Quantum Dots-Based Point-of-Care Measurement of Procalcitonin in Finger-Prick Blood and Venous Whole Blood Specimens.
To determine whether the performance of a new quantum dots-based point-of-care test (POCT) devices is qualified for procalcitonin testing. Finger-prick and venous blood specimens from 153 patients were measured with a quantum dots-based POCT device; the results were compared with those from the reference method. The quantum dots-based POCT device correlated well with the reference method in measuring plasma, venous whole blood, and finger-prick blood. No significant bias was observed (-0.08 ng/mL). At 0.5 ng per mL cutoff value, the concordances were 96.6%, 94.6%, and 90.5% for plasma, venous whole blood, and finger-prick blood, respectively. And at 2 ng per mL cutoff value, the concordances were 98.0%, 96.6%, and 95.3%, respectively. The quantum dots-based POCT device measured procalcitonin with multiple specimen types, high sensitivity, wide detection range, and short turnaround time. It would allow a more widespread use of procalcitonin and help lessen the burden of overcrowding in healthcare facilities in China.


PERFORMANCE OF CONVENTIONAL PCRs BASED ON PRIMERS DIRECTED TO NUCLEAR AND MITOCHONDRIAL GENES FOR THE DETECTION AND IDENTIFICATION OF Leishmania spp.
In visceral leishmaniasis, the detection of the agent is of paramount importance to identify reservoirs of infection. Here, we evaluated the diagnostic attributes of PCRs based on primers directed to cytochrome-B (cytB), cytochrome-oxidase-subunit II (coxII), cytochrome-C (cytC), and the minicircle-kDNA. Although PCRs directed to cytB, coxII, cytC were able to detect different species of Leishmania, and the nucleotide sequence of their amplicons allowed the unequivocal differentiation of species, the analytical and diagnostic sensitivity of these PCRs were much lower than the analytical and diagnostic sensitivity of the kDNA-PCR. Among the 73 seropositive animals, the asymptomatic dogs had spleen and bone marrow samples collected and tested; only two animals were positive by PCRs based on cytB, coxII, and cytC, whereas 18 were positive by the kDNA-PCR. Considering the kDNA-PCR results, six dogs had positive spleen and bone marrow samples, eight dogs had positive bone marrow results but negative results in spleen samples and, in four dogs, the reverse situation occurred. We concluded that PCRs based on cytB, coxII, and cytC can be useful tools to identify Leishmania species when used in combination with automated sequencing. The discordance between the results of the kDNA-PCR in bone marrow and spleen samples may indicate that conventional PCR lacks sensitivity for the detection of infected dogs. Thus, primers based on the kDNA should be preferred for the screening of infected dogs.


Effects of prednisolone on the systemic release of mediators of cell-mediated cytotoxicity during human endotoxemia.
Corticosteroids are widely used for the suppression of cell-mediated cytoxicity. This process is mediated by natural killer cells and cytotoxic T lymphocytes, and their activation can be monitored by levels of the chemokines CXCL9 and CXCL10, the degranulation product granzymes A and B, and by levels of secretory phospholipase A2. The current study aimed to determine the effects of increasing doses of prednisolone on the release of these mediators in healthy humans exposed to LPS. Therefore, 32 healthy men received prednisolone orally at doses of 0, 3, 10, or 30 mg (n = 8 per group) at 2 h before intravenous injection of Escherichia coil LPS (4 ng/kg). Prednisolone dose-dependently attenuated the LPS-induced rises in the plasma concentrations of the chemokines CXCL9 and CXCL10, as well as of granzymes A and B levels. CXCL10 and granzyme B release were most sensitive to prednisolone, with a significant inhibition already achieved at the lowest prednisolone dose (3 mg). The levels of secretory phospholipase A2 were increased after LPS administration but were not significantly affected by prednisolone. This study demonstrates that prednisolone differentially inhibits the systemic release of mediators involved in cell-mediated cytotoxicity in humans in vivo.


Biopsy pathology of acquired immune deficiency syndrome (AIDS).
Between January 1982 and May 1986 279 biopsy specimens from 82 patients with acquired immune deficiency syndrome (AIDS) were examined. A wide variety of infectious conditions were diagnosed, the commonest being Pneumocystis pneumonia (n = 36), cytomegalovirus (n = 21), a variety of fungi (n = 8), mycobacteria (n = 7). Kaposi's sarcoma was the commonest tumour (n = 40), and there were two cases of extranodal lymphoma. Striking features were the unusual sites of disease and the occasional paucity of organisms.


Binding of CIB1 to the αIIb tail of αIIbβ3 is required for FAK recruitment and activation in platelets.
It is believed that activation of c-Src bound to the integrin β3 subunit initiates outside-in signaling. The involvement of αIIb in outside-in signaling is poorly understood. We have previously shown that CIB1 specifically interacts with the cytoplasmic domain of αIIb and is required for αIIbβ3 outside-in signaling. Here we evaluated the role of CIB1 in regulating outside-in signaling in the absence of inside-out signaling. We used αIIb cytoplasmic domain peptide and CIB1-function blocking antibody to inhibit interaction of CIB1 with αIIb subunit as well as Cib1-/- platelets to evaluate the consequence of CIB1 interaction with αIIb on outside-in signaling. Fibrinogen binding to αIIbβ3 results in calcium-dependent interaction of CIB1 with αIIb, which is not required for filopodia formation. Dynamic rearrangement of cytoskeleton results in CIB1-dependent recruitment of FAK to the αIIb complex and its activation. Disruption of the association of CIB1 and αIIb by incorporation of αIIb peptide or anti-CIB1 inhibited both FAK association and activation. Furthermore, FAK recruitment to the integrin complex was required for c-Src activation. Inhibition of c-Src had no effect on CIB1 accumulation with the integrin at the filopodia, suggesting that c-Src activity is not required for the formation of CIB1-αIIb-FAK complex. Our results suggest that interaction of CIB1 with αIIb is one of the early events occurring during outside-in signaling. Furthermore, CIB1 recruits FAK to the αIIbβ3 complex at the filopodia where FAK is activated, which in turn activates c-Src, resulting in propagation of outside-in signaling leading to platelet spreading.


Metabolic Study of Cancer Cells Using a pH Sensitive Hydrogel Nanofiber Light Addressable Potentiometric Sensor.
We report a simple, fast, and cost-effective approach that measures cancer cell metabolism and their response to anticancer drugs in real time. Using a Light Addressable Potentiometric Sensor integrated with pH sensitive hydrogel nanofibers (NF-LAPS), we detect localized changes in pH of the media as cancer cells consume glucose and release lactate. NF-LAPS shows a sensitivity response of 74 mV/pH for cancer cells. Cancer cells (MDA MB231) showed a response of ∼0.4 unit change in pH compared to virtually no change observed for normal cells (MCF10A). We also observed a drop in pH for the multidrug-resistant cancer cells (MDA-MB-435MDR) in the presence of doxorubicin. However, inhibition of the metabolic enzymes such as hexokinase and lactate dehydrogenase-A suggested an improvement in the efficacy of doxorubicin by decreasing the level of acidification. This approach, based on extracellular acidification, enhances our understanding of cancer cell metabolic modes and their response to chemotherapies, which will help in the development of better treatments, including choice of drugs and dosages.


Preventing Vanishing Gradient Problem of Hardware Neuromorphic System by Implementing Imidazole-Based Memristive ReLU Activation Neuron.
With advances in artificial intelligent services, brain-inspired neuromorphic systems with synaptic devices are recently attracting significant interest to circumvent the von Neumann bottleneck. However, the increasing trend of deep neural network parameters causes huge power consumption and large area overhead of a nonlinear neuron electronic circuit, and it incurs a vanishing gradient problem. Here, a memristor-based compact and energy-efficient neuron device is presented to implement a rectifying linear unit (ReLU) activation function. To emulate the volatile and gradual switching of the ReLU function, a copolymer memristor with a hybrid structure is proposed using a copolymer/inorganic bilayer. The functional copolymer film developed by introducing imidazole functional groups enables the formation of nanocluster-type pseudo-conductive filaments by boosting the nucleation of Cu nanoclusters, causing gradual switching. The ReLU neuron device is successfully demonstrated by integrating the memristor with amorphous InGaZnO thin-film transistors, and achieves 0.5 pJ of energy consumption based on sub-10 µA operation current and high-speed switching of 650 ns. Furthermore, device-to-system-level simulation using neuron devices on the MNIST dataset demonstrates that the vanishing gradient problem is effectively resolved by five-layer deep neural networks. The proposed neuron device will enable the implementation of high-density and energy-efficient hardware neuromorphic systems.


New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.
Mutations of CIAS1 have recently been shown to underlie familial cold urticaria (FCU) and Muckle-Wells syndrome (MWS), in three families and one family, respectively. These rare autosomal dominant diseases are both characterized by recurrent inflammatory crises that start in childhood and that are generally associated with fever, arthralgia, and urticaria. The presence of sensorineural deafness that occurs later in life is characteristic of MWS. Amyloidosis of the amyloidosis-associated type is the main complication of MWS and is sometimes associated with FCU. In FCU, cold exposure is the triggering factor of the inflammatory crisis. We identified CIAS1 mutations, all located in exon 3, in nine unrelated families with MWS and in three unrelated families with FCU, originating from France, England, and Algeria. Five mutations--namely, R260W, D303N, T348M, A439T, and G569R--were novel. The R260W mutation was identified in two families with MWS and in two families with FCU, of different ethnic origins, thereby demonstrating that a single CIAS1 mutation may cause both syndromes. This result indicates that modifier genes are involved in determining either a MWS or a FCU phenotype. The finding of the G569R mutation in an asymptomatic individual further emphasizes the importance of such modifier a gene (or genes) in determining the disease phenotype. Identification of this gene (or these genes) is likely to have significant therapeutic implications for these severe diseases.


[Effect of transplantation of wild-type bone marrow stem cells in mouse model of familial amyotrophic lateral sclerosis].
To determine the effects of wild-type mouse bone marrow stem cells transplants on survival time and motor functions in the human mutant SOD1-G93A mouse model of familial amyotrophic lateral sclerosis (ALS). Bone marrow stem cells derived from the wild-type male mice were delivered intravenously into 25 ALS transgenic female mice (carrying the human SOD1 gene with Gly 93 Ala mutation) that had been pretreated with 5.5-6.5 Gy gamma-ray 5-7 days before. The onset time of limbs paralysis, lifespan and the graft versus host disease (GVHD) symptoms were observed in the treated group and statistically compared with control group of 15 media-injected ALS transgenic mice. The Sry gene (sex determine region on the Y chromosome) were detected by polymerase chain reaction technique in the blood sample of treated female ALS mice after 8 weeks of transplantation. A series of animal motor tests including rotating rods, rotated wheel and extension reflex were performed in both two groups at the same age of 16-17 weeks to assess the mice survival motor functions. Results A few treated mice (7/25) had different clinical presentations of GVHD. The semi-quantity evaluation score of average GVHD among the treated ALS mice was not over 1-2. The detection of Sry gene on these treated female ALS group was positive. The average onsets of limb paralysis and survival time were prolonged for about 5 weeks. At the age of 16-17 weeks, the motor function in the treated group was significantly better than in the ALS control group (P < 0.01). Transplantation of wild-type mice bone marrow stem cells can prolong survival in the recipient mice and ameliorate motor dysfunction. Intravenous administration of normal bone marrow stem cells may have therapeutic values for ALS.


Purification of mitochondrial proteins HSP60 and ATP synthase from ascidian eggs: implications for antibody specificity.
Use of antibodies is a cornerstone of biological studies and it is important to identify the recognized protein with certainty. Generally an antibody is considered specific if it labels a single band of the expected size in the tissue of interest, or has a strong affinity for the antigen produced in a heterologous system. The identity of the antibody target protein is rarely confirmed by purification and sequencing, however in many cases this may be necessary. In this study we sought to characterize the myoplasm, a mitochondria-rich domain present in eggs and segregated into tadpole muscle cells of ascidians (urochordates). The targeted proteins of two antibodies that label the myoplasm were purified using both classic immunoaffinity methods and a novel protein purification scheme based on sequential ion exchange chromatography followed by two-dimensional gel electrophoresis. Surprisingly, mass spectrometry sequencing revealed that in both cases the proteins recognized are unrelated to the original antigens. NN18, a monoclonal antibody which was raised against porcine spinal cord and recognizes the NF-M neurofilament subunit in vertebrates, in fact labels mitochondrial ATP synthase in the ascidian embryo. PMF-C13, an antibody we raised to and purified against PmMRF, which is the MyoD homolog of the ascidian Phallusia mammillata, in fact recognizes mitochondrial HSP60. High resolution immunolabeling on whole embryos and isolated cortices demonstrates localization to the inner mitochondrial membrane for both ATP synthase and HSP60. We discuss the general implications of our results for antibody specificity and the verification methods which can be used to determine unequivocally an antibody's target.


Pulmonary function in patients with amyotrophic lateral sclerosis at disease onset.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Deteriorating pulmonary function as a reflection of progressive respiratory muscle weakness is a common feature, accounting for the majority of deaths. The aim of the study was to describe a trend in initial pulmonary function tests (PFT) of amyotrophic lateral sclerosis (ALS) patients, in addition, differentiating between the types of disease onset, bulbar, limb muscle, and a combination. Initial PFT were gathered from 32 consecutive patients in our clinic with the diagnosis of ALS, they were categorized by the type of disease onset. Values obtained were referenced to the 95% confidence limits for normality. There was evidence of significant reductions in both the FEV1 (64.7% predicted) and FVC (61.2%), with preservation of the FEV1/FVC (81.7%). The MVV was significantly reduced (43%). Total lung capacity was 93.2%, the residual volumes was increased at 145.7%. Subgroup analysis failed to show significant differences between types of disease onset. In the bulbar onset group (versus the limb group) there was a trend for the MVV to be further reduced (p = 0.15) and the RV to be higher (157.4% versus 135.9%, P = 0.24). ALS is a devastating disease that invariably leads to respiratory failure. Abnormal spirometric variables such as the FVC and MVV, likely reflect inspiratory muscle weakness and increased RV likely reflect expiratory muscle weakness. The type of disease onset did not result in a different pattern of PFT abnormalities.


Giant subcutaneous leiomyosarcoma of anterior abdominal wall.
Subcutaneous leiomyosarcomas are rare tumors accounting for 1% to 2% of all superficial soft tissue malignancies. Although they may arise anywhere in the body, they most frequently occur in the lower extremities. The incidence of subcutaneous LMS affecting the anterior abdominal wall is very rare. We herein report the case of a patient with a giant subcutaneous leiomyosarcoma arising in the anterior abdominal wall. It was diagnosed by histopathology and immunohistochemistry and treated accordingly.


[Clinical studies using a photometric method for determining serum lipase activity].
Results of measurement of serum lipase activity as determined by a UV-test described by Myrick and a titrimetric assay as described by Rick were compared as far as sensitivity and specificity in diagnosis of pancreatitis is concerned. Sensitivity of the UV assay is low (45% falsely normal values), and specificity as well (falsely pathological values in 55.5% of patients with liver disease and 9% of normal persons). In the UV assay lipoproteinlipases are measured as well as hepatic esterases: in 17 samples from persons having received heparin lipase activity was increased 3-8 fold. In a total of 99 samples no correlation was found between the results of the 2 assays. As a consequence it can be stated that the UV-test as described by Myrick has no relevance in diagnosis of pancreatitis; the commercially available assay kit is withdrawn in the meantime.


Body Composition Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma Treated with Sorafenib.
Previous studies have suggested body composition as a predictor of sorafenib toxicity and outcome in patients with advanced hepatocellular carcinoma (HCC). Large studies on the impact of body composition parameters in European HCC patients are lacking. Our aim was to validate the prognostic value of body composition parameters in Dutch patients with HCC treated with sorafenib. A retrospective analysis was performed in a cohort of HCC patients treated with sorafenib at two Dutch tertiary referral centers between 2007 and 2016. Body composition (adipose and skeletal muscle tissue) was measured at baseline by computed tomography (CT). Low skeletal muscle mass (SMM) and density were defined using published cut-offs. Body composition parameters were correlated with overall survival (OS), time to progression, response rate, and toxicity. A total of 278 patients were included, mostly Child-Pugh class A (85%) and Barcelona Clinic Liver Cancer (BCLC) stage C (73%), with a median OS of 9.5 months (95% CI 8.1-11.0). Patients with combined low SMM and low total adipose tissue index (TATI) (n = 68, 25%) had a poor median OS (5.8, 95% CI 4.8-6.8) compared with other patients (11.7, 95% CI 9.4-14.0). Combined low SMM and low TATI remained an independent predictor of OS (HR 1.56, 95% CI 1.15-2.11, p = 0.004) after adjusting for known prognostic factors. There was no association between body composition and sorafenib toxicity. In Dutch HCC patients treated with sorafenib, the combined presence of low SMM and low TATI was associated with impaired survival, independent of known prognostic factors. CT assessment of body composition may provide additional prognostic information prior to sorafenib treatment.


Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia.
To determine if antibodies to cyclic citrullinated peptide (anti-CCP) are found in chronic hepatitis C virus (HCV) infection. Rheumatoid factor (RF) and anti-CCP were measured in sera from 50 patients with HCV infection but without cryoglobulinemia, sera from 29 patients with mixed cryoglobulinemia (including 13 with rheumatic symptoms and 5 with arthritis), and sera from 20 normal blood donors. Anti-CCP was measured by second-generation enzyme-linked immunosorbent assay (ELISA). No sera with elevated anti-CCP were found in patients with HCV infection without cryoglobulinemia, and in that population, the maximum anti-CCP was 10 units, well below the positive cutoff of 20 units. Positive findings on RF testing >13 IU/ml were present in 22 (44%) of the HCV patients, with RF >50 IU/ml in 8 (16%) and a maximum RF of 526 IU/ml. Of the cryoglobulinemia patients, 22 (76%) had positive results on tests for RF, including 18 (62%) with RF >50 IU/ml and a maximum RF of 5,540 IU/ml. Two (6.9%) of the cryoglobulinemia patients had borderline-positive findings on tests for anti-CCP (25 units and 37 units), which were false-positive results caused by nonspecific binding in the ELISA. No association between the RF and the anti-CCP concentrations was found. Whereas RF was frequent in patients with HCV infection with and without cryoglobulinemia, anti-CCP was not observed in patients with uncomplicated HCV infection. Borderline-positive anti-CCP results were observed infrequently in patients with mixed cryoglobulinemia and were caused by nonspecific binding to plastic. Measurement of anti-CCP may help in diagnosing RA in patients with chronic HCV infection.


Uric Acid and Cardiovascular Disease: An Update.
In recent years, serum uric acid (SUA) as a determinant of cardiovascular (CV) risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia SUA are at increased risk of cardiac, renal and vascular damage and CV events. There is now some evidence to suggest that urate-lowering treatment may reduce CV risk in this group and, thus, may represent a new strategy in risk reduction.


A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway.
Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum.


When disaster strikes: getting ready for the next big one: part I.
This two-part article deals with the role of the physician when disaster strikes. The first part concentrates on disaster planning and emergency preparedness as it pertains to the staff and the practice. It suggests points to consider in preparing a disaster plan for the practice or institution so that everyone knows what to do in the event of a crisis. This disaster plan is also a blueprint for recovery once the disaster has passed that will assure the financial health of the practice.


Comparison of subsequent injury categorisation (SIC) models and their application in a sporting population.
The original subsequent injury categorisation (SIC-1.0) model aimed to classify relationships between chronological injury sequences to provide insight into the complexity and causation of subsequent injury occurrence. An updated model has recently been published. Comparison of the data coded according to the original and revised subsequent injury categorisation (SIC-1.0 and SIC-2.0) models has yet been formally compared. Medical attention injury data was prospectively collected for 42 elite water polo players over an 8 month surveillance period. The SIC-1.0 and SIC-2.0 models were retrospectively applied to the injury data. The injury categorisation from the two models was compared using descriptive statistics. Seventy-four injuries were sustained by the 42 players (median = 2, range = 0-5), of which 32 injuries (43.2%) occurred subsequent to a previous injury. The majority of subsequent injuries were coded as occurring at a different site and being of a different nature, while also being considered clinically unrelated to the previous injury (SIC-1.0 category 10 = 57.9%; SIC-2.0 clinical category 16 = 54.4%). Application of the SIC-2.0 model resulted in a greater distribution of category allocation compared to the SIC-1.0 model that reflects a greater precision in the SIC-2.0 model. Subsequent injury categorisation of sport injury data can be undertaken using either the original (SIC-1.0) or the revised (SIC-2.0) model to obtain similar results. However, the SIC-2.0 model offers the ability to identify a larger number of mutually exclusive categories, while not relying on clinical adjudication for category allocation. The increased precision of SIC-2.0 is advantageous for clinical application and consideration of injury relationships.


[Application of combination of capillary electrophoresis with laser-induced fluorescence: measurement of glutamate and arginine in PAG microdialytes of conscions morphine-withdrawal rats].
Microdialysis technique in free-moving animals can be used to monitor continuously the changes of many extracellular neurotransmitters in certain brain areas and study the relationship between neurotransmitter and functions. Using detection of capillary electrophoresis combined with laser-induced fluorescence (CE-LIF) further improves the above-mentioned technique. In the present study, fluorescein isothiocyanate (FITC) was used to derivatizate amino acid in very low concentration. We found that increasing derivatization temperature could shorten derivatization time and that the derivatizative efficiency was not different from that when experiment was performed under the traditional derivatization condition (room temperature for 16 h). We also got an optimized condition of amino acid derivatization with FITC at 30 degrees C water bath for 5 h. Using the optimized condition of amino acid derivatization, we investigated the changes in L-arginine (L-Arg) and L-glutamate (L-Glu) concentration in periaqueductal gray matter (PAG) microdialytes of free-moving morphine-withdrawal rats. The results indicated that there was no significant difference in the concentration of L-Arg and L-Glu in PAG between non-dependent and dependent rats. The concentration of L-Arg and L-Glu in PAG increased by 63% and 105%, respectively, in the first 10 min after naloxone-precipitated withdrawal and then declined gradually. These changes were in correspondence with the scores of morphine withdrawal symptom.


Ethanol-induced changes in morphology and strength of femurs of rats.
Chronic ingestion of ethanol resulted in ultrastructural and mechanical changes in rat femurs. Scanning electron microscopy of the distal end of the femur revealed that the trabeculae of bones from ethanol-fed rats were thinner, more columnar, and more extensive than those from control rats. Three-point bending tests of the rat femurs showed that the maximum force or so-called "strength" required to break the bone was less in ethanol- than in control-fed animals. A significant inverse correlation was observed between the strength required to break the femur and the dose of ethanol calculated on a body weight basis. For the first time our study presents quantitative proof that a relationship exists between bone strength and the consumption of ethanol in rats. The study revealed that ethanol consumption resulted in a weaker femur compared to controls. We suggest that a common mechanism may be responsible for the decreased bone strength of ethanol-fed rats and the increased incidence of fractures in human alcoholics.


Current issues regarding the pathobiology of asbestosis: a chronologic perspective.
Asbestosis is a pneumoconiosis that results from the inhalation of asbestos fibers. There is a body of evidence that implicates the alveolar macrophage in the pathogenesis of asbestosis because of its prominence in asbestos-related histologic lesions. Injury to the alveolar epithelium also may contribute to the pathogenesis of asbestosis. Evidence is presented to suggest that pulmonary fibrosis may result from the persistent release of inflammatory mediators (chemoattractants, lysosomal enzymes, toxic oxygen radicals, arachidonic acid metabolites, interleukins, and fibroblast growth factors) at sites of asbestos deposition. Histologic features of asbestosis can be detected within months after the initial contact with asbestos. In contrast, the stigmata of asbestos-related disease usually are not radiologically detectable, even by the most sensitive imaging techniques, until after a latency period of at least a decade, and often considerably longer. There is, therefore, a long diagnostic delay between the time when asbestosis is histologically detectable and when it is radiographically detectable.


Recombinant human erythropoietin in the treatment of myelodysplastic syndromes. An interim report.
It has recently been demonstrated that erythropoietin increases hemoglobin levels in anemia secondary to chronic renal failure. Some recent experiences have suggested a possible role in the treatment of anemia in patients with myelodysplastic syndrome (MDS). From April, 1990 to March, 1991, 16 patients (11 males and 5 females, median age 58.5 years) affected by low-risk myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and reduce transfusional requirement. All patients received high doses of rHuEPO (400 U/Kg s.c. twice weekly for 3 months). A partial response, defined as a stable increase in Hb levels > 1g/dL and/or a reduction in transfusional need > 50% lasting at least 3 months, was achieved by 5/16 patients. Those who responded received an additional course of treatment with rHuEPO at an increased dosage (600 U/Kg twice weekly for 3 months), and one of these five showed a progressive rise in Hb level up to normalization, while the other 4 remained stable. The treatment was well tolerated and no adverse reactions were observed. These results suggest that some patients with MDS may benefit from rHuEPO treatment.


Reversible ON-OFF switching of single-molecule-magnetism associated with single-crystal-to-single-crystal structural transformation of a decanuclear dysprosium phosphonate.
{Dy5(EDDC)2(μ3-AcO)2(μ5-C15H11PO3)(μ4-C15H11PO3)(μ2-AcO)2(AcO)2(H2O)(CH3OH)2}2(μ4-C2O4)·xH2O (I), where H2EDDC is N',N'',E,N',N'',E-N',N''-(ethane-1,2-diylidene)dipyrazine-2-carbohydrazide and C15H11PO3H2 is 9-anthrylmethylphosphonic acid, is found to undergo two consecutive single-crystal-to-single-crystal transformations. The first is under UV irradiation (λ = 365 nm for 3 d in air) to {Dy5(EDDC)2(μ3-AcO)2(μ5-C15H11PO3)2(μ2-AcO)2(AcO)2(H2O)3}2(μ4-C2O4)·xH2O (I-UV) where the two CH3OH are replaced by two H2O and the second by annealing under N2 at 100 °C on a diffractometer or under Ar in a glovebox to {Dy5(EDDC)2(μ3-AcO)2(μ5-C15H11PO3)2(μ2-AcO)4(H2O)}2(μ4-C2O4) (I-A-N2 or I-A-Ar) where it has lost two H2O molecules. The second transformation is reversible by exposure to air at room temperature (I-A-N2-cool). While the overall structures are the same (retaining the space group P21/c), there is a considerable expansion of the unit cell from I (8171 Å3) to I-UV (8609 Å3) and I-A-N2 (8610 Å3) and the coordinations of the Dy atoms undergo major reconstructions. This is associated with switching the single-molecule-magnetism (SMM) from OFF for I to ON for I-UV and to OFF again for I-A-Ar in air. Such a switching mechanism associated with the retention of crystallinity is unique in the chemistry of dysprosium. The structure of the molecule is formed from two symmetry related pentamers joined by an oxalate. A related compound containing two isolated neutral pentamers {Dy5(EDDC)2(μ3-AcO)2(μ5-C15H11PO3)2(μ2-AcO)3(AcO)2(H2O)2}{Dy5(EDDC)2(μ3-AcO)2(μ5-C15H11PO3)(μ4-C15H11PO3)(μ2-AcO)3(AcO)2(CH3OH)2}·2CHCl3 (II) has also been isolated with closely related Dy coordination and it exhibits similar SMM behaviour in zero field.


Autologous Fat Grafting for Treating Blepharoplasty-induced Lower Eyelid Retraction.
Autologous fat grafting for blepharoplasty-induced lower eyelid retraction offers potential for a long-term solution while avoiding the morbidity associated with posterior lamellar spacer grafts. By combining traditional methods of lifting the retracted lower eyelid with autologous fat grafting, both functional and aesthetic concerns can be successfully addressed in these patients.


The Utility of Pre- and Post-Transplant Oral Glucose Tolerance Tests: Identifying Kidney Transplant Recipients With or at Risk of New Onset Diabetes After Transplant.
Background: New onset diabetes after transplant (NODAT) is common in kidney transplant recipients (KTRs). Identifying patients at risk prior to transplant may enable strategies to mitigate NODAT, with a pre-transplant oral glucose tolerance test (OGTT) suggested by the KDIGO 2020 Guidelines for this purpose. Methods: We investigated the utility of pre- and post-transplant OGTTs to stratify risk and diagnose NODAT in a retrospective, single-centre cohort study of all non-diabetic KTRs transplanted between 2003 and 2018. Results: We identified 597 KTRs who performed a pre-transplant OGTT, of which 441 had their post-transplant glycaemic status determined by a clinical diagnosis of NODAT or OGTT. Pre-transplant dysglycaemia was identified in 28% of KTRs and was associated with increasing age (p < 0.001), BMI (p = 0.03), and peritoneal dialysis (p < 0.001). Post-transplant dysglycaemia was common with NODAT and impaired glucose tolerance (IGT) occurring in 143 (32%) and 121 (27%) patients, respectively. Pre-transplant IGT was strongly associated with NODAT development (OR 3.8, p < 0.001). Conclusion: A pre-transplant OGTT identified candidates at increased risk of post-transplant dysglycaemia and NODAT, as diagnosed by an OGTT. Robust prospective trials are needed to determine whether various interventions can reduce post-transplant risk for candidates with an abnormal pre-transplant OGTT.


Effects of phosphate loading on 2,3-diphosphoglycerate and maximal oxygen uptake.
Increased concentration of red blood cell 2,3-diphosphoglycerate (RBC 2,3-DPG) shifts the hemoglobin-oxygen dissociation curve to the right, thus theoretically allowing better oxygenation of tissues. To determine whether such a shift is physiologically significant, we investigated the effects of oral phosphate loading on several parameters including plasma phosphate concentration, RBC 2,3-DPG, hematocrit and hemoglobin concentration, maximal oxygen uptake (VO2max), and degree of lactic acidemia in 10 well-trained distance runners. After control determinations were made, either a phosphate load or a placebo was given for 3 d before the athlete was restudied. A placebo and two phosphate-loading studies were performed at weekly intervals, followed by 2 wk of rest and another post-intervention control study. Blood samples for control values were drawn before and after a standard warm-up period, after treadmill exercise at a 10% grade, and at the completion of the VO2 determination. After oral phosphate loading there was a significant increase in serum phosphate and RBC 2,3-DPG. Maximal oxygen uptake was significantly increased and correlated with the rise in RBC 2,3-DPG (r = 0.81). The increase in blood lactate after exercise on the 10% grade was attenuated during sessions which followed phosphate loading.


Animal toxins and renal ion transport: Another dimension in tropical nephrology.
Renal vascular and tubular ion channels and transporters involved in toxin injury are reviewed. Vascular ion channels modulated by animal toxins, which result in haemodynamic alterations and changes in blood pressure, include ENaC/Degenerin/ASIC, ATP sensitive K channels (KATP ), Ca activated K channels (Kca) and voltage gated Ca channels, mostly L-type. Renal tubular Na channels and K channels are also targeted by animal toxins. NHE3 and ENaC are two important targets. NCC and NKCC may be involved indirectly by vasoactive mediators induced by inflammation. Most renal tubular K channels including voltage gated K channels (Kv1), KATP , ROMK1, BK and SK are blocked by scorpion toxins. Few are inhibited by bee, wasp and spider venoms. Due to small envenoming, incomplete block and several compensatory mechanisms in renal tubules, serum electrolyte charges are not apparent. Changes in serum electrolytes are observed in injury by large amount of venom when several channels or transporters are targeted. Envenomings by scorpions and bees are examples of toxins targeting multiple ion channels and transporters.


Accessing N-Acyl Azoles via Oxoammonium Salt-Mediated Oxidative Amidation.
An operationally simple, robust, metal-free approach to the synthesis of N-acyl azoles from both alcohols and aldehydes is described. Oxidative amidation is facilitated by a commercially available organic oxidant (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and proceeds under very mild conditions for an array of structurally diverse substrates. Tandem reactions of these activated amides, such as transamidation and esterification, enable further elaboration. Also, the spent oxidant can be recovered and used to regenerate the oxoammonium salt.


The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli.
A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.


[The role of the primary care physician in the care of the psychotic patient].
The primary care physician (PCP) plays an important role in the outpatient care of psychotic patients, particularly in the early detection of these disorders. Through the PCP's status as a trusted individual who knows the patient and his/her family, his/her opinion and attitude influence treatment acceptance and, consequently, the prognosis. By ensuring the continuity of care, in collaboration with a psychiatrist, the PCP helps prevent relapse and the evolution towards chronicity and long-term handicaps. A high incidence of cardiopulmonary disease and concomitant substance abuse in the population of chronic psychotic patients, as well as the monitoring of potential somatic side effects of psychotropic medication, require regular somatic follow-up by the PCP.


Antinociceptive, brain-penetrating derivatives related to improgan, a non-opioid analgesic.
The antinociceptive profile of selected histamine H(2) and histamine H(3) receptor antagonists led to the discovery of improgan, a non-brain-penetrating analgesic agent which does not act on known histamine receptors. Because no chemical congener of improgan has yet been discovered which has both antinociceptive and brain-penetrating properties, the present study investigated the antinociceptive effects of a series of chemical compounds related to zolantidine, a brain-penetrating histamine H(2) receptor antagonist. The drugs studied presently contain the piperidinomethylphenoxy (PMPO) moiety, hypothesized to introduce brain-penetrating characteristics. Following intracerebroventricular (i.c.v.) dosing in rats, six of eight drugs produced dose- and time-related antinociception on both the tail flick and hot plate tests over a nearly eight-fold range of potencies. Ataxia and other motor side effects were observed after high doses of these drugs, but two of the compounds (SKF94674 and loxtidine) produced maximal antinociception at doses which were completely devoid of these motor effects. Consistent with the hypothesis that PMPO-containing drugs are brain-penetrating analgesics, SKF94674 and another derivative (JB-9322) showed dose-dependent antinociceptive activity 15 to 30 min after systemic dosing in mice, but these effects were accompanied by seizures and death beginning 45 min after dosing. Other drugs showed a similar pattern of antinociceptive and toxic effects. In addition, loxtidine produced seizures without antinociception, whereas zolantidine produced neither effect after systemic dosing in mice. Although several of the drugs tested have histamine H(2) receptor antagonist activity, neither the antinociception nor the toxicity was correlated with histamine H(2) receptor activity. The present results are the first to demonstrate the existence of brain-penetrating antinociceptive agents chemically related to zolantidine and improgan, but further studies are needed to understand the mechanisms of both the pain relief and toxicity produced by these agents.


In vivo and in vitro immunosuppression by boar seminal vesicle fluid fraction.
Boar seminal vesicle fluid inhibits blast transformation of porcine lymphocytes. Boar seminal vesicle fluid was precipitated in 8% ethanol and the dissolved precipitate separated into two peaks upon chromatography on a Sephacryl S-200 column. The inhibitory activity was found predominantly in the second peak. This peak was rechromatographed on the Sephacryl S-200 column, and the fractions with inhibitory activity were pooled and passed down a Sephadex G-75 column. This chromatography run separated the accompanying protease inhibitor from the immunosuppressive fraction. The molecular mass, estimated by chromatography on the Sephadex G-75 column, was 25,000-27,000 for the immunosuppressive factor and 7,500 for the protease inhibitor. Activity for the immunosuppressive fraction was also demonstrated in vivo.


Water in micro- and nanofluidics systems described using the water potential.
This Tutorial Review shows the behaviour of water in micro- and nanofluidic systems. The chemical potential of water ('water potential') conveniently describes the energy level of the water at different locations in and around the system, both in the liquid and gaseous state. Since water moves from high to low potential, the water potential enables us to predict and describe the direction of water movement inside systems and between systems and their surroundings. Practical examples of microfluidic devices illustrate the different contributions to the water potential (capillary, gravitational, entropic (osmotic) in liquid water; the partial vapour pressure in atmospheric water and van der Waals forces in water films) and the resulting water movement.


The day of week of elective colorectal cancer surgery has no impact on mortality and morbidity.
Recent studies have reported an asso-ciation between the day of week of surgery and post-operative mortality, meaning that patients undergoing surgery at the end of the week or during weekends may be at higher risk. The aim of this study was to investigate the influence of the day of week of surgery on mortality and morbidity rates in a national Danish cohort of patients undergoing major elective surgery for colorectal cancer. In a register-based study design, all patients undergoing elective major surgery for colorectal cancer in Denmark during a ten-year period (2005-2014) were studied. Patients were identified in the National Colorectal Cancer Database. Any associations between short-time mortality and morbidity rates within 30 days after operation and the day of week of surgery, as well as patient characteristics, treatment data and socioeconomic data were analysed. We were unable to show that the day of week had a significant impact on short-term mortality or on surgical or medical complications. There was no evidence that patients undergoing surgery on Fridays had more risk factors or were more socioeconomically deprived than patients undergoing surgery from Monday to Thursday. The day of week of operation could not be shown to have any significant impact on the risk of post-operative surgical or medical complications or on short-term mortality in patients undergoing elective surgery for colorectal cancer in Denmark. none. not relevant.


Quantitation of contacts among sensory, motor, and serotonergic neurons in the pedal ganglion of aplysia.
Present models of long-term sensitization in Aplysia californica indicate that the enhanced behavioral response is due, at least in part, to outgrowth of sensory neurons mediating defensive withdrawal reflexes. Presumably, this outgrowth strengthens pre-existing connections by formation of new synapses with follower neurons. However, the relationship between the number of sensorimotor contacts and the physiological strength of the connection has never been examined in intact ganglia. As a first step in addressing this issue, we used confocal microscopy to examine sites of contact between sensory and motor neurons in naive animals. Our results revealed relatively few contacts between physiologically connected cells. In addition, the number of contact sites was proportional to the amplitude of the EPSP elicited in the follower motor neuron by direct stimulation of the sensory neuron. This is the first time such a correlation has been observed in the central nervous system. Serotonin is the neurotransmitter most closely examined for its role in modulating synaptic strength at the sensorimotor synapse. However, the structural relationship of serotonergic processes and sensorimotor synapses has never been examined. Surprisingly, serotonergic processes usually made contact with sensory and motor neurons at sites located relatively distant from the sensorimotor synapse. This result implies that heterosynaptic regulation is due to nondirected release of serotonin into the neuropil.


Effect of Zinc Supplementation on Growth Outcomes in Children under 5 Years of Age.
(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I² and τ² statistic, stratified analyses, and meta-regression, and publication bias by Egger's and Begg's tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: -0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52-1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09-0.38), weight (WMD = 0.14 kg, 95%CI: 0.07-0.21), and weight-for-age Z-score (WMD = 0.04, 95%CI: 0.001-0.087), but not height-for-age Z-score (WMD = 0.02, 95%CI: -0.01-0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: -0.03-0.06). Child age at zinc supplementation appeared to modify the effects on height (P-interaction = 0.002) and HAZ (P-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50-2.25; WMD for HAZ = 0.12, 95%CI: 0.05-0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.


Measurement of circulating troponin Ic enhances the prognostic value of C-reactive protein in haemodialysis patients.
Cardiac Troponin I (cTnI) levels are considered an important diagnostic tool in acute coronary events. They could be of predictive value in haemodialysis (HD) patients. However, the relationship between cTnI and the HD-induced inflammatory state remains unclear. The aim of this study was to explore the prognostic relevance to all-cause and cardiovascular mortalities in HD patients of cTnI, in combination with highly sensitive C-reactive protein (hs-CRP) levels. We measured cTnI and hs-CRP at baseline (March 10 to November 16, 2001) in 191 HD patients without clinical signs of acute coronary artery disease [median age 66.7 years (range 22.3-93.5), 94 females, 97 males]. We used a cTnI concentration with a total imprecision of 10% (0.03 microg/l), determined in the laboratory, as the analytical threshold value. Patients were followed for mortality until 1 January, 2003 (median follow-up 418 days). The adjusted relative risks (RRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. A significant proportion (25.1%) of patients had elevated CTnl, > or =0.03 microg/l; 40.3% of patients had CRP concentrations > or =10 mg/l. During follow-up, 29 patients died, 44.8% due to cardiac causes. Elevated cTnI or CRP levels were associated with increased mortality [RR adjusted for age, sex and duration of dialysis 4.2 (1.9-9.0) for cTnI > or =0.03 microg/l and 3.6 (1.6-8.1) for CRP > or =10 mg/l], cTnI being particularly predictive of cardiovascular death. Moreover, the combination of elevated hs-CRP (> or =10 mg/l) and circulating cTnI (> or =0.03 microg/l) dramatically impaired the HD survival rate [adjusted RR for all-cause mortality 16.9 (4.5-63.8)]. Circulating cTnI was associated with poor prognosis, especially when combined with elevated CRP, strongly supporting the adoption of regular cTnI testing in HD patients.


Prevalence of urinary incontinence among women in Saudi Arabia: a cross-sectional study.
Urinary incontinence is defined as involuntary loss of urine, a common health condition that is more frequent in women. It disturbs the affected individuals and interferes with their daily activities. This study aimed to estimate the prevalence of urinary incontinence among Saudi women in the western area of the Kingdom of Saudi Arabia. A descriptive cross-sectional design was used for this study. A survey was administered to Saudi women in the western area of the Kingdom of Saudi Arabia ranging in age from 18 to 70 years. The data were collected using the Arabic version of the Questionnaire for Urinary Incontinence Diagnosis. Descriptive statistics were generated by calculating numbers and percentages of information on the prevalence of incontinence in women. p-values < 0.05 were considered statistically significant. The prevalence of urinary incontinence was 44.2%, with the urge type being the most reported. Stress urinary incontinence was reported by 155 women (15.4%), urgency urinary incontinence by 257 women (25.6%), and mixed urinary incontinence by 102 women (10.15%). Urinary incontinence is prevalent in women in Western Saudi Arabia. Age, multiparty obesity, and vaginal surgery are significant risk factors influencing its occurrence.


Synthesis of complement by alveolar macrophages from patients with sarcoidosis.
Sarcoidosis is a granulomatous disorder of unknown aetiology. Alveolar macrophages (AM) in sarcoidosis release a variety of mediators important to the pathogenesis of the disease. Complement is essential for the inflammatory response and we investigated whether there were any major defects in the potential for sarcoidosis AM to synthesize complement in vitro. AM from 11 patients with active sarcoidosis and three healthy controls were cultured under serum-free conditions. There was a significant binding of polyclonal (anti-C5, -C6, -C7, -C8) and monoclonal anti-complement antibodies (anti-C3c and anti-C9 neoepitope (aE11] to agarose beads incubated with unstimulated AM for 24, 48, or 72 h. A significant and inhibitable production of soluble C3c, C5, C9, and S-protein was found in the harvested medium as detected by enzyme immunoassays. Activated C3 and C9 were also detected based on neoepitope expression. Presence of co-cultured agarose beads reduced the amount of soluble S-protein due to deposition on the agarose. We argue that the C9 neoepitope is an integral part of the terminal complement complex (TCC), both in the fluid and solid phase when bound to the agarose. In the fluid phase, SC5b-9 was generated, whereas the agarose-bound S-protein is assumed not to be associated with TCC on the beads. The results demonstrate for the first time that AM from sarcoidosis patients synthesize the functional alternative and terminal pathway of complement.


OP16, a novel ent-kaurene diterpenoid, potentiates the antitumor effect of rapamycin by inhibiting rapamycin-induced feedback activation of Akt signaling in esophageal squamous cell carcinoma.
Hyperactivation of mTOR signaling pathway has been viewed as a significant molecular pathogenesis of cancer. However, inhibition of mTOR by rapamycin and its analogs could induce numerous negative feedback loops to attenuate their therapeutic efficacy. As a traditional Chinese herbal medicine, Rabdosia rubescens has been used to treat esophageal squamous cell carcinoma (ESCC) for hundreds of years, and its major effective component is oridonin. Here we reported that OP16, a novel analog of oridonin, showed potent inhibition of cell proliferation and Akt phosphorylation in ESCC cells. The combination of OP16 and rapamycin possesses synergistic anti-proliferative and pro-apoptotic effects both in ESCC cells and ESCC xenografts, and no obvious adverse effect was observed in vivo. Mechanistic analysis revealed that OP16 could inhibit rapamycin-induced Akt activation through the p70S6K-mediated negative feedback loops, and the combination of OP16 and rapamycin was more effective in activating caspase-dependent apoptotic signaling cascade. This study supports the combined use of OP16 with rapamycin as a feasible and effective therapeutic approach for future treatment of ESCC.


Determination of iodine concentration and distribution in rat thyroid follicles by electron-probe microanalysis.
The concentration and the distribution of iodine in various sized follicles of rat thyroid glands have been analyzed by electron-probe microanalysis. The results of the iodine analysis were grouped according to uncorrected lumen diameter size. No significant differences in iodine concentration were observed among the various size categories. When the results for all follicles from a given sample were pooled, the standard error of the mean was approximately 4%. Usually 40-50 follicles per animal were analyzed. The concentration of iodine ranged from 0.9 to 2.1% by weight among individual animals. Scanning pictures and step-scan analysis showed the iodine distribution to be quite uniform across the colloid area. Several techniques of sample preparation were used; they produced no significant differences in the iodine concentrations observed. Sodium concentration, also determined in all samples, was found to vary from 2 to 9% by weight. Because of the mobility of the sodium ion, its distribution was greatly affected by the method of sample preparation. The technique that best preserved the natural chemistry of the sample was that of freezing the tissue, sectioning, and then freeze-drying.


Preschoolers' understanding of the role of communication and cooperation in establishing property rights.
Property as a social "agreement" comprises both a communicative component, in which someone makes a claim that she is entitled to some piece of property, and a cooperative component, in which others in the community respect that claim as legitimate. In the current study, preschool children were (a) given the opportunity to mark some objects as "theirs" (to claim them in the face of other fictitious children who would supposedly enter the room later); and (b) confronted with stickers in various spatial arrangements (e.g., piled up neatly vs. scattered), told that a fictitious child had previously chosen some for herself but had to suddenly leave the room, and then invited first to choose some stickers for themselves and second to identify which stickers had already been claimed by the fictitious child. Five-year-olds but not 3-year-olds were skillful in both of these tasks, demonstrating an understanding of the crucial role of communication in asserting property claims and the crucial role of cooperation in respecting them.


Static and dynamic impact trauma of the human larynx.
The response of fresh human larynges to static and dynamic compressive loading has been determined for 24 specimens. Mean static force values producing thyroid and cricoid cartilage fractures were 15.8 and 20.8 kg, respectively, and the similarity of this experimental injury to a mild clinical laryngeal fracture syndrome is discussed. Dynamic fracture loading, at velocities up to 11 mph, caused cartilage fractures at forces averaging 30% more, and comparison with the static data is made. Interaction of the thyroid and cricoid cartilages to impact force are analyzed in reference to airway protection. The 50% compressive strain level, at which structural collapse is imminent, averaged 55 kg. The significance of these previously unreported low force levels producing fracture is discussed with reference to automotive design.


Psychomotor development after ganciclovir selectively treated congenital and perinatal cytomegalovirus infection.
To study the development of children with selectively treated cytomegalovirus infection. We studied prospectively a risk group of 12 children with cytomegalovirus infection. These children were diagnosed by serological screening in the first three months after birth and are defined as congenital and perinatal infections. Thirteen infants with no serological evidence of previous or present cytomegalovirus infection at 4-12 months of age were used as controls. Ganciclovir in a dose of 10-15 mg/kg/day for at least 2 weeks followed by 5-7.5 mg/kg/day administered intravenously for at least 2 weeks more was given to 4 children from the risk group with PCR confirmed cytomegalovirus infection: to one with suspected congenital infection that presented with encephalitis, to two children with abnormal auditory evoked potentials (AEPs) and other non-neurological symptoms of a suspected congenital infection, and to one child with proven congenital infection with systemic manifestations. There was no infant with cytomegalic inclusion disease in the study. All other children in the risk group that had clinically manifested infection received isoprinosine in a dose of 50 mg/kg for one month. Psychomotor development delay at age three was found in two children from the risk group and in one child in the control group. There was no difference between the two groups regarding the frequency of paroxysmal events, sensory deficiency or frequent illnesses. The prognosis in cases of cytomegalovirus infection diagnosed at three years of age and treated selectively can be similar to that in infection free 3-year-old children (if there are no cases of CMV inclusion disease).


Chromosomal loci that influence oral nicotine consumption in C57BL/6J x C3H/HeJ F2 intercross mice.
Several studies have demonstrated that there are genetic influences on free-choice oral nicotine consumption in mice. In order to establish the genetic architecture that underlies individual differences in free-choice nicotine consumption, quantitative trait loci (QTL) mapping was used to identify chromosomal regions that influence free-choice nicotine consumption in male and female F(2) mice derived from a cross between C57BL/6J and C3H/HeJ mice. These two mouse strains were chosen not only because they differ significantly for oral nicotine consumption, but also because they are at or near phenotypic extremes for all measures of nicotine sensitivity that have been reported. A four-bottle choice paradigm was used to assess nicotine consumption over an 8-day period. The four bottles contained water or water supplemented with 25, 50 or 100 microg/ml of nicotine base. Using micrograms of nicotine consumed per milliliter of total fluid consumed per day as the nicotine consumption phenotype, four significant QTL were identified. The QTL with the largest LOD score was located on distal chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL appear to be responsible for up to 62% of the phenotypic variance in oral nicotine consumption.


SCAI statement on ad hoc versus the separate performance of diagnostic cardiac catheterization and coronary intervention.
Coronary intervention may be combined with diagnostic cardiac catheterization or performed separately. In the early years of angioplasty, performing these procedures separately was standard practice. Gradually, ad hoc intervention (performing diagnostic angiography and coronary intervention within the same session) has become more common, largely because of its convenience for patients and efficiency for physicians. However, the safety and potential cost savings of this approach remain uncertain. Criteria for the appropriate use of ad hoc intervention have not been established. Ad hoc intervention is reasonable for many, but not appropriate for all patients and should not be considered standard therapy. This document updates an earlier review of this topic and provides suggestions for the use of ad hoc intervention as a routine strategy.


Efficacy of birth ball exercises on labour pain management.
To evaluate the efficacy of a birth ball exercise programme conducted by physiotherapists on pain relief, psychological care, and facilitation of the labour process at a labour ward in a regional hospital. Case series with before-after comparisons. Kwong Wah Hospital, Hong Kong. Chinese women admitted to the labour ward for spontaneous vaginal delivery between April and August 2012 were recruited. Physiotherapists taught birth ball exercises in groups or individually for 30 minutes. Labour pain intensity, back pain intensity, frequency of labour pain, stress and anxiety levels, and subjective pressure level over the lower abdomen were captured before and after birth ball exercises. Most of the parameters were measured using self-reported visual analogue scales. After the exercise session, physiotherapists measured the women's satisfaction level. Midwives recorded pethidine usage. A total of 203 pregnant women participated in this programme; 181 were in the latent phase group, whereas 22 were categorised into the no-labour-pain group. In both groups, there were statistically and clinically significant differences in back pain level, stress and anxiety levels, as well as pressure level over the lower abdomen before and after the exercise (P<0.05). In the latent phase group, significant decreases in labour pain and frequency of labour pain were demonstrated. Mean satisfaction scores were high, with visual analogue scale scores higher than 8.2 in both groups. Pethidine usage showed a further decreasing trend (6.4%) compared with the past 2 years. Birth ball exercise could be an alternative means of relieving back pain and labour pain in the labour ward, and could decrease pethidine consumption in labouring women.


[Randomized control study of medical adhesive products decreasing postoperative abdominal effusion in patients with gastric cancer].
To determine the value of medical adhesive products for decreasing abdominal effusion after clearing up lymph nodes in patients with gastric cancer. Seventy patients with gastric cancer and undergoing D(2 ) or D(2 )(+) radical excision were randomly divided into group A and B based on envelope method from June 2002 to December 2003. In group A (n=35),medical adhesive products was dripped on the retroperitoneal regions where perigastric lymph nodes were cleared up, while not in group B(n=35). Four items including the volume of intraperitoneal drainage, the loss of protein, erythrocyte and hemoglobin were compared between group A and B from the first day to the 5th day after operation. No patients died in group A and B. The volume of intraperitoneal drainage and loss of protein in group A were less than those in group B (P< 0.01) from the first day to the 3th day after operation,but there was no significant difference at the 4th day and 5th day after operation(P > 0.05). The total volume of intraperitoneal drainage and loss of protein in group A were less than those in group B (P< 0.01) from the first day to the 5th day after operation. The loss of erythrocyte and hemoglobin reached the peak at the first day after operation both in group A and B, then gradually decreased, so there was no significant difference between group A and B later. The medical adhesive products can decrease abdominal effusion effectively after clearing up perigastric lymph nodes and facilitate patients' recovery from operation.


Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy.
A direct relationship exists between the intensity of hookworm infection and blood loss. Other parasites may also contribute to blood loss. Our objective was to assess the relationship between the intensity of soil-transmitted helminth infections and anemia in pregnant women in a highly endemic area of Peru. Recruitment occurred between April and November 2003. Overall, 47.31% of 1,042 women had anemia (hemoglobin < 11 g/dL), 47.22% were infected with hookworm and 82.25% with Trichuris. Prevalences of infections were not associated with anemia. However, those infected with moderate and heavy intensities of hookworm infection (OR = 1.84; 95% CI: 1.06, 3.17) and those with moderate and heavy intensities of both hookworm and Trichuris infections (OR = 2.13; 95% CI: 1.10, 4.13) were more likely to suffer from anemia than women having no or light intensities. These results support routine anthelminthic treatment within prenatal care programs in highly endemic areas.


Premedication with benzodiazepines for upper gastrointestinal endoscopy: Comparison between oral midazolam and sublingual alprazolam.
Premedication with orally administered benzodiazepines is effective in reducing anxiety and discomfort related to endoscopic procedures. We evaluated the efficacy and safety of oral midazolam in comparison to sublingual alprazolam as premedication for esophagogastroduodenoscopy (EGD). Adult candidates for diagnostic EGD received either oral midazolam (7.5 mg in 15 cc apple juice) or sublingual alprazolam (0.5 mg) 30 min before EGD. Procedural anxiety and pain/discomfort were assessed using 11-point numerical rating scales. Patients' overall tolerance (using a four-point Likert scale) and willingness to repeat the EGD, if necessary, were also assessed. Blood pressure, heart rate, and arterial oxygen saturation were monitored from medication to 30 min after the procedure. Patients experienced a similar reduction in procedural anxiety after medication with oral midazolam and sublingual alprazolam; mean (standard deviation [SD] of 1.86 [1.63] and 2.02 [1.99] points, respectively, P = 0.91). Compared to oral midazolam, pain/discomfort scores were lower with sublingual alprazolam; mean (SD) of 4.80 (3.01) versus 3.68 (3.28), P = 0.024. There was no significant difference between the two groups in patients' tolerance, willingness to repeat the procedure, or hemodynamic events. Oral midazolam and sublingual alprazolam are equally effective in reducing EGD-related anxiety; however, EGD-related pain/discomfort is lower with alprazolam. Both benzodiazepines are equally safe and can be used as premedication for patients undergoing diagnostic EGD.


Preparing for an Aging World: Engaging Biogerontologists, Geriatricians, and the Society.
Although the demographic revolution has produced hundreds of millions people aged 65 and older, a substantial segment of that population is not enjoying the benefits of extended healthspan. Many live with multiple chronic conditions and disabilities that erode the quality of life. The consequences are also costly for society. In the United States, the most costly 5% of Medicare beneficiaries account for approximately 50% of Medicare's expenditures. This perspective summarizes a recent workshop on biomedical approaches to best extend healthspan as way to reduce age-related dysfunction and disability. We further specify the action items necessary to unite health professionals, scientists, and the society to partner around the exciting and palpable opportunities to extend healthspan.


Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.
A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.


MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation".
Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.


Paraneoplastic optic neuritis and external ophthalmoplegia.
A 58 year old man developed bilateral optic neuritis and external ophthalmoplegia nine months before presentation with a small cell carcinoma of the lung. There was no evidence of central nervous system metastases and his ocular symptoms responded to corticosteroid therapy.


An exploratory study of the interaction of cognitive complexity, dogmatism, and repression-sensitization among college students.
Two hundred nineteen male and female college students returned questionnaire measures relating to cognitive complexity, dogmatism, and repression-sensitization. Analyses revealed very complex interactions among the variables. Highly dogmatic repressors were low in cognitive complexity, and open- minded sensitizers were high in cognitive complexity. Ss exhibiting other combinations of dogmatism and repression-sensitization (e.g., highly dogmatic sensitizers, open-minded repressors) were moderate in cognitive complexity. Many of the conclusions about the behavioral correlates of cognitive complexity, dogmatism, and repression-sensitization may be confounded if these variables are not conjointly assessed.


Identification of lymphocyte antigens in human dental pulps.
The aim of the experiment was to study the immune reaction of cells in both healthy and inflamed human dental pulps. For this it was necessary to identify, in particular, populations of lymphocytes in the pulp, and also other cells involved in the immune reaction. By using monoclonal antibodies which specifically recognize subpopulations of the T lymphocytes, we were able: 1) to directly determine the phenotype of the cells of the pulp, 2) to examine the interactions of the different cell populations. The study was based on 30 permanent human dental pulps and the method was that of indirect immunofluorescence on frozen sections. The monoclonal antibodies used were the antibodies OKT and anti-Leu of types anti-Leu1, anti Leu3a, OKT4, OKT8 and OK1a. The results obtained were evaluated statistically. Two important points stand out from this study: 1) in the healthy samples there is preferential localization of lymphocytes at the periphery of the pulp and 2) there is a predominance of the OKT8+ cytotoxic suppressor subpopulation in both the healthy and the inflamed pulps.


First Record of Colletotrichum gloeosporioides Causing Anthracnose of Banana in Pakistan.
Banana (Musa spp.) is one of the most widely grown and consumed fruits in Pakistan and all around the world due to their distinct aroma and taste. In 2018, anthracnose symptoms were observed on banana fruit harvested from different plantations of Sindh- a major banana producing Province of Pakistan. Approximately, 25% of banana fruit collected from different plantations were infected. The symptoms consisted of small brown to reddish-brown spots on the fruit surface and then became sunken lesions as the disease progressed. To identify the pathogen, infected tissues (5 mm in diameter) from the margin of the lesions were surface sterilized by dipping in 1% sodium hypochlorite (NaOCl) for 2 min, 70% ethanol for 30 s, and then rinsed twice with sterile distilled water, plated onto potato dextrose agar (PDA), and incubated at 27°C for 5 days with 12 h light and darkness cycle. Colonies with a similar pattern were consistently isolated and all colonies were sub-cultured using the single-spore method. Colonies first appeared with white colored mycelium and later turned to dark gray. Conidia produced in acervuli were cylindric, hyaline, straight, and aseptate, with both ends rounded. Conidia measured 14.0 ± 0.5 × 3.4 ± 0.6 μm. Conidiomata were dark brown and spherical. On the basis of morphological characterization, the pathogen was identified as Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. (Weir et al. 2012). Two independent isolates (PDL2031 and PDL2032) were used for further genetic analysis. The internal transcribed spacer (ITS) region and chitin synthase 1 (CHS-1) gene were amplified from genomic DNA using primer pairs of ITS1/ITS4 and CHS-79F/CHS-345R, respectively (White et al. 1990; Damm et al. 2012). The GenBank accession numbers (MW493198, MW504711 for ITS and MW530421, MW530422 for CHS-1) of the sequences exhibited 99% to 100% identity to multiple sequences of C. gloeosporioides. To conduct a pathogenicity test, 10 healthy fruits were selected and surface sterilized with 70% ethanol followed by a wash of sterilized water. The fruits were stabbed with a sterile needle and a drop of 20 µl of spore suspension (106 spores/ml) was placed on each wound independently. Meanwhile 10 fruits inoculated with sterile water were treated as controls. The fruits were incubated at 27°C with 90% relative humidity for 10 days. Inoculated fruits exhibited symptoms similar to the original infection. No visible lesions appeared on control fruit. C. gloeosporioides was successfully reisolated from the inoculated fruit, confirming Koch's postulates. Anthracnose of banana is known to be caused by C. musae, C. gloeosporioides, C. siamense, C. tropicale, C. chrysophilum, C. theobromicola, and C. scovillei (Kumar et al. 2017; Peres et al. 2001; Vieira et al. 2017; Zakaria et al. 2009; Zhou et al. 2017). To our knowledge, this is first report of anthracnose of banana caused by C. gloeosporioides in Pakistan. The new disease primarily reduces the quality and yield of Banana. Effective measures should be taken to manage this disease.


Beta-adrenoceptor distribution in murine lymphoid cell lines.
beta-Adrenergic receptors (R) on several tumor lymphoid cell lines were characterized both directly by beta radioligand binding of 125iodo-cyanopindolol (125I-CYP) to intact cells and membranes, and functionally by assessing hormone-dependent changes in cyclic 3',5' adenosine monophosphate (cAMP) levels on intact cells and measuring adenylate cyclase (a.c.) activity on membranes. Only two lymphoid cell types, BW 5147 (a T cell derived lymphoma cell line) and TIB 221 (a B cell derived line) displayed significant amounts of beta-adrenergic R by 125I-CYP specific binding. Despite this, no stimulation of the a.c. activity was found in the presence of beta-adrenergic agonists in these cells in comparison with native lymphocytes or cells of the well-known S49 cell line used as a positive control. beta-Adrenoceptor specific uncoupling was confirmed by aluminum tetrafluoride (AlFl4) direct activation of the a.c. system in the beta R-bearing cell membranes and by an increase in cAMP production induced by PGE1, another hormone that activates the a.c. Structural characterization of beta-adrenoceptors by photoaffinity-labeling demonstrates that uncoupling was not due to a structural alteration of the beta-adrenergic R expressed in these lymphoma cell lines, as these R gave similar results as native or S49 cells. It can be concluded that functional beta-adrenoceptors are absent in these lymphoma cells. The possible implication of alternative transmission pathways and original neuroendocrine control in tumor lymphoid cells is discussed.


Therapeutic hypothermia for intracerebral hemorrhage: Systematic review and meta-analysis of the experimental and clinical literature.
Intracerebral hemorrhage remains the deadliest form of stroke worldwide, inducing neuronal death through a wide variety of pathways. Therapeutic hypothermia is a robust and well-studied neuroprotectant widely used across a variety of specialties. This review summarizes results from preclinical and clinical studies to highlight the overall effectiveness of therapeutic hypothermia to improve long-term intracerebral hemorrhage outcomes while also elucidating optimal protocol regimens to maximize therapeutic effect. A systematic review was conducted across three databases to identify trials investigating the use of therapeutic hypothermia to treat intracerebral hemorrhage. A random-effects meta-analysis was conducted on preclinical studies, looking at neurobehavioral outcomes, blood brain barrier breakdown, cerebral edema, hematoma volume, and tissue loss. Several mixed-methods meta-regression models were also performed to adjust for variance and variations in hypothermia induction procedures. Twwenty-one preclinical studies and five human studies were identified. The meta-analysis of preclinical studies demonstrated a significant benefit in behavioral scores (ES = -0.43, p = 0.02), cerebral edema (ES = 1.32, p = 0.0001), and blood brain barrier (ES = 2.73, p ≤ 0.00001). Therapeutic hypothermia was not found to significantly affect hematoma expansion (ES = -0.24, p = 0.12) or tissue loss (ES = 0.06, p = 0.68). Clinical study outcome reporting was heterogeneous; however, there was recurring evidence of therapeutic hypothermia-induced edema reduction. The combined preclinical evidence demonstrates that therapeutic hypothermia reduced multiple cell death mechanisms initiated by intracerebral hemorrhage; yet, there is no definitive evidence in clinical studies. The cooling strategies employed in both preclinical and clinical studies were highly diverse, and focused refinement of cooling protocols should be developed in future preclinical studies. The current data for therapeutic hypothermia in intracerebral hemorrhage remains questionable despite the highly promising indications in preclinical studies. Definitive randomized controlled studies are still required to answer this therapeutic question.


A natural and renewable biosorbent phase as a low-cost approach in disposable pipette extraction technique for the determination of emerging contaminants in lake water samples.
This study proposes an efficient analytical methodology using a biosorbent (cork) as an extraction phase in disposable pipette extraction technique for the rapid determination of the emerging contaminants methyl paraben, ethyl paraben, benzophenone, 3-(4-methylbenzylidene) camphor and 2-(ethylhexyl)-4-(dimethylamino) benzoate in lake water samples using high-performance liquid chromatography with diode array detection. The optimized conditions were comprised of 800 μL of sample, three cycles of 30 s each for the extraction, pH 6, addition of 30% w/v of NaCl. For the desorption step, the optimized desorption conditions were achieved with 100 μL of a mixture comprised of 50% methanol and 50% acetonitrile v/v, using one cycle of 30 s. Excellent analytical performance was achieved with limits of detection of 0.6 μg/L for methyl paraben to 1.4 μg/L for 3-(4-methylbenzylidene) camphor, and the limit of quantitation varied from 2 μg/L for methyl paraben to 4.3 μg/L 3-(4-methylbenzylidene) camphor, respectively. The correlation coefficients ranged from 0.9962 for ethyl paraben to 0.9980 for methyl paraben. The method accuracy varied from 71-132%, and the intraday precision ranged from 3 to 23% (n = 3) and interday from 9 to 23% (n = 9). The robustness was evaluated through Youden and Lenth's methods and indicated no significant variations in the results.


Effects of near infrared laser radiation associated with photoabsorbing cream in preventing white spot lesions around orthodontic brackets: an in vitro study.
The present study aims to investigate the effect of a low-power infrared laser on the inhibition of bovine enamel demineralization around orthodontic brackets. Near infrared lasers have been suggested as alternative approaches because they may produce an increase in resistance to dental caries. Forty-eight blocks of enamel obtained from bovine incisor teeth were divided into six groups: Group 1 (control), without treatment; Group 2 (C), photoabsorbing cream; Group 3 (CF), photoabsorbing cream with fluoride; Group 4 (L), irradiation with low-level infrared laser (λ=830 nm) at an energy density of 4.47 J/cm2; Group 5 (L+C), photoabsorbing cream followed by low-level infrared laser irradiation; and Group 6 (L+CF), photoabsorbing cream with fluoride followed by low-level infrared laser irradiation. After these procedures, the enamel blocks received an assortment of orthodontic brackets and were then submitted to pH cycling to simulate a highly cariogenic challenge. The enamel surface demineralization around the orthodontic brackets, according to the different treatments, was quantified by fluorescence loss analysis by quantitative light-induced fluorescence (QLF). The fluorescence loss, expressed as ΔF (percentage of loss fluorescence), was statistically examined by analysis of variance and the Tukey test. The control group (-10.48±2.85) was statistically similar to Group C (-14.52±7.80), which presented the lowest values of ΔF when compared with Groups FC (-3.67±3.21), L (-2.79±1.68), CL (-1.05±0:50), and CFL (-0.60±0:43). However, Groups FC, L, CL, and CFL showed no statistically significant differences among them. It can be concluded that both the low-level infrared laser and photoabsorbing cream with fluoride were effective in inhibiting the development of caries in enamel around orthodontic brackets, even in situations of high cariogenic challenge.


Heterodimers of heterometallic rings.
Nine new complexes are reported involving linked heterometallic rings; one ring is designed as a ligand for the second, and the compounds produced can be regarded as molecular prototypes for implementing quantum gates featuring two subtly different qubits.


Grignard reaction with chlorosilanes in THF: a kinetic study.
Kinetics of the reactions of phenylmagnesium chloride and bromide and diphenylmagnesium with chlorosilanes were investigated in tetrahydrofurane (THF) and in THF-hydrocarbon mixtures. The reaction in THF is much faster than that in diethyl ether. Assuming coordination of magnesium halides with three molecules of THF, concentrations of all the species involved in Schlenk equilibrium were calculated. In the Grignard reaction, species R(2)Mg and RMgX react competitively accompanied by additional reaction paths involving electrophilic catalysis by magnesium halide. This conclusion also proved to be valid for the Grignard reaction with a ketone and probably can be expanded to any Grignard reaction. When Schlenk equilibrium is shifted far to the RMgX species, the catalytic pathways are insignificant. Substituents at the silicon center control the rate of the reaction through their inductive and steric effects.


Development of electrospun, biomimetic tympanic membrane implants with tunable mechanical and oscillatory properties for myringoplasty.
Most commonly, autologous grafts are used in tympanic membrane (TM) reconstruction. However, apart from the limited availability and the increased surgical risk, they cannot replicate the full functionality of the human TM properly. Hence, biomimetic synthetic TM implants have been developed in our project to overcome these drawbacks. These innovative TM implants are made from synthetic biopolymer polycaprolactone (PCL) and silk fibroin (SF) by electrospinning technology. Static and dynamic experiments have shown that the mechanical and oscillatory behavior of the TM implants can be tuned by adjusting the solution concentration, the SF and PCL mixing ratio and the electrospinning parameters. In addition, candidates for TM implants could have comparable acousto-mechanical properties to human TMs. Finally, these candidates were further validated in in vitro experiments by performing TM reconstruction in human cadaver temporal bones. The reconstructed TM with SF-PCL blend membranes fully recovered the acoustic vibration when the perforation was smaller than 50%. Furthermore, the handling, medium adhesion and transparency of the developed TM implants were similar to those of human TMs.


[About the risk to communicate risk].
An understanding of risk requires an understanding of probabilities and a minimum of statistical thinking. This understanding is the basis of an adequate risk communication, which is especially important in the field of medicine. Every day a practicing doctor is confronted with the question of how likely a patient is to have a disease when tested positive. Clinicians are not only asked to provide a correct answer to their patients but also a comprehensible one, if they want to assure that a patient is enabled to make an informed decision. Several studies suggest, however that clinicians struggle somewhat to come up with correct judgments concerning this issue and tend to heavily overestimate the risk. We will argue in this article that this problem is mainly based on how risks are presented. We will reveal some of the common pitfalls and make suggestions on how to interpret and communicate risks in an easy fashion.


Focus on the future: Episodic future thinking reduces discount rate and snacking.
Obesity seems related to a preference for immediate gratification. By changing this focus on short term benefits to a more future-oriented outlook, delay discounting (impulsive decision making) can be changed by a manipulation of episodic future thinking (EFT). EFT comprises a vivid mental simulation of general future experiences. EFT may also affect consumption of unhealthy foods, which can be seen as a choice for immediate gratification. Recent research shows that future orientation should be tailored to the behavior at outcome. We therefore hypothesize that the effectiveness of EFT on food intake could be enhanced by making the content food-related. We conducted a 2 (future vs past thinking) by 2 (food vs non-food related thoughts) between-subject design experiment in female undergraduates (N = 94), to compare the efficacy of EFT versus the recalling of episodic past events in reducing discount rate and caloric intake. Content of imagery was either unrestricted or food-related. Participants engaged in EFT or control episodic imagery while snacks were offered to freely consume, and next the Monetary Choice Questionnaire was completed as a measure of delay discounting, while again being engaged in EFT or control imagery. Both types of EFT reduced delay discounting, however, only food-related EFT lead to more restricted caloric consumption. Thus, we found evidence that EFT reduced discount rate during decision making. However, in order to restrict caloric intake, EFT should entail food-related imagery. As discount rate and caloric intake were not related in the current sample, the underlying mechanism remains to be discovered. Results however suggest that EFT is a promising technique to resist immediate gratification.


Quantitative determination of coumestrol in dried alfalfa and alfalfa leaf protein concentrates containing chlorophyll.
An improved analytical method for the determination of coumestrol in dried alfalfa and leaf protein concentrates is described. In this method, chlorophyll is removed from an alcohol extract prior to the paper chromatographic-fluorometric measurement of coumestrol. Ninety-eight per cent of the coumestrol added to alfalfa leaf protein concentrates is recovered by this method. This improved method gives replicate values with lower standard deviations and coefficients of variation than the literature method.


Antifungal prophylaxis in stem cell transplantation centers in Turkey.
This study aimed to determine the current state of antifungal prophylaxis in Turkish stem cell transplantation (SCT) centers. he were 38 active stem cell transplantation centers in Turkey, 28 of which were registered with the European Group for Blood and Marrow Transplantation (EBMT). Survey questionnaires were sent to the 28 EBMT centers in an effort to collect data on antifungal prophylaxis in different settings. In all, 24 of the centers completed the survey; 1 of the 24 centers was excluded from the study, as it was under construction at the time and was not performing transplantation. In all, 15 (65%) of the 23 centers were adult SCT centers, 7 (31%) were pediatric SCT centers, and 1 center treated both adult and pediatric patients. All centers (23/23) performed both allogeneic and autologous transplants, 20 centers performed non-myeloablative transplants, 8 performed cord blood transplants, and 7 performed unrelated transplants. Primary antifungal prophylaxis was used at all 23 centers during allogeneic transplants, whereas 18 of the 23 centers used it during every autologous transplant and 2 of the 23 centers used it during autologous transplants on a per case basis. The most common drug used for prophylaxis was fluconazole (F) (21/23), followed by itraconazole (I) (3/23), amphotericin-B (2/23), and posaconazole (1/23). Among the 23 centers, 3 reported that for allogenic transplants they changed the antifungal prophylactic in cases of graft versus host disease (GVHD), and 12 of the 23 centers reported that they changed the antifungal prophylactic in case of nearby construction. All 23 centers performed secondary prophylaxis. Antifungal prophylaxis for hematopoetic SCT patients was the standard protocol in the 23 centers included in the study, usually with such azoles as F. The introduction of posaconazole in Turkey and the potential approval of voriconazole for antifungal prophylaxis will eventually alter prophylaxis practice in Turkey, which we plan to assess in the future.


Sedation for endoscopy: midazolam or diazepam and pethidine?
One hundred patients received either diazepam given with pethidine, antagonized with naloxone, or midazolam alone in a double-blind randomized study of sedation for upper gastrointestinal endoscopy. Midazolam produced better amnesia for the procedure (P less than 0.0001) but diazepam and pethidine resulted in less retching during the procedure (P less than 0.01) and less sedation after the procedure, as judged by a simple performance test (P less than 0.02) and patient recall of results (P less than 0.02).


Initial Tumor Necrosis Factor-Alpha and Endothelial Activation Are Associated with Hemorrhagic Complications during Extracorporeal Membrane Oxygenation.
Studies on inflammatory markers, endothelial activation, and bleeding during extracorporeal membrane oxygenation (ECMO) are lacking. Blood samples were prospectively collected after ECMO initiation from 150 adult patients who underwent ECMO for respiratory failure between 2018 and 2021. After excluding patients who died early (within 48 h), 132 patients were finally included. Their tumor necrosis factor-alpha (TNF-α), tissue factor (TF), soluble thrombomodulin (sTM), and E-selectin levels were measured. A Cox proportional hazards regression model was used to estimate the hazard ratio for hemorrhagic complications during ECMO. The 132 patients were divided into hemorrhagic (n = 23, H group) and non-complication (n = 109, N group) groups. The sequential organ failure assessment score, hemoglobin level, and ECMO type were included as covariates in all Cox models to exclude the effects of clinical factors. After adjusting for these factors, initial TNF-α, TF, sTM, E-selectin, and activated protein C levels were significantly associated with hemorrhagic complications (all p < 0.001). TNF-α, TF, and E-selectin better predicted hemorrhagic complications than the model that included only the aforementioned clinical factors (clinical factors only (area under the curve [AUC]: 0.804), reference; TNF-α (AUC: 0.914); TF (AUC: 0.915); E-selectin (AUC: 0.869)). Conclusions: TNF-α levels were significantly predictive of hemorrhagic complications during ECMO.


Exploring Genetic Information with Ease: The Linkout Plugin for JBrowse 2.
JBrowse 2 is a next-generation genome browser that can be run as a web or desktop application. We describe a new plugin, the Linkout Plugin, that enables users to link features to external databases based on their IDs and the remote URLs on JBrowse 2 desktop or web. As a result, genome analysis time and effort are reduced, enabling researchers to gain insights more quickly. The Linkout Plugin fills a common need scientists have: looking for more information on a gene. Overall, the Linkout Plugin is a valuable and practical addition to the JBrowse functionality.