[An investigation of TS-1 single-agent therapy administered as first-line therapy for unresectable advanced gastric cancer].
We report an investigation of the therapeutic efficacy and safety of TS-1 single-agent therapy administered as first-line therapy in 23 cases of unresectable advanced gastric cancer treated at our institution. TS-1 was administered at 80 mg-120 mg (divided into two doses) per day for 28 days followed by a 14-day rest interval, making up a single cycle. The response rate for its antitumor efficacy was 39.1%, with partial response in nine cases, no change in seven cases, progressive disease in five cases, and two cases not evaluable (9 5% confidence interval: 19.7%-61.5%). By site, the response rate was 43.5% for primary tumors (10/23), 33.3% for lymph nodes (3/9), and 16.7% for liver metastasis (1/6). In 1 patient, the carcinomatous ascites disappeared,and in 3 patients they decreased remarkably. No significant differences were observed with regard to age (70 and over/under 70) or histological type (differentiated/undifferentiated). The one-year survival rate was 32.8%, and the 50% survival period was 29 9 days. The most common side effect was leucopenia in seven cases (30.4%), followed by decreased hemoglobin, loss of appetite, hepatic dysfunction and the like. Most side effects, however, were mild and did not exceed grade 2; grade 3 side effects were seen only in two cases (8.7%) of leucopenia and two (8.7%) of hepatic dysfunction, a low rate of occurrence. The outpatient follow-up ratio(outpatient period/total treatment period) was high at 69.6%, meaning that first-line single-agent therapy with TS-1 is beneficial in terms not only of efficacy but also in maintaining quality of life.


A Case of the Intrapulmonary Spread of Recurrent Respiratory Papillomatosis With Malignant Transformation.
To describe an individual with recurrent respiratory papillomatosis that extended into the lung parenchyma and underwent malignant transformation and to discuss the characteristic imaging findings associated with this condition. The clinical presentation of an individual with this unusual malignant transformation was reviewed. A literature search was performed to characterize the epidemiology, imaging findings and management of this condition. The patient underwent 30 courses of surgery over 21 years and presented disseminated pulmonary papilloma after childbirth. The interval between dissemination into the lung and malignant transformation was 2.5 years. The tracheal papilloma was positive for type 6 of human papilloma virus (HPV-6). She died because she refused further treatment. The clinician should have a high index of suspicion for lung papillomatosis in patients with a tracheotomy. Appropriate diagnostic imaging studies will be helpful in reaching this diagnosis and determining whether a malignancy exists. Treatment options have limited success when lung papillomatosis becomes malignant.


The reciprocal interaction between fluoride release of glass ionomers and acid production of Streptococcus mutans biofilm.
The aim of this study was to demonstrate the mode of action of glass ionomers (G-Is) against cariogenic biofilms in the slow fluoride release phase by analyzing the reciprocal interaction between fluoride release from G-Is and acid production of Streptococcus mutans biofilm. G-Is discs in the slow fluoride release phase were prepared and 51 h-old S. mutans biofilms were formed on these discs. The interrelationship between the acid production of the biofilm and the fluoride release of the G-Is discs was investigated by analyzing both factors simultaneously during the biofilm formation period. The composition of the 51 h-old biofilms was then examined using microbiological, biochemical, and confocal laser scanning microscopic methods. Acid production by the cariogenic biofilm, particularly at < pH 5, promotes G-Is fluoride release. Conversely, G-Is fluoride release inhibits the acid production of the cariogenic biofilm. This reciprocal interaction results in the reduction of virulence such as extracellular polysaccharides formation and cariogenic biofilm bio-mass, which may reduce the potential of secondary caries development around G-Is. These results suggest that G-Is may play a role in preventing the development of secondary caries during the slow fluoride release phase.


Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.
In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.


Mild cognitive impairment: what's in a name?
Nowadays the term mild cognitive impairment (MCI) is used to fill the gap between cognitive changes associated with normal ageing and those associated with dementia. Despite some agreement in general definitions, MCI is still a heterogeneous clinical syndrome for which no DSM-IV criteria have yet been established. Criteria by Petersen et al. are presently the most applied in clinical practice. Moreover, little attention has been paid to the specific relation between MCI and depression. This review highlights some concerns about the concept of MCI and provides guidelines within the field of neuropsychology to solve them. In a second part, the paper focuses on the specific relationship between depression in the elderly and MCI. We hypothesize that certain test instruments can be used to operationalize the criteria proposed by Petersen et al. Moreover, we suggest that cued recall might be of help to differentiate between progressive and non-progressive MCI. Concerning the specific relation between depression and MCI, we assume that elderly depression with concomitant cognitive problems can be seen as an MCI. The proposed adjustments and additions (neuropsychological instruments and the incorporation of depressive symptoms) in the diagnostic flowchart of Petersen may serve as useful tools for clinicians when making a diagnosis of MCI.


Dexmedetomidine as an Additive to Spinal Anaesthesia in Orthopaedic Patients Undergoing Lower Limb Surgeries: A Randomized Clinical Trial Comparing Two Different Doses of Dexmedetomidine.
Use of dexmedetomidine as an additive to spinal anaesthesia is gaining popularity; but there seems to be no clear consensus on the ideal dose to be used. Because of dose related prolongation of duration of motor blockade along with increase in the incidence of side effects of dexmedetomidine namely hypotension and bradycardia, use of higher doses is not recommended. To evaluate the efficacy of two different doses of dexmedetomidine (3 μg and 5 μg) given in combination with 0.5% hyperbaric bupivacaine via intrathecal route with regard to the quality of anaesthesia namely the time to attain highest sensory and motor blockade, side effects of dexmedetomidine and time to first rescue analgesia. Sixty American Society of Anaesthesiologist (ASA) Grade I and II orthopaedic patients undergoing lower limb surgeries between the ages of 20-60 years and height >150 cm were randomly divided into two groups of 30 patients each: Group D3 to receive 3 μg of Inj. Dexmedetomidine (0.5 ml, reconstituted using normal saline) along with 12.5 mg (2.5 ml) of 0.5% hyperbaric bupivacaine and Group D5 to receive 5 μg of inj. Dexmedetomidine (0.5 ml, reconstituted using normal saline) along with 12.5 mg (2.5 ml) of 0.5% hyperbaric bupivacaine keeping the total volume of study drug constant in all 60 patients (3 ml). Data recordings were done for time to reach best sensory and motor block, intraoperative haemodynamic changes and time to first postoperative rescue analgesia. Statistical analysis was done using student's t-test and Chi-square test with p-value of <0.05 considered to be significant. The two groups analysed were similar in terms of demographic profile, time to reach highest sensory block (T10) dermatome, time to reach Bromage scale 4, time to surgical incision after spinal and the total duration of surgery (p>0.05). The change in haemodynamics was similar (p>0.05). A statistically significant difference (p<0.001) was observed in time to first rescue analgesia after skin closure with Group D3 having 206.47 minutes while in Group D5 the time was 271.33 minutes. Used in a dose of 5 μg (in 0.5 ml volume) as an additive in spinal anaesthesia maximal beneficial effect of dexmedetomidine can be obtained without any side effects.


Insulin requirements in 242 patients with type II diabetes mellitus.
The purpose of this study was to determine the subcutaneous insulin requirements for rapid, effective regulation of blood glucose in patients with poorly controlled type II diabetes mellitus by using an intravenous insulin infusion protocol. The insulin infusion achieved a mean (+/-SD) overnight blood glucose concentration of 101 +/- 15 mg/dL and 24-hour glucose concentration of 118 +/- 18 mg/dL. The intravenous insulin requirement of 81 +/- 32 U/day correlated well (P<0.001) with the subsequent subcutaneous insulin requirement of 84 +/- 43 U/day necessary to maintain preprandial glucose values of 112 +/- 15 mg/dL. Insulin requirements ranged from 0.2 to 2.0 U/kg per day (95% confidence interval, 0.4 to 1.6). Weaker correlations were noted between total insulin requirements and weight (r = 0.60) or body mass index (r = 0.57); no correlations were observed with age, duration of diabetes, or antecedent glycemic control as reflected by glycosylated hemoglobin values. These findings may be useful for initiating insulin treatment on an ambulatory basis.


[The application of the modern phototherapeutic technologies for the medical rehabilitation of the children].
This literature review is focused on the application of polychromatic and monochromatic polarized light for the treatment of various diseases of the childhood including those in the newborns and the premature babies. The analysis of the data of scientific research gives evidence of the beneficial effect of polychromatic polarized light on the clinical course of various skin diseases in the newborn children. Moreover, the improved immunological and reparative processes were revealed after the surgical interventions for congenital heart defects in the newborns. The light-induced changes in the skin contribute to the realization of therapeutic effects of polarized polychromatic light in such children's diseases as atopic dermatitis, bronchitis, bronchial asthma, neurogenic urinary bladder dysfunction, and the traumatic injuries of the limbs. The biologically positive physiological effects of monochromatic polarized light are known to contribute to the improvement of the clinical and functional status in the children presenting with bronchial asthma and in the patients frequently suffering from acute respiratory diseases. The versatility of the biological effects of polarized light taken together with the possibility of its application from the first days of the child's life, the short duration of the procedure, the absence of unpleasant sensations and contact between the damaged surface and the device as well as the simplicity of using the equipment determine the promising prospects for the use of the proposed method in the clinical pediatric practice.


Genome-wide mapping of matrix attachment regions in Drosophila melanogaster.
Eukaryotic genome acquires functionality upon proper packaging within the nucleus. This process is facilitated by the structural framework of Nuclear Matrix, a nucleo-proteinaceous meshwork. Matrix Attachment Regions (MARs) in the genome serve as anchoring sites to this framework. Here we report direct sequencing of the MAR preparation from Drosophila melanogaster embryos and identify >7350 MARs. This amounts to ~2.5% of the fly genome and often coincide with AT rich non-coding regions. We find significant association of MARs with the origins of replication, transcription start sites, paused RNA Polymerase II sites and exons, but not introns, of highly expressed genes. We also identified sequence motifs and repeats that constitute MARs. Our data reveal the contact points of genome to the nuclear architecture and provide a link between nuclear functions and genomic packaging.


Molecular identification of species of Taenia causing bovine cysticercosis in Ethiopia.
Bovine cysticercosis causing damage to the beef industry is closely linked to human taeniasis due to Taenia saginata. In African countries, Taenia spp. from wildlife are also involved as possible sources of infections in livestock. To identify the aetiological agents of bovine cysticercosis in Ethiopia, cysticerci were collected from 41 cattle slaughtered in the eastern and central areas during 2010-2012. A single cysticercus per animal was subjected to the polymerase chain reaction (PCR)-based DNA sequencing of mitochondrial cytochrome c oxidase subunit 1 gene, and the resultant sequence was compared with those of members of the genus Taenia. Although 38 out of 41 cysticerci (92.7%) were identified as T. saginata, three samples (7.3%) showed the hitherto unknown sequences of Taenia sp., which is distantly related to Taenia solium, Taenia arctos and Taenia ovis. Old literatures suggest it to be Taenia hyaenae, but morphological identification of species could not be completed by observing only the larval samples.


Extended N-sulfated domains reside at the nonreducing end of heparan sulfate chains.
Heparan sulfate (HS) serves as a cell-surface co-receptor for growth factors, morphogens, and chemokines. These HS and protein binding events depend on the fine structure and distribution of domains along an HS chain. A given domain can vary in terms of uronic acid epimer, N- and O-sulfate, and N-acetate content. The most highly sulfated regions of HS chains, N-sulfated (NS) domains, play prominent roles in HS and protein binding. We have analyzed HS oligosaccharides from various mammalian sources and provide evidence that NS domains residing at the nonreducing end (NRE) are, on average, longer than those residing in the internal regions of the chain. Additionally, they are more highly sulfated than their internal counterparts. These features are independent of the sulfation pattern of the bulk HS chains. From disaccharide analysis, it is clear that NS domains do not always occupy HS NREs. However, when they do, they tend to terminate in a subset of N-sulfated disaccharides. Our observations are consistent with a significant role of NRE NS domains in HS-growth factor interactions.


Combination Gene Delivery Reduces Spinal Cord Pathology in Rats With Peripheral Neuropathic Pain.
Although peripheral neuropathic pain is caused by peripheral nerve injury, it is not simply a peripheral nervous system disease. It causes abnormalities in both the central and peripheral nervous systems. Pathological phenomena, such as hyperactivation of sensory neurons and inflammation, are observed in both the dorsal root ganglion and spinal cord. Pain signals originating from the periphery are transmitted to the brain via the SC, and the signals are modulated by pathologically changing SC conditions. Therefore, the modulation of SC pathology is important for peripheral NP treatment. We investigated the effects of KLS-2031 (recombinant adeno-associated viruses expressing glutamate decarboxylase 65, glial cell-derived neurotrophic factor, and interleukin-10) delivered to the dorsal root ganglion on aberrant neuronal excitability and neuroinflammation in the SC of rats with peripheral NP. Results showed that KLS-2031 administration restored excessive excitatory transmission and inhibitory signals in substantia gelatinosa neurons. Moreover, KLS-2031 restored the in vivo hypersensitivity of wide dynamic range neurons and mitigated neuroinflammation in the SC by regulating microglia and astrocytes. Collectively, these findings demonstrated that KLS-2031 efficiently suppressed pathological pain signals and inflammation in the SC of peripheral NP model, and is a potential novel therapeutic approach for NP in clinical settings. PERSPECTIVE: Our study demonstrated that KLS-2031, a combination gene therapy delivered by transforaminal epidural injection, not only mitigates neuroinflammation but also improves SC neurophysiological function, including excitatory-inhibitory balance. These findings support the potential of KLS-2031 as a novel modality that targets multiple aspects of the complex pathophysiology of neuropathic pain.


Characterizing current noise of commercial constant-current sources by using an optically pumped rubidium atomic magnetometer.
This paper introduces a method for characterizing the current noise of commercial constant-current sources (CCSs) using a free-induction-decay (FID) type optically pumped rubidium atomic magnetometer driven by a radio frequency magnetic field. We convert the sensitivity of the atomic magnetometer into the current noise of CCS by calibrating the coil constant. At the same time, the current noise characteristics of six typical commercial low-noise CCSs are compared. The current noise level of the Keysight model B2961A is the lowest among the six tested CCSs, which is 36.233 ± 0.022 nA/Hz1/2 at 1-25 Hz and 133.905 ± 0.080 nA/Hz1/2 at 1-100 Hz. The sensitivity of the atomic magnetometer is dependent on the current noise level of the CCS. The CCS with low noise is of great significance for high-sensitivity atomic magnetometers. This research provides an important reference for promoting the development of high precision CCS, metrology, and basic physics research.


The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc.
Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate that targeting PCAT-1 with miR-3667-3p, which does not target MYC, is able to reverse the stabilization of cMyc by PCAT-1. This work establishes a basis for the oncogenic role of PCAT-1 in cancer cell proliferation and is the first study to implicate lncRNAs in the regulation of cMyc in prostate cancer.


Factors associated with post-cesarean stillbirth in 12 hospitals in Benin: a cross-sectional.
In spite of free caesarean section applied in Benin since 2009, high rates of stillborn babies continue to be recorded. This study aimed to determine the factors associated with post-caesarean stillborn in Benin. Cross-sectional study that covered all women who have delivered by caesarean from December 2013 to February 2014 in twelve hospitals chosen by simple random selection in each of the twelve departments of Benin. Data collected by chart review have been analyzed using the statistical software Epi info 3.5.1. Univariate analysis and multivariable logistic regression were used to identify factors associated with post-caesarean stillbirth at the significance threshold of 5%. There were 66 stillborn per 1,000 births of which 58% died before admission to hospital. The risk factors identified were the reference (p = 0.0011), general anesthesia (p = 0.0371), the low birth weight (p = 0.0001), the retro-placental hematoma (p = 0.0083), and the umbilical cord prolapse (p = 0.0229). Acute fetal distress (p = 0.0308) and anesthesia administered by an anesthetist nurse or midwife (p = 0.0337) were protective factors. The majority of cases, in utero death occurred before admission to hospital. Strengthening antenatal refocused consultation, a better access to quality obstetric care and the grant of all obstetric care could reduce stillbirths from caesarean sections in Benin.


PLCgamma is enriched on poly-phosphoinositide-rich vesicles to control nuclear envelope assembly.
Nuclear envelope assembly is an essential event in each cell cycle but the proteins and lipids involved in its regulation remain mostly unknown. Assembly involves membrane fusions but neither specific SNAREs nor Rab GTPases have been identified in its control. We report that a precursor membrane population (MV1) required for NE assembly has a unique lipid composition consisting prominently of poly-phosphatidylinositides. The lipid composition was determined by adapting HPLC electrospray ionisation tandem mass spectrometry to phosphoinositide analysis, revealing the capacity of this technique to document dynamic lipid transitions of functional importance in natural membrane populations. MV1 is >100-fold enriched in endogenous PLCgamma and >25-fold enriched in the PLC substrate phosphatidylinositol bisphosphate (PtdInsP2) compared to the second membrane population, derived largely from endoplasmic reticulum (ER), that contributes most of the NE. During NE formation PLCgamma becomes transiently phosphorylated at the tyrosine 783 site indicative of its activation. In addition specific inhibition of PLCgamma blocks nuclear envelope formation. In vivo, PLCgamma is concentrated on vesicles of similar size to purified MV1. These associate with nuclei during the period of NE formation and are distinct from ER membranes. The unprecedented concentration of PLCgamma and its substrate PtdInsP2 in a subset of membranes that binds to only two regions of the nucleus, and activation of PLCgamma by GTP during initial stages of NE formation provide a mechanism for temporal control of NE assembly and offer an explanation for how such a process of membrane fusion can be spatially regulated.


The clonal nature of enteropathogenic Escherichia coli strains.
Enteropathogenic Escherichia coli belonging to O groups O111 and O55 and isolated from cases of infantile diarrhea in 26 countries all over the world during 1950-1960 were examined for their outer-membrane protein (OMP) patterns; nine O:H serotypes of O111 and 11 serotypes of O55 were represented. Characteristic biotypes have earlier been described as closely associated with the most common O:H serotypes: O111:H2, O111:H12, O55:H6, and O55:H7. Different OMP patterns characterized each of the common O:H serobiotypes. The OMP patterns can be looked upon as another set of stable phenotypic characters in addition to the serotype antigens and the fermentative characters. The description of geographically widely spread, stable sero-/bio-/OMP types supports the concept that the typical enteropathogenic E coli strains also have a clonal connection.


Fluid dynamics analysis and experimental study for solar radiation error correction of sounding humidity sensor.
In order to correct the solar radiation error of relative humidity, the mainstream capacitive sounding humidity sensor HC103M2 is selected and investigated by simulation analysis and experimental verification. First, the basic theories for solar radiation error and sensor error itself are elaborated, and simulational and experimental platforms are introduced. The computational fluid dynamics (CFD) method is utilized to theoretically investigate the dry error of the humidity sensor caused by solar radiation heating, which is related to radiation intensity, altitude, and solar elevation angle as well as reflectivity, thickness, and shape of the shield. Then, in order to verify the accuracy of the simulation, an experimental platform including a humidity sensor and two temperature sensors to measure the solar radiation heating is built to analyze the relative error of humidity obtained by the CFD simulation and experiment. It is found that their maximum deviation is 3.30% and the average error is 1.94%, which indicates that the calculation using the CFD method is accurate and feasible. In order to easily and operationally predict the solar radiation heating of the humidity sensor, a back propagation (BP) neural network fusion algorithm based on three inputs of radiation intensity, air pressure, and solar elevation angle is proposed. Compared with the solar radiation heating obtained by CFD simulation, the maximum absolute error is about 0.2 K, and the relative error of humidity is about ±1.30%. Finally, a case of vertical humidity profile correction considering the temperature-sensitive error of HC103M2 is analyzed. The response time of sensor measurement and the airflow into the shield are discussed as well. The corrected results after taking solar radiation heating into account are more similar to those measured by RS92 and cryogenic frost point hygrometer (CFH). This result shows that the prediction model is accurate, which may be applied to correct the dry error and further improve the accuracy of humidity measurement.


Asthma Exacerbation Coincident with Saddle Pulmonary Embolism and Paradoxical Embolism.
Saddle pulmonary embolism (PE) and paradoxical embolism (PDE) are life-threatening disorders carrying a risk of sudden death, and their prompt diagnosis is extremely important. Saddle PE is a radiologic definition and refers to a thrombus that straddles the bifurcation of the pulmonary artery trunk, carrying a risk of sudden hemodynamic collapse. PDE is defined as a systemic arterial embolus due to the passage of a venous thrombus though a right-to-left shunt, such as patent foramen ovale (PFO). We herein present the rare case of asthma exacerbation coincident with saddle PE and PDE. A 69-year-old woman with asthma was suffering from dyspnea, pulse attenuation of the left radial artery and left upper limb pain. An arterial blood gas analysis revealed hypoxemia, and a pulmonary function test demonstrated an obstructive pattern. Enhanced computed tomography (CT) revealed saddle PE, right popliteal venous thrombosis, and left brachial artery occlusion. After the treatment with edoxaban, an anticoagulant, and aspirin, the PE was significantly alleviated, and the brachial artery occlusion was recanalized. Subsequently, the right-to-left shunt through PFO was confirmed, and PDE was suspected of inducting her brachial artery embolism. In the present case, the pulse attenuation of the radial artery and upper limb pain prompted us to consider peripheral vascular disease or coagulation disorders. Physicians should keep in mind that patients with asthma are at considerable risk of PE, and it is important to be aware of possible PFO in patients presenting with the coexistence of PE and systemic arterial embolism.


[Application of lateral malleolus hook-plate in treatment of stage II supination-adduction type medial malleolus fracture].
To investigate the application of lateral malleolus hook-plate for the treatment of stage II supination-adduction type medial malleolus fractures. Between January 2011 and June 2013, 21 patients with stage II supination-adduction type ankle fractures were treated with lateral malleolus hook-plate, including 12 males and 9 females with an average age of 55.5 years (range, 27-65 years). The injury causes were sprain in 17 cases and traffic accident in 4 cases. The mean time between injury and admission was 12.4 hours (range, 2-72 hours). The tibial distal medial articular surface collapse was found in 7 cases by CT examination and in 3 cases by X-ray film. Of 21 cases, there were 12 cases of low transverse fractures of lateral malleolus, 7 cases of short oblique fractures of lateral malleolus, and 2 cases of ankle joint lateral collateral ligament injury without fractures of lateral malleolus. After operation, the clinical outcome was evaluated according to the talus-leg angle, the recovery of Coin-sign continuity, inside-outside and top ankle gap, talus slope, American Orthopedic Foot and Ankle Society (AOFAS) score, Olerud-Molander score, Kofoed evaluation standards, and patient satisfaction. Seventeen cases were followed up 18.7 months on average (range, 12-25 months). Primary healing was obtained in 16 cases except 1 case of delayed healing. Fracture healed at an average of 14.6 weeks (range, 12-16 weeks). All cases achieved anatomical reduction, the continuity of Coin-sign, and consistency of inside and outside joint gap; no talus tilt occurred. There was no complication of reduction loss, loosening or breakage of internal fixation, or osteoarthritis during follow-up. The talus-leg angle of the affected side was significantly improved to (83.4 ± 1.8)° at 1 week after operation from preoperative (74.8 ± 7.1)° (t = 5.370, P = 0.000), but no significant difference was found when compared with normal side (83.8 ± 2.3)° (t = 0.676, P = 0.509). The AOFAS score, Olerud-Molander score, and range of motion at 1 week, 3 months, and 1 year after operation were significantly improved when compared with preoperative ones (P < 0.05). According to Kofoed evaluation standard, the outcome was excellent in 15 cases and good in 2 cases; the excellent and good rate was 100%. According to patient satisfaction, the outcome was excellent in 13 cases, good in 3 cases, and poor in 1 case; the excellent and good rate was 94.1%. The use of lateral malleolus hook-plate for fixation of stage II supination-adduction type medial malleolus fracture not only can effectively maintain anatomical reduction and supporting function, but also can prevent re-collapsing of the reset joint surface. The surgical method can not increase soft tissue complication, so it is a safe and effective method.


Remodeling of apolipoprotein E-containing spherical reconstituted high density lipoproteins by phospholipid transfer protein.
Phospholipid transfer protein (PLTP) transfers phospholipids between HDL and other lipoproteins in plasma. It also remodels spherical, apolipoprotein A-I (apoA-I)-containing HDL into large and small particles in a process involving the dissociation of lipid-free/lipid-poor apoA-I. ApoE is another apolipoprotein that is mostly associated with large, spherical HDL that do not contain apoA-I. Three isoforms of apoE have been identified in human plasma: apoE2, apoE3, and apoE4. This study investigates the remodeling of spherical apoE-containing HDL by PLTP and the ability of PLTP to transfer phospholipids between apoE-containing HDL and phospholipid vesicles. Spherical reconstituted high density lipoproteins (rHDL) containing apoA-I [(A-I)rHDL], apoE2 [(E2)rHDL], apoE3 [(E3)rHDL], or apoE4 [(E4)rHDL] as the sole apolipoprotein were prepared by incubating discoidal rHDL with low density lipoproteins and lecithin:cholesterol acyltransferase. PLTP remodeled the spherical, apoE-containing rHDL into large and small particles without the dissociation of apoE. The PLTP-mediated remodeling of apoE-containing rHDL was more extensive than that of (A-I)rHDL. PLTP transferred phospholipids from small unilamellar vesicles to apoE-containing rHDL in an isoform-dependent manner, but at a rate slower than that for spherical (A-I)rHDL. It is concluded that apoE enhances the capacity of PLTP to remodel HDL but reduces the ability of HDL to participate in PLTP-mediated phospholipid transfers.


Anatomic and functional topography of the dorsal raphe nucleus.
Serotonergic systems play an important and generalized role in regulation of sleep-wake states and behavioral arousal. Recent in vivo electrophysiologic recording studies in animals suggest that several different subtypes of serotonergic neurons with unique behavioral correlates exist within the brainstem raphe nuclei, raising the possibility that topographically organized subpopulations of serotonergic neurons may have unique behavioral or physiologic correlates and unique functional properties. We have shown that the stress-related and anxiogenic neuropeptide corticotropin-releasing factor can stimulate the in vitro neuronal firing rates of topographically organized subpopulations of serotonergic neurons within the dorsal raphe nucleus (DR). These findings are consistent with a wealth of behavioral studies suggesting that serotonergic systems within the DR are involved in the modulation of ongoing anxiety-related behavior and in behavioral sensitization, a process whereby anxiety- and fear-related behavioral responses are sensitized for a period of up to 24 to 48 h. The dorsomedial subdivision of the DR, particularly its middle and caudal aspects, has attracted considerable attention as a region that may play a critical role in the regulation of acute and chronic anxiety states. Future studies aimed at characterization of the molecular and cellular properties of topographically organized subpopulations of serotonergic neurons are likely to lead to major advances in our understanding of the role of serotonergic systems in stress-related physiology and behavior.


Early human renal allograft fibrosis: cellular mediators.
The development of early renal interstitial fibrosis (IF) in renal allografts is likely to depend on multiple factors. We studied retrospectively renal biopsies from cadaveric human renal allografts, transplanted from 1996 to 1998, with the intention of detecting early fibrotic changes and determining the underlying cellular mediators. We studied 23 transplant patients whose 46 renal biopsies were analysed, including a donor biopsy taken routinely at implantation from each patient and 23 follow-up biopsies, taken as clinically indicated over a period of 3 months following transplantation. Histological evaluation of induction and progression of fibrosis relied on point count analysis of conventional (Masson's trichrome/MT) and immunohistochemical staining for collagen III and IV, and alpha-smooth muscle actin (alpha-SMA) as a marker of myofibroblast differentiation. Mast cells (MC) were counted in sections stained with an anti-human mast cells tryptase monoclonal antibody. Activated macrophages as well as total, helper and cytotoxic T-lymphocytes were identified on frozen sections by direct immunofluorescence using mouse anti-CD71, CD3, CD4 and CD8 antibodies respectively. Eosinophils (E) were counted in hematoxylin and eosin (HE)-stained sections. Changes in interstitial fibrosis (IF) scores were evaluated and correlated with myofibroblasts, MC, E and lympho-monocytic cells. We noted a significant increase in IF over a 3 months period following transplantation. There was also a significant increase in alpha-SMA+ cells, MC and E counts from implantation to follow-up biopsies. Similarly, there was a significant increase in interstitial infiltration by T-lymphocytes (modal category = 2 versus 0, p = 0.012) but not by macrophages. MC at implantation and follow-up were found to be predictive of IF (immunostainable collagen III) at follow-up (R(2) = 0.510, p = 0.023 and p = 0.030). Further, the predictive value for total T-lymphocyte infiltration at follow-up was also significant (R(2) = 0.617, p = 0.036). A strong correlation was found between alpha-SMA+ cells and MC counts at implantation (r = 0.7259, p < 0.001) and in follow-up biopsies (r = 0.5183, p < 0.01). However, there was no correlation between E counts and either alpha-SMA+ cells or MC either at implantation or in follow-up biopsies. Based on changes in interstitial immunostainable alpha-SMA, our patients were divided arbitrarily into 2 groups; group 1 (n = 12) with >100% increase in alpha-SMA and group 2 (n = 11) with <100% increase. Group 1 patients differed significantly from group 2 regarding the degree of MC infiltration at follow-up (t = 0.4519, p < 0.05) with the mean increase in MC count from implantation to follow-up biopsies being +5.1 cells/high power field (HPF) in group 1 and +0.8 cell/HPF in group 2 (p = 0.0237). MC counts in group 1 were associated with a higher modal category (greater than one) of cytotoxic: helper T-lymphocytes ratio compared to group 2 (2:1 versus 1:1 respectively). Multiple cells may contribute to early interstitial fibrosis in a subgroup of human renal allograft recipients with MC playing a major role.


Potential of biosynthesized silver nanoparticles using Stenotrophomonas sp. BHU-S7 (MTCC 5978) for management of soil-borne and foliar phytopathogens.
Stenotrophomonas sp. is emerging as a popular microbe of global concern with various potential ecological roles. Biosynthesis of gold and silver nanoparticles (AgNPs) using this bacterial strain has shown promising applications in life sciences. However, there is no report on efficient agricultural applications of biosynthesized AgNPs using Stenotrophomonas sp. In this regard, successful biosynthesis of AgNPs using Stenotrophomonas sp. BHU-S7 (MTCC 5978) was monitored by Uv-visible spectrum showing surface plasmon resonance (SPR) peak at 440 nm. The biosynthesized AgNPs were spherical with an average mean size of ~12 nm. The antifungal efficacy of biosynthesized AgNPs against foliar and soil-borne phytopathogens was observed. The inhibitory impact of AgNPs (2, 4, 10 μg/ml) on conidial germination was recorded under in vitro conditions. Interestingly, sclerotia of Sclerotium rolfsii exposed to AgNPs failed to germinate on PDA medium and in soil system. Moreover, AgNPs treatment successfully managed collar rot of chickpea caused by S. rolfsii under greenhouse conditions. The reduced sclerotia germination, phenolic acids induction, altered lignification and H2O2 production was observed to be the probable mechanisms providing protection to chickpea against S. rolfsii. Our data revealed that AgNPs treated plants are better equipped to cope with pathogen challenge pointing towards their robust applications in plant disease management.


Evaluation of cholinergic treatment in demented patients by P300 evoked related potentials.
Centrally acting cholinesterase inhibitors (ChEls) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment tools which includes standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response is necessary. Thirty two patients were treated with ChEls for dementia (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed before ChEls (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), ADAS-cog and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4 to 27.4 p = 0.08) while MMSE remained almost unchanged (20.1 to 19.8). Mean P300 latency reduced significantly by 24 msec (from 383 msec to 359 msec, p = 0.0001) thus reflecting the clinical improvement. However mean amplitudes did not change from baseline to endpoint (13 microvolts). Significant correlation was found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.452 p = 0.014, R = 0.567 p = 0.001 respectively). Strong correlation was found between mean MMSE and P300 latency at Baseline (R = -0.335 p = 0.07), and significant correlation was found at endpoint (R = -0.613 p < 0.001). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEls in demented patients.


Splanchnic extraction of 3,3'-diiodothyronine and 3',5'-diiodothyronine in hyperthyroidism.
The splanchnic extraction of 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was studied in 7 hyperthyroid patients and 20 normal subjects employing the hepatic venous catheterization technique. A significant net uptake by splanchnic tissues was found for both diiodothyronines . The fractional splanchnic extraction calculated as the arterio-hepatic venous plasma concentration difference divided by the arterial concentration was unaffected by hyperthyroidism as compared to normal values. There was a close positive correlation between the arterio-hepatic venous concentration difference and arterial concentration, 3,3'-T2: r = 0.988, and 3',5'-T2: r = 0.932 (P less than 0.001). The splanchnic extraction was nonsaturable at endogenous plasma concentrations of 3,3'-T2 up to at least 17.0 ng/dl and of 3',5'-T2 up to at least 15.2 ng/dl. The data suggest that the splanchnic extraction of 3,3'-T2 and 3',5'-T2 obeys first order kinetics, the fractional extraction being unaffected by hyperthyroidism. Furthermore, changes in the net splanchnic extraction of 3,3'-T2 and 3',5'-T2 do not seem to contribute to changes in circulating levels of these iodothyronines. It is suggested that tissues other than the liver contribute significantly to the deiodination process both in normal and in hyperthyroid man.


Perinatal factors associated with severe intracranial hemorrhage.
The purpose of this study was to assess the incidence of perinatal factors that are associated with severe intracranial hemorrhage in a large and recent multicenter experience. Retrospective analyses of nonanomalous newborns who were admitted to 100 neonatal intensive care units from 23 to 34 6/7 weeks' gestation were analyzed by multiple regression. There were 12,578 premature newborns with a mean (+/- SD) gestational age of 31.3 +/- 2.9 weeks and a birth weight of 1685 +/- 571 g, respectively. The overall incidence of severe intracranial hemorrhage was 2.9%; in 4575 newborns who weighed < or = 1500 g the incidences of intracranial hemorrhage was 7.1%. Factors with positive and negative associations with severe intracranial hemorrhage are listed in order of decreasing statistical significance: gestational age (negative), surfactant (positive), antenatal indomethacin (positive), neonatal transport (positive), cesarean birth (negative), poor prenatal care (positive), 5-minute Apgar score of < 7 (positive), chorioamnionitis (positive), antenatal terbutaline (negative), preterm premature rupture of fetal membranes (negative), and abruption (positive). The incidence of severe intracranial hemorrhage has dramatically declined over the past 2 decades. Antenatal steroids were not associated with reductions in severe intracranial hemorrhage.


Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population.
Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case-control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case-control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12-3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.


Some observations on the course and composition of the cingulum bundle in the rhesus monkey.
The course and composition of the cingulum bundle was examined by using the autoradiographic tracer technique in the rhesus monkey. The cingulum bundle is observed to consist of three major fiber components originating from thalamus, cingulate gyrus, and cortical association areas. Following isotope injections in the anterior and lateral dorsal thalamic nuclei, labelled fibers form an arch in the white matter behind the cingulate sulcus and occupy the ventral sector of the cingulum bundle. The fibers from the anterior thalamic nucleus coursing in the cingulum bundle extended rostrally to the frontal cortex and caudally to area 23 and the retrosplenial cortex. In contrast, the fibers from lateral dorsal nucleus reached the retrosplenial cortex as well as the parahippocampal gyrus and presubiculum. Efferent fibers from the cingulate gyrus occupy a dorsolateral sector of the cingulum bundle. Those fibers from area 24 of the cingulate gyrus are directed to the premotor and prefrontal regions as well as area 23 and retrosplenial cortex. The fibers from area 23 extend rostrally to the prefrontal cortex and caudoventrally to the presubiculum and parahippocampal gyrus. Finally, an association component originates mainly from prefrontal cortex and posterior parietal region. These fibers occupy a more dorsal and lateral periphery in the cingulate white matter. Cingulum bundle fibers from the prefrontal cortex extend up to the retrosplenial cortex while those from the posterior parietal cortex extend caudally to the parahippocampal gyrus and presubiculum, and rostrally up to the prefrontal cortex.


Pigeonpea (Cajanus cajan L. Millsp.).
Pigeonpea [Cajanus cajan (L.) Millsp.], also known as redgram, is one of the major grain legume (pulses) crops grown in the semiarid tropics (SAT) extending between 30 degrees N and 30 degrees S; it is the second most important food legume of India. It is cultivated in about 50 countries of Asia, Africa, and the Americas for a variety of uses (food, fodder, fuel wood, rearing lac insects, hedges, wind breaks, soil conservation, green manure, roofing, and so on). The constraints of enhancing its productivity include the damage caused by various fungi, bacteria, viruses, and insect pests. Conventional plant breeding methods have not been successful for the improvement of pigeonpea because of genetic variation and incompatibility among the wild varieties. Genetic engineering technology can therefore be used as an additional tool for the introduction of agronomically useful traits into established varieties. The development of plant transformation techniques has been a major breakthrough in overcoming constraints to achieve precision in genetic manipulation. The development of efficient plant regeneration protocols is a prerequisite for recombinant technology to carry out genetic transformation. This chapter describes an Agrobacterium-mediated transformation protocol for pigeonpea, a simple, efficient, and reproducible method that is applicable across diverse genotypes of pigeonpea.


Human anaplasmosis in north-eastern Poland: seroprevalence in humans and prevalence in Ixodes ricinus ticks.
Sera of 500 inhabitants of north-eastern Poland, 450 suspected for Lyme borreliosis and 50 blood donors (control group), were analysed for the presence of IgG antibodies against Anaplasma phagocytophilum, the causative agent of human anaplasmosis (HA), known so far as human granulocytic ehrlichiosis (HGE). Forty one (9.1 %) sera of the study group and one serum (2 %) of the control group were positive using indirect fluorescence assay (IFA). The seropositivity tended to be more frequent among males (10.3 %) than females (7.6 %) and among the rural (10.3 %) than urban population (7.5 %); however, differences were of no statistical significance (p = 0.4). No age difference was found between the seropositive and the seronegative individuals (p = 0.77). The only factor increasing the risk of HA seropositivity found was forestry employment (p < 0.05). Additionally, a total of 559 Ixodes ricinus ticks, collected in the same area as sera, were investigated for the presence of A. phagocytophilum by the polymerase chain reaction (PCR) and 41 (8.7 %) of them were found to be positive. The infection level ranged from 2.3-13.7 %, depending on the area studied. Bacteria were significantly less frequently detected in nymphs - 2.1 % (5/235) than in adult ticks - 13.6 % (44/324) and in males--4.2 % (74/165) than in females--23.3 % (37/159) (p < or = 0.05). The obtained results confirm both the occurrence of HA foci in north-eastern Poland with I. ricinus as the principal vector of the A. phagocytophilum infection, and forestry workers as the main group at risk.


Occurrence, spatial variation and risk assessment of pharmaceuticals and personal care products in urban wastewater, canal surface water, and their sediments: A case study of Lahore, Pakistan.
Due to the lack of wastewater treatment facility in Pakistan, the wastewater is directly discharged via urban drains, which might cause a high load of contaminants of emerging concerns and potential environmental risks. The present study focused on the occurrence and risk assessment of 52 pharmaceuticals and personal care products (PPCPs) of diversified classes in the water and sediment samples of urban drains and canal of Lahore, Pakistan. Non-steroidal anti-inflammatory drugs were the predominant PPCPs detected in the wastewater of urban drains and surface water of canal. The highest concentration was observed for acetaminophen, with median concentration of 13,880 ng/L followed by caffeine with median concentration of 6200 ng/L. Antibiotics were the predominant PPCPs in the sediment samples with highest concentration of ofloxacin (median value of 1980 μg/kg) followed by ciprofloxacin and oxytetracycline. Spatial variation showed that the population density has significant correlation with the level of many PPCPs in surface water while one of the drainage systems is affected by the direct wastewater discharge from the nearby industrial area. Ecological risk assessment in terms of risk quotient revealed that most of the PPCPs may cause high risk to the aquatic community. This high risk may lead to further contamination of food and crops, therefore enforcement of environmental legislations for treatment of wastewater is recommended.


Simultaneous synthesis and assembly of gold nanoparticles in cuttlebone-derived organic matrix: a "green" pathway for gold nanocomposite.
We demonstrate herein a "green" pathway for the formation of a gold nanocomposite using the cuttlebone-derived organic matrix. The gold nanocomposite is achieved through the first exposure of the organic matrix to HAuCl4 solution at room temperature and its subsequent heating at 80 degrees C. The process results in the formation of a macro porous gold nanocomposite consisting of gold nanoparticles embedded in the cuttlebone-derived organic matrix background, which shows the characteristic plasma absorption of gold nanostructures. UV-vis-IR spectrophotometer and transmission electron microscope (TEM) were used to characterize the gold nanocomposite and trace the formation process. A highlight of the research is that we adopted a nontoxic and renewable reagent of cuttlebone-derived organic matrix, which functioned as the reducing reagent, stabilizer and scaffold for the synthesis of gold nanoparticles.


Functional immune boosters; the herb or its dead microbiome? Antigenic TLR4 agonist MAMPs found in 65 medicinal roots and algae's.
Humans have been consuming medicinal plants (as herbs/ spices) to combat illness for centuries Herbs while ascribing beneficial effects predominantly to the plant/phytochemical constituents, without recognizing Edible microbiome the power of obligatory resident microorganism' communities (MOCs) (live/dead bacteria, fungus, yeast, molds Medicinal microbiome etc.) which remain after industrial microbial reduction methods. Very little is known about the taxonomic Bugs as drugs identity of residual antigenic microbial associated molecular patterns (MAMPs) debris in our botanical over the Immune boosting counter (OTC) products, which if present would be recognized as foreign (non-self) antigenic matter by host pattern recognition receptors (PRRs) provoking a host immune response; this the basis of vaccine adjuvants. As of today, only few research groups have removed the herbal MAMP biomass from herbs, all suggesting that immune activation may not be from the plant but rather its microbial biomass; a hypothesis we corroborate. The purpose of this work was to conduct a high through put screening (HTPS) of over 2500 natural plants, OTC botanical supplements and phytochemicals to elucidate those with pro-inflammatory; toll like receptor 4 (TLR4) activating properties in macrophages. The HTPS was conducted on RAW 264.7 cells vs. lipopolysaccharide (LPS) E. coli 0111:B4, testing iNOS / nitric oxide production (NO2-) as a perimeter endpoint. The data show not a single drug/chemical/ phytochemical and approximately 98 % of botanicals to be immune idle (not effective) with only 65 pro-inflammatory (hits) in a potency range of LPS. Method validation studies eliminated the possibility of false artifact or contamination, and results were cross verified through multiple vendors/ manufacturers/lot numbers by botanical species. Lead botanicals were evaluated for plant concentration of LPS, 1,3:1,6-β-glucan, 1,3:1,4-β-D-glucan and α-glucans; where the former paralleled strength in vitro. LPS was then removed from plants using high-capacity endotoxin poly lysine columns, where bioactivity of LPS null "plant" extracts were lost. The stability of E.Coli 0111:B4 in an acid stomach mimetic model was confirmed. Last, we conducted a reverse culture on aerobic plate counts (APCs) from select hits, with subsequent isolation of gram-negative bacteria (MacConkey agar). Cultures were 1) heat destroyed (retested/ confirming bioactivity) and 2) subject to taxonomical identification by genetic sequencing 18S, ITS1, 5.8 s, ITS2 28S, and 16S. The data show significant gram negative MAMP biomass dominance in A) roots (e.g. echinacea, yucca, burdock, stinging nettle, sarsaparilla, hydrangea, poke, madder, calamus, rhaponticum, pleurisy, aconite etc.) and B) oceanic plants / algae's (e.g. bladderwrack, chlorella, spirulina, kelp, and "OTC Seamoss-blends" (irish moss, bladderwrack, burdock root etc), as well as other random herbs (eg. corn silk, cleavers, watercress, cardamom seed, tribulus, duckweed, puffball, hordeum and pollen). The results show a dominance of gram negative microbes (e.g. Klebsilla aerogenes, Pantoae agglomerans, Cronobacter sakazakii), fungus (Glomeracaea, Ascomycota, Irpex lacteus, Aureobasidium pullulans, Fibroporia albicans, Chlorociboria clavula, Aspergillus_sp JUC-2), with black walnut hull, echinacea and burdock root also containing gram positive microbial strains (Fontibacillus, Paenibacillus, Enterococcus gallinarum, Bromate-reducing bacterium B6 and various strains of Clostridium). This work brings attention to the existence of a functional immune bioactive herbal microbiome, independent from the plant. There is need to further this avenue of research, which should be carried out with consideration as to both positive or negative consequences arising from daily consumption of botanicals highly laden with bioactive MAMPS.


Androgen-induced production of colony-stimulating factor (CSF) and colony-inhibitory factor (CIF) in the submandibular gland in female mice.
Both testosterone (T) and 5 alpha-dihydrotestosterone (DHT) significantly increased colony-stimulating factor (CSF) as well as colony-inhibitory factor (CIF) in the submandibular gland (SMG) in female mice. The CIF activity was completely inactivated by heating at 60 degrees C for 15 min, while the CSF activity was stable against the heat treatment. It was found that the CSFs obtained from the androgen-treated female mice and from normal male mice behaved identically in chromatography on hydroxylapatite and Ultro-gel AcA 34 columns. The potency of DHT to increase CSF activity was about 10 times greater than that of T.


Biological parameters influencing the human umbilical cord-derived mesenchymal stem cells' response to retinoic acid.
Human umbilical cord-derived mesenchymal stem cells (HUCMSCs) are multipotent fetal stem cells that differentiate into various cell lineages. In recent years, they have gained attention for therapeutic applications but very little is known about their sensitivity to chemical agents such as widely used retinoic acid (RA). As a morphogen inducing differentiation of mesenchymal stem cells, RA has for a long time been known to be a potent teratogen promoting craniofacial and limb abnormality in vertebrate embryos. Here, using MTT assay and EB/AO staining as well as TUNEL assay we show that RA in a concentration-dependent manner induces apoptosis through upregulating Caspase expression and increasing Bax/Bcl2 ratio. Moreover, different biological parameters such as initial time seeding, cell density, passage number and duration of RA treatment play a major role in HUCMSCs cytotoxic response to this agent.


[The place of anatomo-pathological study in the diagnosis of enterocolitis complicated by Yersinia pseudo-tuberculosis].
Over a period of 3 months, 3 patients were operated on for subacute enterocolitis. The first case was a 3 years old boy with a transverse colonic perforation near the right angle and gross lymphadenopathy. The second case was a 21 years old man who had subacute terminal ileitis. Histopathological study showed specific lesions in those two cases: ovoïd or starry abscesses with preepithelioïd cells, rare giant Langhans cells, rare altered polynuclear cells in necrosis, massive lymphoïd hyperplasia. The third case was a 27 years woman with mild appendicitis showing masses of bacteria in the wall of appendix, surrounded by lymphocytes without polynuclear. Serological study showed anti YPST agglutinins significantly modified in all 3 cases. In the absence of bacteriological study, the role of pathological findings is discussed.


Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus.
The Directigen Flu A+B enzyme immunoassay and the Abbott TestPack RSV enzyme immunoassay were each compared with a multiplex RT-PCR ELISA by testing 635 nasopharyngeal aspirates collected from children aged < 16 years who had been hospitalised with acute respiratory tract infection during the epidemic season 2002-2003. In this study, the sensitivity of the Directigen Flu A+B assay was unacceptably low (29.3% and 10.0%, respectively) for the detection of influenza A and B viruses. The sensitivity of the Abbott TestPack RSV assay (77.4%) was acceptable and in agreement with the multiplex RT-PCR ELISA.


Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery.
Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM.


Transcription of individual tRNA1Gly genes from within a multigene family is regulated by transcription factor TFIIIB.
Members of a multigene family from the silkworm Bombyx mori have been classified based on their transcriptions in homologous nuclear extracts, into three groups of highly, moderately and poorly transcribed genes. Because all these gene copies have identical coding sequences and consequently identical promoter elements (the A and B boxes), the flanking sequences modulate their expression levels. Here we demonstrate the interaction of transcription factor TFIIIB with these genes and its role in regulating differential transcriptions. The binding of TFIIIB to the poorly transcribed gene -6,7 was less stable compared with binding of TFIIIB to the highly expressed copy, -1. The presence of a 5' upstream TATA sequence closer to the coding region in -6,7 suggested that the initial binding of TFIIIC to the A and B boxes sterically hindered anchoring of TFIIIB via direct interactions, leading to lower stability of TFIIIC-B-DNA complexes. Also, the multiple TATATAA sequences present in the flanking regions of this poorly transcribed gene successfully competed for TFIIIB reducing transcription. The transcription level could be enhanced to some extent by supplementation of TFIIIB but not by TATA box binding protein. The poor transcription of -6,7 was thus attributed both to the formation of a less stable transcription complex and the sequestration of TFIIIB. Availability of the transcription factor TFIIIB in excess could serve as a general mechanism to initiate transcription from all the individual members of the gene family as per the developmental needs within the tissue.


[The role of gap-junction in suspended animation for hemorrhagic shock with brain injury: experiment with rats].
To investigate the role of gap-junction in suspended animation for hemorrhagic shock with brain injury. Twenty-four SD rats were made into models of uncontrolled hemorrhagic shock and occlusion of bilateral common carotid arteries and randomly divided into 3 equal groups: traditional resuscitation group (Group I) undergoing traditional resuscitation, hypothermy resuscitation group (Group II) undergoing temperature lowering by ice-cap, and carbenoxolone resuscitation group (Group III) undergoing injection of carbenoxolone 50 microg/200 g. The process was divided into 3 periods: traumatic hemorrhagic period (30 min), pre-hospital treatment period (60 min), and in-hospital cardiopulmonary resuscitation period (60 min). The levels of left ventricular systolic pressure (LVSP), maximum change rate of left ventricular pressure rise and fall (+/- dp/dt(max)), mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were recorded at the beginning and the end of traumatic hemorrhagic period (T1 and T2), the end of pre-hospital treatment period (T3), and the end of in-hospital cardiopulmonary resuscitation period (T4). The survival time was recorded after in-hospital cardiopulmonary resuscitation period. Then the left brain was taken out and the hippocampal neurons apoptosis was observed by flow cytometry, chemiluminescence was used to detect the ATP, and IL-6 and tumor necrosis factor (TNF)-alpha were detected by enzyme linked immunosorbent assay (ELISA). The survival time of Groups II and III were (2.9 +/- 0.6) h and (2.6 +/- 1.0) h respectively, both significantly longer than that of Group I [(1.4 +/- 0.3) h, both P < 0.01]. The apoptotic rates of hippocampal neurons of Groups II and III were (72 +/- 6)% and (75 +/- 9)% respectively, both significantly lower than that of Group [83 +/- 5)% P < 0.05]. The ATP levels in hippocampus of Groups II and III were (2.0 +/- 0.3) and (1.9 +/- 0.4) pg/g respectively, both significantly higher than that of Group I [(1.4 +/- 0.5 pg/g, both P < 0.05). The TNF-alpha and IL-6 levels of Groups II were (1.7 +/- 0.3) pg/g and (19 +/- 3) pg/g respectively, both significantly lower than those of Group I [(2.2 +/- 0.6) and (24 +/- 3) pg/g respectively, both P < 0.05]. The IL-6 level of Group III was (26 +/- 4) pg/g, significantly higher than that of Group II (P < 0. 01). There were no significant difference between Groups II and III in the values of survival time, hippocampal neuron apoptosis, dissipation of ATP, and liberation of TNF-alpha (all P > 0.05), but there was significant difference in IL-6 (P < 0.01). Both hypothermy resuscitation and carbenoxolone resuscitation protect the brain of cerebral ischemia on hemorrhagic shock with brain injury, and suggest that Gap junctions play an important role in suspended animation to treat hemorrhagic shock with brain injury.


Mechanism of the photorelease of alcohols from the 9-phenyl-9-tritylone protecting group.
The 9-phenyl-9-tritylone photoremovable protecting group was examined using both photoproduct analysis and laser flash photolysis in order to determine the details of its mechanism of alcohol release. It is shown that formation of the tritylone anion radical is required for alcohol release. Attempts to trigger release via intramolecular photoinduced electron transfer were unsuccessful due to rapid back electron transfer reactions of the triplet diradical anion.


Effects of dopamine on prolactin: interactions with cocaine self-administration by female rhesus monkeys.
The effects of dopamine on regulation of prolactin secretion were studied in female rhesus monkeys before cocaine exposure and again after 2 months to 2.7 years of daily cocaine self-administration. During chronic cocaine exposure, basal prolactin levels increased by 227 to 350% above drug-free control levels (P < .05). On each endocrine study day, three successive 80-min dopamine infusions (10 micrograms/kg/min i.v.) were alternated with 20-min interruptions of dopamine infusions to assess the degree of prolactin suppression and the magnitude of postdopamine prolactin increases. Dopamine significantly reduced prolactin below base-line levels within 60 to 80 min under all conditions (P < .05-.01). In four drug-naive follicular phase females, postdopamine increases in prolactin never exceeded predopamine base-line levels of 6.2 (+/- 1.8) ng/ml. After an average of 74 days of cocaine self-administration [3.7 (+/- 0.11) mg/kg/day], the postdopamine prolactin increases were significantly higher than during drug-free control conditions (P < .01) and reached hyperprolactinemic levels of 57.6 ng/ml. After an average of 300 days of cocaine self-administration [6.5 (+/- 0.06) mg/kg/day], postdopamine prolactin increases peaked at 339% above predopamine basal prolactin levels. After an average of 433 days of cocaine self-administration [6.45 (+/- 0.08) mg/kg/day] postdopamine prolactin increases remained significantly higher (P < .01) than during drug-free conditions. A similar pattern of postdopamine prolactin increases to hyperprolactinemic levels (ranging from 44.5 to 141.2 ng/ml) also were measured in two other females studied after 19 to 20 months of cocaine self-administration [6.21 (+/- 0.11) and 7.49 (+/- 0.17) mg/kg/day]. After 2.7 years of cocaine self-administration, one monkey developed persistent hyperprolactinemia and basal prolactin levels averaged 326 ng/ml after 89 days of cocaine abstinence. These data suggest that the prolactin secretory response to dopamine perturbation may provide a sensitive index of changes in dopaminergic regulation of prolactin during chronic cocaine exposure.


Thyroid peroxidase as an autoantigen.
Thyroid peroxidase (TPO) evokes high-affinity, IgG-class autoantibodies [TPO autoantibodies (TPOAbs)] and TPO-specific T cells that are markers of thyroid infiltration or implicated in thyroid destruction, respectively. A diverse repertoire of human monoclonal TPOAbs, unparalleled in other autoimmune diseases, provides invaluable probes for investigating antibody epitopes. Human TPOAbs recognize an immunodominant region comprising overlapping A and B domains on conformationally intact TPO. Amino acids recognized by TPOAbs are located in the regions with homology to myeloperoxidase (MPO) and the complement control protein (CCP) but not in the epidermal growth factor (EGF)-like region. T cells recognize epitopes in the MPO-like region but not in the CCP- or EGF-like regions in humans. Monoclonal human TPOAbs modulate processing of TPO protein to provide peptides for some T cells. A human T cell clone expressed transgenically in mice induces lymphocytic infiltration and hypothyroidism. This T cell's epitope is only generated by thyrocyte processing of endogenous TPO. Further, intact TPO expressed in vivo is also required for induction of TPOAbs in mice that resemble human autoantibodies. Overall, some TPO-specific T cells and the majority of autoantibodies in humans develop in response to TPO presented by thyroid cells, rather than to TPO released by damaged thyrocytes.


[Radiosensitization by oxygen in Ehrlich tumor receiving artificial blood substitute (FOB 20%)].
To enhance tissue PO2 of radioresistant hypoxic cells of tumor, artificial blood substitute (FOB) was applied, because it is excellent solvent for oxygen and allows the blood circulation system to recover and consequently increase the oxygen supply from blood to the tissue. When trasplanted Ehrlich tumor of mice on thigh grew about 1,000 mm3 in volume, those were divided into three groups, group 1: 60Co gamma-ray irradiation alone, group 2: irradiation under breathing oxygen, and group 3: irradiation under breathing oxygen after exchange transfusion with FOB. The radiosensitization of FOB was studied by comparing with the OER values of three groups for 50% TGD time, 50% SD time, and 50% and 75% TCP. The OER values of 50% TGD time, 5, 10 and 50% SD time 10 of oxygen group were 1.46, 1.29, and 1.22, respectively, and oxygen effect was observed in this group. Those values of FOB group were 2.02, 1.56, and 1.56, respectively and oxygen effect of FOB group was greater than those of oxygen effect of FOB group was greater than those of oxygen group. Animals receiving FOB were apparently radiosensitized by oxygen against animals breathing oxygen at small doses irradiation effect (50% TGD time, and 50% SD time). The OER values of 50% and 75% TCP at 30 days and 90 days after irradiation of oxygen group were about 1.5 (1.46-1.61) and these of FOB group about 1.3 (1.15-1.38). Radiosensitization by oxygen of animals receiving FOB was not clearly recognized against animals breathing oxygen in TCP effect at high dose irradiation. These results indicate that radioresistant hypoxic cells of tumor receiving artificial blood substitute (FOB) increase the sensitivity of 60Co gamma-ray irradiation, especially at small dose irradiation.


Stem Cells - SMi's second annual conference: achieving success in science and commercialisation.
SMi's second annual Stem Cells conference, held in London, included topics covering research developments in the field of stem cell biology and regenerative medicine. This conference report highlights selected presentations on big pharma's perspective on the field, stem cell-based therapies for chronic liver disease and age-related macular degeneration, and strategies to gain approval for the conduct of clinical trials involving stem cells. Investigational drugs discussed include GRNOPC-1 (Geron Corp).


Prevalence of a haemochromatosis among men with clinically significant bradyarrhythmias.
Cardiac involvement in haemochromatosis includes development of congestive heart failure and/or cardiac arrhythmias. To elucidate the importance of this disorder among patients with severe cardiac bradyarrhythmias necessitating treatment with a permanent pacemaker, such patients were screened for evidence of iron overload. Serum ferritin was determined in 232 men treated with a permanent pacemaker. In six patients (2.6%) the serum ferritin values were twice the upper normal limit. In three of these, causes other than iron overload were found (liver cancer, myeloma and amiodarone treatment), while in three (1.3%) iron overload was suspected. All the latter three had atrioventricular block of second to third degree. In these patients percutaneous liver biopsy was performed. The specimens were examined by light and electron microscopy and the iron content was determined by atomic absorption spectrophotometry. The results of these investigations showed iron overload in the liver. The prevalence of iron overload (2.0%) among this male pacemaker-treated population with AV block II-III is significantly higher than the rates previously found in urban populations in Sweden. The present data indicate that screening for haemochromatosis is of importance among males with second and third degree atrioventricular-block of unknown etiology.


Does motoneuron adaptation contribute to muscle fatigue?
To help reduce the gap between the cellular physiology of motoneurons (MNs) as studied "bottom-up" in animal preparations and the "top-down" study of the firing patterns of human motor units (MUs), this article addresses the question of whether motoneuron adaptation contributes to muscle fatigue. Findings are reviewed on the intracellularly recorded electrophysiology of spinal MNs as studied in vivo and in vitro using animal preparations, and the extracellularly recorded discharge of MUs as studied in conscious humans. The latter "top-down" approach, combined with kinetic measurements, has provided most of what is currently known about the neurobiology of muscle fatigue, including its task and context dependencies. It is argued that although the question addressed is still open, it should now be possible to design new "bottom-up" research paradigms using animal preparations that take advantage of what has been learned with the use of relatively noninvasive quantitative procedures in conscious humans.


Induced charge electro-osmosis over controllably contaminated electrodes.
Recent studies in nonlinear electrokinetics reveal the standard theory to generally overpredict measured velocities, sometimes dramatically. Contamination of the driving surface provides a natural mechanism for electrokinetic suppression. We measure induced charge electro-osmosis over gold electrodes "contaminated" with silica layers of controlled thickness for nearly a thousand distinct conditions, in a system that enables direct comparisons between theoretical predictions and experimental measurements. Both the magnitude and frequency dependence of the measured slip velocity are captured quantitatively over the entire range of experiments by accounting for the physical capacitance and surface chemistry of the dielectric layer. More generally, the quantitative characterization enabled by our apparatus will prove invaluable for the rational design and prediction of electrokinetic systems.


Comment on "The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients".
We have read with great care and interest the article by Li et al The authors provide interesting elements with respect to the possible entry of severe acute respiratory syndrome coronavirus 2 at the brain area and plead for an implication of the central nervous system in respiratory problems linked to coronavirus disease. Here we provide additional elements that support those observations, notably the role of brainstem structures located in the medulla oblongata in modulating respiration. We also discussed the possible pathways the virus uses to cross the brain blood barrier and reach the brainstem.


Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy.
Colorectal cancer (CRC) is one of the most prevalent neoplastic diseases worldwide, and effective treatment remains a challenge. Here, we found that the macrolide antibiotic brefeldin A (BFA) exhibits considerable antitumor activity both in vitro and in vivo. Induction of complete autophagic flux is characterized as a key event in BFA-induced CRC suppression. Mechanistically, BFA provokes endoplasmic reticulum stress-mediated binding immunoglobulin protein (Bip) expression, leading to increased Bip/Akt interaction and resultant decreased Akt phosphorylation, thereby activating autophagy. Autophagy inhibition or Bip suppression relieves BFA-induced cell death, suggesting a key role for Bip-regulated autophagy in the antitumor properties of BFA. Moreover, BFA acts synergistically with paclitaxel or 5-fluorouracil in CRC suppression. Collectively, our study provides an important molecular basis for BFA-induced autophagy and suggests that the antibiotic BFA could be repositioned as a potential anticancer drug for CRC treatment.-Zhou, L., Gao, W., Wang, K., Huang, Z., Zhang, L., Zhang, Z., Zhou, J., Nice, E. C., Huang, C. Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy.


Arginine flux and intravascular nitric oxide synthesis in severe childhood undernutrition.
Although nutritionally dispensable amino acids are not essential in the diet, adequate synthesis is necessary for maintenance of good health. Whereas children with edematous severe childhood undernutrition (SCU) can maintain production rates of glycine and serine despite a slower body protein breakdown rate, it is unknown whether the same is true for the semidispensable amino acid arginine. We aimed to measure arginine flux and intravascular nitric oxide synthesis in children with SCU. Arginine flux and the fractional and absolute synthesis rates of plasma nitrite plus nitrate were measured postabsorptively by using a 6-h infusion of [(15)N(2)]-arginine in 2 groups of children with edematous (n = 14) or nonedematous (n = 7) SCU when they were infected and malnourished (postadmission day approximately 3; clinical phase 1), when they were no longer infected (postadmission day approximately 15; clinical phase 2), and when they were recovered (postadmission day approximately 55; clinical phase 3). Arginine flux was slower (P < 0.01) and plasma arginine concentrations were lower in the edematous group than in the nonedematous group at clinical phase 1. At clinical phase 2, flux doubled to a value that was not significantly different from the value at clinical phase 3. There were no significant differences in the plasma concentration or fractional or absolute synthesis rate of plasma nitrite plus nitrate between the groups at any clinical phase and among clinical phases within each group. Whereas children with nonedematous SCU can maintain arginine flux at the same rate as when recovered, children with edematous SCU cannot. The slower arginine flux was not, however, associated with slower nitric oxide synthesis.


Epitope-Based Specific Antibody Modifications.
Modified antibodies have essential roles in analytic, diagnostic, and therapeutic uses, and thus, these antibodies are required to have optimal physical and biological properties. Consequently, the development of methods for site-selective antibody modification is crucial. Herein, we used epitope-based affinity labeling to introduce a Fab region-selective antibody modification method. Although labeling that exploits the high affinity between an antibody and its epitope may appear straightforward, it remains challenging probably because of the loss of target affinity caused by modification around the epitope-binding site. By thoroughly screening the modifying agent structure, reaction conditions, and purification methods, we developed an efficient method for the selective modification of the Fab region of the antibody while maintaining the high affinity for the epitope.


Temperature dependence of commercially available diode detectors.
Temperature dependence of commercially available n- and p-type diodes were studied experimentally under both high instantaneous dose rate (pulsed) and low dose rate (continuous) radiation. The sensitivity versus temperature was measured at SSD = 80 or 100 cm, 10 x 10 cm2, and 5 cm depth in a 30 x 30 x 30 cm3 water phantom between 10 degrees C and 35 degrees C. The response was linear for all the diode detectors. The temperature coefficient (or sensitivity variation with temperature, svwt) was dose rate independent for preirradiated diodes. They were (0.30 +/- 0.01)%/degrees C, (0.36 +/- 0.03)%/degrees C, and (0.29 +/- 0.08)%/degrees C for QED p-type, EDP p-type, and Isorad n-type diodes, respectively. The temperature coefficient for unirradiated n-type diodes was different under low dose rate [(0.16 to 0.45)%/degrees C, continuous, cobalt] and high instantaneous dose rate [(0.07 +/- 0.02)%/degrees C, pulsed radiation]. Moreover, the temperature coefficient varies among individual diodes. Similarly, the temperature coefficient for a special unirradiated QED p-type diode was different under low dose rate (0.34%/degrees C, cobalt) and high instantaneous dose rate [(0.26 +/- 0.01)%/degrees C, pulsed radiation]. Sufficient preirradiation can eliminate dose rate dependence of the temperature coefficient. On the contrary, preirradiation cannot eliminate dose rate dependence of the diode sensitivity itself.


Antioxidant superoxide dismutase - a review: its function, regulation in the testis, and role in male fertility.
Extracellular superoxide dismutase (SOD(EX)), an antioxidant enzyme, was found to be present in the testis at a relatively high concentration versus other organs. In a more detailed survey of several rat tissues and cells by reverse transcriptase-polymerase chain reaction, it was shown that germ cells expressed approximately one-third that of Sertoli cells, suggesting both cell types are equipped with the machinery needed to defend themselves from radical-induced damage. When we used an in vitro model in which germ cells were co-cultured with Sertoli cells at a Sertoli:germ cell ratio of 1:1, we failed to detect any changes in the mRNA level of SOD(EX). However, the addition of increasing concentrations of germ cell secretory proteins into Sertoli cell cultures resulted in a decrease in Sertoli cell SOD(EX) expression, illustrating that germ cells can indeed regulate Sertoli cell SOD(EX). On the other hand, Sertoli cell SOD(EX) expression was stimulated when human recombinant interleukin-1alpha (IL-1alpha), a germ cell product, was included into Sertoli cells in vitro. These results, taken collectively, suggest SOD(EX) is an important antioxidant molecule in the testis that is under germ cell regulation.


An in vitro line of the B cell tumor BCL1 can be activated by LPS to secrete IgM1.
An in vitro line of the B cell tumor BCL1 was developed. The cell line carried u-, S-, and A-chains on the cell surface as judged by analysis of surface iodinated proteins but did not secret Ig. ASfter stimulation with LPS, limpid A, or bacterial lipoprotein, 20 to 40% of the tumor cells matured to IgM secretors when detected in a plaque assay. Two other polyclonal B cell activators, namely dextransulphate and PPD, had at most a marginal stimulatory effect. The ability of the cells to become activated to IgM secretion as well as the expression of cell surface IgM and IgD makes the BCL1 unique among murine B cell tumors.


A prospective study of 1212 cases of acute poisoning: general epidemiology.
A prospective multicentre study of all acute poisonings among adults admitted to hospital (n = 1145) or dying outside hospital (n = 67) in Oslo was performed during 1980. Of the 1212 episodes, 98.3% were self-poisonings, giving an annual incidence of 2.8 per 1000 inhabitants (0/00), 3.1 0/00 in males and 2.6 0/00 in females. The main toxic agents among the self-poisoned patients were ethanol (19.7%), benzodiazepines (17.8%), opiates (14.9%), neuroleptics (10.4%) and antidepressants (9.3%). In 58.9% of the episodes more than one toxic agent was taken. Abuse among the self-poisoned patients was significantly (p less than 0.005) more common among males than females (64.2 v. 34.5%). The rate of suicide attempts was significantly (p less than 0.005) higher among females than males (20.2 v. 12.9%), females showing increasing rate with age. However, when excluding abusers the rate of suicide attempts was similar in both sexes (27.6 v. 25.0%). Compared to a reference population self-poisonings were most common in the lower middle and the lowest social classes. Patients in these social classes, however, showed a lower rate of suicide attempts than those in the two highest social classes. Overall mortality was 6.0% (n = 73), but 91.8% of all deaths occurred outside hospital indicating the importance of including these figures when self-poisonings are studied.


Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma.
We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.


Patient activation and health literacy as predictors of health information use in a general sample of Dutch health care consumers.
In demand-led health care systems, consumers are expected to play an informed, active role in health care decisions by making use of health information. The ability to seek and use this information depends on specific knowledge, skills, and self-confidence. In this study, the authors validated a translated instrument to measure patient activation (Dutch PAM-13) in a general sample of Dutch health care consumers. Furthermore, the authors examined the relative contribution of patient activation and functional health literacy to the seeking and use of health information in The Netherlands. The mean patient activation score in the Dutch sample was higher for younger health care consumers and for those with a higher education, higher income, and better self-reported general and mental health status. More activated consumers were more likely to seek and use health information. Patient activation proved to be a stronger predictor for seeking and using health information than functional health literacy.


Postoperative opioid prescribing practices and the impact of the hydrocodone schedule change.
In 2014, hydrocodone was moved from Schedule III to II, thus it could no longer be "called in" to a pharmacy. We analyzed current postoperative opioid prescribing patterns and the impact of the schedule change on the type and amount prescribed. Opioid prescriptions for common surgeries at 1 medical center from 2013 to 2016 were analyzed retrospectively. Milligram morphine equivalents prescribed before and after the schedule change were compared by t tests, and interrupted time series models and drug frequencies were compared by χ2 and Fisher exact tests. Data from 7,046 patients (7,361 prescriptions) after 29 different operations were analyzed. Milligram morphine equivalents prescribed for minor open procedures ranged from 211 to 342 milligram morphine equivalents, from 323 to 1297 for major open procedures, from 238 to 359 for basic laparoscopic procedures, and from 221 to 868 for complex laparoscopic procedures. Mean milligram morphine equivalents prescribed were not affected for most procedures, but over the entire population, milligram morphine equivalents prescribed began decreasing after the rule change. The percentage of hydrocodone prescriptions decreased after the rule change (from 33.8% down to 27.0%) and oxycodone and tramadol prescriptions increased. Before versus after the rule change, hydrocodone prescriptions decreased and oxycodone and tramadol prescriptions increased. Milligram morphine equivalents prescribed varied considerably across and within classes of procedures, but the schedule change did not affect mean milligram morphine equivalents prescribed for most procedures.


Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly.
To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects. The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model. In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated. Chronic use of omeprazole was not associated with the occurrence of OF in elders.


A review of the landscape: Challenges and gaps in trauma response to civilian high threat mass casualty incidents.
The ultimate goal of the emergency response and trauma system is to reduce potentially preventable death from trauma. Tremendous advances in trauma care emerged from the past 15 years of United States' combat engagements around the globe. Unfortunately, combat and insurgency tactics have also metastasized to the civilian world, resulting in increasingly complex and dynamic acts of intentional mass violence. These high threat active violent incidents (AVIs) pose significant preparedness, response, and clinical care challenges to the civilian healthcare systems. Currently, there are several operational and policy gaps that limit the successful preparedness and response to AVIs and dynamic MCIs in the United States.


Social and economic development and pregnancy mental health: secondary analyses of data from rural Vietnam.
This study aimed to establish whether changes in the socioeconomic context were associated with changes in population-level antenatal mental health indicators in Vietnam. Social, economic and public policies introduced in Vietnam (1986-2010) were mapped. Secondary analyses of data from two cross-sectional community-based studies conducted in 2006 (n = 134) and 2010 (n = 419), involving women who were ≥ 28 weeks pregnant were completed. Data for these two studies had been collected in structured individual face-to-face interviews, and included indicators of antenatal mental health (mean Edinburgh Postnatal Depression Scale Vietnam-validation (EPDS-V) score), intimate partner relationships (Intimate Bonds Measure Vietnam-validation) and sociodemographic characteristics. Socioeconomic characteristics and mean EPDS-V scores in the two study years were compared and mediation analyses were used to establish whether indicators of social and economic development mediated differences in EPDS-V scores. Major policy initiatives for poverty reduction, hunger eradication and making domestic violence a crime were implemented between 2006 and 2010. Characteristics and circumstances of pregnant women in Ha Nam improved significantly. Mean EPDS-V score was lower in 2010, indicating better population-level antenatal mental health. Household wealth and intimate partner controlling behaviours mediated the difference in EPDS-V scores between 2006 and 2010. Changes in the socioeconomic and political context, particularly through policies to improve household wealth and reduce domestic violence, appear to influence women's lives and population-level antenatal mental health. Cross-sectoral policies that reduce social risk factors may be a powerful mechanism to improve antenatal mental health at a population level.


Assessing musical ability quickly and objectively: development and validation of the Short-PROMS and the Mini-PROMS.
The study of musical ability has gained considerable traction across disciplines in recent years. In comparison, less effort has been invested in the development of sound measures of musical ability. To redress this gap, we conducted four studies to empirically validate two brief measures derived from the Profile of Music Perception Skills (PROMS)-an exceptionally inclusive battery of musical abilities that takes about 1 h to complete. In the Short-PROMS, test duration was reduced to less than half an hour by substantially reducing the number of trials per subtest. In the Mini-PROMS, the number of subtests was reduced to four, resulting in a battery that takes 15 min to complete. Both measures exhibited good internal consistency and retest reliability. Support for convergent, discriminant, and criterion validity was found across the studies. Additional strengths of the new instruments include their suitability for online administration and a feature called Modular PROMS, which offers researchers the possibility to request customized batteries that may include any combination of the subtests. The role of refining objective assessment instruments in research on music and the mind is discussed.


[Surgical management of intrahepatic cholelithiasis--two case reviews].
Intrahepatic lithiasis (IHL) has a low incidence rate in countries with high social-economical level, with mostly secondary ethiology. The commonest signs include: cholangoitis, obstruction icterus, liver absces and secondary biliary cirrhosis. Although a wide range of treatment methods is available, in some cases, surgical management is the only alternative. The authors present two case reviews of IHL patients. The first case includes a 56-year old male, unsuccessfuly operated in another clinic. The patient was referred to the author's clinic for a relaps of septic complications. He underwent extensive revision of his bile ducts up to the segmental bile duct level with a mechanical removal of concrements, introduction of the T-drain and postoperative cholangiography for secondary IHL of the left hepatic duct. A resection procedure was not indicated due to absence of the liver parenchyma impairment. The other patient, a 77-year old male, underwent left lateral bisegmentectomy for a primary IHL of the SII and SIII liver segments with signs of irreversible bile duct impairment, which could not be managed endoscopically. No complications during the first patient's postoperative course were recorded. A postoperative Day 7 cholangiographic examination detected free intrahepatic bile ducts. The patient has not shown any signs of a IHL relaps. The second patient's postoperative course was complicated by biliary secretion from the drain, which was managed endoscopically. A histological examination confirmed the preoperative diagnosis. IHL which cannot be managed by endoscopy or other procedures, is indicated for surgery. The type of the surgical procedure depends on the extent of the intrahepatic bile duct and liver parenchyma impairment.