels and Oxidative Stress in Peripheral Blood Mononuclear Cells in Experimental Type 1 Diabetes Mellitus.
Type 1 diabetes mellitus was modeled in Wistar rats by intraperitoneal injection of streptozotocin (25 mg/kg for 5 days), which led to the appearance of the main symptoms of insulin-dependent diabetes. In peripheral blood mononuclear cells isolated by centrifugation on a Ficoll density gradient, the production of ROS and the level of intracellular lipids were evaluated by flow cytofluorimetry. In rats with type 1 diabetes mellitus, an increase in ROS levels in isolated peripheral blood monocytes, but not in the lymphocytic fraction was revealed. Incubation of isolated monocytes in a medium containing 1 mM oleic acid led to a 1.5-fold increase of intracellular lipid levels. After incubation of the lymphocyte fraction in this medium, no differences from the control were revealed. Disorders of carbohydrate and lipid metabolism in type 1 diabetes mellitus leading to an increase of free fatty acids and ROS levels can be detected ex vivo in isolated peripheral blood mononuclear cells.


Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children.
Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-β%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score (-0.58 (-0.66; -0.50)), triglycerides (-0.35 (-0.45; -0.25) mmol/L) and triglyceride glucose index (-0.29 (-0.37; -0.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome.


Azteca protection of Cecropia: ant occupation benefits juvenile trees.
In this 15 month investigation I experimentally demonstrated that sapling Cecropia aff. obtusifolia in lowland western Ecuador grow more vigorously when occupied by the ant Azteca constructor than when the ants have been removed. Thus the interaction is directly beneficial to Cecropia juveniles. The difference in growth is associated with differences in herbivory and vine cover. Removal of ants significantly increases nocturnal Coleoptera herbivory on unoccupied plants. In contrast to the influence on beetle numbers, Azteca are ineffective against Homoptera and cecidomyiid gall flies. Although ant-occupied saplings had less chewing herbivore damage throughout the study, the ants were more effective protectors in the dry season than in the rainy season, when herbivore pressure increased. In addition to reducing herbivory, Azteca efficiently remove vines from occupied saplings.


Gunshot pellet embolus to the middle cerebral artery.
A 24-year-old man sustained a gunshot wound to the upper right hemithorax and neck, with injury to the subclavian and carotid arteries. A cerebral artery pellet embolus resulted in contralateral hemiplegia. The injured vessels were repaired, but the middle cerebral artery pellet was left undisturbed. Neurologic improvement occurred. Fifteen cases of foreign body embolus to cerebral vessels are reviewed and the management of this unusual injury is discussed.


The effect of working memory capacity and training on intertemporal decision making in children from low-socioeconomic-status families.
Individuals differ in their tendency to discount delayed rewards. Low socioeconomic status (SES) has been found to be associated with strong delayed reward discounting (DRD), which in turn contributes to risky decision making and adverse behaviors. However, research on possible cognitive mediators of the negative association between SES and DRD, and on effects of cognitive training in low-SES adolescents, is largely lacking. In examining Chinese adolescents (aged 11-15 years; N = 207), Study 1 assessed which aspect of working memory (WM)-simple maintenance, simple manipulation, or updating-serves as mediator, which proved to be WM updating. Based on this outcome, in Study 2 Chinese adolescents (aged 12-14 years; N = 73) with low family SES were assigned to a WM updating training condition or a control condition. All participants performed DRD and WM tasks before and after treatment. The trained adolescents showed positive training effects on DRD, and this effect was specifically correlated with beneficial training effects on performance on a WM updating transfer task. These results support the role of WM updating in DRD and might inform training programs to promote more favorable decision making in low-SES adolescents.


A comparative study of intravenous cannulae--'Venflon' with valved sideport and 'Intraflux' with membranous sideport.
The rate of contamination of the inner surface of 'Venflon' type cannulae with valved injection sideports was compared with that of 'Intraflux' type cannulae with membranous injection sideports. Of 46 'Venflon' cannulae and 34 'Intraflux' cannulae, 17.4 per cent and 20.6 per cent, respectively, were contaminated and no correlation of contamination of lumen was found with frequency of use of the sideports in the different cannulae, or with duration of use of the cannulae.


The social distribution of explanations of health and illness among adolescents in São Paulo, Brazil.
The present paper reports on a study, which investigated explanations of health and illness among adolescents from three socio-economic backgrounds in São Paulo, Brazil. Interviews and group discussions were used to elicit definitions of health and illness, explanations of illness causality and prevention and maintenance of health among 31 deprived adolescents with recent experience of living on the streets, 20 adolescents from poor families and 20 adolescents from privileged families. The findings showed that adolescents from different socio-economic conditions draw upon similar explanatory models to make sense of health and illness. There were also clear distinctions between the groups. Health and illness were presented as being dependent upon multiple factors such as resistance of the body and socio-economic status among privileged adolescents. In contrast, the explanations offered by deprived and poor adolescents for both health and illness rested on behaviour or exposure to environmental hazards. Moreover, drugs, sexually transmitted diseases and faith in God were prominent features of the accounts from deprived adolescents. The findings suggest a need for health professionals to be sensitive to people's perspectives of health and illness and their link to socio-economic conditions. To emphasize individuals' behaviour in the provision of health-related information among deprived adolescents might be counter productive and reinforce victim blaming.


Correlation between intra-abdominal and intracranial pressure in nontraumatic brain injury.
To examine on the basis of a large number of measurements whether increased IAP is associated with increased ICP and decreased CPP in ventilated patients with nontraumatic brain injury. Observational clinical study in the medical and surgical intensive care unit of a tertiary teaching hospital. We included 11 patients with nontraumatic brain injury who had an ICP and an IAP-monitoring device because of ischemic (n=4), hemorrhagic (n=5), and metabolic (n=2) encephalopathy. IAP was continuously measured in the stomach, and ICP was continuously measured through an intraventricular catheter; 214 consecutive measurements were compared. Because of repeated measurements in the patients we used analysis of covariance to control for the variation in ICP and CPP between patients. Patients' mean IAP was 3.8-11.8 mmHg, ICP 6.7-15 mmHg, and CPP 70.8-123 mmHg. For ICP the regression coefficient associated with IAP was 0.64+/-0.05 (95% CI 0.56-0.73, partial correlation 0.70) and for CPP -1.36+/-0.3 (95% CI -1.94 to -0.78; partial correlation -0.30). Increases in IAP are associated with increases in ICP and decreases in CPP in ventilated patients with nontraumatic brain injury, even at low levels of IAP.


Teaching complementary medicine at an academic oncology department.
The increased use of complementary and alternative medicine (CAM) by patients with cancer is a significant phenomenon in cancer care and suggests the need for increased knowledge by clinicians of these therapies. Aiming at bridging the gap in knowledge of the philosophy and practice of major CAM modalities in cancer care, an elective course was offered to physicians and nurses in a large academic center. The course also aimed at providing the tools necessary to establish open and trusting clinician-patient dialogue regarding CAM. Exposure to the course was successful in improving knowledge and attitudes.


Molecular dynamics through 2H spin-lattice relaxation time measurements with an enzyme-inhibitor complex: lysozyme and methyl N-acetyl glucosaminides.
Deuteron spin-lattice relaxation times of specifically labelled methyl N-acetyl-D-glucosaminides associated to lysozyme were measured from 1H and 2H NMR spectra through bandshape analysis and FT inversion-recovery technique, respectively. Model calculations were carried out in order to assess the limits of the extreme narrowing approximation for the systems studied. Rotational correlation times of the acetamido methyl groups were analyzed in terms of anisotropic overall reorientation combined with internal rotation. The acetamido methyl group undergoes fast internal rotation in the alpha-glycoside complex about an axis nearly parallel with the major ellipsodial axis of lysozyme. More rotational freedom is likely to occur in the beta-glycoside complex.


School and electronic bullying among adolescents: Direct and indirect relationships with sadness, sleep, and suicide ideation.
Bullying is an increasing concern for education, health, and policy. Adolescence is a particularly vulnerable period for the development of depressive symptoms and suicidality following exposure to bullying. However, limited research investigating the potential impact of depressive symptoms on the bullying-suicide relationship exists. Using national data (N = 13,677) from the most recent 2019 Youth Risk Behavior Survey, the aim of the present study was to examine the prevalence among adolescents' (school/electronic) bullying victimization, depressive symptoms (sadness; sleep), and suicide ideation as well as their associations including direct and indirect relationships including exploring differences by gender and race/ethnicity. Descriptive results indicated an increase in the prevalence of adolescents being bullied (both on school property and electronically), experiencing feelings of sadness, and hopelessness as well as a decrease in getting more than 8 h of sleep between 2017 and 2019. In 2019, over one-third of respondents felt sad or hopeless almost every day for 2 weeks or more in a row, which stopped them from doing some usual activities. Structural equation modeling indicated that (school/electronic) bullying was directly associated with feelings of sadness/hopelessness and suicide ideation, with sadness mediating the link between bullying and suicide ideation. Now more than ever, it is critical to promote the collaboration between educators, mental health specialists, policymakers, and researchers to develop and implement evidence-based strategies and approaches to preventing and reducing both bullying victimization and the associated psychological distress and mental health outcomes.


Identification of a GABA-activated chloride-mediated synaptic potential in rat pars intermedia.
Intracellular recordings from melanotrophs in acutely isolated, intact pituitaries revealed inhibitory postsynaptic potentials (IPSPs) resulting from both pituitary stalk stimulation and exogenous gamma-aminobutyric acid (GABA) application. The stalk-stimulated and GABA-evoked IPSPs displayed identical conductance increases to chloride ions. Both responses reversed in polarity at the same membrane potential and were blocked with bicuculline, a GABAA antagonist. We conclude that activation of this synapse releases GABA which acts on a classical GABAA receptor to increase conductance to chloride in the melanotroph.


Differences in contributory factors among hemicentral, central, and branch retinal vein occlusions.
Hemicentral retinal vein occlusion (HRVO) is an anatomic variant of central retinal vein occlusion (CRVO) and thus different from branch retinal vein occlusion (BRVO). Therefore, the risk factors for HRVO should be similar to those of CRVO and different from those of BRVO. To test this, the authors compared 15 demographic and clinical variables of 28 HRVO patients with those of 117 CRVO and 214 BRVO patients. Mean age of onset and sex ratio were not significantly different among the groups. Elevated erythrocyte sedimentation rate (ESR) (P = 0.019) and elevated intraocular pressure (IOP) (P = 0.025) were significantly more prevalent in the HRVO than the BRVO group. In addition, when the authors compared CRVO with BRVO, elevated ESR (P = 0.003), elevated IOP (P = 0.015), and positive purified protein derivative (PPD) (P = 0.003) were significantly more prevalent in the CRVO than the BRVO group, whereas hypertension (P = 0.03) and hyperopia (P = 0.008) were significantly more prevalent in the BRVO group. However, of the variables tested between HRVO and CRVO patients, no significant differences were found.


A translational rat model to assess glomerular function changes with vancomycin.
Vancomycin (VAN) causes acute kidney injury as defined by serum creatinine (SCr) increase. Glomerular filtration rate (GFR) is the gold standard for defining kidney function, and SCr is often used as a GFR surrogate; however, SCr changes can lag behind acute functional decline. We sought to define the rate and extent of GFR change for VAN in a translational rat model. Male Sprague Dawley rats received VAN 150 mg/kg/day intravenously (n = 6) or saline (n = 5) once daily followed by an intravenous injection of fluorescein isothiocyanate-sinistrin (FITC-sinistrin) for 3 days. FITC-sinistrin fluorescence was monitored transdermally prior to VAN administration and daily during treatment. GFR was calculated from FITC-sinistrin clearance. A mixed-effects model compared urinary biomarkers and GFRs between treatments and across days of dosing. Urinary biomarkers for injury and GFR were compared between treatment groups and correlated with VAN kidney accumulation. Mean GFR for saline-treated animals was 1.07, 1.20, 1.15 and 1.24 mL/min/100g body weight (b.w.) pre-treatment and at Days 1-3, respectively. VAN-treated rats had lower GFR after treatment (0.457, 0.584 and 0.759 mL/min/100g b.w. on Days 1-3, respectively; P ≤ 0.05). KIM-1 and clusterin were elevated on Day 1 for VAN-treated animals. The relationship between VAN accumulation in the kidney with GFR and biomarkers followed a four-parameter Hill slope (R2 = 0.6 and R2 = 0.9, respectively). Rats receiving VAN had a significant decline in GFR immediately following the first dose, which correlated with increasing VAN concentrations in the kidney and urinary biomarkers.