Fibroid embolization.
The most common surgical treatment for fibroids is hysterectomy and approximately 30,000 are carried out annually in the UK for this condition. The operation, however, carries a significant complication rate. Since the first case was carried out in 1989 there has been increasing interest in the interventional radiological procedure called fibroid embolization where angiographic techniques are used to occlude the vascular supply of fibroids. This article is a review of the world experience of fibroid embolization, its development, techniques, indications, results and complications. So far evidence indicates very promising mid-term results but more long-term comprehensive data is needed from large trials.


Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.
A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab. Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue-modified human papillomavirus (TTMV) DNA was quantified in plasma. Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% [90% confidence interval (CI), 0.43-0.57]. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59-0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05). The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.


An audit of patient referrals to the sedation department of Newcastle Dental Hospital.
To audit the quality of external referral communications sent to the Department of Sedation at Newcastle Dental Hospital. A retrospective analysis was undertaken of a sample of 226 consecutive external referrals received by the sedation department of Newcastle Dental Hospital during May-July 2008. A data-collection form was used to record information provided in referrals relevant to the practice of sedation and the set standard was based on the recommendations of the Scottish Intercollegiate Guidelines Network (SIGN). Of the 226 referrals sampled, the majority (222; 98.2%) were from general dental practitioners. Seventy-six per cent were by letter and 24% by pro forma. Although of particular relevance to sedation referrals, a medical history was provided in only 59.0% of referrals and details of previous dental treatment in only 27.5%. The use of a pro forma significantly increased the provision of information compared to a letter in the following areas: patient's telephone number, patient's medication, doctor's name and doctor's address. Significantly less information was provided in the pro forma compared to the letters concerning the name of the referring practitioner and referring practitioner's telephone number. No difference was found between letter and pro forma referrals for medical history, treatment already attempted and reason for referral. The findings indicate a need to improve the amount of information provided in referrals to the sedation department of Newcastle Dental Hospital in order to ensure appropriate allocation to sedation services. The quality of referrals may be improved by the distribution of referral guidelines, the use of electronic referral templates or changes to the current pro forma.


FOXO1 and ANGPT2 relative gene expression in non-ST-segment elevation myocardial infarction among patients with or without type 2 diabetes.
It is well known that chronic hyperglycemia or chronic inflammation leads to both FOXO1 and Ang-2 gene (ANGPT2) expression induction in endothelial cells. ANGPT2 and FOXO1 relative gene expression in peripheral blood cells in diabetes and myocardial ischemia were not researched extensively. Our objective was to evaluate ANGPT2 and FOXO1 gene expression in peripheral blood cells in patients with non-ST elevation myocardial infarction (NSTEMI), both with and without type 2 diabetes mellitus (T2DM), and compare them to the results obtained from T2DM and control subjects. This was a multi-center, prospective study of 138 NSTEMI patients with/without T2DM, T2DM and a control group. FOXO1, ANGPT2, TBP (TATA box binding protein - as a reference gene) gene expression levels in peripheral blood cells were measured in each patient. Electrocardiography and echocardiography with assessment of ejection fraction (EF) were performed. Patients with NSTEMI underwent urgent (< 24 h) coronarography and the SYNTAX score and GRACE 2.0 score were calculated. The ANGPT2 gene relative expression in buffy coat in the analyzed samples was very low and detectable only in 11 patients from all groups (8.66% of all patients). The level of FOXO1 gene relative expression was significantly higher in patients with NSTEMI (median relative expression = 1.39) than in non-NSTEMI patients (median = 1.09) (W = 1578, p < 0.05) regardless of the presence of T2DM. The FOXO1 gene relative expression was not correlated with GRACE 2.0 score or SYNTAX score of NSTEMI patients. We did not observe any significant change in FOXO1 gene expression after successful angioplasty. On the basis of our results we can conclude that analyzing the ANGPT2 gene relative expression in peripheral blood cells has no role in assessment of CAD complexity among patients with and without T2DM. FOXO1 gene relative expression in blood peripheral cells is elevated in patients with NSTEMI regardless of the presence of T2DM. FOXO1 expression does not decrease after successful percutaneous coronary intervention and is not correlated with the severity of CAD in patients with NSTEMI.


Case report: Increased troponin level in 125 children during COVID-19.
Increase in cardiac biomarkers during Coronavirus disease 2019 (COVID-19) was frequent regardless of the presence of myocarditis and multisystem inflammatory syndrome in children (MIS-C). Several studies described MIS-C, but few papers evaluated cardiac manifestations in children with SARS-CoV-2 infection without MIS-C and investigated the role of troponin in absence of electrocardiogram (ECG) and echocardiographic alterations. The aim of this case series is to describe the cardiac manifestations during COVID-19 in children, trying to explain the meaning of laboratory findings during COVID-19, especially of increased troponin. We conducted a retrospective case series of children aged <18 years admitted at the Department of Pediatrics, University of Chieti, for SARS-CoV-2 infection between 1st March 2020 and 31th July 2022. All patients with documented SARS-CoV-2 infection underwent a laboratory evaluation at admission. Children with increased troponin I and/or BNP underwent electrocardiographic and echocardiographic exams. 125 children were admitted for SARS-CoV-2 infection to our Department of Pediatrics, of whom 17 (13.6% of cases) with different patterns of cardiac involvement. Specifically, 5 subjects (4.0% of admitted children) were diagnosed as MIS-C and 12 children (9.6%) manifested a cardiac involvement in terms of increased troponin with or without ECG and echocardiography anomalies. Troponin, C-reactive protein, procalcitonin and BNP values resulted higher in patients with MIS-C compared to patients without MIS-C. Furthermore, patients with MIS-C had higher neutrophils and lower lymphocytes compared to patients without MIS-C. ECG abnormalities were found in 4/5 patients with MIS-C and in 2/12 patients without MIS-C. Echocardiographic anomalies were found in all patients with MIS-C, especially in terms of valve regurgitation and ejection fraction reduction and in 2/12 patients without MIS-C, especially in terms of pericardial effusion. Despite high troponin levels, children presented a favorable clinical evolution. The increase in troponin level in children with COVID-19 could also be due to respiratory causes or a massive inflammatory state. In our case series, patients with increased troponin associated to COVID-19 presented a favorable clinical course with clinical and laboratory remission almost always within 7 days.


A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection.
SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.


Classification of Soft Tissue Grafting Materials Based on Biologic Principles.
Since periodontal plastic surgery's recent emergence and continuous, extensive development, various treatment modalities and materials have been developed alongside it to help clinicians pursue optimal esthetics and long-term stability around natural teeth and dental implants. To achieve satisfying and predictable long-term outcomes, promote more predictable results, and reduce complications following periodontal plastic surgery procedures, the authors reviewed articles published in peer-reviewed journals to better understand the biologic principles and potential of the soft tissue grafting materials and techniques being applied. That information was used to support a new classification system. This system aims to give clinicians guidance when selecting the most appropriate grafting materials and techniques for periodontal plastic surgery, using the graft materials' two most important features to guide the consideration/decision process: the source of blood supply and whether the grafts contain vital cells.


Simple Microwave-Assisted Synthesis of Amphiphilic Carbon Quantum Dots from A3/B2 Polyamidation Monomer Set.
Highly fluorescent and amphiphilic carbon quantum dots (CQDs) were prepared by microwave-assisted pyrolysis of citric acid and 4,7,10-trioxa-1,13-tridecanediamine (TTDDA), which functioned as an A3 and B2 polyamidation type monomer set. Gram quantities of fluorescent CQDs were easily obtained within 5 min of microwave heating using a household microwave oven. Because of the dual role of TTDDA, both as a constituting monomer and as a surface passivation agent, TTDDA-based CQDs showed a high fluorescence quantum yield of 29% and amphiphilic solubility in various polar and nonpolar solvents. These properties enable the wide application of TTDDA-based CQDs as nontoxic bioimaging agents, nanofillers for polymer composites, and down-converting layers for enhancing the efficiency of Si solar cells.


Anti-obesity and anti-diabetic effects of CL316,243, a highly specific beta 3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat.
The anti-obesity and anti-diabetic effects of a highly specific beta 3-adrenoceptor agonist, CL316,243 (CL; beta 1: beta 2: beta 3 = 0:1:100,000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and Long-Evans Tokushima Otsuka (control) rats. Daily injection of CL (0.1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27%; control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5'-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters. These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.


[Anatomopathology of breast cancer and hormone receptors].
The authors present the results obtained from a series of 511 operable adenocarcinomas (were excluded sarcoma, non infiltrating carcinoma and tumours too small for dosage). Estrogen (ER) and progesterone (PR) receptors were determined on the cytosol with a single saturating-dose method (5nM). The cut-off between positive and negative tumours was 100 fm/g tissue with a border area (100-200 fm/g). Correlation between ER, PR and the followed histological characters were studied: 1) Anatomic size of the tumour: no correlation was found. 2) Histological type: there was a significant correlation (p less than 0.001) between ER, PR and current histological types: among the infiltrating ductal carcinoma, the highly differentiated ones were more often ER+, PR+ (69%) than the atypical one (33%). This correlation remained according to the hormonal status of the patients. The particular types but infiltrating lobular carcinoma were mainly without receptors. 3) Histological grading: there was a significant correlation (p less than 0.001) between this character and the (ER, PR) rate of the tumour: 25% of the tumours of grade III were (ER+, PR+) against 57% of the grade I. As for the histological type, this correlation remained according to the hormonal status of the patients. 4) Stromal reaction: there was a significant correlation between (ER, PR) and inflammatory reaction (p = 0.002) or elastosis (p = 0.002) respectively. Inflammatory reaction was more often reported in tumours without receptors (73% in ER-, PR- tumours against 56% in ER+, PR+ ones). On the opposite, elastosis was correlated with the presence of receptors (52% in ER+, PR+ tumours against 34% in ER-, PR- ones). 5) Lymph-nodes involvement: no correlation was found with hormonal receptors (47% ER+, PR+ in the N- cases against 48% in the N+ cases).


Hyperactivity of medial prefrontal cortex pyramidal neurons occurs in a mouse model of early-stage Alzheimer's disease without β-amyloid accumulation.
The normal function of the medial prefrontal cortex (mPFC) is essential for regulating neurocognition, but it is disrupted in the early stages of Alzheimer's disease (AD) before the accumulation of Aβ and the appearance of symptoms. Despite this, little is known about how the functional activity of medial prefrontal cortex pyramidal neurons changes as Alzheimer's disease progresses during aging. We used electrophysiological techniques (patch-clamping) to assess the functional activity of medial prefrontal cortex pyramidal neurons in the brain of 3xTg-Alzheimer's disease mice modeling early-stage Alzheimer's disease without Aβ accumulation. Our results indicate that firing rate and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) were significantly increased in medial prefrontal cortex neurons from young Alzheimer's disease mice (4-5-month, equivalent of <30-year-old humans) compared to age-matched control mice. Blocking ionotropic glutamatergic NMDA receptors, which regulate neuronal excitability and Ca2+ homeostasis, abolished this neuronal hyperactivity. There were no changes in Ca2+ influx through the voltage-gated Ca2+ channels (VGCCs) or inhibitory postsynaptic activity in medial prefrontal cortex neurons from young Alzheimer's disease mice compared to controls. Additionally, acute exposure to Aβ42 potentiated medial prefrontal cortex neuronal hyperactivity in young Alzheimer's disease mice but had no effects on controls. These findings indicate that the hyperactivity of medial prefrontal cortex pyramidal neurons at early-stage Alzheimer's disease is induced by an abnormal increase in presynaptic glutamate release and postsynaptic NMDA receptor activity, which initiates neuronal Ca2+ dyshomeostasis. Additionally, because accumulated Aβ forms unconventional but functional Ca2+ channels in medial prefrontal cortex neurons in the late stage of Alzheimer's disease, our study also suggests an exacerbated Ca2+ dyshomeostasis in medial prefrontal cortex pyramidal neurons following overactivation of such VGCCs.


Telephone-delivered psychotherapy for late-life anxiety.
A randomized controlled trial (RCT) of telephone-delivered cognitive-behavioral therapy (CBT) was compared with usual care for late-life anxiety disorders. Client satisfaction, as assessed by the Client Satisfaction Questionnaire, was high (M = 27.4, range 8-32), and attrition rates were low (8.3%). Preliminary results suggest that participants receiving CBT, compared with usual care, experience declines in general anxiety, worry, anxiety sensitivity, and insomnia.


A Dense RNN for Sequential Four-Chamber View Left Ventricle Wall Segmentation and Cardiac State Estimation.
The segmentation of the left ventricle (LV) wall in four-chamber view cardiac sequential image is significant for cardiac disease diagnosis and cardiac mechanisms study; however, there is no successful reported work on sequential four-chambered view LV wall segmentation due to the complex four-chamber structure and diversity of wall motion. In this article, we propose a dense recurrent neural network (RNN) algorithm to achieve accurately LV wall segmentation in a four-chamber view MRI time sequence. In the cardiac sequential LV wall process, not only the sequential accuracy but also the accuracy of each image matters. Thus, we propose a dense RNN to provide compensation for the first long short-term memory (LSTM) cells. Two RNNs are combined in this work, the first one aims at providing information for the first image, and the second RNN generates segmentation result. In this way, the proposed dense RNN improves the accuracy of the first frame image. What is more is that, it improves the effectiveness of information flow between LSTM cells. Obtaining more competent information from the former cell, frame-wise segmentation accuracy is greatly improved. Based on the segmentation result, an algorithm is proposed to estimate cardiac state. This is the first time that deals with both cardiac time-sequential LV segmentation problems and, robustly, estimates cardiac state. Rather than segmenting each frame separately, utilizing cardiac sequence information is more stable. The proposed method ensures an Intersection over Union (IoU) of 92.13%, which outperforms other classical deep learning algorithms.


Physical activity and its relation to cancer risk: a prospective study of college alumni.
Previous investigations regarding the influence of physical activity on cancer risk generally have utilized a single assessment of activity, thus failing to account for changes over time. Additionally, one assessment may be somewhat imprecise. We attempted to overcome these problems in a study of 17,607 men (aged 30-79 yr), followed from 1962 or 1966 (1962/1966) through 1988. We assessed physical activity (based on self-reported stair climbing, walking and participation in sports or recreational activities) twice: in 1962/1966 and again in 1977. A total of 280 colon, 53 rectal, 454 prostatic, 262 lung, and 88 pancreatic cancers developed during follow-up. Among alumni with Quetelet's index > or = 26 units, those highly active (energy expenditure > or = 2,500 kcal [> or = 10,460 kJ].wk-1) had 0.19 (95% confidence interval, 0.02-1.52) to 0.56 (0.29-1.09) times the colon cancer risk of those inactive (< 1,000 kcal [< 4,184 kJ].wk-1). Colon cancer risk was unrelated to level of activity among alumni with Quetelet's index < 26 units. Highly active alumni also had 0.39 (95% confidence interval, 0.18-0.85) to 0.62 (0.45-0.85) times the lung cancer risks of their inactive colleagues. Physical activity was not significantly associated with risks of rectal, prostatic, or pancreatic cancers. The biologic basis for a protective effect of increased activity on cancer risk appears plausible.


The Ambivalent Students' Cognition to Be English Teachers for Young Learners: A Longitudinal Study.
This longitudinal study analyzed university students' cognition in learning an English for young learners (EYL) course. A qualitative method was used to get the data from 28 students who took the tiered EYL courses, EYL 1, EYL 2, and EYL 3, at a private university by giving them open-ended questionnaires for three semesters, or one and a half years. Semi-structured interviews with those 28 students were also used as the triangulation data at the end of each semester. The findings indicate a very extreme change in pre-service teachers' cognition, such as motivation, perception, and belief. At the end of their lecture, students initially interested in learning English for young learners did not want to become EYL teachers. On the other hand, students who enrolled in the EYL course for non-academic reasons wanted to have a profession as an EYL teacher after completing the EYL courses. It proves that students' interest in teaching English to young learners and the length of time spent studying EYL teaching knowledge do not assure those pre-service teachers are increasingly convinced to have a teaching profession.


Diagnostic value of multiple tumor-associated autoantibodies in lung cancer.
Lung cancer is the leading cause of cancer-related deaths. Survival rate improves significantly with early detection of lung cancer. Effective methods of early detection can reduce lung cancer mortality to a large extent as well as benefit the whole public health. The diagnostic value of one single marker is relatively low. Combined autoantibodies (AABs) can improve the sensitivity significantly rather than rely on one AAB and serve as good reservoir for early detection of lung cancer. We designed three parts in our experiment. In training set we measured the expression levels of AABs in 100 non-small-cell lung cancer (NSCLC) patients and 60 healthy controls by using ELISA detection method. A blinded validation was subsequently performed in 254 NSCLC patients, 125 healthy controls, and 71 nodule patients. A prospective expansion set was performed to evaluate the diagnosis value of AABs combined detection. Both in training set and validation set, the concentrations of SOX2, GAGE 7, MAGE A1, and P53 in NSCLC group increased prominently when compared to the healthy group (P<0.05). The concentration of GBU4-5 in adenocarcinoma group was higher than in the squamous cell carcinoma (SCC) group (P<0.05); the PGP9.5, which was opposite, in SCC group was higher than in the adenocarcinoma group (P<0.05). The positive rate of each AAB did not show any bias with age, gender, smoking history, and tumor location. Most importantly, different choice of biomarkers led to different detection results. Our study confirmed the diagnostic value of tumor-associated AABs. They may be useful as latent tumor markers to facilitate the detection of early lung cancer.


3-DOF Force-Sensing Motorized Micro-Forceps for Robot-Assisted Vitreoretinal Surgery.
In vitreoretinal surgery, membrane peeling is a prototypical task where a layer of fibrous tissue is delaminated off the retina with a micro-forceps by applying very fine forces that are mostly imperceptible to the surgeon. Previously we developed sensitized ophthalmic surgery tools based on fiber Bragg grating (FBG) strain sensors, which were shown to precisely detect forces at the instrument's tip in two degrees of freedom perpendicular to the tool axis. This paper presents a new design that employs an additional sensor to capture also the tensile force along the tool axis. The grasping functionality is provided via a compact motorized unit. To compute forces, we investigate two distinct fitting methods: a linear regression and a nonlinear fitting based on second-order Bernstein polynomials. We carry out experiments to test the repeatability of sensor outputs, calibrate the sensor and validate its performance. Results demonstrate sensor wavelength repeatability within 2 pm. Although the linear method provides sufficient accuracy in measuring transverse forces, in the axial direction it produces a root mean square (rms) error over 3 mN even for a confined magnitude and direction of forces. On the other hand, the nonlinear method provides a more consistent and accurate measurement of both the transverse and axial forces for the entire force range (0-25 mN). Validation including random samples shows that our tool with the nonlinear force computation method can predict 3-D forces with an rms error under 0.15 mN in the transverse plane and within 2 mN accuracy in the axial direction.


Wheat germ agglutinin is selectively transported to multivesicular bodies.
Colloidal iron dextran particles bearing wheat germ agglutinin (WGA/FeDex) were bound by glycoconjugates expressed at the surface of HepG2 cells. Bound WGA/FeDex was internalized when cells were incubated at 37 degrees C and accumulated in intracellular structures which have the same buoyant density as the plasma membrane when examined on Percoll density gradients. The intracellular structures containing WGA/FeDex were identified as multivesicular bodies (MVB) by transmission electron microscopy. WGA/FeDex was not transported to lysosomes nor did it interfere with uptake and transport of GalBSA to lysosomes by the asialoglycoprotein receptor. WGA/FeDex was seen predominantly in non-coated invaginations at the cell surface, suggesting it may enter cells at a different site than GalBSA/FeDex. Highly enriched plasma membranes and MVBs containing superparamagnetic [125I]WGA/FeDex particles were prepared by high gradient magnetic affinity chromatography (HIMAC). Plasma membranes prepared by HIMAC were enriched 30-fold for [125I]WGA/FeDex, 15-fold for alkaline phosphodiesterase I, and 9-fold for galactosyltransferase relative to the crude post-nuclear homogenate and consisted entirely of plasmalemmal sheets. Intracellular structures containing WGA/FeDex were enriched 35-fold for [125I]WGA/FeDex, 10-fold for alkaline phosphodiesterase I, and 10-fold for galactosyltransferase but did not contain lysosomal beta-galactosidase. WGA/FeDex has a different ultimate destination in HepG2 cells than ligands internalized by the asialoglycoprotein receptor and can be used to obtain highly enriched plasma membranes and MVBs from cultured cells.


Health characteristics by longest held occupation and industry of employment: United States, 1980.
Occupational and industrial hazards are unevenly distributed in the workplace. National estimates for selected health indices of persons aged 17 years and over in the civilian noninstitutionalized population are presented for categories of longest held occupation and industry of employment. These estimates were based on data collected by the National Center for Health Statistics (NCHS) in the 1980 National Health Interview Survey (NHIS) and the Occupational Supplement, the first survey to collect data on longest held, in addition to current, occupation and industry of employment. Data on length of longest held job, limitation of activity, disability days, incidence of acute conditions, persons injured, hospitalizations, and utilization of medical and dental services are presented.


Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury.
In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.


Activated clotting time (ACT)-guided intravenous dalteparin dosing during percutaneous coronary intervention.
The activated clotting time (ACT) has been reported to be sensitive to the anticoagulant activity of the low-molecular weight heparin dalteparin following intravenous (IV) administration. To evaluate the feasibility of an ACT-guided dalteparin dose adjustment strategy during percutaneous coronary intervention (PCI). This was a retrospective study of 104 consecutive patients who underwent PCI using an ACT-guided strategy of IV dalteparin. All patients received an initial IV bolus of 50 IU/kg of dalteparin. The minimum target ACT was 175 seconds for patients who received glycoprotein IIb/IIIa inhibitors and 200 seconds for patients who did not. Patients who did not achieve the target ACT after the initial 50 IU/kg were given supplemental boluses of dalteparin based on the assumption that for every additional 10 IU/kg of dalteparin, the ACT will rise by approximately 10 seconds. After the initial bolus of dalteparin, the mean baseline ACT rose from 138 +/- 41 seconds to 235 +/- 78 seconds. In the 36 patients (35% of the study population) who required a mean supplemental dose of 14 +/- 6 IU/kg/kg, the mean ACT after the supplemental dose was 239 +/- 79 seconds. The composite endpoint of in-hospital death, target vessel revascularization (TVR) and myocardial infarction (MI) was 5.8%. Major and minor bleeding rates were 1% each. The composite incidence of death/MI/TVR was comparable to, and the bleeding complications were lower than, those achieved in the SYNERGY and STEEPLE trials. ACT-guided dose adjustment of intravenously administered dalteparin during PCI appears to constitute a feasible strategy.


[A new and effective therapeutic method for the treatment of leishmaniasis].
Life for millions of people is at stake in the development of new techniques for homing drugs on to specific targets in the body. The use of artificial phospholipid vesicles known as liposomes is one of the most promising of the new approaches. Recent studies show that encapsulating drugs in liposomes, can make them more than 700 times more effective than unencapsulated (free) drugs.


Microbiology sampling in non-cystic fibrosis bronchiectasis cases from northern Alberta.
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease resulting in chronic cough, thick sputum, and lower airway microbial colonization, akin to patients with cystic fibrosis (CF). NCFB is a common, yet under recognized entity which inflicts significant morbidity and mortality particularly to older individuals, with a rising prevalence in the developed world. Given that sputum cultures are a non-invasive method to characterize the lower airway microbiota in NCFB patients, for which pathogenic organisms are associated with worsened outcomes, we sought to characterize the microbiological pattern and clinical outcomes associated with sputum culture in a cohort of NCFB patients from Western Canada. A total of 20 subjects were prospectively recruited from various bronchiectasis clinics across the Greater Edmonton area. A retrospective chart review and a symptoms questionnaire was performed, gathering information not limited to symptoms, comorbidities, exacerbations, hospitalizations, sputum production, and sputum culture results over the prior 5 years. Subjects reported frequent hospitalization alongside a significant burden of symptoms. A large majority of sputum cultures grew pathogenic organisms such as Haemophilus influenzae and Pseudomonas aeruginosa. We also note the considerable waste and inefficiency associated with sputum cultures, outlining areas for which this important diagnostic modality can be improved. Accurate characterization of the airway microbiota alongside efficient delivery of health services are key to ensuring the proper treatment of individuals with NCFB, given their high disease burden and frequent hospitalization.


Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1).
All-trans-retinoic acid is a metabolite of vitamin A (all-trans-retinol) that functions as an activating ligand for a family of nuclear retinoic acid receptors. The intracellular levels of retinoic acid in tissues are tightly regulated, although the mechanisms underlying the control of retinoid metabolism at the level of specific enzymes are not completely understood. In this report we present the first characterization of the retinoid substrate specificity of a novel short-chain dehydrogenase/reductase (SDR) encoded by RalR1/PSDR1, a cDNA recently isolated from the human prostate (Lin, B., White, J. T., Ferguson, C., Wang, S., Vessella, R., Bumgarner, R., True, L. D., Hood, L., and Nelson, P. S. (2001) Cancer Res. 61, 1611-1618). We demonstrate that RalR1 exhibits an oxidoreductive catalytic activity toward retinoids, but not steroids, with at least an 800-fold lower apparent K(m) values for NADP+ and NADPH versus NAD+ and NADH as cofactors. The enzyme is approximately 50-fold more efficient for the reduction of all-trans-retinal than for the oxidation of all-trans-retinol. Importantly, RalR1 reduces all-trans-retinal in the presence of a 10-fold molar excess of cellular retinol-binding protein type I, which is believed to sequester all-trans-retinal from nonspecific enzymes. As shown by immunostaining of human prostate and LNCaP cells with monoclonal anti-RalR1 antibodies, the enzyme is highly expressed in the epithelial cell layer of human prostate and localizes to the endoplasmic reticulum. The enzymatic properties and expression pattern of RalR1 in prostate epithelium suggest that it might play a role in the regulation of retinoid homeostasis in human prostate.


May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer?
The study aimed to evaluate changes in hematologic parameters, including white blood cell, platelet count, platelet indices, the platelet to lymphocyte and neutrophil to lymphocyte ratios in patients with early and advanced stages of epithelial ovarian cancers. The study included 100 patients with epithelial ovarian cancer who underwent primary staging exploratory laparotomy. Preoperative hematologic parameters, tumor histopathologic type, grade, stage and serum CA-125 levels were retrospectively analyzed. These parameters were compared between the patients with early (stage I-II) and advanced (stage III-IV) ovarian cancer. White blood cell count and platelet indices, including mean platelet volume, platelet distribution width and platelet crit did not show a statistically significant difference between groups with early and advanced ovarian cancer. However, the neutrophil to lymphocyte ratio, platelet count, the platelet to lymphocyte ratio and CA-125 level showed a statistically significant difference between the two groups (p<0.05, p<0.01, p<0.001, p<0.01 respectively). It was found that the neutrophil to lymphocyte ratio, platelet count and the platelet to lymphocyte ratio increased with the increasing stage of ovarian cancer. Furthermore, it was seen that the platelet to lymphocyte ratio is an independent prognostic factor related to the stage of epithelial ovarian cancer.


The use of oxidative stress biomarkers in live animals (in vivo) to predict meat quality deterioration postmortem (in vitro) caused by changes in muscle biochemical components.
This study was conducted to determine whether circulating concentrations of blood isoprostanes can be used as an effective biomarker in lambs to predict degradation of color and/or lipid stability in meat. Lambs ( = 84) were fed diets of either lucerne pasture, annual ryegrass pasture, a commercial feedlot pellet, or a combination of annual ryegrass and feedlot pellet for 8 wk, including a 2-wk adaptation period. Blood isoprostane concentration at wk 0, 4, 6 or 8 of feeding was determined. Blood isoprostane concentration for each animal was then correlated with muscle biochemical components that impact color and/or lipid oxidative status during retail display. This included lipid oxidation levels in muscle assessed by thiobarbituric acid reactive substances and meat redness determined by a HunterLab colorimetric spectrometer. Lambs that consumed the commercial feedlot pellet had a lower muscle vitamin E level (< 0.01) and a greater level of -6 PUFA ( < 0.001) compared with lambs finished on annual ryegrass or lucerne. Lipid oxidation levels were greatest for lambs finished on the feedlot ration, lowest in lambs finished on the ryegrass diet, and intermediate for lambs finished on lucerne and ryegrass-feedlot combination ( < 0.01). After 8 wk of feeding, blood isoprostane concentration was positively correlated with lipid oxidation of meat displayed for 72 h in simulated retail conditions ( < 0.01). There was a negative linear relationship between isoprostane concentration and muscle vitamin E concentration ( = 0.07), lipid oxidation and muscle vitamin E concentration ( < 0.01) but a positive linear relationship between isoprostane concentration and muscle -6 PUFA ( < 0.001) or lipid oxidation and muscle -6 PUFA concentration ( < 0.001). Blood isoprostane concentration and lipid oxidation in meat were influenced by muscle vitamin E and -6 PUFA but not by -3 PUFA. There was no significant relationship observed between blood isoprostane concentration at 0, 4, 6 or 8 wk feeding vs. overall meat color (redness of meat) at 0 and 72 h of display, stored under simulated retail conditions. The results indicate that circulating blood isoprostane concentration can be a useful tool to predict the oxidative status of postmortem meat. Future work will examine the impact of this relationship on meat flavor/aroma deterioration post farm.


Idiopathic cardiomyopathies in Korean children. - 9-Year Korean Multicenter Study-.
Idiopathic cardiomyopathies (CMPs) are an important heterogeneous group of diseases. With the advance of therapeutic strategies, epidemiologic data on CMP have become very important, but only a few have been reported in Asian children. We conducted a retrospective epidemiologic study of primary CMP in Korean children. Using a multicenter survey, we studied primary CMP among Korean children from January 1998 to December 2006 based on classification (2006) of CMP by the American Heart Association. A total of 277 primary CMP patients were reported from 17 cardiovascular centers. The average annual occurrence of new cases of primary CMP was 0.28 per 100,000 Korean children younger than 15 years of age (95% confidence interval (CI) 0.24-0.31). Dilated CMP (DCMP) was 66.43%, hypertrophic CMP (HCMP) 23.47%, restrictive CMP (RCMP) 6.50% and others 3.61%. The point prevalence of primary CMP at the end of the study was estimated as 2.11/100,000 (95%CI 1.83-2.43), DCMP 1.39/100,000, HCMP 0.51/100,000, RCMP 0.16/100,000 and others 0.04/100,000. Survival rates over 9 years were 69.8% in DCMP, 90.3% in HCMP, and 47.2% in RCMP. Recent point prevalence of childhood primary CMP in Korea was estimated as 2.11/100,000. Further epidemiologic study with a nationwide survey is necessary.


Approaches to studying cellular signaling: a primer for morphologists.
Many research projects will lead to understanding tissue and/or cell responses to extracellular influences either from soluble factors or the surrounding extracellular matrix. These types of investigations will require the understanding of signal transduction. This particular cell biological field has literally exploded with information and new technical approaches in the past 10 years. This article is directed toward investigators interested in using these new approaches to study their systems. An overview of the general principles of signal transduction events including the types of receptors and intracellular signaling events is followed by an introduction to methods for visualizing signal transduction. This is followed by an introduction to biochemical analysis and an example of combining several approaches to understanding a tissue response to extracellular matrix stimulus.


Anesthetic management for carbon dioxide laser surgery of the larynx.
Fifty-one patients underwent 71 carbon dioxide laser procedures under general anesthesia for various intralaryngeal pathology. Anesthesia was induced with thiopental sodium, followed by succinylcholine to facilitate endotracheal intubation. For maintenance of anesthesia, 70% nitrous oxide was supplemented with halothane, enflurane or small doses of fentanyl. Succinylcholine, d-tubocurare or pancuronium were used to maintain muscular relaxation of jaw, pharyngeal and laryngeal muscles for a smooth lasing procedure. Small diameter (16-22 Fr.), red rubber, cuffed endotracheal tubes provided maximum working space, facilitated the controlled ventilation and reduced the explosion hazard of the anesthetic gases. Safely eyeglasses were used by all the personnel in the operating room against accidental injury to the cornea by the laser beam. Anesthetic management provided excellent operative conditions with maximum safety to the patient and the personnel in the operating room.


Vitamin A losses to plastic intravenous infusion devices and an improved method of delivery.
This study was designed to reevaluate the kinetics of vitamin A losses in the plastic intravenous infusion system used clinically in premature infants and to attempt to establish an improved method of delivery that would avoid significant and unpredictable losses. The losses of retinol, retinyl acetate, and retinyl palmitate were assessed in the presence of various concentrations of the emulsifier Tween 20. For a period of more than 24 h and at a concentration of 0.0085% Tween 20, retinol and retinyl acetate were delivered at 17.4 and 33.9% of the originally intended dose, respectively, while retinyl palmitate was at 100%. At 1% Tween 20, retinyl acetate was completely delivered but even at 2% Tween 20 only 51% of the retinol was delivered. The data suggest that predictable infusions of vitamin A may be attained by using retinyl palmitate rather than retinol in multivitamin preparations.


Suppression of Low-Frequency Electronic Noise in Polymer Nanowire Field-Effect Transistors.
The authors report on the reduction of low-frequency noise in semiconductor polymer nanowires with respect to thin-films made of the same organic material. Flicker noise is experimentally investigated in polymer nanowires in the range of 10-10(5) Hz by means of field-effect transistor architectures. The noise in the devices is well described by the Hooge empirical model and exhibits an average Hooge constant, which describes the current power spectral density of fluctuations, suppressed by 1-2 orders of magnitude compared to thin-film devices. To explain the Hooge constant reduction, a resistor network model is developed, in which the organic semiconducting nanostructures or films are depicted through a two-dimensional network of resistors with a square-lattice structure, accounting for the different anisotropy and degree of structural disorder of the active nanowires and films. Results from modeling agree well with experimental findings. These results support enhanced structural order through size-confinement in organic nanostructures as effective route to improve the noise performance in polymer electronic devices.


Long noncoding RNA LINC00511 promoted cell proliferation and invasion via regulating miR-124-3p/EZH2 pathway in gastric cancer.
Growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for survival in patients with gastric cancer (GC). In this study, we mainly focused on the potential roles of LINC00511 in the development process of GC. RT-PCR was used to detect the expressions of LINC00511 and miR-124-3p in GC tumor tissues, adjacent tissues and GC cell lines. Furthermore, correlations between LINC00511 with miR-124-3p, and miR-124-3p with EZH2, were analyzed by Correlation analysis. Moreover, the overall survival (OS) of patients was analyzed using Kaplan-Meier method. Additionally, proliferation ability was measured by CCK-8 assay and invasion ability of GC cell line was detected by transwell assay. Besides, Western blot was performed to measure protein levels of GC tissues and GC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between LINC00511 and miR-124-3p, miR-124-3p and EZH2. We found that LINC00511 was significantly increased in GC tissues and GC cell lines, which was associated with tumor growth, metastasis and predicted poor diagnosis of GC patients. MiR-124-3p was decreased in GC tissues and GC cell lines, which was negatively correlated with LINC00511 and EZH2. Furthermore, EZH2 was increased in GC tissues and GC cell lines, which was positively correlated with LINC00511. Moreover, LINC00511 inhibition repressed cell proliferation and invasion in MKN28 cells, the protein levels of Cyclin D1, ICAM-1, VCAM-1 and N-cadherin were repressed, while E-cadherin was increased. Besides, Luciferase gene reporter assay indicated that LINC00511 could sponge with miR-124-3p, which could directly target at EZH2, an oncogenic gene. We found that miR-124-3p/EZH2 axis regulated cell proliferation and invasion in MKN28 cells. Finally, the inhibited cell proliferation and invasion abilities were eliminated following with miR-124-3p inhibition in MKN28 cells with LINC00511 knockdown. According to the results, we found that LINC00511 was increased in GC tissues, which was associated with the poor OS in patients with GC. We uncovered a previously unappreciated LINC00511/miR-124-3p/EZH2 signaling axis in promoting cell proliferation and invasion in GC patients and GC cell lines, which suggested that it might be a potential target for treating human GC.


Splanchnectopia Accompanied With Atrial Septal Defect: A Case Report.
Splanchnetopia accompanied with atrial septal defect is a rare congenital malformation clinically. Recent studies show that the patients are susceptible to lung disease. We present a case of a 62-year-old man who presented to our hospital with cough, palpitation and short of breath after activity. On physical examination, we found cyanosis of lips and face, swollen jugular vein, bubble sounds at the lung bottom, irregular heart rhythm, the large liver under the left rib and the lower limbs edema. Laboratory studies revealed white blood cell 18.6 × 109/L and neutrophils 73.9%. Electrocardiogram showed disappearance of P wave and substituted F wave with irregular R-R interval. Ultrasound cardiogram indicated that there was a 24 mm-long gap in the middle of the atrial septal. Dextrocardia, pulmonary artery extrudes and infection of lung were found by chest x-ray. The abdomen ultrasound indicated organ flip. Clinical diagnosis was congenital heart disease, splanchnectopia, atrial septal defect, Eisenmenger's syndrome, atrial flutter, cardiac function class III and pneumonia. The patient left hospital after 2-week treatment. Its clinical significance is when the thoracic and celiac organs are ill, the position of the symptoms and physical signs are contrary to the normal place. Therefore, we should make a careful and systematic examination of the patients in order to avoid misdiagnosis and delay in treatment.


Novel crystalloid structures in suprasellar paraganglioma.
A-52-year-old woman was admitted to a hospital because of 2-year history of abnormal behavior and impaired visual acuity. Magnetic resonance imaging delineated a sizable mass at the suprasellar region. The partially removed tumor was arranged in irregular lobules composed of an admixture of clusters of cobblestone-like small cells and process-bearing cells with ovoid nuclei, surrounded by a fine, neuropil-like matrix. The Zellballen structure was inconspicuous, and mitosis was absent. Immunohistochemically, the tumor cells were positive for chromogranin A, synaptophysin, class III beta-tubulin and neurofilament, while negative for glial fibrillary acidic protein, cytokeratin and all 6 pituitary hormones. S100 protein expression was limited to cells adjacent to stroma. The MIB-1 labeling index was 0.5%. Histopathological diagnosis was paraganglioma of abortive architecture. Ultrastructurally, numerous dense-cored vesicles were found within the processes and cytoplasm. Synapse formation was not demonstrated. Interestingly, crystalloids up to 3 microm in size were frequently found. They had hexagonal or quadrilateral architecture without limiting membranes. The interval between periodically arranged fibrils was variable, ranging from approximately 20 - 50 nm. Retrospective examination by light microscopy failed to reveal corresponding structures. Crystalloids are rare manifestation of paragangliomas, yet undescribed in those of intracranial origin. Furthermore, the ultrastructure of the present case differs from those of previous cases.


Precise optical modeling for silicate-based white LEDs.
In this paper, as to our best knowledge, we propose and demonstrate the first precise phosphor modeling scheme to simulate the chromatic performance of white LEDs with silicate phosphors. The phosphor model is useful to accurately simulate the power ratio of the blue and yellow lights emitted by the white LEDs and is important in white LED package.


A novel beta-lactam antibiotic activates tumor cell apoptotic program by inducing DNA damage.
Many of the anticancer drugs in current use are toxic and thus limited in their efficacy. It therefore becomes essential to develop novel chemotherapeutic agents with lower levels of toxicity. The beta-lactam antibiotics have been used for many years to treat bacterial infections with limited or no toxicity. Until now, it has never been shown that beta-lactams could kill tumor cells. Here, for the first time, we have discovered and characterized the apoptosis-inducing properties of a family of novel beta-lactam antibiotics against human leukemia, breast, prostate, and head-and-neck cancer cells. We found that one particular lead compound (lactam 1) with an N-methylthio group was able to induce DNA damage and inhibit DNA replication in Jurkat T cells within a 2-h treatment. This was followed by p38 mitogen-activated protein kinase activation, S phase arrest, and apoptotic cell death. p38 was found to be a central player in beta-lactam-induced apoptosis and resided downstream of DNA damage but upstream of caspase activation. Accompanying caspase-8 activation was cleavage of the pro-apoptotic Bcl-2 family protein Bid, and release of the mitochondrial cytochrome c. This was also associated with activation of caspase-9 and -3. Analogs of lactam 1 in which the N-methylthio group was replaced with other organothio chains exhibited progressive decreased potencies to induce DNA damage, p38 kinase activation, S phase arrest, and apoptosis, demonstrating requirement of the N-methylthio group. Because of the ease of synthesis and structural manipulation, we believe these beta-lactams may have the potential to be developed into anticancer agents.


Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact.
Murine gammaherpesvirus-68 (MHV-68), a natural pathogen of mice, is being evaluated as a model of Epstein Barr Virus (EBV) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. Immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. Prior to examination of MHV-68 as a suitable model for EBV, better characterization of the MHV-68 model was desirable. Characterization of the MHV-68 model involved development of assays for detecting virus and for demonstration of safety when present in murine colonies. Limited information is available in the literature regarding MHV-68 transmission, although recent reports indicate the virus is not horizontally spread in research facilities. To further determine transmission potential, immunocompetent and immunodeficient mice were infected with MHV-68 and co-habitated with naïve animals. Molecular pathology assays were developed to characterize the MHV-68 model and to determine viral transmission. Horizontal transmission of virus was not observed from infected animals to naïve cagemates after fluorescence microscopy assays and quantitative PCR (qPCR). Serologic analysis complemented these studies and was used as a method of monitoring infection amongst murine colonies. Overall, these findings demonstrate that MHV-68 infection can be controlled and monitored in murine research facilities, and the potential for unintentional infection is low.


Unusual involvement of IgG4-related sclerosing disease in lacrimal and submandibular glands and extraocular muscles.
Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject.


2-Iminobiotin Superimposed on Hypothermia Protects Human Neuronal Cells from Hypoxia-Induced Cell Damage: An in Vitro Study.
Perinatal asphyxia represents one of the major causes of neonatal morbidity and mortality. Hypothermia is currently the only established treatment for hypoxic-ischemic encephalopathy (HIE), but additional pharmacological strategies are being explored to further reduce the damage after perinatal asphyxia. The aim of this study was to evaluate whether 2-iminobiotin (2-IB) superimposed on hypothermia has the potential to attenuate hypoxia-induced injury of neuronal cells. In vitro hypoxia was induced for 7 h in neuronal IMR-32 cell cultures. Afterwards, all cultures were subjected to 25 h of hypothermia (33.5°C), and incubated with vehicle or 2-IB (10, 30, 50, 100, and 300 ng/ml). Cell morphology was evaluated by brightfield microscopy. Cell damage was analyzed by LDH assays. Production of reactive oxygen species (ROS) was measured using fluorometric assays. Western blotting for PARP, Caspase-3, and the phosphorylated forms of akt and erk1/2 was conducted. To evaluate early apoptotic events and signaling, cell protein was isolated 4 h post-hypoxia and human apoptosis proteome profiler arrays were performed. Twenty-five hour after the hypoxic insult, clear morphological signs of cell damage were visible and significant LDH release as well as ROS production were observed even under hypothermic conditions. Post-hypoxic application of 2-IB (10 and 30 ng/ml) reduced the hypoxia-induced LDH release but not ROS production. Phosphorylation of erk1/2 was significantly increased after hypoxia, while phosphorylation of akt, protein expression of Caspase-3 and cleavage of PARP were only slightly increased. Addition of 2-IB did not affect any of the investigated proteins. Apoptosis proteome profiler arrays performed with cellular protein obtained 4 h after hypoxia revealed that post-hypoxic application of 2-IB resulted in a ≥ 25% down regulation of 10/35 apoptosis-related proteins: Bad, Bax, Bcl-2, cleaved Caspase-3, TRAILR1, TRAILR2, PON2, p21, p27, and phospho Rad17. In summary, addition of 2-IB during hypothermia is able to attenuate hypoxia-induced neuronal cell damage in vitro. Combination treatment of hypothermia with 2-IB could be a promising strategy to reduce hypoxia-induced neuronal cell damage and should be considered in further animal and clinical studies.


A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer.
We have studied the forms of prostate-specific antigen (PSA) in serum of patients with prostatic cancer and benign prostatic hyperplasia. Fractionation of serum by gel filtration and assay of the fractions for PSA showed that a considerable part of the PSA immunoreactivity in serum consisted of complexes that were larger than PSA. The complexes were assayed by time-resolved immunofluorometric assays based on an antibody against PSA on the solid phase and europium-labeled antibodies against various protease inhibitors as indicator antibodies. In addition to its monomeric form, PSA was found to occur in complex with alpha 1-antichymotrypsin. The proportion of the alpha 1-antichymotrypsin complex was a major form of PSA and it increased with increasing PSA concentrations, being over 85% at PSA levels exceeding 1000 micrograms/liter. A complex with alpha 1-protease inhibitor was also observed in serum of patients with prostatic cancer and very high levels of PSA. Complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor were detected, but their concentrations were low and similar in sera of cancer patients, normal men, and normal women, suggesting that they were not prostate derived. Commercial immunoradiometric assays for PSA were found to measure free PSA and its complexes with alpha 1-antichymotrypsin but not the complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor. The proportion of the PSA-alpha 1-antichymotrypsin complex was higher in patients with prostatic cancer than in those with benign hyperplasia. Therefore, assay of the complex had a higher sensitivity for cancer than assay of total PSA immunoreactivity.


Elevated plasma prolactin in abstinent methamphetamine-dependent subjects.
Methamphetamine (MA) use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have, however, not been studied before in MA-dependent human subjects. To determine if MA-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D(2) receptor availability during early abstinence from MA. MA-dependent subjects (N = 31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [(18)F]fallypride was performed to determine dopamine D(2) receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N = 23) participated as a comparison group. MA-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D(2) receptor availability. MA-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D(2) receptor availability. MA dependence is associated with elevated prolactin levels, which may contribute to medical comorbidity in afflicted individuals.


[Children with a specific weakness in mathematics in a referred population].
In the present study children with dycalculia were described and compared with children with specific reading and spelling disabilities and children without clinical diagnosis. All children were referred to a child psychiatric outpatient and inpatient department. The comparison was carried out over clinical data drawn from the general data documentation and from written case reports including diagnostical, anamnestical, symptomatological and developmental neurological data. More than 50% of the dyscalculic children displayed other child psychiatric disorders, especially emotional disorders. It is questioned in the light of developmental psychological understanding if the developmental neurological deficits of the dyscalculic children can be seen as etiological significant in the sense of basical disorders concerning the deficient development of stable conceptions of an inner number space.


A PCB Electronic Components Detection Network Design Based on Effective Receptive Field Size and Anchor Size Matching.
Vision-based recognizing and positioning of electronic components on the PCB (printed circuit board) can improve the quality inspection efficiency of electronic products in the manufacturing process. With the improvement of the design and the production process, the electronic components on the PCB show the characteristics of small sizes and similar appearances, which brings challenges to visual object detection. This paper designs a real-time electronic component detection network through effective receptive field size and anchor size matching in YOLOv3. We make contributions in the following three aspects: (1) realizing the calculation and visualization of the effective receptive field size of the different depth layers of the CNN (convolutional neural network) based on gradient backpropagation; (2) proposing a modular YOLOv3 composition strategy that can be added and removed; and (3) designing a lightweight and efficient detection network by effective receptive field size and anchor size matching algorithm. Compared with the Faster-RCNN (regions with convolutional neural network) features, SSD (single-shot multibox detectors), and original YOLOv3, our method not only has the highest detection mAP (mean average precision) on the PCB electronic component dataset, which is 95.03%, the smallest parameter size of the memory, about 1/3 of the original YOLOv3 parameter amount, but also the second-best performance on FLOPs (floating point operations).


Research Progress of Polymer Biomaterials as Scaffolds for Corneal Endothelium Tissue Engineering.
Nowadays, treating corneal diseases arising from injury to the corneal endothelium necessitates donor tissue, but these corneas are extremely scarce. As a result, researchers are dedicating significant efforts to exploring alternative approaches that do not rely on donor tissues. Among these, creating a tissue-engineered scaffold on which corneal endothelial cells can be transplanted holds particular fascination. Numerous functional materials, encompassing natural, semi-synthetic, and synthetic polymers, have already been studied in this regard. In this review, we present a comprehensive overview of recent advancements in using polymer biomaterials as scaffolds for corneal endothelium tissue engineering. Initially, we analyze and present the key properties necessary for an effective corneal endothelial implant utilizing polymer biomaterials. Subsequently, we focus on various emerging biomaterials as scaffolds for corneal endothelium tissue engineering. We discuss their modifications (including natural and synthetic composites) and analyze the effect of micro- and nano-topological morphology on corneal endothelial scaffolds. Lastly, we highlight the challenges and prospects of these materials in corneal endothelium tissue engineering.


Redesigning and teaching veterinary microbiology laboratory exercises with combined on-site and online participation during the COVID-19 pandemic.
The COVID-19 (coronavirus disease 2019) pandemic has forced universities to find new ways to conduct learning and teaching, as traditional face-to-face teaching has been prevented or restricted to an absolute minimum in many instances. Therefore, we redesigned and taught second-year veterinary student microbiology laboratory exercises (labs) with a hybrid learning approach. For this, a novel 'remote partner' model was implemented in which students present on-site in the laboratory worked synchronously pairwise with their remote partner present online. A student feedback survey revealed that in this remote partner model, both on-site and online participation in the labs were experienced as being useful in improving their laboratory skills. The students' overall performance in hands-on microbiological laboratory skills and safe working practices was similar in the hybrid learning approach (the 2021 class) and in the traditional on-site participation approach (the 2018-20 classes). This study suggests that the remote partner model is an effective way to acquire microbiological laboratory skills. This learning approach can be used in the non-pandemic future and/or also be applied to other fields.


Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid Beta peptide in traumatic axonal injury.
Immunohistochemical studies demonstrate accumulation of the beta-amyloid precursor protein (APP) within injured axons following traumatic brain injury (TBI). Despite such descriptions, little is known about the ultimate fate of accumulating APP at sites of traumatic axonal injury (TAI). Recently, caspase-3-mediated cleavage of APP and subsequent Abeta deposition was linked to apoptotic neuronal death pathways in hippocampal neurons following ischemic and excitotoxic brain injury. Given that (1) APP is known to accumulate within traumatically injured axons, (2) caspase-3 activation has been demonstrated in traumatic axonal injury (TAI), and (3) recent studies have identified a caspase-3 cleavage site within APP, we initiated the current investigation to determine whether caspase-3-mediated cleavage of APP occurs in TAI. We further assessed whether these events were found in relation to Abeta peptide formation. To this end, we employed antibodies targeting APP, the caspase-3-mediated breakdown product of APP proteolysis, and the Abeta peptide. Rats were subjected to impact acceleration TBI (6 h to 10 days survival), and their brains were processed for single-label bright field and multiple double-label immunofluorescent paradigms using the above antibodies. By 12 h postinjury, caspase-3-mediated APP proteolysis (CMAP) was demonstrated within the medial lemniscus (ML) and medial longitudinal fasciculus (MLF) in axons undergoing TAI, identified by their concomitant APP accumulation. Immunoreactivity for CMAP persisted up to 48 h postinjury in the ML and MLF, but was notably reduced by 10 days following injury. Further, CMAP was colocalized with Abeta formation in foci of TAI. The current study demonstrates that caspase-3 cleavage of APP occurs in TAI and is associated with formation of Abeta peptide. These findings are of interest given recent epidemiological studies supporting an association between TBI and later risk for AD development.


A comparison of MMPI profiles of heroin addicts based on multiple methods of classification.
MMPI profiles of 442 male narcotic addicts in a drug treatment program were classified according to one of three methods: (a) highest 2-point code, (b) cluster analysis, and (c) concordance with common actuarial rules of profile fit. Profiles were then compared with those previously reported in the research literature. While each method resulted in slightly different perspectives, each reported modal profiles analogous to the 49'/94', 42'/24', and 48'/84' profiles. A frequency table of 33 different profiles by rates per thousand were presented as prototypal base rates for future comparison.


[Risk factors for bacterial vaginosis - a 3-year study in four medical centers].
Bacterial vaginosis (BV) is the most common infection of the lower genital tract among women of reproductive age. The purpose of this study was to determine the frequency of BV and the important etiological agent Gardnerella vaginalis in Bulgarian patients of different age groups, as well as, the risk factors forBV METHODS: One thousand five hundred and twenty-three (1523) women aged 16 to 45 years without previous antimicrobial therapy were included in this study. The methods used were: scoring of Gram staining of vaginal smear and polymerase chain reaction (PCR) assay for G. vaginalis. Positive for BV according to the microscopic examination criteria were 47.80% from the 1523 tested women. In 88.87% from the positive samples G. vaginalis was detected using PCR, thus demonstrating high comparability of the both methods and the leading role of G. vaginalis. The most affected with BV is the age group of 21-25 years (33.21% of all subjects with BV). The most important detected risk factors were: smoking (more than 55% with BV), single marital status (only 15% with BV are married), more than I sexual partner (more than 36% had changed the sexual partner), early onset of sexual activity (75% of B V asocciated subjects started their sexual activity by the age 15-18 years). The established early age for aquiring BV among Bulgarian women is very important and alarming sign. This is the first study on the etiological role of G. vaginalis and on the risk factors for BV in Bulgaria.


How to translate nursing care into costs and staffing requirements: part two in the Zebra system.
The purpose of this paper is to describe part two of the Zebra system-the activity study: how such a study can be conducted, which requirements must be met and how the data are processed and can be used. The activity studies described were conducted in two of the wards of the oncology department in the University Hospital of Lund, Sweden. The results of the studies make it possible to calculate the distribution of different activities for nurses and practical nurses during 24 hours and the total nursing care minutes per patient and category of care. Together with the patient classification, part one in the Zebra system, it is possible to calculate nursing costs per patient stay and the patients'staffing requirements. It will be possible to relate nursing costs and staffing requirements to actual nursing care given instead of fixed standard costs and staffing figures.


Interpretation of hormone levels in older patients: points for consideration.
Blood hormone and tumor marker concentrations are usually determined by immunochemical methods which are based on an unique reaction between antigen and assay capture antibody. Despite the speed and simplicity of assays performance on automatic immunochemistry platforms, the interpretation of final results requires a deep knowledge of method fallibility. General lack of immunoassays standardization, presence of cross-reacting substances in patient's sample, limitation of free hormones measurement due to abnormal analyte binding protein concentrations, assay interferences due to patient's autoantibodies, and heterophilic antibodies, as well as proper interpretation of very low- and very high-sample analyte levels, are the main points discussed in respect to hormones and tumor markers measurement in geriatric population.


Symptom management during the radiation oncology treatment course: a practical guide for the oncology clinician.
Symptom management during radiation therapy is critical to providing high-quality care for patients receiving treatment. Symptoms are varied and dependent on the site irradiated. Common symptoms associated with radiation therapy include dermatitis, xerostomia, mucositis, and pneumonitis. Treatment strategies include prevention, anticipation, and development of clinical practice enabling rapid identification and management of emerging symptoms. Understanding the spectrum of symptomatology affecting irradiated patients is integral to improved quality of life and treatment efficacy.


Impact of the evolution in health care delivery on the academic medical center.
The academic medical center is currently being affected by major changes in the national health care delivery system. These changes include the rapid growth in prepaid health plans, the emerging surplus of physicians, and the continued escalation of health care costs. The potential effects of these changes are only now becoming appreciated and may have significant ramifications for the entire medical education system. In this article, the author traces the impact of these changes on one major academic medical center. He presents a methodology for pinpointing other centers that may soon be affected and discusses ways to minimize the undesirable consequences of these changes.


The Inflammatory Contribution of B-Lymphocytes and Neutrophils in Progression to Osteoporosis.
Osteoporosis is a bone disease characterized by structural deterioration and low bone mass, leading to fractures and significant health complications. In this review, we summarize the mechanisms by which B-lymphocytes and neutrophils contribute to the development of osteoporosis and potential therapeutics targeting these immune mediators to reduce the proinflammatory milieu. B-lymphocytes-typically appreciated for their canonical role in adaptive, humoral immunity-have emerged as critical regulators of bone remodeling. B-lymphocytes communicate with osteoclasts and osteoblasts through various cytokines, including IL-7, RANK, and OPG. In inflammatory conditions, B-lymphocytes promote osteoclast activation and differentiation. However, B-lymphocytes also possess immunomodulatory properties, with regulatory B-lymphocytes (Bregs) secreting TGF-β1 to restrain pathogenic osteoclastogenesis. Neutrophils, the body's most prevalent leukocyte, also contribute to the proinflammatory environment that leads to osteoporotic bone remodeling. In aged individuals, neutrophils display reduced chemotaxis, phagocytosis, and apoptosis. Understanding the delicate interplay between B-lymphocytes and neutrophils in the context of impaired bone metabolism is crucial for targeted therapies for osteoporosis.


Liposomal adhesion via electrostatic interactions and osmotic deflation increase membrane tension and lipid diffusion coefficient.
Membrane adhesion is a ubiquitous phenomenon in cells and is related to various biological events such as migration, morphogenesis, and differentiation. To understand the physicochemical aspects of membrane adhesion, liposome-liposome adhesion and liposome-substrate adhesion have been studied. Although membrane adhesion has been shown to increase membrane tension and inhibit lipid diffusion, the relationship between these changes and the degree of membrane adhesion have not been quantified. Here, we analyzed the dependence of membrane tension and lipid diffusion on the degree of membrane adhesion, i.e., area fraction of the adherent region. For this purpose, we developed a simple method to prepare adhered liposomes by simple electrostatic interactions between the membranes and by osmotic deflation. We found that the membrane tension of the adhered liposomes increases slightly with an increase in the area fraction of the adherent region. In addition, the lipid diffusion coefficient of the adhered liposomes is larger than that of isolated liposomes, which is consistent with the theoretical prediction. The analysis provides a framework to understand the correlation between cell adhesion and bio-membrane properties such as membrane tension and molecular diffusion.


Haemophagocytic lymphohistiocytosis after heart transplantation: a case report.
Haemophagocytic lymphohistiocytosis (HLH) is an uncommon but serious systemic inflammatory response with high mortality rates. It can be triggered by malignancy or infectious agents, often in the context of immunosuppression. Literature covering HLH in heart transplantation (HTx) is scarce. A 25-year-old male with a history of celiac disease underwent HTx at Sahlgrenska Hospital in 2011 due to giant cell myocarditis and was treated with tacrolimus, mycophenolate mofetil (MMF), and prednisolone. He developed several episodes of acute cellular rejections (ACR) during the first 3 post-HTx years, which subsided after addition of everolimus. In May 2017, the patient was admitted to the hospital due to fever without focal symptoms. He had an extensive inflammatory reaction, but screening for infectious agents was negative. Haemophagocytic lymphohistiocytosis was discussed early, but first dismissed since two bone marrow biopsies revealed no signs of haemophagocytosis. Increasing levels of soluble IL-2 were considered confirmative of the diagnosis. Even with intense immunosuppressant treatment, the patient deteriorated and died in progressive multiorgan failure within 2 weeks of the symptom onset. A 25-year-old HTx recipient with an extensive inflammatory response, fulfilled criteria for HLH, but the diagnosis was delayed due to normal bone marrow biopsies. A background with autoimmune reactivity and immunosuppressive therapy may have contributed to HLH, but the actual trigger was not identified. Haemophagocytic lymphohistiocytosis can occur in HTx recipients in the absence of malignancy, identifiable infectious triggers and signs of haemophagocytosis. Early diagnosis and intervention are likely to be of importance for a favourable outcome.


Practical considerations in the evaluation and management of adrenocortical cancer.
Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and management of ACC. We conclude that the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) remains unclear and that it should be employed sparingly. Biopsies should be performed only when metastatic disease is present and a primary tumor has not been clearly established. Care should be taken in using the Weiss criteria to make decisions regarding prognosis. Surgery is the preferred intervention initially and at the time of recurrence, and every effort should be made to attempt a surgical resection. The latter should be an open resection; laparoscopic resection should not be performed if there is a high suspicion of ACC. The use of mitotane in patients without evidence of disease remains controversial. Systemic chemotherapy is effective in patients with widely metastatic disease or as an adjunct to a surgical intervention and should focus on regimens that have been shown to effect responses; "novel targeted therapies" should not be employed as first-line treatment. Radiofrequency ablation (RFA) and cryoablation can be very helpful but are still under evaluation; embolization with or without chemotherapy may be used as a surgical adjunct. The role of radiation remains to be defined. Finally, physicians caring for these patients need to recognize that Cushing's disease is a debilitating problem that should be managed aggressively; expecting chemotherapy to solve this complication is not appropriate.


Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.
To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.


Knockdown of CHCHD2 inhibits migration and angiogenesis of human renal cell carcinoma: A potential molecular marker for treatment of RCC.
Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), a novel cell migration determinant, is able to co-express with other genes of the oxidative phosphorylation pathway by using a computational expression screening technique. However, little is known about the expression and biological function of CHCHD2 in human renal cell carcinoma (RCC). Western blotting was performed to detect CHCHD2 expression levels in normal renal cells and carcinoma cells. Immunohistochemistry was performed to detect an association between CHCHD2 expression and clinicopathological parameters in 75 RCC tissues using a tissue microarray. The function of CHCHD2 in the migration and angiogenesis of RCC cells was investigated using Transwell migration and tube formation assays. CHCHD2 expression was markedly increased in human RCC cells. The results of immunohistochemical analysis revealed that CHCHD2 expression was markedly associated with tumor grade (P<0.001). Notably, CHCHD2 knockdown inhibited RCC migration and tube formation of human umbilical vascular endothelial cells. CHCHD2 knockdown further suppressed matrix metalloproteinase-2 protein levels and enzyme activity. An ELISA identified that CHCHD2 knockdown decreased the secretion of vascular endothelial growth factor. The gathered data disclose information on the association of CHCHD2 with migration and angiogenesis of human RCC, and may strengthen the feasibility of targeting CHCHD2 as a potential therapeutic target.


Experimental infection of brown-marbled grouper, Epinephelus fuscoguttatus (Forskal), with Vibrio parahaemolyticus identifies parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain, differentially expressed in resistant grouper.
The mechanisms through which brown-marbled grouper accomplishes resistance to infection, particularly against Vibrios, are not yet fully understood. In this study, brown-marbled grouper fingerlings were experimentally infected with Vibrio parahaemolyticus, to identify disease resistance grouper, and the serum proteome profiles were compared between resistant and susceptible candidates, via two-dimensional gel electrophoresis (2-DE). The results showed that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain proteins were among proteins that significantly overexpressed in the resistant fish as compared to the susceptible group of fish, whereas apolipoprotein E and immunoglobulin light chain proteins were observed to be differentially overexpressed in the susceptible fish. Further analysis by peptide sequencing revealed that the immunoglobulin light chain proteins identified in the resistant and susceptible groups differed in amino acid composition. Taken together, the results demonstrated for the first time that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain are among important proteins participating to effect disease resistance mechanism in fish and were overexpressed to function collectively to resist V. parahaemolyticus infection. Most of these molecules are mediators of immune response.


Population balance models and Monte Carlo simulation for nanoparticle formation in water-in-oil microemulsions: implications for CdS synthesis.
We address controlled CdS nanoparticle formation by tuning experimental synthesis conditions. To this end, a bivariate population balance equation (PBE) model has been developed based on time scale analysis, to explain the mechanism of nanoparticle formation in self-assembled templates. It addresses the process of mixing two water-in-oil (w/o) microemulsions, each containing a pre-dissolved reactant in the microemulsion drops. Brownian collision and coalescence of two water drops of nanometer size results in mixing and exchange of reactant molecules, leading to chemical reaction. The water insoluble reaction product nucleates to form a nanoparticle in an individual drop, which subsequently grows internally by consuming the excess product and by coalescence-exchange with other drops. Finite rates of nucleation and coalescence-exchange are accounted for in the PBE, while the rates of reaction and internal growth of nanoparticles are found to be instantaneous. Experimentally proven binomial redistribution of reactant and product molecules upon drop coalescence is implemented in the present work. This results in a very good prediction of experimental data of the mean aggregate number (MAN) and hence size of CdS nanoparticles. Both our model and Monte Carlo (MC) simulation quantitatively capture the reported variation of MAN with molar excess of Cd2+ concentration and microemulsion drop size. Our results together with previous experimental data establish that usage of stoichiometrically five times or more of excess Cd2+ concentration can cause surface adsorption and desirable enhanced emission intensity of CdS nanoparticles, without altering particle size. We also propose a simplified and computationally efficient univariate PBE model. The univariate model gives very fast (in minutes) and accurate estimates (for low reactant concentrations) of the number and mean size of CdS nanoparticles. Time-scale analysis offers a good a priori choice of the appropriate model based on range of reactant concentrations.


M2-like macrophage polarization in high lactic acid-producing head and neck cancer.
Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro-inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC.


Epidemiology of cancers: I. Cancerous diseases of the large bowel.
A pilot study of cancerous diseases of the large bowel in Canterbury is described. The experience of 346 patients derived from the Cancer Registry for 1970-72 is presented. The feasibility of the method is demonstrated with the identification of guidelines for future work. The preliminary results suggest some special features in New Zealand. While demographic characteristics do not appear to help in defining persons at high risk from cancerous diseases of the large bowel, nevertheless other features of the natural history of this disorder indicate that it might be feasible to define high risk profiles.


Transcriptional expression of type-I interferon response genes and stability of housekeeping genes in the human endometrium and endometriosis.
Endometriosis is a painful chronic female disease defined by the presence of endometrial tissue implants in ectopic (Ec) locations. The pathogenesis is much debated, and type-I interferons (IFNs) could be involved. The expression of genes of the type-I IFN response were profiled by a specific PCR array of RNA obtained from Ec and eutopic (Eu) endometrium collected from nine endometriosis patients and nine healthy control women. Transcriptional expression levels of selected IFN-regulated and housekeeping genes (HKGs) were investigated by real-time quantitative reverse transcriptase PCR (qRT-PCR). Stably expressed HKGs for valid normalization of transcriptional studies of endometrium and endometriosis have not yet been published. Here, seven HKGs were evaluated for stability using the GeNorm and NormFinder software. A normalization factor based on HMBS, TBP and YWHAZ expression was suitable for normalization of qRT-PCR studies of Eu versus Ec endometrium. In the endometrial cell lines HEC1A, HEC1B, Ishikawa and RL95-2, HMBS and HPRT1 were the most stably expressed. The IFN-specific PCR array indicated significantly different expression of the genes BST2, COL16A1, HOXB2 and ISG20 between the endometrial tissue types. However, by correctly normalized qRT-PCR, levels of BST2, COL16A1 and the highly type-I IFN-stimulated genes ISG12A and 6-16 displayed insignificant variations. Conversely, HOXB2 and ISG20 transcriptions were significantly reduced in endometriosis lesions compared with endometrium from endometriosis patients and healthy controls. In conclusion, appropriate HKGs for normalization of qRT-PCR studies of endometrium and endometriosis have been identified here. Abolished expression of ISG20 and HOX genes could be important in endometriosis.


Economically optimal timing for crop disease control under uncertainty: an options approach.
Severe large-scale disease and pest infestations in agricultural regions can cause significant economic damage. Understanding if and when disease control measures should be taken in the presence of risk and uncertainty is a key issue. We develop a framework to examine the economically optimal timing of treatment. The decision to treat should only be undertaken when the benefits exceed the costs by a certain amount and not if they are merely equal to or greater than the costs as standard net-present-value (NPV) analysis suggests. This criterion leads to a reduction in fungicide use. We investigate the effect of the model for disease progress on the value required for immediate treatment by comparing two standard models for disease increase (exponential and logistic growth). Analyses show that the threshold value of benefits required for immediate release of treatment varies significantly with the relative duration of the agricultural season, the intrinsic rate of increase of the disease and the level of uncertainty in disease progression. In comparing the performance of the delay strategy introduced here with the conventional NPV approach, we show how the degree of uncertainty affects the benefits of delaying control.


Design and Manufacturing of a Novel Trabecular Tibial Implant.
The elastic modulus of traditional solid titanium alloy tibial implants is much higher than that of human bones, which can cause stress shielding. Designing them as a porous structure to form a bone-like trabecular structure effectively reduces stress shielding. However, the actual loading conditions of bones in different parts of the human body have not been considered for some trabecular structures, and their mechanical properties have not been considered concerning the personalized differences of other patients. Therefore, based on the elastic modulus of the tibial stem obtained from Quantitative Computed Tomography (QCT) imaging between 3.031 and10.528 GPa, and the load-bearing state of the tibia at the knee joint, a porous structure was designed under compressive and shear loading modes using topology optimization. Through comprehensive analysis of the mechanical and permeability properties of the porous structure, the results show that the Topology Optimization-Shear-2 (TO-S2) structure has the best compressive, shear mechanical properties and permeability and is suitable as a trabecular structure for tibial implants. The Gibson-Ashby model was established to control the mechanical properties of porous titanium alloy. A gradient filling of porous titanium alloy with a strut diameter of 0.106-0.202 mm was performed on the tibial stem based on the elastic modulus range, achieving precise matching of the mechanical properties of tibial implants and closer to the natural structure than uniformly distributed porous structures in human bones. Finally, the new tibial implant was printed by selective laser melting (SLM), and the molding effect was excellent.


Giant haemangioma of the liver: observation or resection?
Haemangiomata are the most frequent benign solid liver lesion. The management of giant (> or =5 cm) haemangiomata of the liver remains controversial. A search of relevant peer-reviewed literature was conducted using PubMed and original articles were reviewed. The vast majority of giant haemangiomata remain asymptomatic and have a benign and uncomplicated natural history. Decisions regarding the optimal management of giant haemangiomata depend on a high level of confidence in diagnostic imaging. Diagnostic biopsy to differentiate giant haemangiomata from malignant lesions should be discouraged. Despite limitations and alternative modalities, surgery remains the only consistently effective curative treatment for giant haemangiomata. Surgery is not generally justified to prevent complications in asymptomatic patients. Principal indications for the surgical management of giant haemangiomata include established complications, incapacitating symptoms and uncertainty of diagnosis. Patients should only be selected for surgery based on a careful assessment of risks and benefits of intervention.