Genomic Characterization of Chicken Anemia Virus in Broilers in Shandong Province, China, 2020-2021.
Chicken infectious anemia (CIA), caused by chicken anemia virus (CAV), is an immunosuppressive disease characterized by growth retardation, aplastic anemia, lymphoid depletion, and immunodepression in young chickens. In this study, 33 CAV strains were isolated from broilers in Shandong Province during 2020-2021. Phylogenetic analysis of full-length genome sequences showed that most CAV strains isolated in this study were scattered across different branches, but mainly clustered in two genotypes, indicating a certain regional characteristic. Analysis of VP1 protein identified several amino acid substitutions which were relevant with the virulence and virus spread efficiency. Interestingly, four putative DNA recombination events were detected in the genomes of novel isolated CAV strains. In summary, this study demonstrated a genomic diversity of CAV in broilers isolated in Shandong Province during 2020-2021, and provided information for the further study of CAV molecular epidemiology and viral evolution.


[Hypnotic pain management during ultrasound-guided infiltration of the hand].
Ultrasound-guided infiltration, performed to relieve pain, is a common and sometimes painful procedure, particularly on the hand. This potential pain, induced by the treatment, can cause apprehension in patients prior to such a procedure. The rheumatology team at the departmental hospital center (CHD) in Vendée hypothesized that a hypnosis session, by creating an imaginary glove on the patient's painful hand prior to the procedure, could help reduce the pain felt, as well as anxiety.


Overview of pharmacotherapy targeting COVID-19 disease based on ACE-2: current challenges and future directions.
The new Severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) triggered the pandemic of COVID-19, which is currently still ongoing. In 2021 a worldwide vaccine campaign was launched, and in parallel the lines of research are continuing to target the most effective drug therapies for the treatment of COVID-19 disease. SARS-CoV‑2 enters host cells via glycoprotein angiotensin-converting enzyme 2 (ACE-2), which plays a major role in renin-angiotensin system interactions and undergoes changes in expression during metabolic and viral diseases, including COVID-19. It seems that the severe lung damage that occurs in several cases of COVID-19 disease may be connected to a deregulated expression of ACE‑2. In this manuscript we focus on the line of research that studies the pharmacological modification of ACE‑2 expression, a promising weapon to counter the severe harms caused by COVID-19.


Ineraid (Utah) multichannel cochlear implants.
For the more than 200,000 individuals in the United States with a bilateral profound sensorineural hearing loss, the cochlear implant offers a means of breaking this barrier of total silence. The pioneers in prosthetic research hoped that direct stimulation of the cochlea might at least give an awareness of sound through the auditory sense. There will be a review of five patients who were consecutively implanted with the Ineraid multichannel cochlear implant, with 1 year follow-up. All individuals were postlingually deafened adults and exhibited a bilateral profound hearing loss.


Promising results of revision total hip arthroplasty using a hexagonal, modular, tapered stem in cases of aseptic loosening.
Modular stems are widely used in revision total hip arthroplasty (THA) with aseptic loosening being a common reason for revision. Despite the good results reported on the use of modular stem designs, there are only few studies focusing on aseptic revisions and few studies on a hexagonal stem design. The goal of this study is to determine stem survival, clinical and functional outcome along with possible risk factors for implant failure in aseptic revision THA. We retrospectively identified 53 patients with aseptic THA revision using a modular hexagonal stem with a minimum follow-up of two years. Femoral bone loss, radiographic and clinical outcomes as well as function measured using the Harris Hip Score (HHS) was assessed. Patients' previous medical history was analyzed for comorbidities and the body mass index. Stem survival was calculated using the Kaplan-Meier method. Possible risk factors for implant failure were analyzed using the log-rank test. The median age at revision was 69 (IQR 62-73) with a median follow up of 74 months. Implant survival rates amounted to 90.4% at 3 and 5 years. The median HHS improved by 47 points (34 (IQR 22-47) vs 81 (IQR 59-90) p<0.001). There was a reduced implant survival after 5 years when the revision stem was used following a previous cemented stem (83.4% vs 100%, p = 0.04). A modular, hexagonal stem can be successfully used in aseptic revision THA with remarkable functional results and excellent survivorship. Revision of a cemented stem using this implant might result in reduced survival which must be considered when planning treatment.


Association of preoperative symptoms of gastric outlet obstruction with delayed gastric emptying after pancreatoduodenectomy.
Delayed gastric emptying (DGE) is among the most common complications after pancreatoduodenectomy (PD) and might demand postoperative nutritional support. The aim of this study was to investigate the association between preoperative symptoms of gastric outlet obstruction and DGE after PD in an attempt to identify patients in whom placement of a feeding tube at time of operation might be beneficial. We analyzed a consecutive series of 401 patients undergoing PD from a prospective database. Preoperative symptoms of nausea, vomiting, loss of appetite, weight loss, postprandial complaints, and dysphagia were retrospectively determined. Primary outcome was clinically relevant DGE according to the International Study Group of Pancreatic Surgery classification and the necessity of postoperative insertion of a nasojejunal feeding tube. The incidence of clinically relevant DGE was 33.2% (133/401 patients). A nasojejunal feeding tube was inserted in 119 patients (29.7%). Patients having ≥2 symptoms of gastric outlet obstruction except weight loss (50 patients; 12.5%), were at a greater risk of developing both DGE (21.1% vs 8.2%; P < .001) and the need for insertion of a feeding tube (21.8% vs 8.5%; P < .001). In multivariable logistic regression analysis, the presence of ≥2 symptoms of gastric outlet obstruction other than weight loss remained a significant predictor of DGE (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.8) and the need for insertion of a nasojejunal feeding tube (OR, 3.1; 95% CI, 1.7-5.7). The preoperative presence of ≥2 symptoms of gastric outlet obstruction is a significant predictor of postoperative DGE after PD. By applying this risk factor, patients in whom placement of a feeding tube during surgery should be considered can be identified.


CT-Guided Pericardiocentesis in a Case of Tension Pneumopericardium and Tamponade Secondary to an Enteropericardial Fistula.
Tension pneumopericardium is most commonly traumatic. Nontraumatic etiologies are rare, but have been reported with gastropericardial and esophagopericardial fistulas. We present the case of a 54-year-old patient who developed a tension pneumopericardium with tamponade secondary to a perforated marginal ulcer in the proximal jejunum with an enteropericardial fistula. (Level of Difficulty: Intermediate.).


Targeted cancer chemotherapy for VX2 tumour implanted in the colon with lipiodol as a carrier.
In this study, we examined the possibility of targeting drug delivery to tumours by dissolving the cytotoxic drug in a lipid fluid that is selectively deposited in tumours. Rabbits bearing VX2 tumour 10-20 mm in diameter in the large bowel received arterial injections of 0.2 ml of mitomycin C (MMC) dissolved in Lipiodol (MMC/Lipiodol), and the antitumour activity and adverse effects were examined. One week after treatment complete necrosis of the tumour was observed in 8 of 10 rabbits that received MMC/Lipiodol (3 mg/ml) without severe adverse effects on the surrounding caecum. In comparison 3/12 control animals that received MMC in saline and Lipiodol also showed complete necrosis. 6 of 7 rabbits killed eight weeks after the injection of MMC/Lipiodol were cured, with no viable tumour cells and with a normal appearance of the surrounding large bowel. In conclusion, MMC dissolved in Lipiodol may be adaptable for the treatment of colon cancer and may achieve antitumour activity without severe adverse effects.


Selection models for repeated measurements with non-random dropout: an illustration of sensitivity.
The outcome-based selection model of Diggle and Kenward for repeated measurements with non-random dropout is applied to a very simple example concerning the occurrence of mastitis in dairy cows, in which the occurrence of mastitis can be modelled as a dropout process. It is shown through sensitivity analysis how the conclusions concerning the dropout mechanism depend crucially on untestable distributional assumptions. This example is exceptional in that from a simple plot of the data two outlying observations can be identified that are the source of the apparent evidence for non-random dropout and also provide an explanation of the behaviour of the sensitivity analysis. It is concluded that a plausible model for the data does not require the assumption of non-random dropout.


A case of a suicide attempt associated with hyperthyroidism.
Hyperthyroidism has profound effects on mental health. The literature is sparse, however, with regard to suicide attempts related to untreated hyperthyroidism. This case report illustrates the presentation of a patient in the intensive care unit after a life-threatening Tylenol overdose presumed to be secondary to adjustment disorder. During the patient's hospitalization, she experienced anxiety, heart palpitations, tachycardia and diaphoresis. The psychiatric consultant, endocrinology consultant and inpatient psychiatry teams helped to diagnose Graves' disease, significantly changing her treatment and trajectory.


Persistent pain in intensive care survivors: a systematic review.
According to earlier studies where the main aim has been quality of life, there is growing evidence of increased levels of persistent pain in survivors of critical illness. The cause of admission and several factors during intensive care may have associated risk factors for pain persistence. This systematic review aims to determine the incidence or prevalence of persistent pain after critical illness and to identify risk factors for it. Six databases were searched, and eventually nine studies were included in the final systematic process. The validity of observational and cross-sectional studies was analysed using the National Institute of Health 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. The incidence of persistent pain after intensive care varied from 28% to 77%. Risk factors for persistent pain were acute pain at discharge from ICU, higher thoracic trauma score, surgery, pre-existing pain, organ failure, longer length of ventilator or hospital stay, and sepsis. No difference in incidence between medical and surgical patients was found. New systematic, observational studies are warranted to identify persistent pain-related factors in intensive care to improve pain management protocols and thereby diminish the risk of persistent pain after ICU stay.


Immunological similarity between the chick oviduct progesterone receptor forms A and B.
A large-scale purification of the progesterone receptor from laying hens is described which yields apparently homogeneous form A and form B receptor in denatured form. The purification procedure is based initially on differential DNA affinity chromatography of both form A and B receptors. Under the conditions of preparation and activation described, progesterone receptor form B binds to DNA-cellulose even in the presence of 100 mM salt. This binding cannot be observed after thermal activation. Receptors obtained at 5% purity using conventional chromatographic purification steps were covalently cross-linked with radioactive ligand by photoaffinity labeling and purified to homogeneity using preparative gel electrophoresis systems under denaturing conditions. This material has been successfully used to generate polyclonal antibodies in rabbits. Immunoblots demonstrated a high degree of cross-reaction between anti-A antibodies and progesterone receptor form B, as well as between anti-B antibodies and progesterone receptor form A, using homogeneous as well as 5% pure receptors as probes. Implications of the immunological data and the novel DNA-binding characteristics of form B are discussed with respect to topological conformation of the progesterone receptor and the structural similarity between forms A and B.


Do patients with chronic heart failure have chest pain?
In questionnaire surveys, patients with chronic heart failure frequently report "pain" as a symptom. We investigated the prevalence of chest pain as a possible cause for pain, particularly in patients with prior myocardial infarction. Questionnaire survey. Community heart failure clinic. 1 786 patients with heart failure due to left ventricular systolic dysfunction (mean ± SD age 70.1 ± 11.0 years; 73% male; left ventricular ejection fraction (LVEF) 35.3 ± 9.9%; 65.6 with underlying ischaemic heart disease (IHD)). Patients with chronic heart failure completed a questionnaire. Answers to the questions: (1) "In the last week, how many days did you get angina chest pain?"; and "In the last month, how much did the following affect you:" (2) "chest pains at rest"; (3) "chest pains during normal activity". 73% of those with IHD, and 84% of those without had had no angina in the previous week; 79% and 82%, respectively, had at most "little" chest pain at rest; 67% and 76%, respectively, had at most "little" chest pain during exertion. Angina increased with NYHA class, but there was no relation between angina and sex of patient, age or LVEF. There was a weak relation between chest pain and an adverse outcome in the patients with ischaemic heart disease. Although pain is commonly reported in patients with chronic heart failure, it seems unlikely that the pain is due to angina, even in patients with underlying coronary heart disease.


Measurement of visual evoked potential during and after periods of pulsed magnetic field exposure.
To study the effect of switched magnetic fields used in MR scanners on the visual evoked potential (VEP) in human subjects. We have used an MRI gradient coil, remote from an MRI magnet to produce a time-varying magnetic field (0.5 kHz, peak field approximately 8.7 T/second) in the human brain without the confounding effects of static field exposure or accompanying acoustic noise. The VEP response to a 2-Hz reversal, 8 x 8 checkerboard, occupying 20 degrees of the visual field was recorded from occipital locations O1 and O2. VEP recordings were made every five minutes before, during, and after a 10-minute magnetic field exposure period for seven subjects. In contradiction to studies previously reported in the literature for fields of 50 Hz and 60 mT, no significant effects on the peak amplitude or latency of the VEP P100 O1 and O2 responses were found. Switched magnetic fields of a level and frequency comparable to those used in MRI do not have a significant effect on primary retinal or visual processing.


Preparation and structural properties of selenium modified heteropolysaccharide from the fruits of Akebia quinata and in vitro and in vivo antitumor activity.
Cancer is a complex disease, and blocking tumor angiogenesis has become one of the most promising approaches in cancer therapy. Here, an exopoly heteropolysaccharide (AQP70-2B) was firstly isolated from Akebia quinata. Monosaccharide composition indicated that the AQP70-2B was composed of rhamnose, glucose, galactose, and arabinose. The backbone of AQP70-2B consisted of →1)-l-Araf, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, →4)-d-Glcp-(1→, →6)-d-Galp-(1→, and →1)-d-Rhap residues. Based on the close relationship between selenium and anti-tumor activity, AQP70-2B was modified with selenium to obtain selenized polysaccharide Se-AQP70-2B. Then, a series of methods for analysis and characterization, especially scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS), indicated that Se-AQP70-2B was successfully synthesized. Furthermore, zebrafish xenografts and anti-angiogenesis experiments indicated that selenization could improve the antitumor activity by inhibiting tumor cell proliferation and migration and blocking angiogenesis.


Gender Differences in Energy Expenditure During Walking With Backpack and Double-Pack Loads.
To investigate gender differences in energy expenditure during walking with backpack and double-pack loads. Studies have reported that energy expenditure during walking with double-pack loads is lower compared with backpack carriage. However, the effect of gender on energy expenditure while walking with these two load distribution systems has not been investigated. Thirty healthy young adults (15 female and 15 male participants) walked on a treadmill with backpack and double-pack loads weighing 30% of their body weight at a speed of 0.89 m/s for 10 min. The energy expenditure in terms of oxygen consumption (VO2) and respiratory exchange ratio (RER) were continuously monitored using a portable gas analyzer throughout each walking exercise. A mixed-design analysis of variance model was adopted to test the effects of gender, pack, and time on VO2 and RER. No time effect was observed on VO2. However, significant gender, pack, and interaction effects were observed. The lowest VO2 was found in female participants under double-pack carriage. No significant gender or pack differences existed in RER. However, RER significantly and incrementally increased in time from the 4th through 6th, 8th, and 10th min. This study revealed that heavy double-pack load carriage for healthy young female participants had significantly lower energy expenditure (normalized by the entire system weight, i.e., the participant's weight plus the weight of the pack) than that of the male participants in a 10-min walking exercise. The findings of this study indicated that healthy young female participants carried a heavy double-pack with less energy cost (normalized by the entire system weight, i.e., the participant's weight plus the weight of the pack) compared with their male counterparts during a 10-min walking exercise.


Electrochemical corrosion behavior and mechanical properties of Ti-Ag biomedical alloys obtained by two powder metallurgy processing routes.
Titanium is frequently used as a biomaterial and the importance of Ti-Ag alloys has increased thanks to the antibacterial behavior of silver. In this study, Ti-Ag alloys (5, 10 and 15 wt% Ag) were obtained by two different powder metallurgy routes: blended elemental (BE) and mechanical alloying (MA). The influence of the powder mixture methodology on both microstructure and electrochemical behavior was analyzed. Powders were compacted at 600 and 900 MPa, respectively, and sintered at high vacuum for 3 h at 950 °C. The obtained Ti-Ag alloys were microstructurally characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS) and X-Ray Diffraction (XRD), and mechanically tested by hardness and bending tests. Electrochemical tests were run using a three-electrode cell in an artificial Fusayama saliva solution. Open-Circuit Potential (OCP), polarization curves, potentiostatic tests and Electrochemical Impedance Spectroscopy (EIS) techniques were employed to evaluate the corrosion resistance of the studied Ti-Ag alloys. The initial characteristics of powders before sintering and after blend/alloying modified the electrochemical behavior of the Ti-Ag-sintered alloys and were determined. The samples obtained with the BE powders better resisted corrosion than the MA samples, and this behavior was directly related to the quantity and distribution of intermetallic Ti2Ag. A large quantity of intermetallics present on both the edge and inside grains reduced the corrosion resistance of TiAg alloys.


A case of squamous cell carcinoma of the scalp after several synthetic hair grafts.
In the early 1970s a novel method for hair restoration was described and gained a large following: hair implantation of artificial synthetic fibers. Though popular, the procedure faced numerous criticisms from the scientific community by the early 1980s, and several major and minor complications in a large number of patients treated were reported. However, there were no reports of any neoplasms as complications of artificial hair implantation. Thus, we report our experience with a novel case of long-term cutaneous neoplastic degeneration of an artificial hair implantation procedure in order to provide new insight on the complications related to this procedure. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266.


Structural analysis of three subunits of laminin from teratocarcinoma-derived parietal endoderm cells.
The structure of the three polypeptide chains of the laminin subunits and the number of glycosylation sites in each polypeptide chain were determined using peptide mapping by high-performance liquid chromatography. Analysis of the [35S]methionine-labeled underglycosylated laminin isolated from tunicamycin (TM)-treated cells revealed that the three subunits of laminin contain unique polypeptide chains. Analysis of [3H]glucosamine-labeled glycosylated laminin subunits showed that they are sialylated and that each subunit has 11-14 glycosylation sites.


[Cardiovascular prevention and rehabilitation].
The distinction between primary and secondary prevention has been abandoned in favor of cardiovascular prevention, mandating individual risk assessment. First, the individual cardiovascular risk of a person is determined by index diseases like myocardial infarction, peripheral arterial disease or other, or, if absent, by a score consisting of a number of conventional risk factors. According to current guidelines, cardiovascular prevention is indicated, as soon as the risk for fatal cardiovascular disease is > or = 5 %, equivalent to a risk for a major cardiovascular event of > or = 20 %. Non-pharmaceutical approaches are: refraining from smoking, mediterranean diet with fatty fish, physical activity and normal body weight. Blood pressure and diabetes mellitus are optimized. In addition, the following agents are used: platelet inhibitors, beta-blockers, ACE-inhibitors, statins and omega-3 fatty acids. A number of structural problems add to individual factors impeding optimal implementation of cardiovascular prevention in Germany.


Amiodarone-Induced Life-Threatening Refractory Hypotension.
Amiodarone is frequently used in emergency departments for treatment of arrhythmias. Incidence of several amiodarone-related adverse events is unknown. The literature is sparse for potentially life-threatening adverse effects of amiodarone. We present a case of a male patient who presented with chest discomfort and rapid atrial fibrillation. He was known to have paroxysmal atrial fibrillation, which did not respond to initial beta-blocker treatment. The second-line drug amiodarone was given to the patient for rate control. He developed severe hypotension related to amiodarone and required inotropic support along with rapid-sequence intubation. Intravenous amiodarone can cause severe and refractory hypotension.


Sex differences in femoral deformity determined using three-dimensional assessment for osteoarthritic knees.
To characterize femoral deformities and determine sex differences in varus knee osteoarthritis (OA), femoral morphology and limb alignment were evaluated by using three-dimensional (3D) assessment, comparing healthy, elderly volunteers with osteoarthritic knees. A total of 178 lower limbs of 169 subjects with knee osteoarthritis (136 women, 33 men; mean age 74.9 ± 5.2 years) and 80 lower limbs of 45 healthy, elderly subjects (24 women, 21 men; mean age 65 ± 4.9 years) were examined. A 3D extremity alignment assessment system was used to examine the subjects under weight-bearing conditions on biplanar long-leg radiographs using a 3D-to-2D image registration technique. The evaluation parameters were (1) femoral bowing in the coronal plane, (2) femoral bowing in the sagittal plane, (3) femoral neck anteversion, (4) hip-knee-ankle angle, and (5) femoral torsion. Higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis were observed in women with OA compared with healthy subjects. No difference in the higher varus malalignment, no alteration in the femoral anterior bowing, and no difference in the lower femoral neck anteversion were found between men and women when comparing healthy and OA subjects. The higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis in women are possibly a structural adaptation to mechanical use. The clinical significance is that the femoral deformities and the sex differences in knee OA have the potential to improve the understanding of the aetiology of primary varus knee OA. IV.


Elective inguinal node irradiation in early-stage T2N0 anal cancer: prognostic impact on locoregional control.
To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.


Clinical characteristics and treatment of renal artery fibromuscular dysplasia with percutaneous transluminal angioplasty: a long-term follow-up study.
Renal artery fibromuscular dysplasia (RAFMD) is a non-atherosclerotic cause of renal artery stenosis often affecting the young. Percutaneous transluminal renal angioplasty (PTRA) is the treatment of choice but there are few studies of the outcome of the procedure. This retrospective analysis included 64 patients (56.2 % female; mean age at diagnosis, 28.0 years) with RAFMD who underwent PTRA between November 2003 and August 2015. Technical and clinical success rates and restenosis rates were evaluated. Seventy-six procedures were performed on 64 RAFMD patients. Technical success was 96.9 %, as defined by <30 % residual stenosis, with stent placement required in 11 patients (17.2 %). In the short term (1 month), the majority (79.7 %) had an immediate clinical benefit, with cure of hypertension in 35.9 %, and improvement in hypertension and a lower requirement for antihypertensive medications in 43.8 %. In the long term (mean, 47.5 months; range, 5-141 months), the survival rate was 96.9 %, freedom from restenosis was 84.4 %, and 76.6 % of patients showed a sustained clinical benefit (cure rate 40.6 %, improvement rate 35.9 %). Eight patients were treated with a second procedure and two had a third procedure, with half of these patients showing an improvement in hypertension. PTRA for symptomatic RAFMD is safe and clinically successful. More than half of patients experience an immediate clinical benefit with sustained long-term effects. For patients with restenosis, there was a good response to a second PTRA.


Mechanical determinants of nectar-feeding energetics in butterflies: muscle mechanics, feeding geometry, and functional equivalence.
We develop a mechanistic model for nectar feeding in butterflies that integrates the two basic components of the feeding process: the fluid dynamics of nectar flow through the food canal and the contractile mechanics of the muscular, cibarial pump. We use the model to predict the relation between rate of energy intake during feeding and nectar concentration. We then identify nectar concentations that maximize energy intake rates (the optimal concentrations). We illustrate the model using measurements of the food canal and cibarium of Pieris butterflies. The model predicts an overall optimal range of nectar concentration of 31-39% sucrose for butterflies, which is in agreement with previously reported laboratory values. The model also predicts an interaction among the geometries of the food canal, the cibarial cavity, and the cibarial muscles, that allows us to identify the combinations of food canal, cibarium, and muscle dimensions that yield the highest rates of energy intake. Nectar-feeding is "functionally equivalent" in butterflies and hummingbirds: two physically different feeding mechanisms can yield identical energy intake rates. This equivalence results from a mathematical and physical similarity between quasi-steady-state fluid flow in hummingbrid tongues and the force-velocity characteristics of contracting cibarial muscle in butterflies.


School absenteeism and school refusal behavior in youth: a contemporary review.
Absenteeism from school is a serious public health issue for mental health professionals, physicians, and educators. The prevalence of unexcused absences from school exceeds that of major childhood behavior disorders and is a key risk factor for violence, injury, substance use, psychiatric disorders, and economic deprivation. This article involves a contemporary research review on absenteeism prevalence, comorbid physical and psychiatric conditions, classification, contextual risk factors, cross-cultural variables, assessment, intervention, and outcome. Contextual risk factors include homelessness and poverty, teenage pregnancy, school violence and victimization, school climate and connectedness, parental involvement, and family variables, among others. A description of intervention includes medical, clinical, and systemic interventions. Medical professionals, community- and school-based mental health professionals, and educators are encouraged to fully understand the parameters of school absenteeism to develop better, consensual policies regarding definition, classification, assessment, and intervention of youths with problematic school absenteeism.


A case of solid pseudopapillary tumour of the pancreas and malignant mesothelioma.
A 59-year-old man with previous exposure to asbestos presented with dyspnoea and pleuritic chest pain, had a pleural effusion and was treated for pneumonia. His symptom recurred and was found to have an abdominal mass. An abdominal computerised tomogram revealed pancreatic body mass arising. Pleural fluid cytology and a pleural biopsy failed to demonstrate malignancy. The pancreatic tumour was resected by distal pancreatectomy, segmental colectomy and splenectomy. The tumour was a solid pseudopapillary pancreatic tumour (SPT) with a high metastatic potential. The patient deteriorated and a repeat biopsy of the thickened pleura confirmed malignancy which was initially thought to be metastases from the SPT. Immunohistochemical staining confirmed malignant mesothelioma. The patient developed liver metastases and died 2 years from the diagnosis of metastatic disease.


Isolation and characterization of a nerve growth factor-regulated Fos kinase from PC12 cells.
Nerve growth factor (NGF) treatment of PC12 cells activates a protein kinase that phosphorylates c-Fos protein at a site near its C terminus, as well as a peptide corresponding to a C-terminal region of c-Fos (Taylor, L. K., Marshak, D. R., and Landreth, G. E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 368-372). This serine/threonine kinase, termed Fos kinase, has been purified > 24,000-fold through five column steps to near homogeneity and is shown to be a 37-kDa protein as determined by SDS-polyacrylamide gel electrophoresis (PAGE) with a pI = 6.0. Fos kinase is distinguishable from previously characterized NGF-regulated kinases by its chromatographic behavior, its response to specific kinase inhibitors, and its substrate specificity. The concentration of NGF required to activate Fos kinase is consistent with signaling from the high affinity NGF receptor. Fos kinase phosphorylates c-Fos at its C terminus as indicated by competitive inhibition with a peptide corresponding to C-terminal phosphorylation sites and lack of phosphorylation of a C-terminal deletion mutant of c-Fos. Hyperphosphorylation of c-Fos in vivo, as detected by reduced electrophoretic mobility of c-Fos, is induced by the same ligands which activate Fos kinase. Moreover, Fos kinase phosphorylation of c-Fos in vitro results in a similar electrophoretic mobility shift, demonstrating that Fos kinase may be responsible for growth factor-stimulated alterations in mobility on SDS-PAGE and phosphorylation of this transcription factor. The ability of this unique growth factor-responsive kinase to phosphorylate c-Fos at its C terminus, a region essential for the transrepressive properties of c-Fos, suggests that Fos kinase may play a role in the regulation of the transcriptional repressive activity of c-Fos.


Evidence for the lack of a specific interaction between cholesterol and sphingomyelin.
The putative specific interaction and complex formation by sphingomyelin and cholesterol was investigated. Accordingly, low contents (1 mol % each) of fluorescently labeled derivatives of these lipids, namely 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PyrPC), n-[10-(1-pyrenyl)decanoyl]sphingomyelin (PyrSM), and increasing concentrations of cholesterol (up to 5 mol %), were included in large unilamellar vesicles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dinervonoyl-sn-glycero-3-phosphocholine (DNPC), and the excimer/monomer fluorescence emission ratio (I(e)/I(m)) was measured. In DNPC below the main phase transition, the addition of up to 5 mol % cholesterol reduced I(e)/I(m) significantly. Except for this, cholesterol had only a negligible effect in both matrices and for both probes. We then compared the efficiency of resonance energy transfer from PyrPC and PyrSM to 22-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBDchol). An augmenting colocalization of the latter resonance energy transfer pair with temperature was observed in a DMPC matrix below the main phase transition. In contrast, compared to PyrSM the colocalization of PyrPC with NBDchol was more efficient in the longer DNPC matrix. These results could be confirmed using 5,6-dibromo-cholestan-3beta-ol as a collisional quencher for the pyrene-labeled lipids. The results indicate lack of a specific interaction between sphingomyelin and cholesterol, and further imply that hydrophobic mismatch between the lipid constituents could provide the driving force for the cosegregation of sphingomyelin and cholesterol in fluid phospholipid bilayers of thicknesses comparable to those found for biomembranes.


The significance of plasma protein binding on the fetal/maternal distribution of drugs at steady-state.
Maternal and fetal plasma differ in their concentrations of the important drug binding plasma proteins, albumin and alpha 1-acid glycoprotein, with albumin being slightly more concentrated in fetal plasma, and alpha 1-acid glycoprotein being only 37% of the maternal concentration at term. In general, these differences relate linearly to the bound to free concentration ratio of drugs associated with these proteins. Although only the free concentration is generally considered to be the pharmacologically active form, these differences can dramatically affect the total concentration and relative distribution of drugs between maternal and fetal plasma. In order to test our hypothesis that plasma protein binding is the major determinant of fetal/maternal drug distribution at steady-state, we examined whether fetal binding could be predicted from adult binding information. Data from studies of maternal plasma protein binding were used to predict fetal plasma protein binding based solely on the differences in protein concentrations. These predictions were compared with observed fetal binding data. This analysis showed a slope near unity and a high correlation (r2 = 0.900) which implies that there are no significant differences between the binding affinities of these proteins. A similar analysis performed using data on drug binding in non-pregnant adults gave an r2 or 0.971. Having established that fetal plasma proteins bind drugs similarly to their maternal counterparts, fetal/maternal plasma drug concentration ratios (F/M) were predicted for various drugs using information from literature on the drug's adult plasma protein binding, the protein to which it binds, and the fetal and maternal plasma concentrations of that binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Electroretinograms from broilers fed aflatoxin and T-2 toxin.
Thirty chicks were fed a commercial broiler grower ration from hatching to 26 days of age. Ten birds received aflatoxin (5 microgram/g. of ration) and 10 received T-2 toxin (5 microgram/g. of ration). The remaining 10 birds served as controls. After the 26 days, electroretinograms were recorded on a graphic recorder from the anesthetized birds. On the basis of wave amplitudes and durations from electroretinograms recorded in light and darkness and from different colored stimuli, no differences were detectable between treated birds and controls. Thus, the photochemistries of the retina were not sufficiently altered in this study to permit early detection of mycotoxicoses by electroretinograms.


Histotripsy Lesion Formation Using an Ultrasound Imaging Probe Enabled by a Low-Frequency Pump Transducer.
When histotripsy pulses shorter than 2 cycles are applied, the formation of a dense bubble cloud relies only on the applied peak negative pressure (p-) exceeding the "intrinsic threshold" of the medium (absolute value of 26-30 MPa in most soft tissues). It has been found that a sub-threshold high-frequency probe pulse (3 MHz) can be enabled by a sub-threshold low-frequency pump pulse (500 kHz) where the sum exceeds the intrinsic threshold, thus generating lesion-producing dense bubble clouds ("dual-beam histotripsy"). Here, the feasibility of using an imaging transducer to provide the high-frequency probe pulse in the dual-beam histotripsy approach is investigated. More specifically, an ATL L7-4 imaging transducer (Philips Healthcare, Andover, MA, USA), pulsed by a V-1 Data Acquisition System (Verasonics, Redmond, WA, USA), was used to generate the high-frequency probe pulses. The low-frequency pump pulses were generated by a 20-element 345-kHz array transducer, driven by a custom high-voltage pulser. These dual-beam histotripsy pulses were applied to red blood cell tissue-mimicking phantoms at a pulse repetition frequency of 1 Hz, and optical imaging was used to visualize bubble clouds and lesions generated in the red blood cell phantoms. The results indicated that dense bubble clouds (and resulting lesions) were generated when the p- of the sub-threshold pump and probe pulses combined constructively to exceed the intrinsic threshold. The average size of the smallest reproducible lesions using the imaging probe pulse enabled by the sub-threshold pump pulse was 0.7 × 1.7 mm, whereas that using the supra-threshold pump pulse alone was 1.4 × 3.7 mm. When the imaging transducer was steered laterally, bubble clouds and lesions were steered correspondingly until the combined p- no longer exceeded the intrinsic threshold. These results were also validated with ex vivo porcine liver experiments. Using an imaging transducer for dual-beam histotripsy can have two advantages: (i) lesion steering can be achieved using the steering of the imaging transducer (implemented with the beamformer of the accompanying programmable ultrasound system), and (ii) treatment can be simultaneously monitored when the imaging transducer is used in conjunction with an ultrasound imaging system.


Prenatal diagnosis of primary congenital glaucoma and histopathological features in a fetal globe with cytochrome p4501B1 mutations.
This study aims to report the developmental and histopathological features of ocular tissues from an electively aborted human fetus with mutations in cytochrome p4501B1, and thus predisposed to primary congenital glaucoma in comparison to an age-matched healthy fetal globe. Both eyes of two 17-week gestational aged fetuses, the first with CYP1B1 mutations and the second as healthy control fetus, were studied. Hematoxylin and eosin, Periodic acid-Schiff, Gomori's trichrome, and Verhoeff-Van Gieson staining protocols in addition to immunohistochemistry staining using anti-cytochrome p4501B1, anti-fibrillin-1, and anti-4-hydroxy-2-nonenal antibodies, as primary antibodies, were performed to assess the effect of the mutations on tissue development, cytochrome p4501B1 protein expression, extracellular matrix structure, and oxidative stress in the developing fetus eye. Quantitative analyses were performed using ImageJ software. Student's t-test was used for statistical analysis and P-values <0.05 were considered as significant. Delayed development in ocular tissues, decreased expression of cytochrome p4501B1 protein, irregular extracellular matrix structure, and increased oxidative stress biomarker were evident in the ocular tissues of the fetus with cytochrome p4501B1 mutations as compared to a normal globe from an age-matched fetus. To the best of our knowledge, this is the first report of prenatal diagnosis of primary congenital glaucoma. We also describe histopathological changes in the primary congenital glaucoma-affected globes revealing the effect of cytochrome p4501B1 deficiency on ocular tissues during early fetal development contributing to the glaucoma phenotype.


The feasibility and accuracy of machine learning in improving safety and efficiency of thrombolysis for patients with stroke: Literature review and proposed improvements.
In the treatment of ischemic stroke, timely and efficient recanalization of occluded brain arteries can successfully salvage the ischemic brain. Thrombolysis is the first-line treatment for ischemic stroke. Machine learning models have the potential to select patients who could benefit the most from thrombolysis. In this study, we identified 29 related previous machine learning models, reviewed the models on the accuracy and feasibility, and proposed corresponding improvements. Regarding accuracy, lack of long-term outcome, treatment option consideration, and advanced radiological features were found in many previous studies in terms of model conceptualization. Regarding interpretability, most of the previous models chose restrictive models for high interpretability and did not mention processing time consideration. In the future, model conceptualization could be improved based on comprehensive neurological domain knowledge and feasibility needs to be achieved by elaborate computer science algorithms to increase the interpretability of flexible algorithms and shorten the processing time of the pipeline interpreting medical images.


Source identification and ecological risks of parent and substituted polycyclic aromatic hydrocarbons in river surface sediment-pore water systems: Effects of multiple factors.
Substituted polycyclic aromatic hydrocarbons (SPAHs) have shown higher health and ecological risks than the corresponding parent PAHs (PPAHs) from laboratory studies, their variations in freshwater system, especially in surface sediment and pore water, remain inadequate understanding. In this study, we revealed the coexistence, ecological risk, and multiple factors affecting variations and sources of PPAHs and SPAHs (nitrated PAHs (NPAHs), oxygenated PAHs (OPAHs)) in the surface sediment-pore water system from a typical urban river in Northern China. The concentration ranges of Σ26PPAHs, Σ10NPAHs, and Σ4OPAHs in the surface sediments were 153.0-5367.4, not detected (N.D.)-105.4, and 42.2-1177.0 ng·g-1 dry weight, and fell within 0.6-38.8, N.D.-297.9, and N.D.-212.6 ng·mL-1 in the pore waters. The t-distributed stochastic neighbor embedding (SNE) coupled with the partitioning around medoids (PAM) elucidated spatiotemporal the variations in PAHs, emphasizing the impacts of industrial activities and sewage discharges. Besides the geochemical and hydrochemical conditions, SPAHs were affected by the potential secondary formation, especially during the wet season. The method comparisons indicated the advantages of principal component analysis-multivariate linear regression (PCA-MLR) and n-alkanes model on source identification. PAHs mainly originated from fossil fuel combustion and vehicular exhaust. The top risk quotient (RQ) values for PAHs occurred in the urban and industrial sections. A majority of the surface sediment samples emerged with low to moderate exposure risks, while all the pore water samples showed high exposure risks. The RQs of OPAHs were significantly higher (p < 0.01) than those of PPAHs. The results suggested the secondary formation of SPAHs as an important role in ecological risks of PAHs in the urban river system.


Suprasegmental neurophysiological monitoring with H reflex and TcMEP in spinal surgery. Transient loss due to hypotension. A case report.
H-reflex is a well known neurophysiological test used to evaluate sensory afferent and motor efferent impulses of S1 root. Despite its simplicity and feasibility, it is not used very often in the operating room. We report the case of a 16-year-old male patient who undergoes a surgical correction for a severe paralytic scoliosis (160°). On account of previous deficits, intraoperative neurophysiological monitoring was achieved through TcMEP and H-reflex. Intraoperative neurophysiological monitoring (IONM) showed a transient and simultaneous loss of bilateral TcMEP and H-reflex, coinciding with an abrupt hypotension during pedicle screw placement. After having dismissed mechanical injury and after increasing blood pressure, TcMEP and H-reflex were equivalent to those at baseline. The H-reflex is a classic neurophysiological test not used very frequently in the operating room. It is a feasible and reliable technique that can be helpful during spine surgery IONM, especially in patients with preexisting neurological deficits. Although simultaneous TcMEP and H-reflex monitoring has been previously described, to our knowledge, this is the first recorded case of a decline in both associated with abrupt hypotension.


An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.
Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, P<0.01; 5.3±0.4% HbA1c, P<0.01) participated. Using a randomized design, subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4±0.4°C water) that increased internal temperature above baseline by ∆1.6±0.4°C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals.


Differential effects of growth hormone on cardiomyocyte and extracellular matrix protein remodeling following experimental myocardial infarction.
Growth hormone (GH) causes cardiomyocyte hypertrophy without development of fibrosis in the normal rat heart. The aim of this study was to evaluate the effects of GH on cardiac remodeling following experimental myocardial infarction (MI). Following ligation of the left coronary artery or sham operation, rats were randomized to receive 2 IU GH/kg/day or vehicle for four weeks (n = 140). Extracellular matrix proteins were assessed in the non-infarcted myocardium of the posterior wall using immunohistochemistry and automatic image analysis. In addition, cardiomyocyte size was measured. Compared to sham, vehicle-treated rats with moderate (20-40%) and large (> 40%) infarct size showed left ventricular (LV)-dilatation, reduced fractional shortening as well as increases in LV end-diastolic and right atrial pressures, LV/body weight (BW) ratio and LV posterior wall thickness. Compared to vehicle-treated MI-rats, treatment with GH considerably increased fractional shortening and attenuated LV-dilatation. Vehicle-treated MI-rats displayed progressive increases in cardiomyocyte width and deposition of collagen I, compared to sham rats. Treatment with GH nearly doubled the increase in cardiomyocyte width and reduced collagen I accumulation by 50%. Our study demonstrates that GH, given early after large MI, elicits a unique pattern of structural effects characterized by enhanced cardiomyocyte hypertrophy and reduced adaptive fibrosis. This attenuation of pathological remodeling translates into a significant improvement in systolic and diastolic LV-function.


Mineralization of a Fully Halogenated Organic Compound by Persulfate under Conditions Relevant to in Situ Reduction and Oxidation: Reduction of Hexachloroethane by Ethanol Addition Followed by Oxidation.
Fully halogenated compounds are difficult to remediate by in situ chemical oxidation (ISCO) because carbon-halogen bonds react very slowly with the species that typically initiate contaminant transformation: sulfate radical (SO4•-) and hydroxyl radical (•OH). To enable the remediation of this class of contaminants by persulfate (S2O82-)-based ISCO, we employed a two-phase process to dehalogenate and oxidize a representative halogenated compound (i.e., hexachloroethane). In the first phase, a relatively high concentration of ethanol (1.8 M) was added, along with concentrations of S2O82- that are typically used for ISCO (i.e., 450 mM). Hexachloroethane underwent rapid dehalogenation when carbon-centered radicals produced by the reaction of ethanol and radicals formed during S2O82- decomposition reacted with carbon-halogen bonds. Unlike conventional ISCO treatment, hexachloroethane transformation and S2O82- decomposition took place on the time scale of days without external heating or base addition. The presence of O2, Cl-, and NO3- delayed the onset of hexachloroethane transformation when low concentrations of S2O82- (10 mM) were used, but these solutes had negligible effects when S2O82- was present at concentrations typical of in situ remediation (450 mM). The second phase of the reaction was initiated after most of the ethanol had been depleted when thermolytic S2O82- decomposition resulted in production of SO4•- that oxidized the partially dehalogenated transformation products. With proper precautions, S2O82--based ISCO with ethanol could be a useful remediation technology for sites contaminated with fully halogenated compounds.


Aptamers targeting rabies virus-infected cells inhibit viral replication both in vitro and in vivo.
Rabies is an acute fatal encephalitis disease that affects many warm-blooded mammals. The causative agent of the disease is Rabies virus (RABV). Currently, no approved therapy is available once the clinical signs have appeared. Aptamers, oligonucleotide ligands capable of binding a variety of molecular targets with high affinity and specificity, have recently emerged as promising therapeutic agents. In this study, sixteen high-affinity single-stranded DNA (ssDNA) aptamers were generated by cell-SELEX. Viral titer assays revealed aptamers could specifically inhibit the replication of RABV in cells but did not inhibit the replication of canine distemper virus or canine parvovirus. In addition, the FO21 and FO24 aptamers, with and without PEGylation, were found to effectively protect mice against lethal RABV challenge. When mice were inoculated with aptamers for 24h prior to inoculation with CVS-11, approximately 87.5% of the mice survived. Here, we report aptamers that could significantly protect the mice from a lethal dose of RABV in vitro and in vivo, as demonstrated by the results for survival rate, weight loss and viral titers. These results indicate that FO21 and FO24 aptamers are a promising agent for specific antiviral against RABV infections.


Incomplete vaccination coverage in European children with end-stage kidney disease prior to renal transplantation.
Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are scarce. Within the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national, retrospective study investigating the vaccination coverage before transplantation of 254 European children with end-stage renal disease (mean age 10.0 ± 5.6 years). Only 22 out of 254 patients (8.7%) presented complete vaccination coverage. In particular, the respective vaccination coverage against human papillomavirus (27.3%), pneumococci (42.0%), and meningococci (47.9%) was low. Patients with complete pneumococcal vaccination coverage had numerically less lower respiratory tract infections during the first 3 years post-transplant than children without vaccination or with an incomplete status (16.4% vs 27.7%, p = 0.081). Vaccine-preventable diseases post-transplant were 4.0 times more frequently in unvaccinated than in vaccinated patients. Factors associated with an incomplete vaccination coverage were non-Caucasian ethnicity (OR 9.21, p = 0.004), chronic dialysis treatment before transplantation (OR 6.18, p = 0.001), and older age at transplantation (OR 1.33, p < 0.001). The vaccination coverage in paediatric kidney transplant candidates is incomplete. Paediatric nephrologists, together with primary-care staff and patients' families, should therefore make every effort to improve vaccination rates before kidney transplantation.


Imaging of Soft Tissue Infections.
Although superficial infections can often be diagnosed and managed clinically, physical examination may lack sensitivity and specificity, and imaging is often required to evaluate the depth of involvement and identify complications. Depending on the area of involvement, radiography, ultrasound, CT, MR imaging, or a combination of imaging modalities may be required. Soft tissue infections can be nonnecrotizing or necrotizing, with the later having a morbid and rapid course. Infectious tenosynovitis most commonly affects the flexor tendon sheaths of the hand, characterized by thickened and enhancing synovium with fluid-filled tendon sheaths.


Plasma lipidomics reveals potential lipid markers for the prediction of delayed neurocognitive recovery after cardiac surgery with cardiopulmonary bypass.
Delayed neurocognitive recovery (DNR) is a cognitive change that affects patients after anesthesia and surgery, with a high incidence, severely impairing their quality of life. We identified relevant metabolic pathways to determine predictive lipid markers and understand the pathogenesis of DNR. A non-targeted lipidomic strategy using Waters Acquity I Class UPLC-Xevo G2-S QTOF UPLC-MS was employed to identify different lipids in the 24 h postoperative plasma of patients whose cognitive function was assessed 7-14 days after surgery. Principal component analysis, orthogonal partial least squares discriminant analysis, and receiver operating characteristic (ROC) curves were used to identify potential biomarkers for predicting DNR. Metabolic pathway analysis was performed using the online platform MetaboAnalyst 5.0. Pre-operative hemoglobin was identified as an independent risk factor for DNR. The individual areas under the ROC curves (AUC) of the 5 representative lipids were all > 0.6, and the AUC of the combined predictor was 0.912. Glycerophospholipid metabolic pathway was dysregulated in patients with subsequent DNR. This study identified a series of potential predictive biomarkers for DNR. These data suggested that glycerophospholipid metabolism may be the mechanism underlying the occurrence and progression of DNR.


Radiopharmacological profiles of tracers under pathophysiological conditions. Bone uptake of 99mTc-phytate in vitamin D deficient rats.
The radiopharmaceutical 99mTc-phytate, formed by reacting the phosphatic ligand, myo-inositol hexakisphosphate with a reduced form of 99mTcO4-, is widely employed in diagnostic nuclear medicine for scinti-imaging the RE system. Despite it being a compound derived from a ligand containing phosphatic functional moieties it does not concentrate to a significant extent in the osseous tissue following i.v. injection into animals or humans. Neither has there been any clinical report citing its localization in the skeletal tissue consequent to its i.v. injection into patients with different types of pathophysiological conditions/metabolic bone disorders. In the course of our study of the homing characteristics of radiopharmaceuticals into specific organ systems or secondary target sites we found that 99mTc-phytate could be directed to some extent into the skeletal tissues of experimental rats by altering its physiological milieu--viz. by decreasing blood calcium levels and increasing bone resorption. Such an altered physiologic condition is obtained by experimentally inducing vitamin D deficiency in animals. Our results show that 8-10% of the administered dose could be redirected to the bone matrix but at the expense of the liver. The study also indicates that many so-called organ specific 99mTc-radiopharmaceuticals could have more than one target tissue/organ system for accumulation consequent to being introduced into the systemic circulation. In a number of instances the secondary target may be masked and may be elicited only under certain specific pathophysiologic conditions.


Particle size distribution of radioactive aerosols after the Fukushima and the Chernobyl accidents.
Following the Fukushima accident, a series of aerosol samples were taken between 24th March and 13th April 2011 by cascade impactors in the Czech Republic to obtain the size distribution of (131)I, (134)Cs, (137)Cs, and (7)Be aerosols. All distributions could be considered monomodal. The arithmetic means of the activity median aerodynamic diameters (AMADs) for artificial radionuclides and for (7)Be were 0.43 and 0.41 μm with GDSs 3.6 and 3.0, respectively. The time course of the AMADs of (134)Cs, (137)Cs and (7)Be in the sampled period showed a slight decrease at a significance level of 0.05, whereas the AMAD pertaining to (131)I increased at a significance level of 0.1. Results obtained after the Fukushima accident were compared with results obtained after the Chernobyl accident. The radionuclides released during the Chernobyl accident for which we determined the AMAD fell into two categories: refractory radionuclides ((140)Ba, (140)La (141)Ce, (144)Ce, (95)Zr and (95)Nb) and volatile radionuclides ((134)Cs, (137)Cs, (103)Ru, (106)Ru, (131)I, and (132)Te). The AMAD of the refractory radionuclides was approximately 3 times higher than the AMAD of the volatile radionuclides; nevertheless, the size distributions for volatile radionuclides having a mean AMAD value of 0.51 μm were very close to the distributions after the Fukushima accident.


Effects of eight-week water versus mat pilates on female patients with chronic nonspecific low back pain: Double-blind randomized clinical trial.
To evaluate the effects of water and mat Pilates on pain, disability, and static and dynamic balance in patients with chronic nonspecific low back pain (CNLBP). Twenty-four participants with CNLBP were randomly allocated into two groups (n = 12) that perform water and mat Pilates exercises for 24 sessions (8-week, 3 sessions per week). The value for pain, disability and balance were measured before and after the exercise program using the Visual Analogue Scale, Oswestry Disability Questionnaire and Biodex Balance System respectively. A paired t-test revealed significant differences in pain severity and disability in both groups after they performed the Pilates program (P ≤ 0.05). Mat Pilates improved static balance as the participants performed the tests with their eyes open and closed (P = 0.02, P = 0.04). Its effect on dynamic balance, however, was not statistically significant (ES = 0/33, P = 0/34). The same Pilates program performed in water did not show significant effects on balance despite a decline in body sway (P˃0/05). There was no difference between the two groups (P˃0/05). The results suggest that both mat and water Pilates exercise program have beneficial effects on the treatment of LBP. Nevertheless, the low impact of the mat and water Pilates program on balance improvement suggests more investigation on Pilates training or complementary exercises to improve balance in patients with CNLBP.


Design, synthesis and evaluation of novel indirubin-based N-hydroxybenzamides, N-hydroxypropenamides and N-hydroxyheptanamides as histone deacetylase inhibitors and antitumor agents.
Several novel indirubin-based N-hydroxybenzamides, N-hydropropenamides and N-hydroxyheptanamides (4a-h, 7a-h, 10a-h) were designed using a fragment-based approach with structural features extracted from several previously reported HDAC inhibitors, such as SAHA (vorinostat), MGCD0103 (mocetinostat), nexturastat A and PXD-101 (belinostat). The biological results reveal that our compounds showed excellent cytotoxicity toward three common human cancer cell lines (SW620, PC-3 and NCI-H23) with IC50 values ranging from 0.09 to 0.007 µM. The cytotoxicity of the compounds was equipotent or even up to 10-times more potent than adriamycin and up to 205-times more potent than SAHA. Among the series of N-hydroxypropenamides, compounds 10a-d were the most potent HDAC inhibitors as well as cytotoxicity toward the cell lines tested. In addition, the strong inhibitory activites toward HDAC of our compounds were observed with IC50 values of below-micromolar range. Especially, compound 4a inhibited HDAC6 with an IC50 value of 29-fold lower than that against HDAC2 isoform. Representative compounds 4a and 7a were found to significantly arrest SW620 cells at G0/G1 phase. Compounds 7a and 10a were found to strongly induce apoptosis in SW620 cells. Docking studies revealed some important features affecting the selectivity against HDAC6 isoform. The results clearly demonstrate the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development.


Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol.
The effectiveness of the prodrug approach in maximizing the ratio of ocular to systemic absorption of topically applied timolol was compared with that based on viscous solutions. The pigmented rabbit was the experimental animal. o-Butyryl timolol, a lipophilic ester prodrug of timolol, was found to be twice as effective as hyaluronic acid and poly(vinyl alcohol) solutions in enhancing the ocular absorption of timolol. In addition, it was slightly more effective than retaining the instilled dose in the conjunctival sac for 240 min via nasolacrimal blockade. On the other hand, due to its inability to minimize contact of the instilled dose with the nasal mucosa, o-butyryl timolol was less capable than the viscous solutions in reducing systemic drug absorption. But this could be corrected by reducing the instilled solution volume from 25- to 5 microliter, resulting in a nine-fold reduction in plasma timolol levels while still providing the same amount of drug in the aqueous humor as a five times higher dose of timolol. The net result was a 15-fold improvement in the ratio of ocular to systemic drug absorption, which was also achieved upon retaining the instilled dose in the conjunctival sac for 240 min. It thus appears that the approach based on improved corneal absorption would be as effective as that based on improved retention in the conjunctival sac in maximizing the ratio of ocular to systemic drug absorption, so long as a smaller instilled dose volume of the prodrug is used.


Wound healing of laparoscopic esophageal myotomy with or without an added gastric patch.
The purpose of this research is to compare the wound healing of the laparoscopic esophagomyotomy with and without a gastric patch. Twelve male pigs were distributed into two groups of six animals. Esophagomyotomy was performed in group A. A gastric patch was associated to the myotomy in group B. On the 21st postoperative day, lumen molding was accomplished to determine the index of stenosis (IS) at the area of myotomy (AM). Macroscopic and microscopic aspects of wound healing were also studied at AM. Three microscopic morphologic patterns were defined for morphometric evaluation: leukocytes (constituted by polymorphonuclear and mononuclear cells), new endothelial cells, and collagen fibers. There was a longer operative duration in group B (93.6 min) than in group A (45 min). At AM, IS was negative (lumen increased) and equivalent in both groups: -11.1% in group A and -12.7% in group B. Mesotelial epithelium covering RM was observed in group A. Inflammatory reaction was greater in group B in comparison with group A (leuCocytes: 22 cells versus 8.6; fibrosis: 25.5 fibers versus 15.6; granulation tissue: 18.7 vessels versus 9.7). Esophagomyotomy followed by gastric patch does not heal adequately and is worsened by the presence of foreign body granulomas around stitches. Myotomy without gastric patch is faster and causes lower inflammation. Myotomy alone or with gastric patch does not lead to esophageal stenosis at RM and does not lead to restoration of the esophageal musculature continuity.


Current status of outpatient heart failure management in Egypt and recommendations for the future.
Heart failure (HF) represents one of the greatest healthcare burdens worldwide, and Egypt is no exception. HF healthcare programmes in Egypt still require further optimization to enhance diagnosis and management of the disease. Development of specialized HF clinics (HFCs) and their incorporation in the healthcare system is expected to reduce HF hospitalization and mortality rates and improve quality of care in Egypt. We conducted a literature search on PubMed on the requirements and essential infrastructure of HFCs. Retrieved articles deemed relevant were discussed by a panel of 10 expert cardiologists from Egypt and a basic HFC model for the Egyptian settings was proposed. A multidisciplinary team managing the HFC should essentially be composed of specialized HF cardiologists and nurses, clinical pharmacists, registered nutritionists, physiotherapists, and psychologists. Other clinical specialists should be included according to patients' needs and size and structure of individual clinics. HFCs should receive patients referred from primary care settings, emergency care units, and physicians from different specialties. A basic HFC should have the following fundamental investigations available: resting electrocardiogram, basic transthoracic echocardiogram, and testing for N-terminal pro-B-type natriuretic peptide. Fundamental patients' functional assessments are assessing the New York Heart Association functional classification and quality of life and conducting the 6 min walking test. guideline-directed medical therapy should be implemented, and device therapy should be utilized when available. In the first visit, once HF is diagnosed and co-morbidities assessed, guideline-directed medical therapy should be started immediately. Comprehensive patient education sessions should be delivered by HF nurses or clinical pharmacists. The follow-up visit should be scheduled during the initial visit rather than over the phone, and time from the initial visit to the first follow-up visit should be determined based on the patient's health status and needs. Home and virtual visits are only recommended in limited and emergency situations. In this paper, we provide a practical and detailed review on the essential components of HFCs and propose a preliminary model of HFCs as part of a comprehensive HF programme model in Egypt. We believe that other low-to-middle income countries could also benefit from our proposed model.


SCE induction in Chinese hamster ovary cells (CHO) exposed to G agents.
Cultured Chinese hamster ovary (CHO) cells were exposed to two neurotoxic organophosphates, either sarin (GBI, GBII) at 1.4 X 10(-3) M or soman (GD) at 1.1 and 2.2 X 10(-3) M for 1 h, grown and their metaphase chromosomes scored for sister-chromatid exchanges (SCE). No cytotoxicity was seen with either agent at any dose level tested. Since histograms of SCE per cell showed that they were non-symmetrically arrayed around the mean, the number of SCEs were analyzed by using the nonparametric tests, Mann-Whitney and Kruskall-Wallis. Agents GBI and GBII did not show any significant increase in SCE over baseline. On the other hand, GD demonstrated a statistically significant increase in SCE with and without metabolic activation. Ethyl methanesulfonate (EMS) alone at 5 X 10(-3) M and cyclophosphamide (CP) at 10(-4) M in the presence of rat microsomes (S9) induced a 3- and 8-fold increase in SCE per cell, respectively.


Genetic models for plant pathosystems.
Deterministic, discrete time, genetics models for a resistant plant host and a virulent pathogen are developed and analyzed. The original model was developed by Leonard in 1977 for a single gene with haploid pathogens and diploid hosts [Ann. N.Y. Acad. Sci. 287 (1977) 207]. The original model is generalized to diploid hosts and pathogens with incomplete dominance of the heterozygote. In addition, the single gene model is extended to two genes and a stochastic model with random selection values is formulated and simulated. It is shown using local stability properties that stability of the polymorphic equilibrium is indeterminant; the equilibrium is non-hyperbolic. The original model of Leonard has this same property. However, with random selection values, solutions tend to converge toward the polymorphic equilibrium.


Simulation methods in neuronal modelling.
The interspike distribution can be modelled as the first-passage-time distribution of suitable diffusion processes with biologically meaningful boundaries. Since various mathematical difficulties arise when one attempts to obtain closed form solutions for first-passage-time problems, one can resort to simulation methods in order to study the problem. In this paper we pinpoint possible overestimations connected with simulations of first-passage-times for diffusion processes and propose a suitable simulation technique to determine the moments and the distribution of the firing times. After checking the validity of the proposed method in some instances where numerical evaluations for such quantities are available, we apply the simulation algorithm to model the spiking activity by means of a particular diffusion process constrained by a suitable time varying threshold.


Hydroxyapatite induction and secondary aggregation of calcium oxalate, two important processes in calcium stone formation.
Stone formation has often been ascribed to crystal aggregation and fixed particle growth on kidney calcifications. In this paper, the influence of hydroxyapatite (HAP) and of preformed calcium oxalate (CaOx) aggregates on CaOx crystallization was studied in freshly voided urine. Crystallization was induced by different oxalate loads and precipitates were analyzed by the spectrophotometric measurement of sedimentation time (ST), which decreases with increasing particle size. The fact that the ST of aggregates (STA) is significantly lower than the ST of other particles demonstrates that STA is a useful indicator for aggregation. At relatively low oxalate loads the addition of HAP to urine increased STA by a factor of 4.3 (P < 0.001). After a second oxalate load, STA decreased by 56% (P < 0.001), indicating secondary growth of the preexisting aggregates. HAP induced and primary CaOx aggregation occurred at low pH at which a high ionic calcium concentration (Ca2+) was measured. In urine, crystals are coated by macromolecules creating a negative surface potential with a consecutive accumulation of cations such as Ca2+. This Ca2+ accumulation could be responsible for the enhancement of aggregation by preexisting particles, which seems to be important for stone formation and which can otherwise hardly be explained in the presence of coated crystals.


Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis.
The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan. Patients with locally advanced or metastatic UC that had not progressed with 4-6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety. In Japanese patients (n = 73) randomized to avelumab + BSC (n = 36) or BSC alone (n = 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8-33.0), respectively (HR, 0.81 [95% CI, 0.41-1.58]), and median PFS was 5.6 months (95% CI, 1.9-9.4) vs 1.9 months (95% CI, 1.9-3.8), respectively (HR, 0.63 [95% CI, 0.36-1.11]). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population. Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Clinicaltrials.gov NCT02603432.


Simultaneous measurement of zolmitriptan and its major metabolites N-desmethylzolmitriptan and zolmitriptan N-oxide in human plasma by high-performance liquid chromatography with coulometric detection.
Zolmitriptan, N-desmethylzolmitriptan, zolmitriptan N-oxide and an internal standard (an analogue of zolmitriptan) were extracted from plasma by a solid-phase extraction (SPE). Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric end-point detection. The standard curves were linear over the range 2-20 ng/ml for zolmitriptan and its metabolites in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 11%. The absolute recovery averaged 87, 58 and 77% for zolmitriptan. N-desmethylzolmitriptan and zolmitriptan N-oxide, respectively. The assay sensitivity was 0.5 ng for each analyte.


Electron microscopic demonstration of glycogen and phosphorylase activity in rat hepatocytes.
The effect of fixation with a bicarbonate-buffered solution of paraformaldehyde and polyvinyl pyrrolidone (PVP) on the ultrastructural demonstration of glycogen and phosphorylase activity in rat hepatocytes has been studied. Phosphorylase was demonstrated by the precipitation of liberated phosphate ions with ferrous ions. 7.5% PVP was included in all steps in the procedure before post-fixaiton in osmium tetroxide. Glycogen particles were well preserved. Structures connecting membranes and glycogen particles were also evident. Phosphorylase activity was rapidly inhibited by the fixative; the fixation time was, therefore, kept very short. The final reaction product was localized on glycogen particles and on endoplasmic membranes in association with glycogen particles. The results support the view that endoplasmic membranes are involved in the metabolism of glycogen in hepatocytes.


Reincorporation of iodinated peptides in vivo and the comparative effectiveness of tungstic and trichloroacetic acids in peptide separation.
The absorption of 125I-bovine IgG after oral administration to young rats has been followed by gel filtration and quantitatively by TCA precipitation. The wide spectrum of protein derivatives crossing the gut wall have been utilised to compare the relative effectiveness of 10% TCA, and 1% tungstic acid, as reagents for the quantitative assessment of radioactive proteins and peptides. Radioactive iodide was the chief radioactive metabolite when 125I-labelled bovine IgG was fed to young rats, there was no significant incorporation of small radioactive metabolites into protein during a second exposure to the gut wall.


Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism.
Acute pulmonary embolism (PE) is associated with high morbidity and mortality because of right ventricular (RV) failure. There is evidence suggesting surgical therapy (surgical embolectomy or venoarterial extracorporeal membrane oxygenation [ECMO]) is safe and effective. The aim of this study was to assess the safety and efficacy of surgical management of acute PE. Surgical embolectomy and/or venoarterial ECMO were compared, between 2005 and 2019, for massive PE (MPE) versus high-risk submassive PE (SMPE). RV recovery was defined as improvements in central venous pressure, pulmonary artery systolic pressure, RV/left ventricular ratio, and RV fractional area change. One hundred thirty-six patients with PE (92 with SMPE and 44 with MPE) were identified. Patients with MPE more often presented with syncope (59.1% [26 of 44] vs. 25.0% [23 of 92]; p = 0.0003), Glasgow Coma Scale score ≤4 (22.7% [10 of 44] vs. 0% [0 of 92]), and failed thrombolysis (18.2% [8 of 44] vs. 4.3% [3 of 92]; p = 0.008). Pre-operative cardiopulmonary resuscitation occurred in 43.2% of patients with MPE (19 of 44). Most patients with SMPE were treated with embolectomy (98.9% [91 of 92]), while ECMO was used more in those with MPE (ECMO in 40.9% [18 of 44], embolectomy in 59.1% [26 of 44]). RV function improved as measured by central venous pressure (from 23.4 ± 4.9 to 10.5 ± 3.1 mm Hg), pulmonary artery systolic pressure (from 60.6 ± 14.2 to 33.8 ± 10.7 mm Hg), RV/left ventricular ratio (from 1.19 ± 0.33 to 0.87 ± 0.23; p < 0.005), and fractional area change (from 26.8 to 41.0; p < 0.005). Mortality was 4.4% (6 of 136; SMPE, 1.1% [1 of 92]; MPE, 11.6% [5 of 44]). Subgroup analysis showed morbidity and mortality were highly associated with pre-operative cardiopulmonary resuscitation. Surgical management of patients with MPE and high-risk SMPE is safe and highly effective at achieving RV recovery.


MiR-875 and miR-3144 switch the human papillomavirus 16 E6/E6* mRNA ratio through the EGFR pathway and a direct targeting effect.
By employing bioinformatics scanning approaches and luciferase reporter, our previous study showed that two less common human miRNAs, miR-875 and miR-3144, target a conserved site in the genomes of most high-risk human papillomaviruses (HR-HPVs). In this study, we found that the site targeted by miR-875 and miR-3144 overlapped with the 5' alternative splice site of E6E7 transcripts in HPV16. Using HPV16+ SiHa cells, we showed that high levels of miR-875 and miR-3144 reduced the abundance of unspliced E6, while they promoted three E6* spliced transcripts and decreased the expression levels of E6/E7 oncoproteins and epidermal growth factor receptor (EGFR). A potential miR-875 target site was predicted in EGFR. Meanwhile, depletion of EGFR resulted in a failure to promote E6* but maintained the suppression of unspliced E6 driven by miR-875 and miR-3144. The data suggest that these two miRNAs switch the E6/E6* ratio through both the EGFR pathway and direct targeting. Here, we demonstrate for the first time that human miRNAs regulate the HPV splice isoforms. Furthermore, miRNA-875 and miRNA-3144 are only found in vertebrates and Homo sapiens, and the binding site in EGFR is highly conserved in Boreoeutheria. Our findings highlight the tumour-suppressing effect of miRNAs that possibly appeared in the late stage of biological evolution.


The health of Saudi youths: current challenges and future opportunities.
The health status of the young people is an important indicator for future health and health care needs of the next generation. In order to understand the health risk factors of Saudi youth, we analyzed data from a large national survey in the Kingdom of Saudi Arabia. The Saudi Health Information Survey sample included 2382 youths aged 15 to 24 years old. The questionnaire included information on socio-demographic characteristics, risk factors, risky behaviors, chronic conditions, functional status, health care utilization, and anthropometric and blood pressure measurements. Only 45.9% of men and 48.4% of women had normal body mass index (BMI). Men were more likely than women to smoke cigarettes or shisha. The prevalence of daily consumption of at least five servings of fruits and vegetables was 6.6%. The prevalence of no or insufficient physical activity was 41.8% in men and 75.6% in women (P < 0.001). Around 40% of men and 25% of women had abnormal blood pressure. Mean BMI and prevalence of insufficient physical activity, current smoking, and hypertension washigher in 20-to 24-year-olds than younger ages. Women were more likely to report that they never use seatbelts (82.2% vs. 65.4%). The prevalence of modifiable risk factors and risky driving behaviors is very high among Saudi youth. If these current behaviors are not reversed during this crucial age period, the burden of disease and injuries will rise in the future. Our findings call for developing health prevention programs for youths in Saudi Arabia.


Narrow Band Imaging: An Effective and Early Diagnostic Tool in Diagnosis of Oral Malignant Lesions.
The management of oral carcinoma leads to both cosmetic and functional deficit to the patient and the confirmatory histopathology is a time consuming process which may be a reason for a reduced follow up and compliance of the patient. We hereby use this study as an opportunity to tell that narrow band imaging (NBI) serves both the above purposes in an earlier period and in a non-invasive manner and thereby improving the lifestyle of the patients. To find out a better non-invasive and time saving diagnostic tool in the management of premalignant and malignant oral lesions in its earlier period. A prospective cross sectional study of 38 patients presenting to the department of ENT, MGMMC, MYH, Indore was taken with suspicious lesions and subjected to endoscopic examination by both white light and NBI and samples were sent to histopathological examination for confirmation. The Intrapapillary Capillary Loop were identified through NBI with Type I (50%) and Type II (31%) to be the most common pattern both correlating with the histopathological squamous cell carcinoma. The sensitivity and specificity of White Light Endoscopy is to be 75.75% and 76.43% respectively and of NBI to be 93.93% and 80% respectively. Narrow band imaging is found to be an optical diagnostic tool in the diagnosis of the lesions at an earlier stage and preventing from further functional and structural deterioration by the disease progression.


Free dermofat grafting for chest deformity in microtia reconstruction.
Chest deformity is one of the complications that occurs after costal cartilage harvesting for auricle reconstruction. In this study, we presented a novel method of free dermofat grafting to repair cartilage defect and aimed to evaluate its effect in ameliorating chest deformity. Seventy-six pediatric patients were included in the study, comprising free dermofat grafting group (n = 38) and control group (n = 38). After harvesting costal cartilage, empty perichondrial space of right seventh costal cartilage was filled with free dermofat grafts in free dermofat grafting group. Thoracic computed tomography (CT) was performed three months after surgery and 3D colormap quantification was performed to quantify chest surface asymmetry. The quantified data were further analyzed to compare chest asymmetry level in free dermofat grafting and control groups. In the free dermofat grafting group, the mean of asymmetry level was 2.2 mm. While in the control group, the mean of asymmetry was 5.7 mm. After a comparison between the two groups, the level of asymmetry showed a significant difference (p < 0.01). Free dermofat grafting method is easy to perform and a feasible option for ameliorating chest deformity in microtia reconstruction.


[Role and regulation of dopamine D1 receptors in the striatum: implications for the genesis of dyskinesia in Parkinson's disease].
L-dopa treatment of Parkinson's disease is complicated in the long term by the appearance of dyskinesia. Hypersensitivity of D1 dopamine receptor has been suggested to play a role in these delayed adverse effects. Hypersensitivity of dopamine D1 receptor in Parkinson's disease can be accounted for by increased levels of Galphaolf, the stimulatory G protein which couples D1 receptor to adenylyl cyclase in the striatum. We here discuss the possible role of D1 receptor signal transduction in the genesis of L-dopa-induced dyskinesia in the light of Galphaolf regulation.


Fluorescence correlation spectroscopy to assess the mobility of nuclear proteins.
Recent developments in cell biology and microscopy techniques enable us to observe macromolecular assemblies in their natural setting: the living cell. These emerging technologies have revealed novel concepts in nuclear cell biology. In order to further elucidate the biochemistry of gene expression, replication, and genome maintenance, the major challenge is now to precisely determine the dynamics of nuclear proteins in the context of the structural organization of the nucleus. Fluorescence correlation spectroscopy (FCS) is an attractive alternative to photobleaching and photoactivation techniques for the analysis of protein dynamics at single-molecule resolution. Here we describe how FCS can be applied to retrieve biophysical parameters of nuclear proteins in living cells.


The gay bowel syndrome: a common problem of homosexual patients in the emergency department.
Sexually transmitted bowel and rectal diseases are common in gay men and are caused by a wide variety of infectious agents. Each of the entities implicated in the gay bowel syndrome is considered separately and epidemiologic considerations responsible for the appearance of such a syndrome are examined. The emergency physician should be prepared to diagnose and initiate treatment of these disorders on a rational basis. Specific practical guidelines for the workup and management of these patients are suggested.


Interactions between Tau and Different Conformations of Tubulin: Implications for Tau Function and Mechanism.
Tau is a multifaceted neuronal protein that stabilizes microtubules (MTs), but the mechanism of this activity remains poorly understood. Questions include whether Tau binds MTs laterally or longitudinally and whether Tau's binding affinity depends on the nucleotide state of tubulin. We observed that Tau binds tightly to Dolastatin-10 tubulin rings and promotes the formation of Dolastatin-10 ring stacks, implying that Tau can crosslink MT protofilaments laterally. In addition, we found that Tau prefers GDP-like tubulin conformations, which implies that Tau binding to the MT surface is biased away from the dynamic GTP-rich MT tip. To investigate the potential impact of these Tau activities on MT stabilization, we incorporated them into our previously developed dimer-scale computational model of MT dynamics. We found that lateral crosslinking activities have a much greater effect on MT stability than do longitudinal crosslinking activities, and that introducing a bias toward GDP tubulin has little impact on the observed MT stabilization. To address the question of why Tau is GDP-tubulin-biased, we tested whether Tau might affect MT binding of the +TIP EB1. We confirmed recent reports that Tau binds directly to EB1 and that Tau competes with EB1 for MT binding. Our results lead to a conceptual model where Tau stabilizes the MT lattice by strengthening lateral interactions between protofilaments. We propose that Tau's GDP preference allows the cell to independently regulate the dynamics of the MT tip and the stability of the lattice.


Endoluminal vessel reconstruction by stent placement in patients with obstructive coronary artery disease who are poor surgical candidates.
To investigate the safety and efficacy of endoluminal vessel reconstruction by intracoronary stenting in patients with single or multivessel disease who have been turned down for surgical revascularisation. An observational, single centre trial of consecutive patients being followed up clinically. Tertiary referral centre. 43 patients treated between 1995 and 1996 with a clinical follow up period of at least six months. Acute procedural success following intervention (defined as a residual stenosis of < 30% with normal antegrade flow and without acute clinical complications); major adverse clinical events (death, myocardial infarction, repeat intervention, clinical restenosis); and functional status during follow up. Acute procedural success was achieved in 39 patients. Failures resulted from a refractory no reflow phenomenon with Q wave myocardial infarction (two patients), and from subacute stent thrombosis (one patient) and saphenous vein graft rupture at stent site (one patient), both manifesting by non-Q wave myocardial infarction. During a follow up period of 17 (8) months (mean (SD)), three of these patients died. Clinical restenosis was treated by repeat percutaneous intervention in 11 patients, while 28 patients remained asymptomatic. On a Kaplan-Meier estimate, the proportion of patients without adverse clinical events at two years was 65%. Percutaneous reconstruction of diseased coronary arteries in patients with single or multivessel disease turned down for surgical revascularisation may be considered as a valuable treatment option. On follow up, more events seem to be encountered than after elective de novo stenting of discrete coronary lesions. This is probably related to higher clinical restenosis rates.


Reactive oxygen species alter autocrine and paracrine signaling.
Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endoplasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A custom ELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-κB pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.


A critical review of the arguments debating the role of the nurse advocate.
This paper critically reviews the arguments for and against undertaking the role of nurse advocate. Advocacy has become a popular concept in nursing literature over the past two decades. By addressing issues of power and accountability, conclusions are drawn about the risks facing nurses who would practice patient advocacy. Review and analysis of theoretical debate. Empirical evidence is sparse and philosophical arguments predominate in the field of patient advocacy. Humanistic arguments that promote advocacy as a moral imperative are compelling. However, in reality nurses appear to lack the power base to comply except by covert means. Informed consent with a knowledge of the consequences of undertaking such an intervention is as relevant to the nurse as it is to the patient. Nurses need to be empowered first, if they are to empower their patients. There may however, be more suitable candidates for the role of patient advocate and nurses should recognize that they do not have a monopoly on ethical decision making.


Elevated serum levels of interleukin-17A in uveitis patients.
T helper 17 cells (Th17) are one of the main pathogenic effectors in autoimmune uveitis, and IL-17A is the signature cytokine of Th17 cells. This study aims to assess serum IL-17A levels in patients with autoimmune uveitis and evaluate associations between IL-17A levels and disease characteristics. Serum IL-17A levels from 87 autoimmune uveitis patients and 60 healthy controls were assessed using an enzyme-linked immunosorbent assay. Among this cohort, 9 patients were followed longitudinally for IL-17A levels during active and inactive stages of their disease. Median serum IL-17A levels were higher among uveitis patients compared to controls (p < 0.0001). Moreover, IL-17A levels were elevated among uveitis patients with active disease compared to those with inactive disease (p = 0.0202). Among the 9 patients followed longitudinally, IL-17A levels were elevated during active disease compared to the inactive stage (p = 0.0078). Serum IL-17A levels are elevated in uveitis patients, particularly in active uveitis.


Parmosidone K, a new meta-depsidone from the lichen Parmotrema tsavoense.
Further phytochemical investigation on P. tsavoense led to one new meta-depsidone, parmosidone K together with one known compound, barbatic acid. Their structures were determined by 1D and 2D NMR analysis, high resolution mass spectroscopy, and comparison their NMR data with those reported in literatures. Parmosidone K was evaluated for α-glucosidase inhibition and revealed the powerful activity with IC50 value of 3.12 µM.