Intraoperative radiation therapy for advanced or recurrent head and neck cancer.
Between 1982 and 1984, we treated 28 patients with advanced head and neck cancer with surgery, combined with intraoperative radiation. All patients had squamous cell carcinoma. One patient had two separate sites treated and a second patient was treated on two occasions, allowing 30 sites for analysis. The overall survival for all patients treated was 67% at 1 year. Local failure occurred in 13% of those with close surgical margins and 25% of those with microscopic residual disease. With gross residual disease 100% had local failure. Patients with gross residual disease had significantly higher local failure than microscopic residual disease (p less than 0.02) or close surgical margins (p less than 0.01). Carotid blowout was the major treatment complication. We believe intraoperative radiation is an effective treatment for advanced or recurrent head and neck cancer when all gross disease has been resected.


Volume of frail patients predicts outcome in frail patients after cardiac surgery.
Recent data from major noncardiac surgery suggest that outcomes in frail patients are better predicted by a hospital's volume of frail patients specifically, rather than overall surgical volume. We sought to evaluate this "frailty volume-frailty outcome relationship" in patients undergoing cardiac surgery. We studied 72,818 frail patients undergoing coronary artery bypass grafting or valve replacement surgery from 2010 to 2014 using the Nationwide Readmissions Database. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Multilevel logistic regression was used to assess the independent effect of frailty volume by quartile on mortality, surgical complications, failure to rescue, nonhome discharge, 30-day readmissions, length of stay, and hospital costs in frail patients. In comparing the highest volume quartiles with the lowest, both overall cardiac surgical volume and volume for frail patients were significantly associated with shorter length of stay and reduced costs. However, frailty volume was also independently associated with significantly reduced in-hospital mortality (odds ratio, 0.79; 95% confidence interval, 0.67-0.94; P = .006) and failure to rescue (odds ratio, 0.83; 95% confidence interval, 0.70-0.98; P = .03), whereas no such association was seen between overall volume and either mortality (odds ratio, 0.94; 95% confidence interval, 0.74-1.10; P = .43) or failure to rescue (odds ratio, 0.98; 95% confidence interval, 0.83-1.17; P = .85). Neither frailty volume nor overall volume showed any significant relationship with the rate of 30-day readmissions. In frail patients undergoing cardiac surgery, surgical volume of frail patients was a significant independent of predictor of in-hospital mortality and failure to rescue, whereas overall surgical volume was not. Thus, the "frailty volume-outcome relationship" superseded the traditional "volume-outcome relationship" in frail patients with cardiac disease.


Nebulized mesenchymal stem cell derived conditioned medium ameliorates Escherichia coli induced pneumonia in a rat model.
Mesenchymal stem cells (MSC) have shown immense therapeutic promise in a range of inflammatory diseases, including acute respiratory distress syndrome (ARDS), and are rapidly advancing through clinical trials. Among their multimodal mechanisms of action, MSCs exert strong immunomodulatory effects via their secretome, which contains cytokines, small molecules, extracellular vesicles, and a range of other factors. Recent studies have shown that the MSC secretome can recapitulate many of the beneficial effects of the MSC itself. We aimed to determine the therapeutic capacity of the MSC secretome in a rat bacterial pneumonia model, especially when delivered directly to the lung by nebulization which is a technique more appropriate for the ventilated patient. Conditioned medium (CM) was generated from human bone marrow derived MSCs in the absence of antibiotics and serum supplements. Post-nebulization lung penetration was estimated through nebulization of CM to a cascade impactor and simulated lung and quantification of collected total protein and IL-8 cytokine. Control and nebulized CM was added to a variety of lung cell culture models and injury resolution assessed. In a rat E. coli pneumonia model, CM was instilled or administered by nebulization and lung injury and inflammation assessed at 48 h. MSC-CM was predicted to have good distal lung penetration and delivery when administered by nebulizer. Both control and nebulized CM reduced NF-κB activation and inflammatory cytokine production in lung cell culture, while promoting cell viability and would closure in oxidative stress and scratch wound models. In a rat bacterial pneumonia model, both instilled and nebulizer delivered CM improved lung function, increasing blood oxygenation and reducing carbon dioxide levels compared to unconditioned medium controls. A reduction in bacterial load was also observed in both treatment groups. Inflammatory cytokines were reduced significantly by both liquid and aerosol CM administration, with less IL-1β, IL-6, and CINC1 in these groups compared to controls. MSC-CM is a potential therapeutic for pneumonia ARDS, and administration is compatible with vibrating mesh nebulization.


Hypoxia induces docetaxel resistance in triple-negative breast cancer via the HIF-1α/miR-494/Survivin signaling pathway.
Cytotoxic chemotherapy is the major strategy to prevent and reduce triple-negative breast cancer (TNBC) progression and metastasis. Hypoxia increases chemoresistance and is associated with a poor prognosis for patients with cancer. Based on accumulating evidence, microRNAs (miRNAs) play an important role in acquired drug resistance. However, the role of miRNAs in hypoxia-induced TNBC drug resistance remains to be clarified. Here, we found that hypoxia induced TNBC docetaxel resistance by decreasing the miR-494 level. Modulating miR-494 expression altered the sensitivity of TNBC cells to DTX under hypoxic conditions. Furthermore, we identified Survivin as a direct miR-494 target. Hypoxia upregulated survivin expression. In a clinical study, the HIF-1α/miR-494/Survivin signaling pathway was also active in primary human TNBC, and miR-494 expression negatively correlated with HIF-1α and survivin expression. Finally, in a xenograft model, both miR-494 overexpression and the HIF-1α inhibitor PX-478 increased the sensitivity of TNBC to DTX by suppressing the HIF-1α/miR-494/Survivin signaling pathway in vivo. In conclusion, treatments targeting the HIF-1α/miR-494/Survivin signaling pathway potentially reverse hypoxia-induced drug resistance in TNBC.


Retracted: The Status Quo of Criminal Responsibility for Aflatoxin Pollution in China: From the Perspective of Judgment Analysis.
[This retracts the article DOI: 10.1155/2022/8212370.].


Initiation and propagation of a neuronal intracellular calcium wave.
The ability to image calcium movement within individual neurons inspires questions of functionality including whether calcium entry into the nucleus is related to genetic regulation for phenomena such as long term potentiation. Calcium waves have been initiated in hippocampal pyramidal cells with glutmatergic signals both in the presence and absence of back propagating action potentials (BPAPs). The dendritic sites of initiation of these calcium waves within about 100 microm of the soma are thought to be localized near oblique junctions. Stimulation of synapses on oblique dendrites leads to production of inositol 1,4,5-trisphosphate (IP(3)) which diffuses to the apical dendrite igniting awaiting IP(3) receptors (IP(3)Rs) and initiating and propagating catalytic calcium release from the endoplasmic reticulum. We construct a reduced mathematical system which accounts for calcium wave initiation and propagation due to elevated IP(3). Inhomogeneity in IP(3) distribution is responsible for calcium wave initiation versus subthreshold or spatially uniform suprathreshold activation. However, the likelihood that a calcium wave is initiated does not necessarily increase with more calcium entering from BPAPs. For low transient synaptic stimuli, timing between IP(3) generation and BPAPs is critical for calcium wave initiation. We also show that inhomogeneity in IP(3)R density can account for calcium wave directionality. Simulating somatic muscarinic receptor production of IP(3), we can account for the critical difference between calcium wave entry into the soma and failure to do so.


Neurotrophin binding to the p75 neurotrophin receptor is necessary but not sufficient to mediate NGF-effects on APP secretion in PC-12 cells.
In the present study the pheochromocytoma cell line (PC-12) was used as a model system to determine the role of the two neurotrophin receptors in the regulation of amyloid precursor protein (APP) secretion by nerve growth factor (NGF). To stimulate TrkA and/or p75NTR signaling in PC-12 cells, we used NGF, brain-derived neurotrophic factor (BDNF), and NGF in the presence of an excess of BDNF or the monoclonal antibody 192IgG, to block p75NTR binding to NGF. Our results demonstrate that NGF stimulates APP secretion in a dose dependent fashion with maximum effects at 10 ng/ml, known to saturate high-affinity NGF binding sites. Treatment of PC-12 cells with varying concentrations of BDNF, 1-1,000 ng/ml, did not alter APP secretion, suggesting that binding to p75NTR alone is not sufficient to affect APP secretion. When blocking NGF binding to p75NTR with BDNF or 192IgG, on the other hand, NGF effects on APP secretion were abolished. These findings suggest that in cells expressing p75NTR and TrkA receptors, binding of NGF to the p75NTR is required to mediate NGF effects on APP secretion. Our data are also consistent with a proposed function of the p75NTR in receptor recruitment and "presentation" of NGF to receptors.


Granulomatosis with polyangiitis (Wegener's).
Granulomatosis with polyangiitis (GPA) (Wegener) is a necrotizing vasculitis combining inflammation of the vascular wall and peri- and extravascular granulomatosis. Clinically, GPA is characterized in its full form by ENT signs, lung, and kidney involvement. One of the key features of GPA is the presence of ANCAs-cytoplasmic in approximately 90% of systemic forms and in 50% of localized forms-directed against proteinase 3 in most cases. PR3-ANCAs are highly specific to GPA and therefore have a high diagnostic value. Treatment of GPA is based on a combination of corticosteroids and cyclophosphamide or rituximab, which allows remission to be achieved in more than 80% of cases. Azathioprine was the most widely used maintenance treatment, but low-dose semi-annual rituximab maintenance infusions further decrease relapses with acceptable safety. Nevertheless, relapses occur in more than 50% of cases. One of the biggest treatment challenges is the occurrence of side effects, the severity and frequency of which are often linked to the prolonged treatment course, which is difficult to avoid.


Allergen-specific IgE and IgG4 antibody levels in sera and the capacity of these sera to sensitize basophil leucocytes in vitro.
Leucocytes from normal non-allergic donors were passively sensitized with sixty-five atopic sera that contained IgE directed against house dust mite (HDM) or guinea-pig dander (GPD). In no serum was there any IgE with an abnormal basophil anaphylactic-sensitizing activity. In sera from patients hypersensitive to GPD, both GPD-specific IgE and IgG4 were measured. A significant correlation was found between the GPD-IgE RAST and the basophil-sensitizing capacity of GPD-positive sera, but no correlation was found between this sensitizing capacity and the GPD-IgG4 RAST. Leucocytes were passively sensitized with serum mixtures that contained the same amounts of total and HDM-specific IgE; these mixtures differed as to sensitizing activity. It is unclear whether this variation is due to differences in IgE or to influences of other factors in serum.


Connective eccentricity index: a novel topological descriptor for predicting biological activity.
A simple, adjacency-cum-path length based, topological descriptor termed the connective eccentricity index has been conceptualized and its discriminating power investigated with regard to antihypertensive activity. A data set consisting of 81 derivatives of N-benzylimidazole was selected for the present investigation. These derivatives are potent, competitive, and nonpeptide angiotensin II receptor antagonists. The value of connective eccentricity index for each derivative was computed and active range identified. Subsequently, each derivative was assigned a biological activity that was compared with the reported antihypertensive activity. The results obtained using connective eccentricity index were better than the corresponding values obtained using Balaban's mean square distance index. The accuracy of prediction was found to be about 80% in the active range using connective eccentricity index.


[Callosal infarction after bilateral occlusion of the internal carotid arteries with hemineglect syndrome and astasia-abasia].
We report a patient who had a callosal infarct, showed by Computer Tomography and Magnetic Resonance Imaging, without injury to the adjacent hemispheres. Angiography revealed an occlusion of both internal carotid arteries. Besides interhemispheric disconnection with unilateral left agraphia, left tactile anomia, left ideomotor apraxia and left ear auditivoverbal extinction, the patient showed signs of left hemineglect and astasia-abasia, both persistent.


Effect of cell shape, membrane deformability and phospholipid organization on phosphate-calcium-induced fusion of erythrocytes.
Fusion of bovine and goat erythrocytes was studied using the phosphate-calcium protocol. Both bovine and goat red cells are resistant to fusion with phosphate and calcium, under conditions that promote fusion of normal human erythrocytes. Fusion resistance is not related to decreased (5%) membrane deformability of erythrocytes of these species, since chicken erythrocytes which are 40% less deformable than human erythrocytes undergo fusion with efficiency similar to human red blood cells. Incorporation of either phosphatidylcholine or phosphatidylserine into bovine erythrocytes mediated by lipid exchange/transfer protein, caused fusion of these erythrocytes. Fluorescence analysis of merocyanine 540 dye labeled erythrocytes, by flow cytometry, showed that the frequency of cells which exhibit dye binding was much less (35%) in dimyristoylphosphatidylcholine (DMPC) incorporated compared to untreated bovine erythrocytes (80%), indicating that incorporation of DMPC caused closed packing of lipids in the external leaflet of the bilayer. These studies show that fusion of bovine erythrocytes, mediated by phosphate and calcium, has a requirement for either specific phospholipids such as phosphatidylcholine, phosphatidylserine, or closed packing of lipids in the external leaflet of the bilayer.


Post irradiation myelopathy: from the physiatrists' point of view.
We describe two patients who developed a severe spinal cord damage long time after cessation of irradiation therapy. The various and unique rehabilitation medicine aspects are discussed and the literature is surveyed.


An environmentally-friendly, highly efficient, gas pressure-assisted sample introduction system for ICP-MS and its application to detection of cadmium and lead in human plasma.
An environmentally friendly and highly efficient gas pressure-assisted sample introduction system (GPASIS) was developed for inductively-coupled plasma mass spectrometry. A GPASIS consisting of a gas-pressure control device, a customized nebulizer, and a custom-made spray chamber was fabricated. The advantages of this GPASIS derive from its high nebulization efficiencies, small sample volume requirements, low memory effects, good precision, and zero waste emission. A GPASIS can continuously, and stably, nebulize 10% NaCl solution for more than an hour without clogging. Sensitivity, detection limits, precision, long-term stability, double charge and oxide ion levels, nebulization efficiencies, and matrix effects of the sample introduction system were evaluated. Experimental results indicated that the performance of this GPASIS, was equivalent to, or better than, those obtained by conventional sample introduction systems. This GPASIS was successfully used to determine Cd and Pb by ICP-MS in human plasma.


Rapidly increased vasopressin promotes acute platelet aggregation and early brain injury after experimental subarachnoid hemorrhage in a rat model.
To investigate the dynamic expression of vasopressin and its potential role in rat brain tissue after experimental subarachnoid hemorrhage (SAH). Male Sprague-Dawley rats were divided into 10min, 1h, 6h, 24h, 48h and 72h groups. The SAH model was established by endovascular puncture. ELISA and immunohistochemistry were performed to evaluate dynamic expression of vasopressin. Immunohistochemistry of GPIIb/IIIa integrin was used to assess platelet aggregation. Double immunofluorescence labeling was carried out to observe the reaction between vasopressin and platelet. Early brain injury was evaluated by apoptotic cells counting. Neurobehavioral score was performed to assess neuroprotective role of SR 49059 (a selective antagonists of vasopressin receptor). In peripheral blood and hypothalamus, vasopressin increased rapidly at 6h and 24h. Expression of GPIIb/IIIa integrin peaked at 24h in cortex and hippocampus. Immunofluorescence showed that vasopressin and GPIIb/IIIa integrin located at the same site. Administration of SR 49059 significantly decreased platelet aggregation and number of apoptotic cells. The neurobehavioral score was promoted significantly after the intervention. The results indicate that rapidly increased vasopressin could induce platelet aggregation and contribute to early brain injury after SAH.


Phenotypic and genotypic comparison of pathogenic group B Streptococcus isolated from human and cultured tilapia (Oreochromis species) in Malaysia.
Group B Streptococcus (GBS) is a major cause of several infectious diseases in humans and fish. This study was conducted to compare human and fish-derived GBS in terms of their antimicrobial susceptibility, serotype, virulence and pili genes and sequence type (ST), and to determine whether there is a potential linkage of zoonotic transmission in Malaysia. GBS isolated from humans and fish had similar phenotypic characteristics and differed in virulence gene profile, antimicrobial susceptibility, serotype and sequence type. Fish GBS isolates had lower genetic diversity and higher antibiotic susceptibility than human isolates. We report a rare detection of the potentially fish-adapted ST283 in human GBS isolates. Both human and fish ST283 shared several phenotypic and genotypic features, including virulence and pilus genes and antimicrobial susceptibility, illustrating the value of monitoring GBS within the One Health scope. In this study, two human GBS ST283 isolates belonging to the variant common in fish hosts were identified, raising awareness of the zoonotic potential between the different species in Malaysia.


[Classic and molecular methodologies for the identification of Enterococcus species].
Enterococcus is a bacterial genus with low virulence. However, in the last years, the importance of some enterococcus species as nosocomial pathogens has increased, specially due to their resistance to some antimicrobial. To identify enterococcus strains using classical biochemical techniques and genomic amplification with Polymerase Chain Reaction (PCR). Three hundred and five enterococcus strains, isolated between 1996 and 1999, from different clinical specimens in hospitals and other centers of the VIIIth Region of Chile, were studied. The isolates were identified, to the species level, according to the scheme proposed by Carvalho et al. Identification of some strains was confirmed by PCR. Eighty nine percent of isolates were identified as E foecalis, 10.2% as E foecium and 3.3% as other species. PCR is a fast and promising technique, useful in the identification of Enterococcus species.


[Case report of Schoenlein-Henoch with neurological complications].
A case of Schönlein-Henoch syndrome with neurological complications in a child is reported. Stress is laid on the fact that these symptoms were predominant throughout the course of the disease. Treatment, primarily based on cortisone, led to complete resolution of the neurological picture.


Bone loss in limbs with decreased or absent sensation: ten year follow-up of the hands in leprosy.
Three hundred and sixty-seven patients with insensitive hands have been studied by correlating radiologic findings with occupational and medical history in order to better define causal factors in bone resorption. This study indicates that nonspecific infection and trauma are the reasons for bone resorption in 98% of cases. The role of intermittent pressure seems to be in soft tissue breakdown, which then allows bone to become infected. Bone resorption can be arrested at any stage of the disease by appropriate therapy of splinting and control of infection.


The short-wavelength mechanisms of Stiles in age-related macular degeneration.
Clinical measurements by the increment-threshold technique of W.S. Stiles are reported in five cases of age-related macular degeneration. Measurements were made on a modified Tübingen perimeter using 1 degree, short-wavelength targets presented on a red field.


The prostate anesthetic block for outpatient prostate surgery.
With the emergence of minimally invasive techniques for the treatment of benign prostate hyperplasia and the need to reduce health care costs, a simple and effective prostate anesthetic block may allow more procedures to be done in an outpatient or office setting. As based on neuroanatomy studies of the prostate, the perineal approach appeared to be the best way to anesthetize the prostate. This technique was used in 43 patients who underwent interstitial laser coagulation an outpatient or office setting. The perineal prostatic block was effective for pain control whether lidocaine or lidocaine/bupivacaine was used as determined by visual analog scale, linear pain scale, or global pain questionnaire. The use of intravenous (i.v.) sedation did not influence the efficacy of the prostate anesthetic block. Thus, the perineal prostate anesthetic block may be employed in patients undergoing minimally invasive surgery for benign prostatic hyperplasia in the outpatient/office location.


Hydrogen peroxide biosensor based on hemoglobin immobilized at graphene, flower-like zinc oxide, and gold nanoparticles nanocomposite modified glassy carbon electrode.
In this work, a highly sensitive hydrogen peroxide (H2O2) biosensor based on immobilization of hemoglobin (Hb) at Au nanoparticles (AuNPs)/flower-like zinc oxide/graphene (AuNPs/ZnO/Gr) composite modified glassy carbon electrode (GCE) was constructed, where ZnO and Au nanoparticles were modified through layer-by-layer onto Gr/GCE. Flower-like ZnO nanoparticles could be easily prepared by adding ethanol to the precursor solution having higher concentration of hydroxide ions. The Hb/AuNPs/ZnO/Gr composite film showed a pair of well-defined, quasi-reversible redox peaks with a formal potential (E(0)) of -0.367 V, characteristic features of heme redox couple of Hb. The electron transfer rate constant (k(s)) of immobilized Hb was 1.3 s(-1). The developed biosensor showed a very fast response (<2 s) toward H2O2 with good sensitivity, wide linear range, and low detection limit of 0.8 μM. The fabricated biosensor showed interesting features, including high selectivity, acceptable stability, good reproducibility, and repeatability along with excellent conductivity, facile electron mobility of Gr, and good biocompatibility of ZnO and AuNPs. The fabrication method of this biosensor was simple and effective for determination of H2O2 in real samples with quick response, good sensitivity, high selectivity, and acceptable recovery.


Lock method using sodium hydroxide solution to clear occluded central venous access devices.
Occlusion of central venous access devices (CVADs) is not an uncommon problem duringlong-term parenteral nutrition. A number of techniques have been developed to deal with obstructed CVADs. This study investigated the effectiveness of the sodium hydroxide (NaOH) lock method for gradual CVAD occlusion. When a progressively declining flow was noticed, 0.1 N NaOH solution was injected into the CVAD and locked. Nineteen CVAD occlusions in 11 home parenteral nutrition patients were treated Sixteen of 19 trials cleared the occlusions, whereas 3 of 19 failed. One of the failures was due to a mechanical occlusion and the other two were able to be restored by using ethanol. There were no significant complications. The benefits of this method are: (1) a shorter treatment time and a lower dose than NaOH infusion therapy, (2) it does not require hospital admission and (3) it does not result in bursting of the catheter.


Two calmodulin genes are expressed in Arbacia punctulata. An ancient gene duplication is indicated.
Calmodulin is highly conserved, and only in the sea urchin Arbacia punctulata have two distinct isotypes been reported. We have isolated and sequenced two cDNAs from a lambda gt 11 library constructed from RNA from ovary tissue of A. punctulata. One clone, designated alpha, encodes a calmodulin isotype previously designated A. It encodes an amino acid sequence that is identical with calmodulin of most vertebrates in positions 1 through 141; however, it does not encode the last seven amino acids. The other clone, designated beta, starts with an open reading frame and encodes the B form of calmodulin from position 11 through the C-terminal position 148. It has only four differences from vertebrate calmodulin, occurring at positions 78 (Asp, beta Glu), 99 (Tyr, beta Phe), 143 (Gln, beta Ala) and 147 (Ala, beta Ser). The nucleic acid sequences of the alpha and beta cDNAs differ at 46 nucleotide positions that are distributed throughout their coding sequences. We conclude that the corresponding mRNAs are not derived from post-transcriptional processing of a single gene, and we infer that they are transcribed from two non-allelic genes. The gene duplication is inferred to have occurred prior to the divergence of the vertebrates and the echinoderms. The expression of these calmodulin mRNAs in ovary tissue and eggs of a single animal differs as judged by hybridization of probes to RNA immobilized to filters.


Detection of mycotic pseudoaneurysm of the ascending aorta using MRI.
Mycotic pseudoaneurysms of the ascending aorta are rare cardiovascular lesions that carry the risk of potentially disastrous complications such as aortic rupture or widespread sepsis. Regardless of its location in the arterial system, this lesion carries a high mortality rate. Early diagnosis of mycotic pseudoaneurysm is paramount for optimizing the chances of surgical therapy. While imaging strategies of this lesion have included aortography, echocardiography, and computed tomography, the information gained from each of these individual studies may be acquired in a single MR imaging session. MRI offers the fundamental advantages of noninvasiveness, nonionization, and multiplanar imaging capabilities. Additionally, MRI provides excellent soft tissue contrast, a wide field of view, qualitative and quantitative flow analysis, and an independence of operator expertise or patient body habitus.


Vastus medialis oblique and vastus lateralis activity during a double-leg semisquat with or without hip adduction in patients with patellofemoral pain syndrome.
The purpose was to investigate the effect of double-leg semisquat with hip adduction on the activation of vastus medialis oblique (VMO) and vastus lateralis (VL) in patients with patellofemoral pain syndrome (PFPS). Thirty patients with PFPS were designated to the study group, while 30 healthy matched subjects were enrolled in the control group. The activation of VL and VMO was recorded with surface electromyography (EMG) during double-leg semisquat (DS) and double-leg semisquat with hip adduction (DS-HA). The time domain and frequency domain indexes of the electromyography data were collected for analysis. In the study group, the time domain indexes (RMS, IEMG) and frequency domain index (MPF) of VL were significant higher than VMO in the test of DS (P < 0.05); and the time domain of VMO was significantly higher in the test of DS-HA when compared to DS (P < 0.05) while there was no difference in the activation of VL. In the study group, an increase in activity of the VMO was observed through the surface EMG signal in the double-leg semisquat exercise with hip adduction compared to the exercise without hip adduction. This finding indicates that VMO activation can be more selectively obtained through the exercise with hip adduction which can help balance the VL and VMO.


Economic evaluation of drug abuse treatment and HIV prevention programs in pregnant women: a systematic review.
Drug abuse and transmission of HIV during pregnancy are public health problems that adversely affect pregnant women, their children and surrounding communities. Programs that address this vulnerable population have the ability to be cost-effective due to resulting cost savings for mother, child and society. Economic evaluations of programs that address these issues are an important tool to better understand the costs of services and create sustainable healthcare systems. This study critically examined economic evaluations of drug abuse treatment and HIV prevention programs in pregnant women. A systematic review was conducted using the criteria recommended by the Panel on Cost-Effectiveness in Health and Medicine and the British Medical Journal (BMJ) checklist for economic evaluations. The search identified 6 economic studies assessing drug abuse treatment for pregnant women, and 12 economic studies assessing programs that focus on prevention of mother-to-child transmission (PMTCT) of HIV. Results show that many programs for drug abuse treatment and PMTCT among pregnant women are cost-effective or even cost-saving. This study identified several shortcomings in methodology and lack of standardization of current economic evaluations. Efforts to address methodological challenges will help make future studies more comparable and have more influence on policy makers, clinicians and the public.


[Efficient organisational structures of in-patient and out-patient practice for satisfactory gynecologico-obstetric attention (author's transl)].
The strong need for integrated management of gynaecologico-obstetric attention as well as the role played by interdisciplinary cooperation as a prerequisite for high-continuity medico-social services are expounded against the background of health policies established for the current period up to 1980 and with close reference to experience obtained in every-day practice. The introduction of demand-oriented organisational forms by which to enhance the standards and effectiveness of health care for mother and child is essential to the general practice of sociogynaecology.


Cardiovascular risk independently predicts small functional bladder storage capacity.
We aimed to determine the potential relationship between atherosclerotic cardiovascular disease (ASCVD) score, which equates to 10-year risk of atherosclerotic cardiovascular events, and functional bladder capacity (FBC) among men in the outpatient urology setting. We secondarily analyzed voiding diaries from men aged 40 to 79 years with nocturia. Patients with a history of cardiovascular disease or who had nocturnal polyuria were excluded. Patients were stratified by whether they met the high-risk ASCVD threshold (≥ 20%) following current cardiology consensus guidelines and assessed for the presence of small FBC (24-h maximum voided volume ≤ 200 ml). Logistic regression analyses were employed to explore associations between small FBC and ASCVD. Eighty-four men (median ASCVD score 18.4 [IQR 12.8-26.9] %, age 66 [61-71] years, body mass index [BMI] 29.4 [26.4-32.7] kg/m2) were included, of whom 36 (42.9%) were high-risk and 48 (57.1%) fell below the high-risk threshold. High-risk patients were more likely to have small FBC (23 [63.9%] vs. 14 [29.2%], p = 0.002). ASCVD risk predicted small FBC on univariate analysis (p = 0.002). No such effect was observed with age (p = 0.116), BMI (p = 0.523), or benign prostatic obstruction (p = 0.180). The association between ASCVD risk and small FBC persisted on multivariate analysis after controlling for BMI and benign prostatic obstruction (p = 0.002). No significant predictors of small FBC were observed when age, a major determinant of ASCVD risk and independent correlate of small FBC, was substituted for ASCVD score (p = 0.108). Small FBC is related to a higher predicted cardiovascular event rate in men with nocturia.


Prognostic value of kallikrein-related peptidase 6 protein expression levels in advanced ovarian cancer evaluated by automated quantitative analysis (AQUA).
Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. In the present study, we sought to determine the prognostic value of kallikrein-related peptidase 6 (KLK6) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of KLK6 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred and thirty-five of 150 cases had sufficient tissue for AQUA analysis. In univariate survival analysis, low tumor KLK6 expression was associated with better outcome for overall survival over 3 years (P = 0.019). There was no association between tumor KLK6 expression and progression-free survival (P = 0.128). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor KLK6 expression level was one of the most significant predictor variable for overall survival (95% confidence interval, 1.19-3.50; P = 0.009). High tumor KLK6 protein expression is associated with inferior patient outcome in ovarian cancer. KLK6 may represent a promising disease biomarker and therapeutic target in ovarian cancer.


Etiology and pathology.
Until the 1920s, TOS was believed to be a vascular condition caused by compression of the subclavian artery by a congenital anomaly, either a cervical rib or tight anterior scalen muscle. Today it is regarded primarily as a neurologic condition caused by neck trauma injuring and scarring the scalene muscles.


Two sides of a cellular coin: CD4(+)CD3- cells regulate memory responses and lymph-node organization.
We propose that CD4(+)CD3(-) cells have two functions: a well-established role in organizing lymphoid tissue during development, and a newly discovered role in supporting T-cell help for B cells both during affinity maturation in germinal centres and for memory antibody responses. As CD4(+)CD3(-) cells express the HIV co-receptors CD4 and CXC-chemokine receptor 4, we think that infection of these cells by HIV, and their subsequent destruction by the host immune system, could help to explain the loss of memory antibody responses and the destruction of lymphoid architecture that occur during disease progression to AIDS.


Sleep and Mood Disorders Among Youth.
This article reviews the literature on mood disorders and sleep disorders among children and adolescents. Research suggests that sleep plays an important role in the development, progression, and maintenance of mood disorder symptoms among children and adolescents. Sleep problems as early as maternal perinatal insomnia may predict and predate depression among youth. Children and adolescents who develop comorbid mood disorders and sleep problems represent a particularly high-risk group with more severe mood episode symptoms, higher rates of self-harm and suicidality, and less responsivity to treatment. Treatment research supports the idea that sleep problems can be improved through behavioral interventions.


Distinct gene expression pattern of RUNX1 mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia.
Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.


Unaltered basal prolactin secretion during short-term oestriol treatment in post-menopausal women.
Six post-menopausal women were submitted, at 1 month interval, to oral oestriol treatment for 14-day periods at daily doses of 2 and 6 mg. Blood samples were collected for LH, FSH and PRL measurements (by RIA) every other day during treatments as well as during a 14-day control period. Through the effect on LH levels was questionable, oestriol resulted in a clear and significant, although moderate, gradual decrease of mean FSH levels. At the doses used, which are effective in thetreatment of menopausal symptoms, but are devoid of any proliferative effect upon the endometrium, oestriol failed to induce any stimulatory effect on basal PRL secretion in these post-menopausal women.


Larger muscle mass of the upper limb correlates with lower amplitudes of deltoid MEPs following transcranial stimulation.
To perform spinal surgery safely, it is important to understand the risk factors, including factors that negatively influence intraoperative neuromonitoring (IONM). Transcranial motor evoked potentials (TcMEPs) are important in IONM. Therefore, we aimed to investigate whether muscle mass affects the waveforms of TcMEPs to understand the risk factors influencing TcMEPs. We enrolled 48 patients with thoracolumbar spinal diseases who underwent surgery at our facility between April 2015 and March 2018. Before surgery, the body composition, including muscle mass and fat mass, of all patients was measured using bioelectrical impedance analysis (BIA). During surgery, cranial stimulation under general anesthesia was used to derive TcMEPs, enabling us to measure the amplitude, using the control wave of the TcMEPs of the deltoid muscles and the abductor digiti minimi (ADM) muscles. We found a negative correlation between the amplitude of deltoid-muscle TcMEPs and muscle mass of the upper limb. The amplitude of deltoid-muscle TcMEPs did not correlate with the skeletal muscle index (SMI), muscle mass of the lower limb, or body fat mass. The amplitude of ADM-muscle TcMEPs did not correlate with SMI, muscle mass of any limb, or body fat mass. In conclusion, a larger muscle mass of the upper limb correlated with a lower amplitude of deltoid-muscle TcMEPs. By contrast, there was no correlation between the muscle mass of the upper limb and the amplitude of ADM-muscle TcMEPs. These findings suggest that TcMEPs of the ADM are less influenced by muscle mass and are more stable than those of the deltoid.


Do Surrogates of Injury Severity Influence the Occurrence of Heterotopic Ossification in Fractures of the Acetabulum?
To determine the relationship between injury severity surrogates and other patient factors with the development and severity of heterotopic ossification (HO) following open reduction internal fixation of acetabular fractures treated with a posterior approach. Retrospective review. Academic level 1 trauma center. Two hundred forty-one patients who were treated through a posterior approach with a minimum of 6-month radiographic follow-up were identified from an acetabular fracture database. None. The occurrence and severity (Brooker Grade III/IV) of HO 6 months postsurgery. Length of stay (LOS) in the intensive care unit (ICU), non-ICU LOS >10 days, and HO prophylaxis with external radiation beam therapy (XRT) were significantly associated with the development of HO in a multivariate model [ICU LOS: 1-2 days, odds ratio (OR) = 4.33, 95% confidence interval (CI): 1.03-18.25; 3-6 days, OR = 4.1, 95% CI, 1.27-13.27; >6 days, OR = 11.7, 95% CI, 3.24-42.22; non-ICU LOS >10 days (vs. 0-6 days): OR = 7.6, 95% CI, 2.6-22.25; XRT HO prophylaxis: OR = 0.29, 95% CI, 0.10-0.85]. Other variables evaluated in multivariate modeling not significantly associated with development and severity of HO included age, gender, mechanism of injury, injury severity score, presence of neurologic injury, Letournel fracture type, occurrence of hip dislocation, interval from injury to surgery, operative time, and estimated blood loss. Surrogates of injury severity, including days in the ICU and non-ICU hospital LOS >10 days, were associated with the development of HO in our cohort of acetabular fracture patients. Prophylaxis with XRT was significantly protective against the development of HO, and the ability to provide prophylaxis is very likely related to the severity of injury. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


[Augmentation of alveolar ridge defects: autologous bone transplant from the zygomatic alveolar crest--a new technique].
The insertion of dental implants with simultaneous loss of alveolar bone still represents a challenge. A traumatical tooth loss within the range of the front of the maxillary is frequently connected with a clear substance defect. The goal of a pre-implantologically treatment must be therefore the hard tissue reconstruction of the defect. Thus the implant camp is optimized and the prosthetical necessary implant position is guaranteed. In this case report the reconstruction of a vertical and horizontal bone loss with a transplant from the Crista zygomatico alveolaris is represented. The withdrawal of the bone transplant took place under indulgence of the vestibular membrane of the maxillary sinus by means of piezosurgery. After an appropriate healing time the single tooth gap was supplied with an ITI implant of the company Straumann (Freiburg, Germany).


Peripheral stellate telangiectasias: a clinical-dermoscopic clue for diganosing cutaneous melanoma metastases.
The clinical and dermoscopic diagnosis of cutaneous melanoma metastases may be challenging especially in patients with unknown primary melanoma. We observed repetitive dermoscopic patterns of peripheral stellate telangiectasias in cutaneous melanoma metastases from 3 patients, of whom 2 had an unknown primary melanoma. Stellate telangiectasias surrounding bluish to purple or red nodules with recent onset may represent a clue for cutaneous melanoma metastases.


Breaking the singleton of germination protease.
Germination protease (GPR) plays an important role in the germination of spores of Bacillus and Clostridium species. A few very similar GPRs form a singleton group without significant sequence similarities to any other proteins. Their active site locations and catalytic mechanisms are unclear, despite the recent 3-D structure determination of Bacillus megaterium GPR. Using structural comparison and sequence analysis, we show that GPR is homologous to bacterial hydrogenase maturation protease (HybD). HybD's activity relies on the recognition and binding of metal ions in Ni-Fe hydrogenase, its substrate. Two highly conserved motifs are shared among GPRs, hydrogenase maturation proteases, and another group of hypothetical proteins. Conservation of two acidic residues in all these homologs indicates that metal binding is important for their function. Our analysis helps localize the active site of GPRs and provides insight into the catalytic mechanisms of a superfamily of putative metal-regulated proteases.


Orf virus encodes a homolog of the vaccinia virus interferon-resistance gene E3L.
A homolog of the vaccinia virus (VAC) interferon resistance gene E3L has been discovered in orf virus strain NZ-2, a parapoxvirus that infects sheep, goats and humans. The gene is located 20 kb from the left terminus of the orf virus genome and is transcribed towards this terminus. RNase protection studies have been used to define the limits of the gene and Northern analysis revealed that it is expressed early in infection. The predicted amino acid sequence of the orf virus protein shares 31% identity (57% similarity) with the VAC E3L protein. Four of the six residues identified as being essential to dsRNA binding in the vaccinia virus protein are conserved in the orf virus protein whilst the other two amino acid changes are conservative substitutions. The orf virus gene has been sequenced in two other orf virus strains which vary markedly in their ability to produce experimental lesions in vivo. Their predicted protein sequences vary by less than 3% from the NZ-2 protein. The recombinant orf virus protein, expressed as a fusion protein in E. coli, bound double-stranded (ds)RNA but not dsDNA, single-stranded (ss)DNA or ssRNA . This is the first demonstration of a VAC E3L-like gene encoded by a parapoxvirus.


Immediate psychological impact on nurses working at 42 government-designated hospitals during COVID-19 outbreak in China: A cross-sectional study.
During an epidemic of a novel infectious disease, frontline nurses suffer from unprecedented psychological stress. This study aimed to assess the immediate psychological impact on frontline nurses in China. A multicenter, cross-sectional survey of frontline nurses was conducted via online questionnaires. Symptoms of depression, anxiety, somatic disorders, and suicidal ideation were evaluated. Demographic, stress, and support variables were entered into logistic regression analysis to identify the impact factors. Of the 4,692 nurses who completed the survey, 9.4% (n = 442) were considered to have depressive symptoms, 8.1% (n = 379) represented anxiety, and 42.7% (n = 2,005) had somatic symptom. About 6.5% (n = 306) respondents had suicidal ideation. The study showed that the overall mental health of frontline nurses was generally poor during COVID-19 outbreak, and several impact factors associated with nurses' psychological health were identified. Further research is needed to ascertain whether training and support strategies are indeed able to mitigate psychological morbidities.


The impact of antibiotic-impregnated catheters on shunt infection in children and neonates.
Infection remains a significant problem with cerebrospinal fluid (CSF) diversion procedures. Antibiotic-impregnated shunt catheters (AIS) have been introduced to prevent infection, mainly in the early post-operative period when most infections occur. We evaluate the impact on infection rates in children following the introduction of catheters impregnated with rifampicin and clindamycin. The study was a retrospective analysis of all paediatric shunt procedures undertaken after the introduction of AIS systems in 2003. All procedures where a complete AIS system was implanted were included. For the purpose of analysis, shunt procedures were classified as de novo (group 1), clean revision (group 2) and following external ventricular drainage with either sterile CSF (group 3) or infected CSF (group 4). Results were compared to a historical cohort of shunt procedures undertaken before the introduction of AIS catheters. A total of 214 AIS were implanted in 150 children between October 2003 and December 2006. There were 4 infections in group 1 (8.5%), 6 infections in group 2 (5.3%) and 11 infections in groups 3 and 4 (20%). The historical control group comprised 77 shunts in 65 children. The infection rate in neonatal de novo shunts reduced from 27 to 10.4% following the introduction of AIS catheters. AIS catheters can reduce the number of shunt infections seen in clinical practice in certain subgroups. This has had a significant impact on the neonatal hydrocephalic population. The high risk of shunt infection after a period of external ventricular drainage raises the issue of emergence of bacterial resistance.


A population-based study of sport and recreation-related head injuries treated in a Canadian health region.
To report the rates of SR-related HIs presenting to EDs in a Canadian population-based sample. Descriptive epidemiology study. Using administrative data, sport and recreation-related emergency department presentations for persons 0-35 years of age, from April 1997 through March 2008, were obtained from the Edmonton Zone (formerly the Capital Health Region), Alberta Health Services through the Ambulatory Care Classification System. Of the 3,230,890 visits to the emergency departments of the five hospitals in Edmonton, 63,219 sport and recreation-related injury records and 4935 sport and recreation-head injury records were identified. Head injuries were most frequently treated for the activities of hockey (20.7%), cycling (12.0%), and skiing/snowboarding/sledding. Males accounted for 71.9% (n=3546) and patients less than 18 years of age sustained 3446 (69.8%) sport and recreation-head injuries. Sport and recreation-related head injuries most frequently treated in emergency departments involve common activities such as hockey, cycling, skiing/snowboarding/sledding, and soccer. Males and those less than 18 years of age sustain the majority of sport and recreation-related head injuries treated in emergency departments. These findings underscore the importance of sport-specific policies and safety promotion for the prevention of head injuries, in sports and recreational activities.


Prevalence and predisposing factors of smartphone addiction, sleep quality and daytime sleepiness of nursing students: A cross-sectional design.
The current study aimed to determine the prevalence of smartphone addiction, sleep quality and daytime sleepiness of nursing students and to identify the predisposing factors of these parameters. The use of smartphones, which has become an indispensable part of daily life, has various effects on addictive behavior and sleep. The present study was performed with a cross-sectional design. The population of the study comprised of nursing students attending all grades at two universities (N = 940). A total of 771 students were included in the study. Data were collected through a personal information form, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and the Smartphone Addiction Scale. Logistic regression analysis was used to evaluate the data. The prevalence of smartphone addiction was 42.4%. Of the students, 57.3% had poor sleep quality and 82.5% had normal daytime sleepiness. Daily smartphone use duration, owning of a smartphone duration, daytime sleepiness and academic success were significant influencing factors for smartphone addiction (p < 0.05). Daily sleep duration, daytime sleepiness and school region were found significant risk factors for sleep quality (p < 0.05). Sleep quality and smartphone addiction significantly influenced daytime sleepiness (p < 0.05). The study revealed that almost half of nursing students presented smartphone addiction and more than half of them had poor sleep quality. The prevalence of normal daytime sleepiness among nursing students was high.


A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer.
To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer. We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment. Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards.


CD40 regulation of death domains containing receptors and their ligands on lymphoma B cells.
Within the tumour necrosis factor (TNF) family the induction of apoptosis is restricted to some ligand-receptors pairs, including TNF-TNF receptor type I (TNFRI/p55), FasL-Fas, TNF-related apoptosis-inducing ligand (TRAIL) and its death-receptors (DR)-4 and -5. The pair CD40L-CD40 belongs to the same family but rescues B cells from apoptosis. To investigate how these opposing actions are cross-linked, purified follicular lymphoma (FL) cells were activated upon a human CD40L-transfected murine fibroblastic layer, then RNA messengers for the above molecules were analysed using RT-PCR. The observed down-modulation of TRAIL and up-regulation of TNF and Fas transcripts might account for CD40-CD40L-mediated FL cell survival.


Thrombin generation in children with sickle cell Anemia is Higher in the presence of platelets⋆ and ⋆.
Cellular and plasma interactions underlie hypercoagulability in sickle cell anemia (SCA). In healthy adults, thrombin generation (TG), a biomarker of hypercoagulability, is similar in plasma with and without platelets. Studies investigating TG in SCA using platelet-poor plasma (PPP) show conflicting results. There are no studies in SCA simultaneously comparing TG using platelet rich plasma (PRP) and PPP. This prospective study compares TG in children with SCA, at steady state, in PPP versus PRP and investigates the association of predefined clinical variables with the difference between PRP and PPP. Our secondary aim was to investigate derangements in the protein C and S pathway measuring TG with and without thrombomodulin (TM). In forty-three paired samples from SCA patients, aged 2-15 years, TG in the presence of platelets was 5.9 % higher [1239 nmol/(min*L) (SD: 224.1) vs. 1151 nmol/(min*L) (SD 223.3); p = 0.026]. The difference was highest in the 6-10 year age group (9.5 %; SD 14.1) followed by the 2-5 year age group (5.4 %; SD 21.4). In a multiple linear regression model, age, gender, current use of hydroxyurea, degree of hemolysis and severity of pain crises were not predictive of the difference between PRP and PPP. In PPP, TG reduction after TM addition was 7.4 % (SD 16.8), signifying activated protein C resistance. In conclusion, TG in children with SCA aged 2-10 years is higher in the presence of platelets. TG using PRP along with TM addition may be a useful biomarker of hypercoagulability in this population.


Violence against refugee women along the Thai-Burma border.
To document the prevalence and characteristics of conflict victimization and its associations with past-year intimate partner violence (IPV) among refugee women affected by the protracted conflict in Burma (Myanmar). A cross-sectional survey was conducted among 861 women living in 3 refugee camps along the Thai-Burma border from February to April 2008. Descriptive statistics were generated regarding experiences of conflict victimization and generalized estimating equations were used to determine the odds of reporting past-year IPV. In all, 9.6% of partnered women reported conflict victimization and 7.9% of women reported experiencing past-year IPV. After accounting for demographic variables, women who experienced conflict victimization were 5.9 times more likely to report past-year IPV than women who had not experienced conflict victimization (95% confidence interval, 5.0-6.9). Given the strong association uncovered in the present study, interventions to reduce the negative effects of conflict victimization should incorporate other forms of violence prevention, including IPV. Future longitudinal research is needed to discern pathways through which these experiences are related.


[Imaging Techniques and Differential Diagnosis for Inflammatory Bowel Disease].
The two main types of inflammatory bowel disease (IBD) are Crohn's disease and ulcerative colitis. Currently, when IBD is suspected, CT enterography is widely used as an initial imaging test because it can evaluate both the bowel wall and the outside of the bowel, helping to differentiate IBD from other diseases. When IBD is suspected, it is necessary to distinguish between Crohn's disease and ulcerative colitis. In most cases this is not difficult; however, in some cases, it is difficult and such cases are called IBD-unclassified. CT findings are often non-specific for ulcerative colitis, making it difficult to differentiate it from other diseases using imaging alone. In contrast, characteristic CT findings for Crohn's disease are often helpful in diagnosis, although diseases, such as tuberculous enteritis can mimic Crohn's disease. Recently, mutations in the gene encoding a prostaglandin transporter called SLCO2A1 have been discovered as the cause of the disease in some patients with multiple ulcers and strictures, similar to Crohn's disease. Therefore, genetic testing is being used to make a differential diagnosis.


In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors.
Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb = 8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.


Galectins and their ligands: negative regulators of anti-tumor immunity.
Cytotoxic CD8(+) T cells are major players of anti-tumor immune responses, as their functional activity can limit tumor growth and progression. Data show that cytotoxic T cells efficiently control the proliferation of tumor cells through major histocompatibility complex class I-mediated mechanisms; nevertheless, the presence of tumor-infiltrating CD8(+) T cells in lesional tissue does not always correlate with better prognosis and increased survival of cancer patients. Similarly, adoptive transfer of tumor-specific cytotoxic T cells has only shown marginal improvement in life spans of patients with metastatic disease. In this report, we discuss experimental evidence showing that expression of tumor-derived galectins, galectin (Gal)-1, Gal-3 and Gal-9, and concomitant presence of their ligands on the surface of anti-tumor immunocytes directly compromise anti-tumor CD8(+) T cell immune responses and, perhaps, undermine the promise of adoptive CD8(+) T cell immunotherapy. Furthermore, we describe novel strategies designed to counteract Gal-1-, Gal-3- and Gal-9-mediated effects and highlight their targeting potential for creating more effective anti-tumor immune responses. We believe that Gal and their ligands represent an efficacious targeted molecular paradigm that warrants clinical evaluation.


AMP-dependent kinase inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis by suppressing the dissociation between c-Abl and Prdx1 proteins in endothelial cells.
Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.


The LUNGe to Model Alveolar Lung Diseases in a Dish.
Obtaining alveolar epithelial type 2 cells (AEC2s) from human pluripotent stem cells (hPSCs) offers great scientific and clinical promise. In this issue of Cell Stem Cell, Jacob et al. (2017) report a method for the directed differentiation of hPSCs into mature AEC2s and demonstrate its application in modeling alveolar lung diseases.


Connective tissue components in normal and atherosclerotic human coronary arteries.
Human coronary arteries with various degrees of atherosclerosis were analyzed for the concentration of different types of glycosaminoglycans (GAGs). The changes in GAGs were considered against the background of macroscopic atherosclerosis, and the concentration of glycoprotein-bound hexosamines, collagen, calcium and cholesterol. The concentration of calcium was increased and that of hyaluronic acid decreased even in mildly atherosclerotic coronary arteries. The additional changes in advanced atherosclerosis included the increase of collagen and dermatan sulphate and the decrease of heparan sulphate. Cholesterol was increased in mild, and even further in advanced, atheroslcerosis. The concentrations of chondroitin sulphates and glycoprotein-bound hexosamines were not significantly affected by atherosclerosis.


Imaging features of gray-scale and contrast-enhanced color Doppler US for the differentiation of transient renal arterial ischemia and arterial infarction.
To characterize the imaging features on gray-scale and contrast-enhanced color Doppler US images which differentiate renal ischemia from renal infarction. The segmental renal arteries of eight healthy rabbits were surgically ligated. In four of these rabbits, the ligated renal artery was released 60 minutes after arterial occlusion to cause transient ischemia. In the remaining four rabbits, the arterial ligation was retained to cause a permanent infarction. The gray-scale and contrast-enhanced color Doppler US imaging features of the involved renal parenchyma of both ischemia and infarction groups were compared with respect to the presence or absence of parenchymal swelling, echogenicity changes, tissue loss and perfusion defects. Parenchyma swelling, echogenic changes, tissue loss and perfusion defects were found to be more extensive in the infarction than the ischemia group. The hyperechoic areas reperfused with blood flow recovered normal echogenicity and perfusion, whereas the hyperechoic areas without reperfusion became renal infarcts. Gray-scale and contrast-enhanced color Doppler US showed that the hyperechoic areas with reperfusion may reverse to normal parenchyma and allow the differentiation of renal ischemia from renal infarction.


Evolution of 3-Dimensional Functional Planning for Total Hip Arthroplasty with a Robotic Platform.
Robotic-assisted surgery was introduced to make various mechanical aspects of a total hip arthroplasty more reproducible. When paired with sophisticated three-dimensional preoperative planning, robotic surgery offers the promise that a surgeon might select and reliably achieve targets for component position to optimize hip center-of-rotation, acetabular anteversion and inclination, femoral offset, as well as limb length. This paper describes a patient-specific step-by-step approach to performing these procedures including taking into account pelvic tilt. It is hoped that these described techniques will further optimize robotic-assisted hip arthroplasty procedures.


[SI-units in radiotherapy and radiation protection--an addendum (author's transl)].
As an extension of a recent paper, this addendum conversion tables between the new SI-unit Sievert (Sv) for the dose equivalent and the unit Rem (rem) used previously, as well as the relations of the corresponding dose rates.


Detection and determination of N-nitrosamino acids by thin-layer chromatography using fluorescamine.
A novel procedure is described for the detection and determination of N-nitrosamino acids (NAAs) on activated silica gel thin-layer chromatographic plates. N-Nitrososarcosine, N-nitrosoproline, and N-nitroso-4-hydroxyproline could be detected as fluorophors at the 200-pmole level (20-30 ng) after being irradiated with ultraviolet light and sprayed with fluorescamine reagent. Spectrophotometric determination of the relative fluorescence of 0.4-40 nmoles of NAAs gave rise to similar calibration curves when plotted on a log-log scale. An application of this method to the detection of NAAs in uncooked bacon is described.


Neonatal haemochromatosis associated with gastroschisis.
We describe, to our knowledge, the first case of progressive neonatal liver failure due to neonatal haemochromatosis (NH) occurring in an infant with a gastroschisis and review the literature regarding these two conditions. A 1,665 g male infant with antenatally diagnosed gastroschisis was born with a severe coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed progressive liver failure, complicated by necrotising enterocolitis. Serum ferritin was elevated at 1,459 microg/L. He died on day 40 and a limited post-mortem examination confirmed significant hepatic siderosis with fibrosis and cholestasis, and siderosis of the pancreas. Although no genetic aetiology for gastroschisis has been identified, an occasional inherited tendency has been observed. There is also evidence to support an autosomal recessive inheritance in NH.


Blood pressure, T cells, and mortality in people with HIV in Tanzania during the first 2 years of antiretroviral therapy.
Cardiovascular disease is now a leading cause of mortality in people with HIV (PWH). High blood pressure is the major driver of cardiovascular disease. Despite this, little is known about blood pressure in PWH during the early years of antiretroviral therapy (ART). In this prospective cohort study in Tanzania, the authors conducted unobserved blood pressure measurements at enrollment, 3, 6, 12, 18, and 24 months in 500 PWH initiating ART and 504 HIV-uninfected adults. The authors excluded measurements taken on antihypertensive medications. Although PWH had a significantly lower blood pressure before ART initiation, they had a significantly greater increase in blood pressure during the first 2 years of ART compared to HIV-uninfected controls. Blood pressure correlates in PWH differed from HIV-uninfected controls. In PWH, lower baseline CD4+ T-cell counts were associated with lower blood pressure, and greater increases in CD4+ T-cell counts on ART were associated with greater increases in blood pressure, both on average and within individuals. In addition, PWH with a systolic blood pressure (SBP) <90 mm Hg at the time of ART initiation had ~30% mortality in the following 3 months due to occult infections. These patients require careful investigation for occult infections, and those with tuberculosis may benefit from corticosteroids.


Profile: the National Association for Gifted Children.
Until the foundation of NAGC in 1966, the general impression was that, of all sections of the child population, gifted children were among the best endowed and therefore the least worthy of our compassion and concern. Work with gifted children over the past 10 years has led us to reconsider the situation. Certainly the majority of them are successful, well-balanced and reach adult life with a large measure of happiness, but a sizeable minority unfortunately do not do so. For these children, giftedness itself brings problems, sometimes referred to as "the handicap of brilliance".


Melatonin stimulates inositol-1,4,5-trisphosphate and Ca2+ release from INS1 insulinoma cells.
The effects of melatonin in mammalian cells are exerted via specific receptors or are related to its free radical scavenging activity. It has previously been reported that melatonin inhibits insulin secretion in the pancreatic islets of the rat and in rat insulinoma INS1 cells via Gi-protein-coupled MT1 receptors and the cyclic adenosine 3',5'-monophosphate pathway. However, the inositol-1,4,5-trisphosphate (IP3) pathway is involved in the insulin secretory response as well, and the melatonin signal may play a part in its regulation. This paper addresses the involvement of the second messengers IP3 and intracellular Ca2+ ([Ca2+]i) in the signalling cascade of melatonin in the rat insulinoma INS1 cell, a model for the pancreatic beta-cell. For this purpose melatonin at concentrations ranging from 1 to 100 nmol/L, carbachol and the nonselective melatonin receptor antagonist luzindole were used to stimulate INS1 cell batches, followed by an IP3-mass assay and Ca2+ imaging. Molecular biological studies relating to the mRNA of IP3 receptor (IP3R) subtypes and their relative abundance in INS1 cells showed expression of IP3R-1, IP3R-2 and IP3R-3 mRNA. In conclusion, we found that in rat insulinoma INS1 cells there is a dose-dependent stimulation of IP3 release by melatonin, which is accompanied by a likewise transient increase in [Ca2+]i concentrations. The melatonin effect observed mimics carbachol action. It can be abolished by 30 micromol/L luzindole and is sustained in Ca2+-free medium, suggesting a mechanism that includes the depletion of Ca2+ from intracellular stores.


Association between sleep duration and rupture of intracranial aneurysms: A single-center retrospective study.
To assess the relationship between sleep duration and risk of rupture of intracranial aneurysms (IAs). According to our inclusion and exclusion criteria, 683 patients admitted to Beijing Tiantan Hospital were included in this study. There were 201 patients in the ruptured group and 482 patients in the unruptured group. Sleep duration was divided into three levels: ≥8 h (long), 6-8 h (normal), ≤6 h (short). Correlation between different sleep duration and rupture of IAs was evaluated by univariate and multivariate regression analysis. The results of multivariate analysis demonstrated that there was a statistical difference between sleep duration of ≤6 h and sleep duration ≥8 h (OR = 1.76, CI = [1.08-2.87], p = 0.025). There was no statistically significant difference between the group with sleep duration of 6-8 h and sleep duration of ≥8 h (OR = 1.04, CI = [0.65-1.67], p = 0.857). Short sleep duration (≤6 h) may be related to the rupture of intracranial aneurysms. The reason for this correlation is not yet clear. We suspect that it may be caused by a series of physiological changes caused by reduced sleep.


Driving delivery vehicles with ultrasound.
Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized.


Determination of the helical screw sense and side-group chirality of a synthetic chiral polymer from Raman optical activity.
Splitting it up: excellent agreement between the experimental and the quantum-chemically simulated Raman optical activity (ROA) spectrum of (+)-poly(trityl methacrylate) shows that the polymer backbone adopts a left-handed helical conformation while the trityl side groups display a left-handed propeller conformation. Thus ROA can be used to determine the complete structure of synthetic chiral polymers in solution.


Study of intact virus-like particles of human papillomavirus by capillary electrophoresis.
Virus-like particles of human papillomavirus (HPV-VLP), resulting from the self-assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native virion. Moreover, two prophylactic vaccines, Gardasil(®) and Cervarix(®), are based on HPV-VLP L1. Analytical techniques currently used to characterize HPV-VLP, such as SDS-PAGE, Western blot, ELISA, are time-consuming and semiquantitative. In this study, CE was evaluated for the analysis of intact HPV16-VLP. The usefulness of capillary inner wall coating as well as various BGEs, pH, and detergent additives were investigated. Reproducible HPV-VLP analysis in CE was achieved using poly(ethylene oxide)-coated capillary and a BGE containing high salt concentration and low SDS concentration. The developed method enables HPV-VLP detection in less than 10 min (migration times RSD: 1.6%). The identity of HPV-VLP peak was confirmed by comparison with a sample obtained from a wild-type baculovirus and with VLP-based vaccine, Gardasil(®) , after adjuvant dissolution. Finally, we applied the developed methodology to VLP-based vaccines, demonstrating that CE could be successfully used for vaccine quality control.


Influence of detergents on the measurement of the fibrinolytic activity of plasminogen activators.
The influence of detergents on the apparent activity of tissue plasminogen activator and of urokinase was investigated. The nonionic detergents Tween 80 and Triton X-100 and the zwitterionic detergent Zwittergent 314 caused a marked increase in the apparent activity of tissue plasminogen activator and, to a lesser degree, of urokinase in the fibrin plate assay, particularly at higher activator concentrations. The detergents did not enhance the plasma clot lysis in the presence of urokinase or tissue plasminogen activator. The anionic detergent sodium dodecyl sulfate had a small inhibitory action on the fibrin plate activity of urokinase and strongly inhibited the fibrin plate activity of tissue plasminogen activator. A systematic study into the mechanism of the stimulatory action of nonionic and zwitterionic detergents is presented.


A comparison of single-port laparoscopic cholecystectomy and an alternative technique without a suspension suture.
Many surgeons face difficulties during single-incision laparoscopic cholecystectomy (SILC) surgery and are forced to use an additional port. We compared the results of a technique that we developed with SILC. Fifty-four patients who were diagnosed with chronic cholelithiasis were prospectively randomized and divided into two groups. An additional 5-mm port (MCAP: with an additional port using a multi-channel device through the umbilicus) was placed in the subxiphoid area instead of a transabdominal suspension suture in one group of patients. The other group was operated on with the SILC technique. The demographic and surgical data of the patients were compared. The MCAP technique shortened the surgery duration by more than half (MCAP: 35.0±12.3, SILC: 79.1±27.7 min) (p<0.05). No difference was found between the two methods in terms of estimated blood loss, length of hospitalization, postoperative day 1 and 7 visual analog scale scores, need for analgesia in the postoperative period, and rate of changing to another technique due to inadequacy of the surgical technique. MCAP is as safe as SILC for cholecystectomy and is easier for the surgeon to perform.


Meningeal and multiorgan disseminated sporotrichosis: A case report and autopsy study.
This case report presents a 36-year old man with a disseminated sporotrichosis who presented with seizures and crusted lesions all over the body. Imaging studies revealed acute ischemic brain event with haemorrhagic transformation in right frontal lobe. Skin biopsy showed Sporothrix schenckii. He was treated with standard amphotericin B. Despite therapy, he developed consciousness loss, multiorgan-failure and eventually expired. Necropsy findings showed renal, hepatic, splenic, prostate, testicles and meningeal/cerebral involvement.


Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency.
Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. Biochemically, these individuals exhibit findings consistent with a combined deficiency of the biotin-dependent carboxylases. We have found that the activity of the enzyme biotinidase is also deficient in the sera of five affected children (0 to 3% of mean control activity, 5.80 +/- 0.89 nmol X min-1 X ml-1 serum), and believe that it represents the primary biochemical defect in this disease. Biotinidase catalyzes the removal of biotin from the epsilon-amino group of lysine, through which biotin is covalently bound to the four known human carboxylases, thereby regenerating biotin for reutilization. The deficient activity in our patients was not due to an inhibitor, particularly biotin. It is also not a consequence of feedback control in affected individuals under treatment with pharmacologic doses of biotin. The biotinidase activities of the parents of those children who were available for study were intermediate between deficient and normal values (46% to 65% of mean normal activity). Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. Our findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.


Hypothesis paper Brain talks with fat--evidence for a hypothalamic-pituitary-adipose axis?
The adipose tissue signals to the brain via its secretory products. However, it is unknown whether the brain itself can directly contact the fat tissue. In order to test this hypothesis, the adipocytic expression of receptors for pituitary hormones and hypothalamic peptides was investigated. Besides FSH- and LH-receptors, adipocytes do express the specific receptors for ACTH, TSH, GH, prolactin, oxytocin and the three receptor subtypes for vasopressin. Thus, the adipose tissue might no longer be regarded as an inert and steady tissue but as a fast acting player downstream of and under the control of the brain. Based on this, the potential existence and clinical impact of a hypothalamic-pituitary-adipose axis should further be investigated.


Dose-Dependent Effect of Intake of Fermented Dairy Foods on the Risk of Diabetes: Results From a Meta-analysis.
Diabetes mellitus (DM) is one of the largest epidemics the world has faced. Given the morbidity and mortality burden of DM, it is important to identify modifiable factors that affect the natural course of the disease. We carried out this meta-analysis of published studies to estimate the overall DM risk of intake of fermented dairy foods, and to reveal the dose-dependent effect on DM risk. We searched the PubMed, Embase and China National Knowledge Infrastructure databases for all articles published between the years 1980 to 2020 on the association between fermented dairy foods intake and DM risk. Fifteen studies met the inclusion criteria for our study, including a total of 485,992 participants and 20,207 incidences of diabetes. Overall, statistical evidence of significantly decreased diabetes risk was found to be associated with higher intake of fermented dairy foods (odds ratio [OR], 0.925; 95% confidence interval [CI], 0.856 to 0.999). In a subgroup analysis, higher yogurt consumption was significantly associated with decreased DM risk (OR, 0.828; 95% CI, 0.729 to 0.941). Our meta-analysis shows that intake of fermented dairy foods is associated with decreased DM risk, and the effect may be dose-dependent.


Innate immunomodulation with recombinant interferon-alpha enhances resistance of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus.
We examined the in vivo immunostimulatory effects of a recombinant Atlantic salmon (Salmo salar) interferon-alpha2 (rSasaIFN-alpha2). The mature rSasaIFN-alpha2, expressed and purified from Escherichia coli, was administered to rainbow trout (Oncorhynchus mykiss) via the oral, immersion, or intraperitoneal (IP) injection route. Injection of rSasaIFN-alpha2 at 0.1microg/g fish gave significantly greater protection than a phosphate buffered saline (PBS) injection against a lethal challenge of infectious hematopoietic necrosis virus (IHNV), with a relative percent survival of 39%. Relative percent survival (RPS) increased significantly to 92% when the fish were injected with rSasaIFN-alpha2 at 1microg/g fish. Antiviral protection was evident for up to 7 days post-injection of rSasaIFN-alpha2. Administration of rSasaIFN-alpha2 by the oral or immersion route was not protective, and the fish succumbed to virus infection. The level of systemic IFN-induced expression of the Mx1 gene was significantly greater (p<0.01) in the IFN-injected group than in the PBS-injected group, and this was correlated with the fish survival rates in the challenge study. We used relative quantitative real-time polymerase chain reactions to examine the systemic expression of several other IFN-induced genes (including genes for IFN1, IFN regulatory factors 1 and 2, MHC-I, STAT1, vig-1, and GBP) and found that their expression was significantly increased 1-day post-rSasaIFN-alpha2 injection. Expression of the IFN-gamma and interleukin-1beta genes was not significantly increased. Thus, a salmonid rIFN-alpha can modulate the innate immune response of rainbow trout and mediate early antiviral protection against IHNV.


The numerical simulation and experimental study of heat release in a heat storage system with various diameters of aluminum tubes.
Phase change materials (PCMs) can be used to store solar energy. The heat released from PCMs is directly influenced by the efficiency of thermal energy storage and the scope of application. In this study, paraffin was used as the PCM, and was encapsulated in an aluminum tube. The temperature of the inner PCM was measured, and the heat release process of the PCM was simulated. The results indicate that the melt temperature of the PCM ranged from 45 °C to 60 °C, and the latent heat was 177 J/g. The heat release processes of the PCM in different aluminum tubes included three stages: 1) the stage during which no phase change occurred at temperatures above the melt temperature and at a rapidly decreasing temperature; 2) the stage during which phase change occurred at very slowly decreasing temperatures; 3) the stage during which no phase change occurred at temperatures lower than the melt temperature. The temperature of the PCM decreased when the radius of the aluminum tube increased. The temperature results obtained via simulation were similar to the actual temperature data. The total energy released from the PCM increased linearly with the time required to complete the energy release process of the PCM in aluminum tubes with different diameters, as well as with the increase in the aluminum tube diameter. The diameter of the PCM exerted no significant influence on the energy release rate. The relationship between the tube diameter and the time required to complete heat release, and the relationship between the amount of heat released, the diameter of the aluminum tube, and the release time, were established. These equations could predict actual values and provide theoretical guidance for heat release in heat storage systems. They could also be used as a guide in practical production.


Correlation between sweat glucose and blood glucose in subjects with diabetes.
Sweat contains glucose that can accurately reflect blood glucose. However, skin surface glucose can confound these measurements. A perfusion method was used to rapidly harvest sweat from forearm sites on human subjects. The sweat samples were analyzed for glucose by high-performance liquid chromatography methods and compared with the results obtained with a blood glucose meter. The results of 23 different studies of seven individual subjects with diabetes show a strong correlation between sweat glucose and blood glucose. Sweat glucose, when properly harvested to prevent contamination from other sources on the skin's surface, can accurately reflect blood glucose levels.


A mono-carbonyl analog of curcumin induces apoptosis in drug-resistant EGFR-mutant lung cancer through the generation of oxidative stress and mitochondrial dysfunction.
Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975. In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC.


Emotional cues enhance the attentional effects on spatial and temporal resolution.
In the present study, we demonstrated that the emotional significance of a spatial cue enhances the effect of covert attention on spatial and temporal resolution (i.e., our ability to discriminate small spatial details and fast temporal flicker). Our results indicated that fearful face cues, as compared with neutral face cues, enhanced the attentional benefits in spatial resolution but also enhanced the attentional deficits in temporal resolution. Furthermore, we observed that the overall magnitudes of individuals' attentional effects correlated strongly with the magnitude of the emotion × attention interaction effect. Combined, these findings provide strong support for the idea that emotion enhances the strength of a cue's attentional response.


OMIP-086: Full spectrum flow cytometry for high-dimensional immunophenotyping of mouse innate lymphoid cells.
This 25-parameter, 22-color full spectrum flow cytometry panel was designed and optimized for the comprehensive enumeration and functional characterization of innate lymphoid cell (ILC) subsets in mouse tissues. The panel presented here allows the discrimination of ILC progenitors (ILCP), ILC1, ILC2, NCR+ ILC3, NCR- ILC3, CCR6+ lymphoid tissue-inducer (LTi)-like ILC3 and mature natural killer (NK) cell populations. Further characterization of ILC and NK cell functional profiles in response to stimulation is provided by the inclusion of subset-specific cytokine markers, and proliferation markers. Development and optimization of this panel was performed on freshly isolated cells from adult BALB/c lungs and small intestine lamina propria, and ex vivo stimulation with phorbol 12-myrisate 13-acetate, ionomycin, and pro-ILC activating cytokines.


The electrophysiological consequences of electrode impalement of peripheral nerves in the rat.
Peripheral nerve fascicles are deliberately impaled during microneurography experiments. We have assessed conduction block under these circumstances. First we recorded compound action potentials (CAP) in the sural nerve following stimulation of the sciatic nerve. The insertion of injection and microneurography electrodes between stimulation and recording sites produced a 20% decrease in the size of the CAP, which was maintained for the 10 min duration of impalement. After withdrawal, the conduction block partially resolved. In other experiments, single-unit action potentials were recorded from L4 and L5 dorsal roots following peripheral nerve stimulation. Microneurography electrodes inserted into the sciatic nerve produced conduction block in 50% of these axons. When axons were blocked, anodal stimulation through the tungsten electrode became more effective than cathodal stimulation. These results suggest that a temporary conduction block occurs in a significant number of myelinated fibers near the site of an inserted electrode.


Pulse Blood Pressure Correlates with Late Outcome in Acute Ischemic Stroke without Significant Culprit Artery Stenosis.
This study was conducted to test the hypothesis that elevated blood pressure at the early stage is associated with unfavorable outcome in acute ischemic stroke patients with stenosis of less than 50% of the culprit artery. Patients with acute ischemic stroke onset within 48 hours and stenosis of less than 50% of the culprit artery from a prospective stroke registry were analyzed. A modified Rankin Scale score of 1 or lower at 3 months was defined as a favorable late outcome. Univariate and multivariate logistic regression analyses were used to analyze the association between hemodynamic parameters and outcome. One hundred thirty-six patients fulfilled the selection criteria. Patients with favorable outcome had lower pulse pressure at emergency department (ED) triage, lower systolic blood pressure (SBP) at 24 hours, lower pulse pressure at 24 hours, and lower heart rate (HR) at 24 hours. The univariate logistic regression analysis showed that history of stroke, elevated SBP at 24 hours, elevated HR at 24 hours, elevated pulse pressure at 24 hours, and higher National Institutes of Health Stroke Scale score at ED triage were associated with a less favorable late outcome. Two separate models of multivariate logistic regression analyses showed that pulse pressure at ED triage and pulse pressure at 24 hours, respectively, were significantly associated with less favorable outcome. Elevated pulse pressure at the early stage is independently associated with unfavorable late outcome in acute ischemic stroke patients with culprit artery stenosis less than 50%.


Complement contributes to antibody-mediated protection against repeated SHIV challenge.
The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization breadth and potency, it remains unclear whether augmenting the effector functions elicited by broadly neutralizing antibodies (bNAbs) may also improve their clinical potential. Among these effector functions, complement-mediated activities, which can culminate in the lysis of virions or infected cells, have been the least well studied. Here, functionally modified variants of the second-generation bNAb 10-1074 with ablated and enhanced complement activation profiles were used to examine the role of complement-associated effector functions. When administered prophylactically against simian-HIV challenge in rhesus macaques, more bNAb was required to prevent plasma viremia when complement activity was eliminated. Conversely, less bNAb was required to protect animals from plasma viremia when complement activity was enhanced. These results suggest that complement-mediated effector functions contribute to in vivo antiviral activity, and that their engineering may contribute to the further improvements in the efficacy of antibody-mediated prevention strategies.


Respiratory system mechanics in ventilated patients: techniques and indications.
For the past 50 years, basic research has provided valuable insights into the concepts of respiratory system mechanics, but clinical application in the critical-care arena remains in its infancy. On the basis of the limited information that is available on critically ill patients, we believe that physicians who are responsible for the care of mechanically ventilated patients must understand the mechanical interactions between humans and machines. With measurements of flow, volume, and pressure, a more precise quantitative evaluation of the respiratory system can be obtained than with clinical assessment alone. In this article, we discuss the principles, techniques, and clinical applications of measurements of respiratory system mechanics in ventilated patients and suggest directions for further research that may prove to be clinically relevant.


SIRT7 inactivation reverses metastatic phenotypes in epithelial and mesenchymal tumors.
Metastasis is responsible for over 90% of cancer-associated mortality. In epithelial carcinomas, a key process in metastatic progression is the epigenetic reprogramming of an epithelial-to-mesenchymal transition-like (EMT) change towards invasive cellular phenotypes. In non-epithelial cancers, different mechanisms must underlie metastatic change, but relatively little is known about the factors involved. Here, we identify the chromatin regulatory Sirtuin factor SIRT7 as a key regulator of metastatic phenotypes in both epithelial and mesenchymal cancer cells. In epithelial prostate carcinomas, high SIRT7 levels are associated with aggressive cancer phenotypes, metastatic disease, and poor patient prognosis, and depletion of SIRT7 can reprogram these cells to a less aggressive phenotype. Interestingly, SIRT7 is also important for maintaining the invasiveness and metastatic potential of non-epithelial sarcoma cells. Moreover, SIRT7 inactivation dramatically suppresses cancer cell metastasis in vivo, independent of changes in primary tumor growth. Mechanistically, we also uncover a novel link between SIRT7 and its family member SIRT1, providing the first demonstration of direct interaction and functional interplay between two mammalian sirtuins. Together with previous work, our findings highlight the broad role of SIRT7 in maintaining the metastatic cellular phenotype in diverse cancers.