Allergic fungal sinusitis associated with allergic bronchopulmonary aspergillosis: an uncommon sinobronchial allergic mycosis.
The identification of allergic fungal sinusitis (AFS) is still controversial and much more recent than that of allergic bronchopulmonary aspergillosis (ABPA). Their association has been reported very rarely in the literature. The aim of this study was to present a review of 6 cases of AFS associated with ABPA from a series of 12 cases of AFS and to compare AFS associated with ABPA and isolated AFS. All cases of AFS presented with chronic rhinosinusitis. The six cases with AFS and ABPA were atopic, asthmatic, with pulmonary infiltrates (five cases), central bronchiectasis (four cases), and both (three cases). The mycological and immunoallergological features of isolated AFS and AFS associated with ABPA were similar: eosinophilic allergic mucin with noninvasive fungi hyphae, high levels of blood eosinophils, total IgE, specific IgE, IgG, and positive skin tests to Aspergillus. The association of AFS and ABPA was concomitant (two cases) or remote in time (four cases). The treatment with oral corticosteroids and sinus surgery (six cases) associated with antifungal drugs (four cases) led to resolution in three cases, considerable improvement in one case, and therapeutic failure in two cases (follow-up longer than 5 years in all cases). Independently of the signs linked to the organs involved (sinuses and bronchi) the mycological and immunoallergological features were similar for AFS and AFS associated with ABPA. AFS and ABPA can be isolated or associated in a sinobronchial allergic


Fusiform Enlargement of the Superficial Temporal Artery in the Cases with Intracranial Aneurysm.
The superficial temporal artery is one of the main terminal branches of the external carotid artery. This artery ascends through the lateralposterior margin of the zygomatic arch to reach the temporal region of the scalp. The superficial temporal artery divides its frontal and parietal branches around the zygomatic arch. The raw data of the Three-dimensional Computerized Tomography Angiography (3D-CTA) were transferred to computer and recorded in a software program. This software program created the three-dimensional images of the superficial temporal artery using these transferred raw data with volume rendering technique. Fifteen cases (5 female and 10 male, mean age 54.26 ± 12.35 years) with intracranial aneurysm were evaluated in terms of the type, location and dimensions of the fusiform enlargements. Fusiform enlargement was bilateral in eleven of the cases. Remaining four cases have unilateral fusiform enlargement of the superficial temporal artery. Fusiform enlargement of the superficial temporal artery may be seen in the cases with intracranial aneurysms. 3D-CTA should be carefully evaluated in the demonstration of extracranial-intracranial vascular pathologies.


Upper limb blocks.
This article discusses recent innovations and changes in practice in upper limb regional anaesthesia, dividing the blocks into those performed above the clavicle, those performed in the area of the clavicle and those performed below it. It offers a critical appraisal of the current status with regard to the use of ultrasound nerve location for upper limb regional anaesthesia and, while accepting that the use of ultrasound in this way has many theoretical advantages and will therefore continue to grow, concludes that there is currently insufficient published evidence to determine conclusively that the use of this technique is associated with nerve blocks that are more successful or safer.


Breastfeeding anaphylaxis case study.
This case describes a woman who experienced an anaphylatic reaction associated with breastfeeding. The reaction occurred with each feeding on day three postpartum and resolved on day four. Possible reasons for this severe reaction are suggested.


Detection of Intravascular Injection During Cervical Transforaminal Epidural Injection: A Comparison of Digital Subtraction Angiography and Real Time Fluoroscopy.
Transforaminal epidural injection (TFEI) with local anesthetics and steroids are effective in treating spinal radicular pain. However, inadvertent intravascular injection can lead to severe neurologic complications. To reduce complications of intravascular injection, use of imaging modality, such as real-time fluoroscopy (RTF) or digital subtraction angiography (DSA), has been recommended. DSA is an imaging technique that can clearly visualize the blood vessels from surrounding bones or dense soft tissues by subtracting the pre-contrast image from the image after injecting contrast medium. In this study, we investigated whether there is a difference between RTF and DSA in the detection of intravascular injection during cervical TFEI. Clinical study. Pain clinic in South Korea. We prospectively examined 137 cervical TFEIs on 128 patients who have a radiating pain from spinal stenosis and herniated nucleus pulposus. The needle position was confirmed using biplanar fluoroscopy and 2 mL of nonionic contrast medium was injected at the rate of 0.5 mL/sec under RTF. Thirty seconds later, 2 mL of nonionic contrast medium was injected at the rate of 0.5 mL/sec under DSA. Intravascular injection was defined as contrast medium spreading throughout the vascular channel during injection of contrast medium under RTF and DSA. This study is registered in the ClinicalTrials.gov (NCT03040648). The detection rate of intravascular injection in RTF was not statistically different compared to that in DSA (30.7 % vs. 34.3%, P > 0.05). We injected 2 mL of contrast medium at the rate of 0.5 mL/sec. Further studies about the ideal injection speed and volume of contrast medium for improvement of detection of intravascular injection during TFEI are needed. This study was a single center study. Therefore, multi-center studies are needed to obtain the high level of evidence. Additionally, the procedural pain physician was not blinded to the type of imaging modality, such as RTF and DSA, to detect intravascular injection. To minimize this confirmation bias and provide homogenous procedural conditions for TFEI, the same procedural physician performed all 137 injections. In this study, there is no significant difference in detection rate of intravascular injection between RTF and DSA during cervical TFEI. Analgesia, bleeding, clinical trials, complications, diagnostic equipment, epidural, radiculopathy, spine.


Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis.
The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis.


Assessment of role of inferior vena cava collapsibility index and variations in carotid artery peak systolic velocity in prediction of post-spinal anaesthesia hypotension in spontaneously breathing patients: An observational study.
Post-spinal anaesthesia hypotension (PSH) is common and can lead to significant morbidity and mortality. The inferior vena cava collapsibility index (IVCCI) and carotid artery peak systolic velocity variations (CAPVV) are two widely used parameters for assessing the volume status of critically ill patients which have also been investigated as predictors of PSH and hypotension after induction of general anaesthesia. In this study, we evaluated the diagnostic accuracy of IVCCI and CAPVV as predictors of PSH. A total of 50 patients aged between 18 and 65 years undergoing elective lower abdominal surgeries under spinal anaesthesia were included. The IVCCI and CAPVV were measured using ultrasound pre-operatively. After administering spinal anaesthesia, haemodynamic data were collected till 15 min. Our primary objective was to evaluate the role of IVCCI and CAPVV to predict PSH. The secondary objectives were to compare the predictive efficacy of these two parameters and to detect other parameters for predicting PSH. We constructed the receiver operator characteristic (ROC) curves for IVCCI and CAPVV and obtained the best cut-off values. The PSH occurred in 34% of the patients. IVCCI >21.15 could predict PSH with 58.8% sensitivity and 69.7% specificity. CAPVV >18.33 predicted PSH with 70.6% sensitivity and 54.6% specificity and IVC max/IVCCI >60 could predict PSH with 58.8% sensitivity and 54.5% specificity. A composite model comprising IVCmax (maximum IVC diameter), CAPVV, and baseline mean blood pressure was able to predict PSH. Both IVCCI and CAPVV have poor diagnostic accuracy in predicting PSH in adult patients undergoing elective infra-umbilical surgery.


Fine needle aspiration cytology of bone tumors.
To study the role of fine needle aspiration cytology (FNAC) in the diagnosis of bone tumors and its impact on therapeutic decisions. A group of 122 cases of bone tumor were evaluated by FNAC. Detailed diagnoses were compared with the available histology. Diagnostic accuracy of FNAC was 90.5% in this study. FNAC could differentiate between various round cell tumors such as Ewing's sarcoma and myeloma, among various giant cell-rich lesions of bone and between the benign and malignant chondroid bone tumors. Some uncommon variants were also correctly diagnosed. In metastatic bone tumors, the source of primary malignancy could not be indicated in the majority (52.9%) because of the poorly differentiated morphology. Osteoid or osteoid-like material was demonstrable in 63.6% cases of osteogenic sarcoma. A case of chondroblastic osteogenic sarcoma that was reported as chondrosarcoma was the only diagnostic error in the study. FNAC obviated the need of open biopsy in 63.8% patients, and therapeutic decisions were made according to the cytologic diagnoses. FNAC plays an important role in the early diagnosis of bone tumors by its accuracy, ease of use and rapidity and is helpful in making the therapeutic decisions.


Muscle relaxation techniques: a therapeutic tool for family physicians.
Muscle relaxation techniques are important adjunctive therapy for anxiety-related conditions. Family physicians can learn to teach the techniques so as to try helping anxious patients themselves rather than automatically referring them to a psychiatrist. The exercises are generally acceptable to patients, are easy to learn and do not require expensive equipment. They are beneficial in insomnia and tension headache, of some value in chronic anxiety states and a useful adjunct in hypertension. In this paper the evidence supporting the value of muscle relaxation therapy is briefly reviewed, methods of teaching and of practising the techniques are described in detail, and answers to some of the questions and problems that may arise are presented.


Childhood-onset schizophrenia: premorbid and prodromal diagnostic and treatment histories.
There is increasing interest in the possible relationship between the early diagnosis and treatment of schizophrenia during adolescence and improved long-term outcome. This study reviews the premorbid and prodromal diagnostic and treatment histories for childhood-onset schizophrenia, to assess whether early identification and treatment is possible in this school-age group. Parents of 17 children with childhood-onset schizophrenia or schizoaffective disorder were questioned retrospectively regarding symptoms, exposure to mental health professionals, diagnoses, and treatments. Initial presenting symptoms clustered around violent aggression and school problems. Age of first recognized psychotic symptoms ranged from 2 to 11 years, followed 2.0+/-2.0 years later by a diagnosis of schizophrenia. Prior to a schizophrenia diagnosis, these children were exposed to stimulants, antidepressants, lower-dose typical neuroleptics, mood stabilizers, alternative treatments, and individual and family therapy. Early diagnosis of childhood-onset schizophrenia is met with caution in the psychological and medical community. These children received many diagnoses before schizophrenia or schizoaffective disorder was diagnosed. A diagnosis of schizophrenia or schizoaffective disorder and utilization of effective atypical neuroleptic treatment was delayed until evaluation by a child and adolescent psychiatrist. Obstacles to early identification and treatment are discussed.


Japanese quince (Chaenomeles japonica) leaf phenol extract as modulator of the inflammatory response in lipopolysaccharide-triggered murine macrophage RAW 264.7 cells.
In the present study we investigated the anti-inflammatory activity of Japanese quince leaf polyphenol-rich extract (JQLPE) in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7). The Q-PCR analysis revealed that JQLPE decreased Nfkb1, Ptgs2, and Il1b expression at the mRNA level by 80%, 50% and 48%, respectively. Similarly, JQLPE significantly attenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) (by 60%, 50%, 67%, 37% and 36%, respectively) at the protein level and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7. Western blot also showed that the expression of nuclear factor kappaB (NF-κB) p65 and p-NF-κB p65 was down-regulated after JQLPE treatment. These results provide the first evidence that JQLPE decreases the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), inflammatory mediators (COX-2, iNOS) and both NF-κB p65 and p-NF-κB p65 in LPS-stimulated RAW264.7 cells, which may suggest its anti-inflammatory activity.


Antichilblain Components in Eggplant Based on Network Pharmacology and Biological Evaluation.
Eggplant, the fruit of Solanum melongena L. (Solanaceae), is applied externally to relieve the symptoms of chilblains in the folk in East Asia. However, the mechanisms and biological ingredients are not clear. A network pharmacology approach was used to shed light on the mechanisms of eggplant against chilblains, which illustrated that anti-inflammation and antioxidation are mainly involved in the curative effects. Bioassay-guided assays led to the isolation of 44 ingredients (1-44), including two new natural compounds (1-2) and 42 known compounds. Thirteen compounds (3-15) were first reported from the Solanum genus. The anti-inflammatory and antioxidative effects of all isolates were evaluated, and the results showed that 11 compounds have anti-inflammatory activity and 27 have antioxidant activity. Fatty acids, flavonoids, alkaloids, phenolic acids, saponins, and lignans from eggplant have certain anti-inflammatory and antioxidant effects. These results provide a scientific basis for eggplant to treat chilblains.


Prothrombin time is predictive of low plasma prothrombin concentration and clinical outcome in patients with trauma hemorrhage: analyses of prospective observational cohort studies.
Fibrinogen and prothrombin have been suggested to become rate limiting in trauma associated coagulopathy. Administration of fibrinogen is now recommended, however, the importance of prothrombin to patient outcome is unknown. We have utilized two trauma patient databases (database 1 n = 358 and database 2 n = 331) to investigate the relationship of plasma prothrombin concentration on clinical outcome and coagulation status. Database 1 has been used to assess the relationship of plasma prothrombin to administered packed red blood cells (PRBC), clinical outcome and coagulation biomarkers (Prothrombin Time (PT), ROTEM EXTEM Coagulation Time (CT) and Maximum Clot Firmness (MCF)). ROC analyses have been performed to investigate the ability of admission coagulation biomarkers to predict low prothrombin concentration (database 1), massive transfusion and 24 h mortality (database 1 and 2). The importance of prothrombin was further investigated in vitro by PT and ROTEM assays in the presence of a prothrombin neutralizing monoclonal antibody and following step-wise dilution. Patients who survived the first 24 h had higher admission prothrombin levels compared to those who died (94 vs.67 IU/dL). Patients with lower transfusion requirements within the first 24 h (≤10 units of PRBCs) also had higher admission prothrombin levels compared to patients with massive transfusion demands (>10 units of PRBCs) (95 vs.62 IU/dL). Admission PT, in comparison to admission ROTEM EXTEM CT and MCF, was found to be a better predictor of prothrombin concentration <60 IU/dL (AUC 0.94 in database 1), of massive transfusion (AUC 0.92 and 0.81 in database 1 and 2 respectively) and 24 h mortality (AUC 0.90 and 0.78 in database 1 and 2, respectively). In vitro experiments supported a critical role for prothrombin in coagulation and demonstrated that PT and ROTEM EXTEM CT are sensitive methods to measure low prothrombin concentration. Our analyses suggest that prothrombin concentration at admission is predictive of mortality and transfusion and indicates that prothrombin and fibrinogen are rate limiting in coagulopathy. Admission PT is predictive of low prothrombin concentration and clinical outcome. PT could therefore be used as a surrogate for prothrombin concentration and further evaluation of point-of-care devices for faster PT analysis is warranted.


In vitro effects of growth factors on rat germ cell RNA synthesis and their modulation by Sertoli cell-secreted proteins.
In vitro rat germ cell RNA synthesis is influenced by growth factors. Basic fibroblast growth factor (0.1 to 100 ng/ml) increases [3H]uridine incorporation in round spermatids (RS) but not in pachytene spermatocytes (PS); this effect is potentiated by insulin (10 micrograms/ml) and blocked in the presence of Sertoli cell-secreted proteins (SCSP). Somatomedin C (0.1 to 100 ng/ml) exhibits a similar effect when used alone without an influence by SCSP. Transforming growth factor beta (0.1 to 10 ng/ml) acts on both cell types, but SCSP amplify this effect only in PS. These data suggest that growth factors synthesized in situ may play a role in the germ cell development and that their effects are modulated by SCSP.


Autophagy inhibition reduces chemoresistance and tumorigenic potential of human ovarian cancer stem cells.
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation. We thus decided to investigate both in vitro and in vivo the autophagic activity and the effects of the perturbation of this pathway in CSC isolated from EOC ascitic effusions. Ovarian CSC, identified according to their CD44/CD117 co-expression, presented a higher basal autophagy compared with the non-stem counterpart. Inhibition of this pathway, by in vitro chloroquine treatment or CRISPR/Cas9 ATG5 knockout, impaired canonical CSC properties, such as viability, the ability to form spheroidal structures in vitro, and in vivo tumorigenic potential. In addition, autophagy inhibition showed a synergistic effect with carboplatin administration on both in vitro CSC properties and in vivo tumorigenic activity. On the whole, these results indicate that the autophagy process has a key role in CSC maintenance; inhibition of this pathway in combination with other chemotherapeutic approaches could represent a novel effective strategy to overcome drug resistance and tumor recurrence.


[Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].
To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.


Short-course human leukocyte interferon in treatment of herpes zoster in patients with cancer.
Because of encouraging results when human leukocyte interferon was given for 5 to 7 days to treat early localized herpes zoster in patients with cancer, a small placebo-controlled, randomized, double-blind trial was set up involving only 48 h of therapy. In this trial, there was no effect on acute pain or disease progression in the primary dermatome. However, a modest but significant effect was noted in that distal cutaneous spread was diminished in the treated patients compared with the controls and the treated patients had diminished severity and duration of postherpetic neuralgia. No evidence of impairment in varicella-zoster-specific lymphocyte transformation was observed in interferon-treated patients.


Which Combinations of Techniques and Modes of Delivery in Internet-Based Interventions Effectively Change Health Behavior? A Meta-Analysis.
Many online interventions designed to promote health behaviors combine multiple behavior change techniques (BCTs), adopt different modes of delivery (MoD) (eg, text messages), and range in how usable they are. Research is therefore needed to examine the impact of these features on the effectiveness of online interventions. This study applies Classification and Regression Trees (CART) analysis to meta-analytic data, in order to identify synergistic effects of BCTs, MoDs, and usability factors. We analyzed data from Webb et al. This review included effect sizes from 52 online interventions targeting a variety of health behaviors and coded the use of 40 BCTs and 11 MoDs. Our research also developed a taxonomy for coding the usability of interventions. Meta-CART analyses were performed using the BCTs and MoDs as predictors and using treatment success (ie, effect size) as the outcome. Factors related to usability of the interventions influenced their efficacy. Specifically, subgroup analyses indicated that more efficient interventions (interventions that take little time to understand and use) are more likely to be effective than less efficient interventions. Meta-CART identified one synergistic effect: Interventions that included barrier identification/ problem solving and provided rewards for behavior change reported an average effect size that was smaller (ḡ=0.23, 95% CI 0.08-0.44) than interventions that used other combinations of techniques (ḡ=0.43, 95% CI 0.27-0.59). No synergistic effects were found for MoDs or for MoDs combined with BCTs. Interventions that take little time to understand and use were more effective than those that require more time. Few specific combinations of BCTs that contribute to the effectiveness of online interventions were found. Furthermore, no synergistic effects between BCTs and MoDs were found, even though MoDs had strong effects when analyzed univariately in the original study.


Long-term hepatotoxicity of polyethylene-glycol functionalized multi-walled carbon nanotubes in mice.
The toxicity of polyethylene-glycol functionalized (PEGylated) multi-walled carbon nanotubes (MWCNTs) and non-PEGylated MWCNTs in vivo was evaluated and compared. Mice were exposed to MWCNTs by intravenous injection. The activity level of glutathione, superoxide dismutase and gene expression in liver, as well as some biochemical parameters and the tumor necrosis factor alpha level in blood were measured over 2 months. The pathological and electron micrographic observations of liver evidently indicate that the damage caused by non-PEGylated MWCNTs is slightly more severe than that of PEGylated MWCNTs, which means that PEGylation can partly, but not substantially, improve the in vivo biocompatibility of MWCNTs.


[EEG characteristics of medial prefrontal cortex in rats with morphine dependent place preference under shuttling condition].
To study the correlation between EEG characteristics of medial prefrontal cortex (mPFC) and drug-seeking behavior of rats with morphine dependent place preference under shuttling condition. Forty rats were randomly divided into four groups (n = 10): morphine PL group, NS PL group, morphine IL group and NS IL group. After embeding the electrode in prelimbic (PL) or infralimbic (IL) cortex of each group by brain stereotaxic operation, the model of morphine dependent conditioned place preference (CPP) in rats was established. The differences of EEG wave percentage in mPFC were telemetered and analyzed when rats shuttled before and after the model. After the model, the withdrawal symptoms were evident in morphine PL and IL group, and the activity time and distance in white box were increased obviously. Compared with control group, after the model, the EEG in morphine PL group showed that: when the rats shuttled to white box, 8 wave decreased obviously, P wave increased obviously. When the rats shuttled to black box, brain waves showed opposite changes. The EEG in morphine IL group showed that: when the rats shuttled to white box, a wave increased obviously, P and a wave decreased obviously. When the rats shuttled to black box, the brain wave had no significant differences compared with control group. The EEG changes are different in PL and IL cortex of morphine CPP rats under shuttling condition, and the EEG changes are also different when rats shuttling to white or black box. There is possibly different mechanism, when different drug-seeking environmental cues caused EEG changes in different regions of mPFC.


Model for hyperthermia with arrays of magnetic nanoparticles: spatial and time temperature distributions in tumor.
A square array of micron-sized needles containing magnetic nanoparticles has been studied theoretically as potential systems to deliver heat to tumor tissue for the hyperthermia treatment. The spatiotemporal distributions of temperature in a tumor were calculated for different arrays of microneedles. The resulting temperature distributions are found to be more uniform within the tumor target than those caused by other heating systems. Moreover, the temperature profiles could be tuned by a proper choice of the combination of the system parameters: the needle radius, the spatial needles period, as well as the filling fraction and parameters of magnetic nanoparticles.


The discovery of pulmonary circulation: From Imhotep to William Harvey.
In his quest to comprehend his existence, Man has long been exploring his outer world (macro-cosmos), as well as his inner world (micro-cosmos). In modern times, monmental advances in the fields of physics, chemistry, and other natural sciences have reflected on how we understand the anatomy and physiology of the human body and circulation. Yet, humanity took a long and winding road to reach what we acknowledge today as solid facts of cardiovascular physiology. In this article, we will review some of the milestones along this road.


The importance of an illicit drug history in the evaluation of suspected spontaneous pneumothorax.
The authors present the case of a 27-year-old man who presented with acute left-sided pleuritic chest pain and dyspnoea managed as for a spontaneous pneumothorax with aspiration and subsequent chest drain insertion following a chest radiograph. Despite intervention, however, his chest radiograph showed what appeared to be a non-resolving pneumothorax. Further history revealed a large cannabis smoking exposure and subsequent CT imaging revealed large apical bullous disease with little residual pneumothorax. The patient was referred for cardiothoracic bullectomy and pleurodesis. The authors review the association between cannabis smoke inhalation and apical bullous lung disease and stress the importance of direct questioning on initial history. If a significant history is found, the authors argue that CT imaging and primary cardiothoracic intervention may then be the investigation and management of choice in a stable patient.


The potential of 4D sonography in the assessment of fetal behavior in high-risk pregnancies.
To assess differences of fetal behavior in normal and high-risk pregnancies. In the 1-year period (1 January 2007-31 December 2007), four-dimensional ultrasound has been used to assess Kurjak antenatal neurodevelopmental test (KANET) in low- and high-risk pregnancies after randomization in prospective longitudinal cohort study. Based on the KANET scores, the fetuses were considered as normal (≥ 14 points), borderline (6-13), or abnormal (0-5). Comparison of KANET scores in low- and high-risk pregnancies were expectedly statistically significant. The largest incidence of fetuses with abnormal KANET was in the group of fetuses who had siblings with cerebral palsy. The largest incidence of the borderline KANET has been found in the group of fetuses whose mothers had fever during pregnancy. The following parameters of KANET test significantly differed between the fetuses from low- and high-risk pregnancies: overlapping cranial sutures, head circumference, isolated eye blinking, facial expressions, mouth movements, isolated hand movements, isolated leg movements, hand to face movement, finger movements, and general movements. KANET test has the potential to detect and discriminate normal from borderline and abnormal fetal behavior in normal and in high-risk pregnancies.


Metabolic interaction between skeletal muscle and liver during bacteremia.
To study the effects of bacteremia on skeletal muscle leucine (LEU) metabolism, mongrel dogs were infused with normal saline or Escherichia coli (10(9)/kg). After a bolus dose (3.6 microCi), L(1-carbon 14) LEU (0.3 microCi/min) was infused directly into the isolated, constant-flow, in vivo gracilis muscle. Arteriovenous differences for amino acids, labeled and unlabeled LEU and alpha-ketoisocaproic acid (KIC), and labeled carbon dioxide were measured at ten-minute intervals for one hour. Bacteremia increased the net release of amino acids and total N2 from muscle. Moreover, plasma LEU that was deaminated and released as KIC was increased, and there was also an increase in decarboxylated plasma LEU during bacteremia. Despite the marked increase in KIC release from skeletal muscle during bacteremia, arterial concentrations were not significantly different from those of controls. An unchanged arterial plasma KIC concentration associated with a marked increase in KIC released from skeletal muscle indicates an increase in LEU metabolism, most likely in the liver. Thus, the increased skeletal muscle catabolism is not a futile cycle but rather an essential event to meet the increased metabolic needs of the body during bacteremia.


PATTERNS OF VARIATION AND LINKAGE DISEQUILIBRIUM IN A FIELD CRICKET HYBRID ZONE.
The distribution of multilocus genotypes found within a natural hybrid zone is determined by the sample of genotypes present when the hybrid zone first formed, by subsequent patterns of genetic exchange between the hybridizing taxa, and by drift and selection within each of the hybrid zone populations. We have used anonymous nuclear DNA restriction fragment polymorphisms (RFLPs) to characterize the array of multilocus genotypes present within a well-studied hybrid zone between two eastern North American field crickets, Gryllus pennsylvanicus and Gryllus firmus. These crickets hybridize along a zone of contact that extends from New England to Virginia. Previous studies have shown that both premating and postmating barriers exist between the two cricket species, but the absence of diagnostic morphological and allozyme markers has made it difficult to assess the consequences of these barriers for genetic exchange. Analyses based on four diagnostic anonymous nuclear markers indicate that hybrid zone populations in Connecticut contain few F1 hybrids, and that nonrandom associations persist among nuclear gene markers, between nuclear and cytoplasmic markers, and between molecular markers and morphology. Field cricket populations within the hybrid zone are not "hybrid swarms" but consist primarily of crickets that are very much like one or the other of the parental species. Despite ample opportunity for genetic exchange and evidence for introgression at some loci, the two species remain quite distinct. Such a pattern appears to be characteristic of many natural hybrid zones.


Repeat Ivermectin Mass Drug Administrations for Malaria Control II: Protocol for a Double-blind, Cluster-Randomized, Placebo-Controlled Trial for the Integrated Control of Malaria.
The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector. The primary objective of the study is to assess the impact of repeated ivermectin MDA on malaria incidence in children aged ≤10 years. Repeat Ivermectin MDA for Malaria Control II is a double-blind, placebo-controlled, cluster-randomized, and parallel-group trial conducted in a setting with intense seasonal malaria transmission in Southwest Burkina Faso. The study included 14 discrete villages: 7 (50%) randomized to receive standard measures (seasonal malaria chemoprevention [SMC] and bed net use for children aged 3 to 59 months) and placebo, and 7 (50%) randomized to receive standard measures and monthly ivermectin MDA at 300 μg/kg for 3 consecutive days, provided under supervision to all eligible village inhabitants, over 2 successive rainy seasons. Nonpregnant individuals >90 cm in height were eligible for ivermectin MDA, and cotreatment with ivermectin and SMC was not permitted. The primary outcome is malaria incidence in children aged ≤10 years, as assessed by active case surveillance. The secondary safety outcome of repeated ivermectin MDA was assessed through active and passive adverse event monitoring. The trial intervention was conducted from July to November in 2019 and 2020, with additional sampling of humans and mosquitoes occurring through February 2022 to assess postintervention changes in transmission patterns. Additional human and entomological assessments were performed over the 2 years in a subset of households from 6 cross-sectional villages. A subset of individuals underwent additional sampling in 2020 to characterize ivermectin pharmacokinetics and pharmacodynamics. Analysis and unblinding will commence once the database has been completed, cleaned, and locked. Our trial represents the first study to directly assess the impact of a novel approach for malaria control, ivermectin MDA as a mosquitocidal agent, layered into existing standard-of-care interventions. The study was designed to leverage the current SMC deployment infrastructure and will provide evidence regarding the additional benefit of ivermectin MDA in reducing malaria incidence in children. ClinicalTrials.gov NCT03967054; https://clinicaltrials.gov/ct2/show/NCT03967054 and Pan African Clinical Trials Registry PACT201907479787308; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8219. DERR1-10.2196/41197.


[Simultaneous laparoscopic treatment for common bile duct stones associated with acute cholecystitis. Results of a prospective study].
Laparoscopy for the management of acute cholecystitis has gained wide acceptance. Although it is well known that acute cholecystitis may be complicated by common bile duct stones in up to 15% of cases, to date there are no published studies addressing the management of common bile duct stones detected during laparoscopy for acute cholecystitis. We postulated that, when found, common bile duct stones associated with acute cholecystitis could be effectively and safety managed during the same laparoscopic procedure. We report on a five-year prospective study (2001-2005) involving 313 unselected patients who presented with a clinical diagnosis of acute cholecystitis (confirmed by specimen examination) and without any contraindication to laparoscopy. At surgery, transcystic cholangiograms were obtained in 289 (92%); the other 24 were excluded from the study. With an established diagnosis of common bile duct stones, attempts were made to clear the common bile duct by transcystic basket retrieval, ERCP or choledochotomy. Prevalence of common bile duct stones in acute cholecystitis, success of laparoscopic common duct clearance, conversion rate, operative time, morbidity, and postoperative hospital stay were the main outcome measures. Common bile duct stones were found in 63 pts (21.7%) presenting with acute cholecystitis. At laparoscopy, 12 patients (19%) required conversion to open surgery, 3 of these being due to failure to achieve common bile duct clearance. Common bile duct stones were cleared entirely laparoscopically in 51 patients (81%) by means of transcystic stone retrieval (38 pts, 75%), ERCP (12 pts, 23%) or choledocotomy (1 pt, 2%). At intention to treat analysis, patients undergoing cholecystectomy plus common bile duct clearance compared to those undergoing cholecystectomy alone, spent significantly more time in the operating theatre (mean 192 min vs 118 min, p < 0.001), needed open conversion more frequently (19% vs 6.1%, p = 0.0045), and had a higher overall morbidity rate (17.4% vs 4.4%, p = 0.015). The simultaneous procedure also adversely affected the postoperative hospital stay (mean 4.8 vs 3.4 days, p = 0.0164). Mortality was nil in both groups. The prevalence of common bile duct stones in patients presenting with acute cholecystitis should not be neglected. When common bile duct stones are found, clearance may be obtained laparoscopically in a substantial number of cases without any need for open surgery. The simultaneous laparoscopic approach for acute cholecystitis and common bile duct stones remains, however, a highly skilled and technically demanding procedure. Although a moderate incidence of drawbacks is observed, the results should be interpreted from the point of view of an all-in-one procedure that allows the patients to be cured without needing any further sequential interventions.


Ionic iridium complex and conjugated polymer used to solution-process a bilayer white light-emitting diode.
Bilayer white light-emitting devices are prepared from solution, using an ionic orange phosphorescent organometallic complex and a neutral fluorescent conjugated polymer. Because of the very different polarity of the two components, they dissolve in orthogonal solvents, allowing for the direct deposition of the blue emitter on top of the orange emitter without the need of cross-linking or special coating methodology. Fine tuning of the layer thickness of both light-emitting layers allows for the color tuning of different types of white light.


Diffuse alveolar hemorrhage as a manifestation of Behçet disease.
Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition which refers to the presence of red blood cells within alveoli deriving from hemorrhage originating in the pulmonary microvasculature. It differs from alveolar filling, in which blood cells derive from localized bleeding, usually of bronchial origin. DAH may be part of diffuse alveolar injury of any origin. DAH should be considered a medical emergency due to the significant morbidity and mortality associated with respiratory failure, when secondary to impaired oxygen uptake from alveoli filled with erythrocytes. Patients with alveolar hemorrhage present with non-specific symptoms like dyspnea, cough and hemoptysis, which is not always present. They may develop acutely or insidiously over a few days. We present a case of a patient with probable Behçet's disease complicated by pulmonary capillaritis and DAH resulting in refractory respiratory failure and death.


[The prevention of disability as a leading priority of caring of mother and child health].
The prevention of disability in children and support of families fostering disabled children and children with limited capacities in health are included into number of main priorities of the state social policy of the Russian Federation. Thereupon, the project "Childhood Decade" is an important stage that includes social care of disabled children and children with limited capacities in health and their integration in modern society according the Decree of the President on implementation of state policy in the field of family and children care. The underestimation of children disability is supposed to be present produced by such causes as social motivation of family, complicacy of legal official registration, harsh requirements of medical social expertise services, inadequate awareness of medical staff about criteria of disability. According the WHO European Regional Bureau, in Russia there are 250 000 children with limitations of life activity mainly caused by somatic pathology, who have no status of disabled person and no state social support. The prevention of children disability is considered as a system of measures of caring mother and child health all along childhood. The priority directions of prevention considering causes of development of disability and its structure according particular disease are marked. The data is presented related to modern technologies of decreasing genetic load on population from position of prevention of hereditary, inborn and orphan diseases. In particular studies non-infectious pathology acquiring greater significance in development of disability in children of various age groups since neonatal period is considered. The new directions of research are proposed to affect the processes of incapacitation of child on more profound pathogenic level and to develop organization of preventive activities in this area.


Postoperative Abdominal Adhesions: Clinical Significance and Advances in Prevention and Management.
Postoperative adhesions remain one of the more challenging issues in surgical practice. Although peritoneal adhesions occur after every abdominal operation, the density, time interval to develop symptoms, and clinical presentation are highly variable with no predictable patterns. Numerous studies have investigated the pathophysiology of postoperative adhesions both in vitro and in vivo. Factors such as type and location of adhesions, as well as timing and recurrence of adhesive obstruction remain unpredictable and poorly understood. Although the majority of postoperative adhesions are clinically silent, the consequences of adhesion formation can represent a lifelong problem including chronic abdominal pain, recurrent intestinal obstruction requiring multiple hospitalizations, and infertility. Moreover, adhesive disease can become a chronic medical condition with significant morbidity and no effective therapy. Despite recent advances in surgical techniques, there is no reliable strategy to manage postoperative adhesions. We herein review the pathophysiology and clinical significance of postoperative adhesions while highlighting current techniques of prevention and treatment.


[Anesthetic management of a patient for giant pulmonary bulla drainage].
Recently it is claimed that the drainage procedure may be a useful method for giant pulmonary bulla in compromised patients. We reported the anesthetic managements of three patients with giant bulla for these procedures. We chose epidural anesthesia in order to prepare for the postoperative analgesia and the expansion of surgical procedure. In selecting circulatory support method, care was taken to choose dobutamine that would cause no suppression of hypoxic ventilatory drive. There is no doubt that right ventricular function is particularly important in patients with chronic obstructive lung disease. We measured right ventricular ejection fraction by thermodilution method and end-tidal CO2 by nasal cannula. These measurements may be useful methods for perioperative monitoring.


Pathologic insights from integrated imaging of reticular pseudodrusen in age-related macular degeneration.
The purpose of this study was to analyze the integrated infrared reflectance, fundus autofluorescence, and fluorescein angiography (integrated confocal scanning laser ophthalmoscopy fundus imaging) features of reticular pseudodrusen and eye-tracked Spectralis high-resolution spectral domain optical coherence tomography (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany). Twenty-two consecutive patients with reticular pseudodrusen were prospectively enrolled and evaluated regarding confocal scanning laser ophthalmoscopy fundus imaging and eye-tracked SD-OCT findings. Integrated fundus imaging revealed a "target" aspect of most reticular pseudodrusen in the 42 included eyes (22 patients; 12 women, 10 men; mean age 81.38 ± 6.47 years). On fundus autofluorescence and infrared reflectance, the center of most reticular pseudodrusen appeared as an area of isoautofluorescence/reflectance surrounded by halos of reduced autofluorescence/reflectance. Similarly, on fluorescein angiography, the center of reticular pseudodrusen appeared as an area of decreased fluorescence surrounded by a faint halo of increased fluorescence. Spectral domain optical coherence tomography showed a well-defined round or triangular hyperreflective deposit localized between, externally, the retinal pigment epithelium layer, and, internally, the external limiting membrane or the outer plexiform layer. Moreover, SD-OCT showed the loss of both outer segment/retinal pigment epithelium interface and inner segment/outer segment interface over the hyperreflective lesions, as well as an abrupt interruption of both these interfaces at the border of the hyperreflective lesions. The peculiar confocal scanning laser ophthalmoscopy fundus imaging and tracked SD-OCT of reticular pseudodrusen suggest the presence of central lipofuscin-like retinal deposits localized above the retinal pigment epithelium. These findings give insights to other possible aspects of age-related retinal changes.


Historical development of neural transplantation.
The techniques of neural transplantation are almost 100 years old. As these techniques begin to be used to treat human neurological disorders, it is important to remember the contributions of the many investigators who have advanced this fascinating area of neurobiology.


Sacrospinous hysteropexy: review and meta-analysis of outcomes.
Sacrospinous hysteropexy is a uterine-preserving procedure for treatment of apical prolapse. We present a literature review evaluating the sacrospinous hysteropexy procedure and its current place in the surgical management of pelvic organ prolapse. Additionally, to assess the efficacy of the procedure, we performed a meta-analysis of studies comparing sacrospinous hysteropexy to vaginal hysterectomy and repair in terms of anatomical outcomes, complications, and repeat surgery. Major literature databases including MEDLINE (1946 to 2 April 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), and Embase (1947 to 2 April 2016) were searched for relevant studies. We used Cochrane Collaboration's Review Manager software to perform meta-analysis of randomized controlled studies and observational studies. Vaginal sacrospinous hysteropexy was first performed in 1989 and is similar in technique to sacrospinous colpopexy. Two randomized controlled trials and four cohort studies (n = 651) were included in the meta-analysis. Apical failure rates after sacrospinous hysteropexy versus vaginal hysterectomy were not significantly different, although the trend favored vaginal hysterectomy [odds ratio (OR) 2.08; 95% confidence interval (CI) 0.76-5.68]. Rates of repeat surgery for prolapse were not significantly different between the two groups (OR 0.99; 95% CI 0.41-2.37). The most significant disadvantage of uterine-preservation prolapse surgery when compared with hysterectomy is the lack of prevention and diagnosis of uterine malignancy. Sacrospinous hysteropexy is a safe and effective procedure for pelvic organ prolapse and has comparable outcomes to vaginal hysterectomy with repair.


pBR322 DNA inhibits simian virus 40 gene expression in Xenopus laevis oocytes.
SV40 DNA form I is expressed efficiently after its injection into the nuclei of Xenopus laevis oocytes, resulting in the synthesis of RNA and protein products of both viral late and early transcription units. However it was observed that injection of SV40 genes cloned into pBR322 or related plasmids yielded vastly reduced quantities of viral DNA and proteins. If SV40 DNA was cleaved from the plasmid, and then recircularized prior to microinjection, viral expression was regained. The inhibition by plasmid DNA was not confined to an effect in cis because coinjection of circular pBR322 DNA along with SV40 DNA, as separate entities, also blocked viral RNA and protein synthesis. As circular but not linear pBR322 DNA was actively transcribed by polymerase II in oocytes, even in the presence of SV40 DNA, it is likely that pBR322 competes for transcription factors required for viral gene expression. Injection of pBR322 as early as two hours after injection of SV40 DNA into the oocyte nucleus did not inhibit SV40 RNA synthesis, indicating that once initiated, SV40 transcription is stable and insensitive to the competition by plasmid DNA. A plasmid vector was developed that allows expression of SV40 DNA in Xenopus laevis oocytes.


Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes.
The in vitro effects of the recreational drugs, ethanol (EtOH) and nicotine, on natural killer (NK) antibody-dependent cellular cytotoxic (ADCC) and lymphokine-activated killer (LAK) cell activities on normal lymphocytes were investigated. Lymphocytes precultured with EtOH at concentrations of 0.4 and 0.6% (v/v) produced significant suppression of NK and ADCC activities. In target-binding assays, EtOH decreased the target-binding capacity of effector cells. EtOH also inhibited the activities of Percoll-separated, NK-enriched large granular lymphocytes. EtOH-induced inhibition of NK activity could be reversed by incubating lymphocytes for 1 hr with interferon. The generation and lytic capacity of LAK cells was also significantly depressed by EtOH when added at the initiation of culture. Nicotine at concentrations of 5 and 10 micrograms/ml, when added directly to mixtures of effector and target cells, produced significant inhibition of NK activity. Nicotine (2 micrograms/ml) and EtOH (0.01, 0.1, and 0.2%) at noninhibitory concentrations when added separately, showed significant suppression of NK activity when used in combination. Pretreatment of target cells with either EtOH or nicotine for 4 hr did not affect cytotoxic activity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or nicotine showed normal 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrate that EtOH and nicotine have significant immunomodulatory effects on the cytotoxic activities of human lymphocytes which may be of clinical relevance.


MR imaging of the postoperative meniscus: repair, resection, and replacement.
Meniscal surgery is one of the most common orthopedic procedures performed in clinical practice today. Increasing awareness of the importance of the meniscus in knee function and stability has resulted in abandonment of the once common complete meniscectomy in favor of meniscus-preserving surgeries and, in some circumstances, meniscal replacement. Although the accuracy of magnetic resonance imaging in the diagnosis of meniscal tears is well established, imaging of the postoperative meniscus has proved more challenging, with debate about the optimal imaging technique. This article discusses normal meniscal anatomy and biomechanics to serve as the background for understanding meniscal pathology and treatment. This is followed by a review of meniscal surgery, with emphasis placed on meniscal repair, partial meniscectomy, and meniscal transplantation. Finally, imaging modalities utilized in the assessment of the postoperative meniscus are reviewed, including their advantages and disadvantages.


Transcriptomic, Physiological, and Metabolomic Response of an Alpine Plant, Rhododendron delavayi, to Waterlogging Stress and Post-Waterlogging Recovery.
Climate change has resulted in frequent heavy and prolonged rainfall events that exacerbate waterlogging stress, leading to the death of certain alpine Rhododendron trees. To shed light on the physiological and molecular mechanisms behind waterlogging stress in woody Rhododendron trees, we conducted a study of Rhododendron delavayi, a well-known alpine flower species. Specifically, we investigated the physiological and molecular changes that occurred in leaves of R. delavayi subjected to 30 days of waterlogging stress (WS30d), as well as subsequent post-waterlogging recovery period of 10 days (WS30d-R10d). Our findings reveal that waterlogging stress causes a significant reduction in CO2 assimilation rate, stomatal conductance, transpiration rate, and maximum photochemical efficiency of PSII (Fv/Fm) in the WS30d leaves, by 91.2%, 95.3%, 93.3%, and 8.4%, respectively, when compared to the control leaves. Furthermore, the chlorophyll a and total chlorophyll content in the WS30d leaves decreased by 13.5% and 16.6%, respectively. Both WS30d and WS30d-R10d leaves exhibited excessive H2O2 accumulation, with a corresponding decrease in lignin content in the WS30d-R10d leaves. At the molecular level, purine metabolism, glutathione metabolism, photosynthesis, and photosynthesis-antenna protein pathways were found to be primarily involved in WS30d leaves, whereas phenylpropanoid biosynthesis, fatty acid metabolism, fatty acid biosynthesis, fatty acid elongation, and cutin, suberin, and wax biosynthesis pathways were significantly enriched in WS30d-R10d leaves. Additionally, both WS30d and WS30d-R10d leaves displayed a build-up of sugars. Overall, our integrated transcriptomic, physiological, and metabolomic analysis demonstrated that R. delavayi is susceptible to waterlogging stress, which causes irreversible detrimental effects on both its physiological and molecular aspects, hence compromising the tree's ability to fully recover, even under normal growth conditions.


COVID-19 modeling and non-pharmaceutical interventions in an outpatient dialysis unit.
This paper describes a data-driven simulation study that explores the relative impact of several low-cost and practical non-pharmaceutical interventions on the spread of COVID-19 in an outpatient hospital dialysis unit. The interventions considered include: (i) voluntary self-isolation of healthcare personnel (HCPs) with symptoms; (ii) a program of active syndromic surveillance and compulsory isolation of HCPs; (iii) the use of masks or respirators by patients and HCPs; (iv) improved social distancing among HCPs; (v) increased physical separation of dialysis stations; and (vi) patient isolation combined with preemptive isolation of exposed HCPs. Our simulations show that under conditions that existed prior to the COVID-19 outbreak, extremely high rates of COVID-19 infection can result in a dialysis unit. In simulations under worst-case modeling assumptions, a combination of relatively inexpensive interventions such as requiring surgical masks for everyone, encouraging social distancing between healthcare professionals (HCPs), slightly increasing the physical distance between dialysis stations, and-once the first symptomatic patient is detected-isolating that patient, replacing the HCP having had the most exposure to that patient, and relatively short-term use of N95 respirators by other HCPs can lead to a substantial reduction in both the attack rate and the likelihood of any spread beyond patient zero. For example, in a scenario with R0 = 3.0, 60% presymptomatic viral shedding, and a dialysis patient being the infection source, the attack rate falls from 87.8% at baseline to 34.6% with this intervention bundle. Furthermore, the likelihood of having no additional infections increases from 6.2% at baseline to 32.4% with this intervention bundle.


Pulmonary Necrobiotic Nodules at Time of Diagnosis in a Patient with Ulcerative Colitis.
Inflammatory bowel disease (IBD) is an umbrella term encompassing intestinal conditions Crohn's disease and ulcerative colitis (UC), characterized by inflammation of intestinal wall, differing in location, depth, pathophysiology, and sequela. Extraintestinal manifestations (EIM) of IBD commonly affect the skin, joints, eyes, and in rare instances, the lungs. Pulmonary involvement affects the large and small airways, serosal surface, and vasculature leading to a range of pathology, including bronchiectasis, pleural effusions, and necrobiotic nodules. The presence of EIM is uncommon at the diagnosis, particularly in regard to pulmonary EIM, most commonly seen years later. We present the case of a 22-year-old African American female who was discovered to have pulmonary involvement of her UC at the time of her diagnosis complicating management of her appendicitis. A 22-year-old female with a history of UC was transferred from an outside hospital for the management of her appendicitis after imaging revealed numerous pulmonary nodules. The presence of multiple cavitary pulmonary nodules delayed surgical intervention leading to a ruptured appendix. The patient had no cardiopulmonary complaints, and review of prior imaging studies showed these nodules to be present six weeks prior, the time of her diagnosis with UC. After antibiotic management failed, the patient required a laparotomy appendectomy with omentectomy due to resulting appendiceal abscess and phlegmon. The nodules were determined to be EIM of UC after sarcoidosis, infectious, and malignant etiologies were ruled out. For the pulmonary nodules, she is following at an outside hospital for the management of her UC as treatment of her underlying UC will result in a decrease or resolution of the EIM. EIM of IBD may present in patients at any time, even before their initial diagnosis of an IBD. While pulmonary manifestations are rare EIM, the presence of pulmonary nodules at the time of initial diagnosis is exceedingly uncommon. Evaluation and management of these nodules, even if asymptomatic in nature, requires diligence and thorough documentation regarding their onset and etiology. In the event of a medical emergency, such as in the case of our patient with appendicitis, a lack of thorough documentation and evaluation of the nodules may result in unnecessary medical testing, invasive procedures, and delay in treatment of their current medical illness.


The impact of inspired oxygen levels on calibrated fMRI measurements of M, OEF and resting CMRO2 using combined hypercapnia and hyperoxia.
Recent calibrated fMRI techniques using combined hypercapnia and hyperoxia allow the mapping of resting cerebral metabolic rate of oxygen (CMRO2) in absolute units, oxygen extraction fraction (OEF) and calibration parameter M (maximum BOLD). The adoption of such technique necessitates knowledge about the precision and accuracy of the model-derived parameters. One of the factors that may impact the precision and accuracy is the level of oxygen provided during periods of hyperoxia (HO). A high level of oxygen may bring the BOLD responses closer to the maximum M value, and hence reduce the error associated with the M interpolation. However, an increased concentration of paramagnetic oxygen in the inhaled air may result in a larger susceptibility area around the frontal sinuses and nasal cavity. Additionally, a higher O2 level may generate a larger arterial blood T1 shortening, which require a bigger cerebral blood flow (CBF) T1 correction. To evaluate the impact of inspired oxygen levels on M, OEF and CMRO2 estimates, a cohort of six healthy adults underwent two different protocols: one where 60% of O2 was administered during HO (low HO or LHO) and one where 100% O2 was administered (high HO or HHO). The QUantitative O2 (QUO2) MRI approach was employed, where CBF and R2* are simultaneously acquired during periods of hypercapnia (HC) and hyperoxia, using a clinical 3 T scanner. Scan sessions were repeated to assess repeatability of results at the different O2 levels. Our T1 values during periods of hyperoxia were estimated based on an empirical ex-vivo relationship between T1 and the arterial partial pressure of O2. As expected, our T1 estimates revealed a larger T1 shortening in arterial blood when administering 100% O2 relative to 60% O2 (T1LHO = 1.56±0.01 sec vs. T1HHO = 1.47±0.01 sec, P < 4*10-13). In regard to the susceptibility artifacts, the patterns and number of affected voxels were comparable irrespective of the O2 concentration. Finally, the model-derived estimates were consistent regardless of the HO levels, indicating that the different effects are adequately accounted for within the model.


Inhibition of P-glycoprotein ATPase activity by procedures involving trapping of nucleotide in catalytic sites.
Fluoroaluminate in combination with nucleotide inhibited ATPase activity of P-glycoprotein (Pgp) in plasma membranes and in pure reconstituted form. Low nucleotide concentrations were effective, e.g., half-maximal inhibition was obtained with 10 microM MgATP. With MgATP or MgADP, reactivation occurred with t1/2 = 7 min at 37 degrees C. With 8-azido-ATP, UV irradiation of inhibited Pgp gave specific photolabeling of both nucleotide sites. Fluoroaluminate therefore provides a valuable tool for functional and structural characterization of P-glycoprotein and probably of other ABC transporters. 2-Azido-ATP, in combination with vanadate, fluoroaluminate, or beryllium fluoride, inhibited Pgp ATPase activity. Low concentrations of 2-azido-ATP were effective. However, after UV irradiation of the inhibited Pgp species, in no case was there evidence of covalent labeling of nucleotide sites. Therefore in the Pgp catalytic sites, under conditions of nucleotide trapping, there is no suitable amino acid side chain adjacent to the photoactivated 2-position of bound 2-azido-nucleotide, and 8-azido-ATP is the preferred photolabeling analog.


Surfactant bolus instillation: effects of different doses on blood pressure and cerebral blood flow velocities.
Fifteen preterm infants suffering from respiratory distress syndrome were randomly allocated to receive either high-dose (200 mg/kg) or low-dose (100 mg/kg) surfactant treatment. Retreatments were done with the low dose. Blood pressure, blood gases and cerebral blood flow velocities were determined before and after 24 bolus instillations. With the high dose mean blood pressure and mean cerebral blood flow velocity dropped significantly. With the low dose only mean cerebral blood flow velocity decreased; the course was unrelated to blood pressure or PCO2 fluctuations. The mechanisms leading to the observed circulatory changes after surfactant instillation remain unclear.


Multidimensional latent trait linear mixed model: an application in clinical studies with multivariate longitudinal outcomes.
Multilevel item response theory (MLIRT) models have been widely used to analyze the multivariate longitudinal data of mixed types (e.g., categorical and continuous) in clinical studies. The MLIRT models often have unidimensional assumption, that is, the multiple outcomes are clinical manifestations of a univariate latent variable. However, the unidimensional assumption may be unrealistic because some diseases may be heterogeneous and characterized by multiple impaired domains with variable clinical symptoms and disease progressions. We relax this assumption and propose a multidimensional latent trait linear mixed model (MLTLMM) to allow multiple latent variables and within-item multidimensionality (one outcome can be a manifestation of more than one latent variable). We conduct extensive simulation studies to assess the unidimensional MLIRT model and the proposed MLTLMM model. The simulation studies suggest that the MLTLMM model outperforms unidimensional model when the multivariate longitudinal outcomes are manifested by multiple latent variables. The proposed model is applied to two motivating studies of amyotrophic lateral sclerosis: a clinical trial of ceftriaxone and the Pooled Resource Open-Access ALS Clinical Trials database. Copyright © 2017 John Wiley & Sons, Ltd.


Investigation of modality-specific distractibility in children.
Seventy-three nonreferred children were administered a battery of cognitive, academic and behavioral measures along with distinct tests of aural and visual distractibility. The data suggest that distractibility is modality specific. Completely distinct groups of visually- and aurally-distractible children were found. In addition, visual distractibility was associated with both a continuous performance test (CPT) measure of inattention and teacher ratings of behavior, but not with cognitive nor academic achievement measures. In contrast, aural distractibility was associated with cognitive functioning and reading scores, but not with the CPT inattention measure nor teacher behavior ratings.


Assuring reliable performance of antibiotic assay media.
The Microbiological Assay Branch of the National Center for Antibiotics Analysis assays over 100,000 samples of antibiotic products annually, using more than 1000 Ib dehydrated media. The media must be consistently dependable to produce accurate, reliable test results. To assure that the supply of media will meet the established requirements, each lot before purchase is subjected to a series of trials designed to examine growth support, sensitivity, and behavioral and physical factors. Actual antibiotic assays are conducted with the test medium, and performance is rated against a control medium. Controls on the system reduce the variables to allow appraisal of the medium itself.


Intraoperative enteroscopy for bleeding angiodysplasias of small intestine.
Six patients with angiodysplasias of the small intestine were diagnosed preoperatively with selective angiography during the past eight years. Enteroscopy was used to identify these vascular lesions intraoperatively. Lesions were ulcerated in four patients, had a bleeding vessel tip in one patient and appeared as a nonulcerated reddish patch in the other. Exact localization of these lesions allowed limited segmental resection of the small intestine to be performed. With complete enteroscopy, we were confident that no bleeding lesion was left undetected. The feeding artery and vein to the resected intestinal segment were separately cannulated, and the resected specimen was prepared and injected with hot barium-gelatine. The lesions were confirmed histopathologically to be angiodysplasias in all six patients. There was no recurrence of gastrointestinal bleeding at a median follow-up study of 34 months. There were no operative deaths, and no complications arose from enteroscopy.


Mechanistic Insights into the P450 TleB-Catalyzed Unusual Intramolecular C-N Bond Formation Involved in the Biosynthesis of Indolactam V.
Indolactam V, a known biosynthetic precursor of indolactam alkaloids, is the main pharmacophore of this family and exhibits potential protein kinase C activation. A key step in the biosynthesis of indolactam V is the formation of an indole-fused nine-membered lactam core by intramolecular C-N bond formation. In this work, we report a computational study of the unique cytochrome P450 TleB enzyme-catalyzed direct and selective C-H bond amination reaction that can generate indolactam V from the dipeptide N-methylvalyl-tryptophanol. By performing molecular dynamics simulations and quantum-mechanical/molecular-mechanical calculations, we revealed that the C-H bond amination involves one step of proton transfer from N1-H of the indole ring to the FeIV═O unit, one step of hydrogen abstraction of N13-H in the side chain of the substrate by the FeIV-OH unit, and diradical coupling, in which two conformational changes of the side chain of the substrate are necessary. In the enzyme-substrate complex of TleB, the N-H bond of the indole ring of the substrate forms a strong hydrogen bond with the FeIV═O unit in compound I, and the porphyrin radical cation accepts an electron from the substrate to form the closed-shell electronic configuration. Thus, compound I in the enzyme-substrate complex cannot be described as FeIV═O coupled to a porphyrin radical cation, which is different from those of other P450 enzymes. Besides, two stages of conformational changes of the side chains of the substrate may increase the relative energies of reaction intermediates by 10-12 kcal/mol. From the structure point of view, it is the rotatable long side chain of the substrate and the large flexible active pocket of TleB that make the intramolecular diradical coupling feasible. Our findings may provide useful information to further understand the Tleb-catalyzed intramolecular C-H bond amination and the other bio-catalyzed intramolecular diradical coupling.


Extreme material parameters accessible by active acoustic metamaterials with Willis coupling.
Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.


Vascular Stem/Progenitor Cell Migration and Differentiation in Atherosclerosis.
Atherosclerosis is a major cause for the death of human beings, and it takes place in large- and middle-sized arteries. The pathogenesis of the disease has been widely investigated, and new findings on vascular stem/progenitor cells could have an impact on vascular regeneration. Recent Advances: Recent studies have shown that abundant stem/progenitor cells present in the vessel wall are mainly responsible for cell accumulation in the intima during vascular remodeling. It has been demonstrated that the mobilization and recruitment of tissue-resident stem/progenitor cells give rise to endothelial and smooth muscle cells (SMCs) that participate in vascular repair and remodeling such as neointimal hyperplasia and arteriosclerosis. Interestingly, cell lineage tracing studies indicate that a large proportion of SMCs in neointimal lesions is derived from adventitial stem/progenitor cells. The influence of stem/progenitor cell behavior on the development of atherosclerosis is crucial. An understanding of the regulatory mechanisms that control stem/progenitor cell migration and differentiation is essential for stem/progenitor cell therapy for vascular diseases and regenerative medicine. Identification of the detailed process driving the migration and differentiation of vascular stem/progenitor cells during the development of atherosclerosis, discovery of the environmental cues, and signaling pathways that control cell fate within the vasculature will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis. Antioxid. Redox Signal. 00, 000-000.


A web-based algorithm to rapidly classify seizures for the purpose of drug selection.
To develop and validate a pragmatic algorithm that classifies seizure types, to facilitate therapeutic decision-making. Using a modified Delphi method, five experts developed a pragmatic classification of nine types of epileptic seizures or combinations of seizures that influence choice of medication, and constructed a simple algorithm, freely available on the internet. The algorithm consists of seven questions applicable to patients with seizure onset at the age of 10 years or older. Questions to screen for nonepileptic attacks were added. Junior physicians, nurses, and physician assistants applied the algorithm to consecutive patients in a multicenter prospective validation study (ClinicalTrials.gov identifier: NCT03796520). The reference standard was the seizure classification by expert epileptologists, based on all available data, including electroencephalogram (EEG), video-EEG monitoring, and neuroimaging. In addition, physicians working in underserved areas assessed the feasibility of using the web-based algorithm in their clinical setting. A total of 262 patients were assessed, of whom 157 had focal, 51 had generalized, and 10 had unknown onset epileptic seizures, and 44 had nonepileptic paroxysmal events. Agreement between the algorithm and the expert classification was 83.2% (95% confidence interval = 78.6%-87.8%), with an agreement coefficient (AC1) of .82 (95% confidence interval = .77-.87), indicating almost perfect agreement. Thirty-two health care professionals from 14 countries evaluated the feasibility of the web-based algorithm in their clinical setting, and found it applicable and useful for their practice (median = 6.5 on 7-point Likert scale). The web-based algorithm provides an accurate classification of seizure types, which can be used for selecting antiseizure medications in adolescents and adults.


Is gene therapy a form of eugenics?
If, as I believe, gene therapy is in principle ethically sound except for its possible connection with eugenics then there are two obvious ways of giving a simple and straightforward answer to a question such as this. The first is to say "yes it is, and so what?" The second is to say "no it isn't so we shouldn't worry". If we accept the first of the above definitions we might well be inclined to give the first of our two answers. If on the other hand, we accept the sort of gloss that Ruth Chadwick gives on Galton's account, "those who are genetically weak should simply be discouraged from reproducing", either by incentives or compulsory measures, we get a somewhat different flavour, and one which might incline a decent person who favours gene therapy towards the second answer.


Surgical Repair of Congenital Abdominal Aortic Aneurysm in a 1-year-old Child with Literature Review.
Reported here is a case of 1-year-old male child who presented with huge abdominal mass, which on radiological investigation was diagnosed as retroperitoneal pseudoaneurysm of the aorta. On exploration, it was found to be a true aneurysm of infrarenal abdominal aorta with inflow agenesis. Aneurysm was excised, and aorta was reconstructed with 10 mm Dacron graft. Postoperative computed tomography angiography showed patent graft with good distal runoff. Literature review revealed that only 26 cases of congenital abdominal aortic aneurysm had been reported so far. None of them had inflow agenesis which can give false impression of pseudoaneurysm on preoperative evaluation. The case highlights the utility of additional complimentary investigations such as Doppler study in clinching diagnosis and helping plan and execute successful treatment in the difficult diagnostic scenario.


Toward an African American genogram.
This article addresses the inadequacy of the standard genogram for African American families because of its underlying assumption that "family" is strictly a biological entity. The author suggests that this assumption is not culturally valid for African American families who have a long history of defining "family" as a kinship based on biological and functional ties. Using this conceptualization, an African American genogram is proposed.


Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists.
4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists.


HSV-1 ICP22: hijacking host nuclear functions to enhance viral infection.
During its productive infection, HSV-1 dramatically remodels the architecture and physiology of the host cell nucleus. The immediate-early proteins, the first viral proteins to be expressed during infection, are key players in this process. Here, we review the known properties and functions of immediate-early protein ICP22. Although this polypeptide has received less attention than other immediate-early proteins, the published evidence indicates that it mediates several striking changes to important host nuclear systems, including those involved in RNA polymerase II transcription, cell cycle regulation and protein quality control. Recent genetic analyses suggest that these alterations can promote HSV-1 productive infection. Thus, future work on ICP22 is likely to reveal novel mechanisms by which herpesviruses, and possibly other DNA viruses, manipulate the host cell nucleus to enhance their replication.


Safety and Traceability in Patient Healthcare through the Integration of RFID Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration-Dispensation-Administration Circuit to Day Hospital Patients.
This work presents the integration of the RFID technology with the aim of ensuring the traceability of patients and minimization of adverse events during the process of prescription-validation-elaboration-dispensation-administration of medication by means of the implementation of various passive and active WIFI RFID systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario Universitario A Coruña. Obtaining patient traceability and using the patient/drug binomial during this process allows us to minimize the occurrence of adverse events. The key points in this work are the unmistakably unique identification and accurate real time location of the controlled items (patients and medication). RFID technology has proved to be invaluable in assisting with the everyday clinical practice of a hospital, and has been successfully implemented in this environment and others. In services such as the day hospital, the implementation of said technology is further justified by the high costs of the service and the high risk to the patient.


The interaction of protein-bound heparin and antithrombin III.
When commercially prepared porcine mucosal heparin is added to human plasma, some of the heparin fractions form a complex with antithrombin III activating it to an immediate inhibitor of thrombin as well as of other serine proteases. Certain fractions of heparin may complex with other proteins such as alpha 2-macroglobulin, another progressive inhibitor of thrombin. Without complexing with antithrombin III, this protein-bound heparin fraction(s) still retains the capacity to activate it to an immediate inhibitor of thrombin. Protamine sulfate inactivates those heparin fractions that bind to antithrombin III but not those bound to alpha 2-macroglobulin. Activated antithrombin III may undergo a molecular change in the presence of protamine which not only changes it back to a progressive inhibitor but makes it resistant to activation by the protein-bound heparin fraction(s). However, it can still be reactivated by other heparin fractions in fresh whole heparin. The observations presented may help explain heparin "rebound" in patients believed adequately neutralized with protamine.


Calcific tendonitis of the longus colli muscle: a noninfectious cause of retropharyngeal fluid collection.
Calcific tendonitis of the longus colli (CTLC) muscle is an underrecognized cause of spontaneous acute or subacute neck pain, dysphagia, or odynophagia. Imaging may reveal a retropharyngeal fluid collection leading to the presumed diagnosis of retropharyngeal abscess. Recognition of this uncommon presentation is important to prevent unnecessary surgical incision and drainage. A 44-year-old otherwise healthy male presented with a 2-week history of progressive neck pain, stiffness, and odynophagia. A noncontrast CT scan of the cervical spine revealed a retropharyngeal fluid collection with a small area of calcification anterior to C2. There was a presumed diagnosis of retropharyngeal abscess. The patient was afebrile with normal vital signs. Flexible nasolaryngoscopy was unremarkable. C-reactive protein was elevated but all other bloodwork was normal with no evidence of an infective process. A CT scan was repeated with IV contrast showing no enhancement around the fluid collection. A diagnosis of CTLC was made. The patient was successfully managed with a short course of intravenous steroids and oral NSAIDs with complete resolution of symptoms. Clinically CTLC can mimic more serious disease processes. Identifying pathognomonic imaging findings often confirms the diagnosis. Awareness of this condition by the otolaryngologist will ensure proper patient management and avoidance of unnecessary procedures.


Affect in response to stressors and coping strategies: an ecological momentary assessment study of borderline personality disorder.
Affect instability is a core symptom of borderline personality disorder (BPD). Ecological momentary assessment allows for an understanding of real-time changes in affect in response to various daily stressors. The purpose of this study was to explore changes in affect in response to specific stressors and coping strategies in subjects with BPD utilizing ecological momentary assessment (EMA) methodology. Subjects (n = 50) with BPD were asked to complete real-time assessments about stressors experienced, affect felt, and coping strategies employed six times per day for a 1-week period. Mixed effect regression models were used to measure the effect of stressors and coping strategies on affect change. While most stressors led to experiencing more negative affect, only being in a disagreement was independently associated with increased negative affect. Among coping strategies, only doing something good for oneself independently reduced negative affect, controlling for all other coping strategies used. These findings provide valuable insights into affective instability in BPD and can help inform treatment with individuals with the disorder.


Spleen-preserving distal pancreatectomy.
Splenectomy is routinely performed in conventional distal pancreatectomies. Spleen removal with its possible sequelae of infections and haematological complications has prompted the development of spleen-preserving techniques. This study aimed to evaluate the safety and clinical outcomes of distal pancreatectomy with preservation of the spleen. A retrospective review of 24 consecutive patients who underwent spleen-preserving distal pancreatectomy in a tertiary care hospital was conducted. There were 17 female and seven male patients, and the mean age was 47 (range 14-77) years. Median American Society of Anesthesiologists score was II (range I-III) . The indications were as follows : mucinous cystadenoma (n = 7), serous cystadenoma (n = 6), insulinoma (n = 3), intraductal papillary mucinous tumour (n = 2), pseudocyst (n = 3), papillary cystic adenoma (n = 1), neuroendocrine neoplasm (n = 1), and metastatic carcinoma of the thyroid (n = 1). Two patients developed postoperative pancreatic fistula and another two patients developed postoperative ileus with spontaneous resolution. Mean operative time was 172 (range 105-250) minutes. Mean length of postoperative hospital stay was 6.7 (range 5-11) days. There was no perioperative mortality in this series. Spleen-preserving distal pancreatectomy can be safely performed with low morbidity, and should be considered in the surgical management of distal pancreatic disease.


Adaptive modifications in the thermoregulatory system of long-distance runners.
In seven long-distance runners (42 km or more) the thermoregulatory responses to acute external cooling and heating, under resting conditions, were recorded and compared with those in physically untrained controls. Sweating as well as shivering thresholds were significantly decreased in the runners when compared either in terms of mean body temperature (Tb) or esophageal temperature (Tes); Tb and Tes were reduced in the runners at rest under thermoneutral conditions. Moreover, cold sensation in the runners occurred at lower Tb. The runners thus behaved as if the "set point" of their thermoregulatory system had been reset to a lower level. As for the sweating threshold, the shift is quantitatively comparable to that found in heat adaptation. The described modifications in long-distance runners would prolong the time period until a dangerous body temperature-one of the important limiting factors in physical endurance-is reached during heavy exercise.


[Bellini duct carcinoma of kidney with invasive growth pattern: a case report].
We report a case of Bellini duct carcinoma of the left kidney with invasive growth pattern. A 39-year-old man was admitted to our hospital with the chief complaint of gross hematuria. Ultrasonography showed left renal swelling but normal reniform configuration of the kidney was maintained. Computed tomography demonstrated a low density tumor infiltrating into the renal cortex and with tumor extension into the renal vein. Renal angiography revealed a hypovascular tumor. We suspected a left renal cell carcinoma with tumor extension into the left renal vein, and performed radical nephrectomy. Macroscopically, the resected kidney had a normal outer contour. The tumor with infiltrative growth pattern existed in renal medulla. Histopathologic examination revealed a papillary adenocarcinoma originated in Bellini duct (pT3bN2M0). The patient underwent systemic chemotherapy (M-VAC). This case showed invasive growth pattern, which were different from the usual renal cell carcinoma and Bellini duct carcinoma.


Spectral densities for Frenkel exciton dynamics in molecular crystals: A TD-DFTB approach.
Effects of thermal fluctuations on the electronic excitation energies and intermonomeric Coulomb couplings are investigated for a perylene-tetracarboxylic-diimide crystal. To this end, time dependent density functional theory based tight binding (TD-DFTB) in the linear response formulation is used in combination with electronic ground state classical molecular dynamics. As a result, a parametrized Frenkel exciton Hamiltonian is obtained, with the effect of exciton-vibrational coupling being described by spectral densities. Employing dynamically defined normal modes, these spectral densities are analyzed in great detail, thus providing insight into the effect of specific intramolecular motions on excitation energies and Coulomb couplings. This distinguishes the present method from approaches using fixed transition densities. The efficiency by which intramolecular contributions to the spectral density can be calculated is a clear advantage of this method as compared with standard TD-DFT.


Salt-induced oligomerization of partially folded intermediates of equinatoxin II.
Equinatoxin II (EqTxII) is a cytolytic, water-soluble protein which binds to and forms cation-selective pores in lipid membranes. To characterize the native and denatured states of EqTxII and to elucidate the biological role of its oligomers, we have studied salt-dependent heat-induced conformational transitions of EqTxII. To this end, we have employed a variety of experimental techniques, including differential scanning calorimetry, circular dichroism and light absorption spectroscopy, ultrasonic velocimetry, electron microscopy, PAGE, and a hemolytic activity assay. This experimental combination has enabled us to monitor and structurally and thermodynamically characterize temperature-induced conformational transitions and oligomerization of EqTxII at different concentrations of NaCl. At pH 3.0 and 25 degrees C, EqTxII retains its native conformation and remains hemolytically active over a broad range of NaCl concentrations. However, an increase in the salt concentration results in a diminution of the thermal stability of EqTxII. Specifically, the calorimetrically determined denaturation temperature, T(d), and enthalpy, DeltaH(cal), of the toxin decrease with an increase in the salt concentration. Our CD data suggest that the heat-induced denatured state of EqTxII lacks rigid tertiary structure while exhibiting well-defined secondary structure. The amount of the induced, non-native secondary structure of EqTxII depends on the solution ionic strength, temperature, time of incubation at an elevated temperature, and protein concentration. Our combined results suggest that, in the presence of salt, an increase in temperature results in formation of the partially unfolded state of the toxin that oligomerizes and forms biologically inactive, water-soluble aggregates.


[Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial ischemia/reperfusion injury].
The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) on major ion transporters were studied in canine cardiac sarcolemmal and sarcoplasmic reticular vesicles. KB-R7943 inhibited the Na+/Ca2+ exchange more potently than the Na+/H+ exchange, the Na+/K(+)-ATPase and the Ca2(+)-ATPase. The effects of KB-R7943 on ischemia/reperfusion-induced injury were studied in isolated rat perfused hearts in comparison with those of diltiazem and lidocaine. In normal hearts, diltiazem (10 microM) and lidocaine (100 microM) markedly reduced contractile function, but KB-R7943 (1, 10 microM) had no such effect. In the hearts subjected to 25-min ischemia and 30-min reperfusion, KB-R7943 concentration-dependently and significantly improved post-ischemic recovery of left ventricular developed pressure, left ventricular dP/dtmax and left ventricular end-diastolic pressure by pre-ischemic treatment (5 min) or post-ischemic treatment (10 min). Diltiazem and lidocaine showed similar improvement of recovery by pre-ischemic treatment, but they had no effect by post-ischemic treatment. Furthermore, the effect of KB-R7943 on arrhythmia was studied in anesthetized rats subjected to 5-min cardiac ischmeia and 10-min reperfusion. KB-R7943 (1, 10 mg/kg, i.v.) dose-dependently reduced the incidence and the duration of ventricular fibrillation. These results indicate that KB-R7943, a selective Na+/Ca2+ exchange inhibitor, has beneficial effects against myocardial ischemia/reperfusion injury and suggest that activation of the Na+/Ca2+ exchange mainly occurs immediately after reperfusion in the pathophysiological process of myocardial ischemia/reperfusion injury.


Prevention of H2O2-induced red blood cell lipid peroxidation and hemolysis by aqueous extracted turmeric.
The protective effect of the aqueous extracted turmeric antioxidant protein on H2O2-induced red blood cell lipid peroxidation and hemolysis was investigated. Turmeric antioxidant protein inhibited lipid peroxidation and hemolysis by 70% and 80%, respectively, and was found to be more effective as an antioxidant than were -tocopherol and curcumin.


[Methods and technique of investigations in the course of sport activities of children (author's transl)].
In order to carry out investigations in the course of sport activities of children an efficient telemetering device is essential, which can also be used on children. The Kinderspital Salzburg has developed a telemetry system in cooperation with the Technische Versuchs- und Forschungsanstalt der Technischen Hochschule Wien and the Messerschmitt-Bölkow-Blohm-Werke München. For the first time in this field a Pulse Code Modulation (P.C.M.) System was utilized, implying high accuracy on data transmission and recovery as required for scientific examinations. The children's physical capacity is determined on a bicycle ergometer, and the performance measured in this fashion is then compared with the performance achieved in sport.


Families that fire together smile together: Resting state connectome similarity and daily emotional synchrony in parent-child dyads.
Despite emerging evidence suggesting a biological basis to our social tiles, our understanding of the neural processes which link two minds is unknown. We implemented a novel approach, which included connectome similarity analysis using resting state intrinsic networks of parent-child dyads as well as daily diaries measured across 14 days. Intrinsic resting-state networks for both parents and their adolescent child were identified using independent component analysis (ICA). Results indicate that parents and children who had more similar RSN connectome also had more similar day-to-day emotional synchrony. Furthermore, dyadic RSN connectome similarity was associated with children's emotional competence, suggesting that being neurally in-tune with their parents confers emotional benefits. We provide the first evidence that dyadic RSN similarity is associated with emotional synchrony in what is often our first and most essential social bond, the parent-child relationship.


Cytomegalovirus infection in children who underwent hematopoietic stem cell transplantation at a single center: a retrospective study of the risk factors.
CMV infection is one of the major causes of morbidity and mortality after HSCT. The aim of this single center retrospective study was to analyze risk factors for CMV infection in pediatric patients who underwent HSCT. We retrospectively reviewed the medical records of 117 pediatric patients who underwent allogeneic HSCT at Asan Medical Center between December 2000 and January 2007. After HSCT, CMV antigenemia was detected by identifying CMV pp65 early antigen in white blood cells. The incidence of CMV antigenemia was 24% (28/117) at a median of 38 days (range: 19-123 days) after HSCT. In multivariate analysis, CMV antigenemia occurred significantly more often in CMV seropositive recipients, patients who received grafts from alternative donors, T-cell depleted grafts, patients on ATG-containing conditioning regimens, or patients who received steroid for acute GVHD (p < 0.05). CMV antigenemia tend to develop earlier in patients who received ATG-containing conditioning regimens (p = 0.09). A second episode of CMV antigenemia was observed in three out of 28 patients (11%). The incidence of CMV disease was 5.9% (7/117) at a median of 97 days (range: 34-120 days). Manifestation of CMV disease included retinitis in two, pneumonitis in two, hepatitis in one, hepatitis with colitis in one, and gastritis in one. Six of the 12 patients (50%) with HG antigenemia (CMV pp65 antigen positivity > or =40 cells) developed clinical CMV disease, a rate that was significantly higher than seen in patients with LG antigenemia (6.25%; p < 0.01). We recommend that patients with these risk factors should carefully undergo regular evaluations for CMV infection. We also suggest that earlier and more aggressive preemptive treatment and serial follow-up of CMV disease is necessary in patients with HG-antigenemia.