Transporter-dependent uptake and metabolism of myocardial interstitial serotonin in the rat heart.
To investigate the roles of the serotonin (5-HT) transporter (SERT) and plasma membrane monoamine transporter (PMAT) in 5-HT uptake and its metabolism in the heart, we monitored myocardial interstitial levels of 5-HT and 5-HIAA, a metabolite of 5-HT by monoamine oxidase (MAO), in anesthetized rats using a microdialysis technique. Fluoxetine (SERT inhibitor), decynium-22 (PMAT inhibitor), or their mixture was locally administered by reverse-microdialysis for 60 min. Subsequently, pargyline (MAO inhibitor) was co-administered. Fluoxetine rapidly increased dialysate 5-HT concentration, while decynium-22 gradually increased it. The mixture induced a larger increase in dialysate 5-HT concentration compared to fluoxetine or decynium-22 alone. Fluoxetine increased dialysate 5-HIAA concentration, and this increase was abolished by pargyline. Decynium-22 and the mixture did not change dialysate 5-HIAA concentration, which were not affected by pargyline. Both SERT and PMAT regulate myocardial interstitial 5-HT levels by its uptake; however, 5-HT uptake via PMAT leads to 5-HT metabolism by MAO.


Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens.
Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans.


Study on fatigue and breakdown properties of Pt/(Pb,Sr)TiO(3)/Pt capacitors.
Pulsed-laser deposited (Pb,Sr)TiO(3) (PSrT) films on Pt/SiO(2)/Si substrate at various ambient oxygen pressures (P(O(2))) are investigated in this work. Films deposited at P(O(2)) below 100 mTorr exhibit the (100) preferred orientation and a tetragonal structure with larger tetragonality. In addition, films deposited at 80 mTorr exhibit the most apparent ferroelectric properties in contrast to those deposited at 200 mTorr. Moreover, films deposited at higher P(O(2)) also exhibit longer lifetimes and higher breakdown fields due to their smaller leakage current density, in terms of the reduction of defects, compensation of oxygen vacancies (OVs), an improved interface and small cluster sizes. An energy band model reveals that fatigue properties of PSrT films are dominated by interfacial states at low P(O(2)) and by deep trapping states at high P(O(2)), which could be ascribed to OVs located at the interfaces and inside films, respectively.


Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones.
Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.


Effect of PGE1 on immediate-type immunologic and pharmacologic respiratory responses of the rhesus monkey.
The effect of prostaglandin (PG)E1 on the acute, immediate-type airway response to antigen, carbocholine, PGF2alpha, histamine, and physostigmine was studied. In contrast to isoproterenol, which affects all abnormalities of pulmonary function, PGE1 selectively reversed only abnormalities of pulmonary resistance and dynamic compliance. Prior exposure to PGE1 minimally inhibited airway responses but when given simultaneously with antigen, it either selectively inhibited some or dampened all pulmonary function abnormalities. It is suggested that PGE1 acts on receptor sites to produce transient bronchodilation primarily in large central airways in contrast to isoproterenol, which produces bronchodilation in all airways. These results may be consistent with the stimulation of different adenylate cyclase systems in the respiratory tract analogous to those suggested for the gastric mucosa.


A healthy dose of scepticism: four good reasons to think again about protective effects of alcohol on coronary heart disease.
Alcohol has been implicated in both the popular press and scientific literature as having a protective effect for at least a dozen conditions including coronary heart disease (CHD). Epidemiological evidence for an apparent protective effect of alcohol on CHD is now being challenged on a number of fronts. This paper is a synopsis of those various challenges as they currently stand. The argument that systematic misclassification of ex-drinkers and occasional drinkers to 'abstainer' categories among epidemiological studies might explain apparent protective effects of moderate alcohol consumption on CHD has recently been supported by new meta-analyses and independent research. The influence of uncontrolled or unknown factors on the relationship between alcohol and disease cannot be ruled out. Exclusion of participants on the basis of ill-health severely reduces study sample size and new analyses suggest that doing so might artificially create the appearance of protective effects. The ability of respondents to accurately recall their own alcohol consumption is in serious doubt and very few individuals maintain one single drinking level or style throughout life. The relationship between alcohol and some conditions might be a function of drinking patterns but few studies have addressed the issue. Popular perceptions regarding the strength of evidence for alcohol's protective effect on a growing number of conditions might be misguided. It is time for the wider research, health and medical community to seriously reflect on the quality of current evidence for apparent protective effects of alcohol on human disease.


Differential quantification of SIgA and SC by two-directional rocket method.
The two-directional rocket method, a newly modified method for quantitative immunoelectrophoresis, was used as the assay for separating SC and SIgA, which have identical antigenicity but differ in mobility. This method proved to be sufficiently simple and sensitive to enable simultaneous assay of SC and SIgA in saliva. The method employs electrophoresis into antibody-containing agarose/agar gel in the presence of heparin-Ca EDTA. The height of the precipitation peaks formed in two directions is proportional to the concentration of the antigens. Concomitant use of agarose which has little electroendosmosis and agar which has high electroendosmosis facilitated cathodic migration of SIgA. Transfer of SC from beta-region to alpha 1-region without influencing the mobilities of SIgA, albumin or IgG was obtained by addition of heparin-Ca EDTA to agarose/agar gel. This effect of heparin-Ca EDTA is vulnerable to changes of pH of the gel, but is almost completely independent of change in composition or concentration of the gel. The function of heparin as a polyanion may be resonsible for it. Carbamylation of antibody was used to accelerate a clear-cut resolution of the cathodic rockets. This technique was found to be a method of choice for analysis of SIgA and SC in large numbers. In using this method as a screening assay for detection of primary immunodeficiency, by studying saliva samples collected from 3 month old infants on the occasion of regular check-up over a 2 year period, two cases of isolated IgA immunodeficiency and two cases of hypoglobulinaemia were discovered in 12,000 infants.


Seroprevalence and comparison of isolates of endometriotropic bovine herpesvirus-4.
Sixty-eight cases of suppurative, ulcerative endometritis associated with Bovine Herpesvirus-4 (BHV-4) in postparturient dairy cows (62 Holsteins and 6 Jerseys, mean age 4.2 years) were confirmed by a combination of histopathology, fluorescent antibody assays, electron microscopic evaluation of uterus, and polymerase chain reaction (PCR). All cases occurred in the 3- to 28-day postpartum period, and histologic lesions among various cows were consistent when compared with postpartum interval. The endometrial lining epithelium was necrotic and ulcerated from 3 to 7 days postpartum, with only mild inflammation in the lamina propria and submucosa. From 1 to 4 weeks postpartum, the ulcers were confluent to diffuse. Epithelium was replaced by fibrinonecrotic, suppurative mats, resulting in severe bacterial pyometra by day 24. Seroprevalence to BHV-4 in one dairy with a history of 18 mortality cases was 36% (107 of 296). In a random sample of 8 cows from this herd, none had serologic titers in blood sampled 2 weeks prepartum, but 3 of 8 seroconverted with significant titers of 1:8 to 1:16 at 2 weeks postpartum. By 10 weeks postpartum, all 8 cows returned to negative serologic status. Two of 6 cats from the premises also had positive titers. Random serum samples taken from 480 dairy cattle at sale barns indicated 76 (16%) were positive by serum neutralization. Clinical signs, postparturient timing, and histologic lesions were very similar to those previously reported in Belgium with BHV-4. But sequence analysis of PCR products of the glycoprotein B region of 4 separate field isolates of endometriotropic BHV-4 suggests these field isolates were more closely related to the North American nonvirulent strain DN-599 than to the endometriotropic European strain V.


[Determination of differentially expressed proteins and it's significance among chronic sinusitis, nasal polyps and normal nasal mucosa].
To investigate the differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa by means of proteomic technology, and select the candidate biomarkers of chronic sinusitis and nasal polyps. Proteins extracted from chronic sinusitis, nasal polyps and normal nasal mucosa were separated and the differentially expressed proteins were identified by series of proteomic tools, including immobilized pH4-7 gradient two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, modified coomassie brilliant blue staining, images scanning by the Image Scanner apparatus, PDQuest analysis software, peptide mass fingerprinting based on matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) by in-gel digestion extract, and Mascot searching in NCBInr and SWISS-PROT databases. The 2-DE patterns with high resolution and reproducibility were obtained. The protein spots separated and visualized in chronic sinusitis, nasal polyps and normal nasal mucosa gel were 1020 +/- 40, 1112 +/- 10 and 1008 +/- 25, respectively. And the match rates were (93 +/- 2)%, (95 +/- 1)% [see text] (90 +/- 3)% respectively. Thirteen differentially expressed spots were found from chronic sinusitis, nasal polyps and normal nasal mucosa gel. We selected and recommend Keratin 8 and APOA1 proteins as candidate biomarkers of nasal polyps, and PLUNC protein, PACAP protein, NKEF-B and SOD as candidate biomarkers of chronic sinusitis. The differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa can be efficiently and relatively reliably identified via the techniques of proteomics. These techniques will play a very important role in the researches for new objective indicators possibly employed in the future classifying, staging and prognosis.


[Menopausal hormone therapy. Effects on bone and body composition].
Changes occurring at menopause can be mitigated by prescribing menopausal hormone replacement therapy (HRT). Recent publications from the CoLaus/OsteoLaus cohorts provide important insights into the effects of HRT and after its discontinuation on bone and body composition. HRT has a beneficial effect on bone mineral density, bone microarchitecture and fracture prevention. The benefits persist after treatment discontinuation, but not beyond 2 to 5 years. The effect of HRT on body composition is more controversial. HRT reduces the accumulation of fat mass, mainly abdominal and visceral fat mass. This is important from the perspective of diabetes and cardiovascular disease prevention. However, the benefits seem to disappear immediately after discontinuation.


Ecological and evolutionary physiology of desert birds: a progress report.
The adaptive significance of mechanisms of energy and water conservation among species of desert rodents, which avoid temperature extremes by remaining within a burrow during the day, is well established. Conventional wisdom holds that arid-zone birds, diurnal organisms that endure the brunt of their environment, occupy these desert climates because of the possession of physiological design features common to all within the class Aves. We review studies that show that desert birds may have evolved specific features to deal with hot desert conditions including: a reduced basal metabolic rate (BMR) and field metabolic rate (FMR), and lower total evaporative water loss (TEWL) and water turnover (WTO).Previous work on the comparative physiology of desert birds relied primarily on information gathered on species from the deserts of the southwestern U.S., which are semi-arid habitats of recent geologic origin. We include data on species from Old World deserts, which are geologically older than those in the New World, and place physiological responses along an aridity axis that includes mesic, semi-arid, arid, and hyperarid environments.The physiological differences between desert and mesic birds that we have identified using the comparative method could arise as a result of acclimation to different environments, of genetic change mediated by selection, or both. We present data on the flexibility of BMR and TEWL in Hoopoe Larks that suggest that phenotypic adjustments in these variables can be substantial. Finally, we suggest that linkages between the physiology of individual organism and its life-history are fundamental to the understanding of life-history evolution.


Prolixibacter denitrificans sp. nov., an iron-corroding, facultatively aerobic, nitrate-reducing bacterium isolated from crude oil, and emended descriptions of the genus Prolixibacter and Prolixibacter bellariivorans.
The facultatively aerobic, non-hydrogenotrophic, iron (Fe0)-corroding, nitrate-reducing Prolixibacter sp. strain MIC1-1(T) was characterized for representation of a novel species of the genus Prolixibacter. Strain MIC1-1(T) grew optimally at 35-37 °C, at pH 6.5 and with 2% (w/v) NaCl. Strain MIC1-1(T) also grew fermentatively on some pentoses, hexoses, disaccharides and soluble starch. Succinic acid was the major end-product from D-glucose fermentation. Strain MIC1-1(T) was differentiated from the type strain of Prolixibacter bellariivorans by cell size, optimum growth temperature, range of temperature and NaCl for growth, and nitrate reduction. On the basis of phenotypic features and the phylogenetic position, a novel species of the genus Prolixibacter is proposed for strain MIC1-1(T), to be named Prolixibacter denitrificans sp. nov. The type strain is MIC1-1(T) ( = JCM 18694(T) = NBRC 102688(T)= DSM 27267(T)). Emended descriptions of the genus Prolixibacter and Prolixibacter bellariivorans are also provided.


Estimating Arctic Sea Ice Thickness with CryoSat-2 Altimetry Data Using the Least Squares Adjustment Method.
Satellite altimeters can be used to derive long-term and large-scale sea ice thickness changes. Sea ice thickness retrieval is based on measurements of freeboard, and the conversion of freeboard to thickness requires knowledge of the snow depth and snow, sea ice, and sea water densities. However, these parameters are difficult to be observed concurrently with altimeter measurements. The uncertainties in these parameters inevitably cause uncertainties in sea ice thickness estimations. This paper introduces a new method based on least squares adjustment (LSA) to estimate Arctic sea ice thickness with CryoSat-2 measurements. A model between the sea ice freeboard and thickness is established within a 5 km × 5 km grid, and the model coefficients and sea ice thickness are calculated using the LSA method. Based on the newly developed method, we are able to derive estimates of the Arctic sea ice thickness for 2010 through 2019 using CryoSat-2 altimetry data. Spatial and temporal variations of the Arctic sea ice thickness are analyzed, and comparisons between sea ice thickness estimates using the LSA method and three CryoSat-2 sea ice thickness products (Alfred Wegener Institute (AWI), Centre for Polar Observation and Modelling (CPOM), and NASA Goddard Space Flight Centre (GSFC)) are performed for the 2018-2019 Arctic sea ice growth season. The overall differences of sea ice thickness estimated in this study between AWI, CPOM, and GSFC are 0.025 ± 0.640 m, 0.143 ± 0.640 m, and -0.274 ± 0.628 m, respectively. Large differences between the LSA and three products tend to appear in areas covered with thin ice due to the limited accuracy of CryoSat-2 over thin ice. Spatiotemporally coincident Operation IceBridge (OIB) thickness values are also used for validation. Good agreement with a difference of 0.065 ± 0.187 m is found between our estimates and the OIB results.


Scurvy resembling cutaneous vasculitis.
Various conditions can imitate cutaneous vasculitis. Scurvy is a less appreciated cause of rash that can resemble vasculitis. Three patients were referred to our rheumatology service for "vasculitis," who subsequently were found to have scurvy. Findings included a purpuric skin rash, myalgias, and malaise. The patients had low vitamin C levels and findings on skin biopsy specimens indicative of scurvy. The three patients were on idiosyncratic diets deficient in vitamin C, and the two patients who allowed us to administer vitamin C therapy improved clinically. We emphasize the importance of a careful dietary history. Early recognition of scurvy is important because it can be treated specifically, and toxic treatment of vasculitis can be avoided.


Risk Factors of Postoperative Vomiting in the Eye of "Real-World Evidence"-Modifiable and Clinical Setting-Dependent Risk Factors in Surgical Trauma Patients.
Numerous studies on postoperative nausea and vomiting (PONV) have been carried out since the early days of contemporary surgery. The incidence of PONV has been greatly reduced in recent years and new drugs for PONV keep evolving in the market; however, a substantial number of patients are still under the threat of PONV. Female gender, non-smokers, a history of PONV/motion sickness, and postoperative opioid use are four well-recognized risk factors of PONV. Many potential risk factors reported in previous studies were not consistently presented as predictors for PONV. Two questions then arise; are risk factors clinical setting dependent and are risk factors modifiable? We attempted to answer the questions through a comprehensive review of perioperative records of surgical patients from the Trauma Department of our hospital. As nausea is subjective and no standard is applicable for its measurement, postoperative vomiting (POV) was used as an endpoint in this study. To the best of our knowledge, this is the first study to address the POV issue in surgical trauma patients. A total of 855 patients were enrolled in this study after excluding age below 20 years old, total intravenous anesthesia, desflurane anesthesia, or records with missing data. Our results showed that female gender (OR 4.89) is the strongest predicting factor, followed by a less potent predicting factor-more intraoperative opioid consumption (OR 1.07)-which favor more POV. More intraoperative crystalloid supply (OR 0.71) and a higher body weight (OR 0.9) favor less POV. Other potential risk factors did not reach statistical significance in this study as independent risk factors. Our results also showed that when the intraoperative crystalloid infusion rate is greater than 4 mL/kg/h (OR 0.20), it favors a lower rate of POV; when intraoperative opioid consumption is greater than 12 mg morphine equivalents, MME (OR 1.87), it favors a higher rate of POV. We concluded that dominance of any independent risk factor over other risk factors depends on how individual factors interact with the clinical setting. Some risk factors could be modified, and a cut-off value could be derived to facilitate a better plan for POV prevention.


Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions.
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a highly personalized type of cancer immunotherapy. TIL-based ACT exploits naturally occurring TILs, derived from the patients' tumor. This treatment has shown consistent clinical responses in melanoma, and recent results point toward a potential use in multiple cancer diagnoses. However, several limitations have restricted the clinical development and adaptation of TIL-based ACT. In this review, we present the principles of TIL-based ACT and discuss the most significant limitations for therapeutic efficacy and its widespread application. The topics of therapeutic resistance (both innate and acquired), treatment-related toxicity, and the novel research topic of metabolic barriers in the tumor microenvironment (TME) are covered. There are many ongoing areas of research focusing on improving clinical efficacy and optimizing TIL-based ACT. Many strategies have shown a great potential, particularly strategies advancing TIL efficacy (such as increasing and harnessing ex vivo the sub-population of tumor-reactive TILs) and manufacturing processes. Novel approaches can help overcome current limitations and potentially result in TIL-based ACT entering the mainstream of cancer therapy across tumor types.


Assessment of Physical Fitness and Health Status of Athletes Based on Intelligent Medical Treatment under Machine Learning.
Machine learning is an interdisciplinary study of how to make computer programs perform similar to human learning, and its techniques are widely used in the medical industry. The purpose of this paper is to study how to use machine learning-based intelligent medicine to analyze and study the assessment of athletes' physique and health status and describe the machine learning algorithm. This paper puts forward the problem of intelligent medical diagnosis, which is based on machine learning, and then elaborates on the concept of machine learning and related algorithms, and designs and analyzes a case of an athlete's physique monitoring and health status assessment system. The experimental results show that the athlete's physical fitness monitoring and health status evaluation system can meet the needs of users. The text classification effect based on the LSTM method is slightly inferior to the SVM effect, in which the recall rate of diabetes is not more than 40%, and the recall rate of cerebral infarction is improved by 26.5% after using fuzzy matching.


[Catecholamines in the human diencephalon].
Catecholamines are chemical compounds which play an important role as neurotransmitters in many vital functions of the organism. The paper presents a short survey of their biosynthesis, disintegration andfunctions, with respect to the neuroanatomical location of cell groups which contain these compounds. Because the authors were most interested in the behavior of catecholamines in the diencephalon, particularly in the hypothalamus, they focussed their attention on cells secreting catecholamines (dopamine, noradrenaline, adrenaline, octopamine). The paper also deals with the connections between cellular structures which emit and receive the neuronal impulses that transport catecholamines as neurotransmitters. These include the following dopaminergic systems: nigrostriatal, tuberohypophysial, retinal, periventricular, periglomerular and dopaminergic systems in mesolimbic, mesocortical and diencephalic regions. The paper also indicates other areas in human brain with adrenaline and noradrenaline secreting cells.


Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy.
In the present study, we aimed to evaluate the safety and efficacy of DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy for the treatment of patients with primary central nervous system lymphoma (PCNSL). We retrospectively examined 21 patients with newly diagnosed PCNSL who received DeVIC chemotherapy followed by whole-brain radiation therapy (WBRT). The median progression-free survival (PFS) in all patients was 37.4 months and the median duration of overall survival (OS) was 47.8 months. Notably, the median duration of OS was significantly longer in patients who achieved a complete response (CR) after DeVIC chemotherapy (49.0 months) than in those without CR (12.8 months). Furthermore, we found that the overall response rate to the initial DeVIC chemotherapy was 95.2%. No treatment-related deaths were observed. Our study investigated the efficacy of DeVIC chemotherapy in PCNSL patients, and found it to result in favorable survival outcomes in these patients, thus warranting further investigation of it as a therapeutic measure against PCNSL.


Persea Americana Agro-Industrial Waste Biorefinery for Sustainable High-Value-Added Products.
Significant problems have arisen in recent years, such as global warming and hunger. These complications are related to the depletion and exploitation of natural resources, as well as environmental pollution. In this context, bioprocesses and biorefinery can be used to manage agro-industrial wastes for obtaining high-value-added products. A large number of by-products are composed of lignin and cellulose, having the potential to be exploited sustainably for chemical and biological conversion. The biorefinery of agro-industrial wastes has applications in many fields, such as pharmaceuticals, medicine, material engineering, and environmental remediation. A comprehensive approach has been developed toward the agro-industrial management of avocado (Persea americana) biomass waste, which can be transformed into high-value-added products to mitigate global warming, save non-renewable energy, and contribute to health and science. Therefore, this work presents a comprehensive review on avocado fruit waste biorefinery and its possible applications as biofuel, as drugs, as bioplastics, in the environmental field, and in emerging nanotechnological opportunities for economic and scientific growth.


FDG-PET/CT as a molecular biomarker in ovarian cancer.
In the clinical setting the vast majority of positron emission tomography (PET) procedures use the glucose analogue F-18 fluorodeoxyglucose (FDG) to visualize the increased glucose consumption of malignant lesions. Co-registered PET/CT has improved the diagnostic accuracy compared to either imaging procedure alone, particularly in ovarian cancer. FDG-PET/CT demonstrates primary malignant ovarian tumors; however, it is often unable to accurately differentiate between benign and malignant pelvic masses and to visualize borderline ovarian tumors. FDG-PET/CT has a suggested role for staging, by improving treatment planning in individual cases, but it is particularly helpful in the setting of disease recurrence when CA125 tumor marker levels are rising and conventional imaging (CT or MR) is inconclusive or negative. The aim of this review is to demonstrate the value of FDG-PET-CT in diagnosis and management of patients with ovarian malignancies, outlining its advantages and limitations.


Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: a vascular Doppler and elastography study.
Hepatic dysfunction is a recognized complication after Fontan palliation of congenital heart disease. We sought to quantitatively measure hepatic stiffness and vascular Doppler indices using ultrasound (US) and shear wave elastography (SWE) in a Fontan cohort. Subjects were prospectively recruited for echocardiography and real-time hepatic duplex US with SWE for hepatic stiffness (kPa). Doppler peak velocities, velocity time integral, resistive, pulsatility, acceleration indices (RI, PI, AI), and flow volume were measured in celiac artery, superior mesenteric artery, and main portal vein (MPV). A subset underwent cardiac catheterizations with liver biopsy. Correlations were explored between SWE, duplex, hemodynamic, and histopathologic data. In all, 106 subjects were studied including 41 patients with Fontan physiology (age 13.8 ± 6 years, weight 45.4 ± 23 kg) and 65 controls (age 15.0 ± 8.4 years, weight 47.9 ± 22 kg). Patients with Fontan physiology had significantly higher hepatic stiffness (15.6 versus 5.5 kPa, P < 0.0001), higher celiac RI (0.78 versus 0.73, P = 0.04) superior mesenteric artery RI (0.89 versus 0.84, P = 0.005), and celiac PI (1.87 versus 1.6, P = 0.034); while MPV flow volume (287 versus 420 mL/min in controls, P = 0.007) and SMA AI (829 versus 1100, P = 0.002) were lower. Significant correlation was seen for stiffness with ventricular end-diastolic pressure (P = 0.001) and pulmonary artery wedge pressure (P = 0.009). Greater stiffness correlated with greater degrees of histopathologic fibrosis. No significant change was seen in stiffness or other duplex indices with age, gender, time since Fontan, or ventricular morphology. Elevated hepatic afterload in Fontan, manifested by high ventricular end-diastolic pressures and pulmonary arterial wedge pressures, is associated with remarkably increased hepatic stiffness, abnormal vascular flow patterns, and fibrotic histologic changes. The MPV is dilated and carries decreased flow volume, while the celiac and superior mesenteric arterial RI is increased. SWE is feasible in this population and shows promise as a means for predicting disease severity on liver biopsy.


Association between fluorine-18-labeled fluorodeoxyglucose uptake and 1p and 19q loss of heterozygosity in World Health Organization Grade II gliomas.
Oligodendroglial tumors harboring combined 1p and 19q loss (1p/19q LOH) are characterized by a favorable prognosis and response to chemotherapy and radiotherapy, but detection of 1p/19q LOH relies on postoperative procedures. The authors investigated the potential of fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) to predict 1p/19q LOH preoperatively in tumors whose appearance on initial magnetic resonance images was consistent with that of low-grade glioma. The study population comprised 25 patients who had undergone preoperative FDG-PET followed by tumor resection. Neuronavigation ensured a precise match of FDG uptake with the site of biopsy. All tumor specimens were graded according to the World Health Organization (WHO) classification system. Microsatellite analysis was used to identify 1p/19q LOH. In this series, 16 of 25 gliomas corresponded to WHO Grade II. In eight of these 16, 1p/19q LOH was detected. Raised glucose utilization within the tumor was seen in the six of eight WHO Grade II gliomas with 1p/19q LOH and in none of the WHO Grade II gliomas without this genetic alteration (p = 0.003). These findings demonstrate the potential of FDG-PET to predict 1p/19q LOH in WHO Grade II gliomas.


RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis.
Deletion of the short arm of chromosome 3 is one of the most frequent genetic alterations in many solid tumors including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3 (RNA binding motif, single stranded interacting protein 3), located at 3p24-p23, has been identified in our previous study. Here, we reported that downregulation of RBMS3 was detected in 3/3 NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional studies using both overexpression and suppression systems demonstrated that RBMS3 has a strong tumor suppressive role in NPC. The tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by upregulating p53 and p21, downregulating cyclin E and CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of MMP2 and β-catenin and inactivation of its downstream targets, including cyclin-D1, c-Myc, MMP7, and MMP9. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC.


Decarboxylation of alpha-ketoisovaleric acid after oral administration in man.
The keto analogues of essential amino acids represent a promising therapeutic modality in hereditary and acquired disorders of nitrogen metabolism. The utilization of these substances in humans has been assayed primarily by nitrogen balance studies. A simple and accurate breath excretion test for 14CO2 enabled us to measure the decarboxylation of 1-14C-alpha-ketoisovaleric acid (KIV, the keto analogue of valine) in two normal and six diseased subjects. Normal volunteers as well as patients with gastrectomy, hepatic failure, renal failure, and myotonic dystrophy were tested in 5-g protein diets supplemented with essential amino acids and KIV (in place of valine). The normal volunteers and the gastrectomy patient were then restudied on 120 g protein/day. With low protein intake, 13 to 32% of ingeted KIV underwent rapid decarboxylation, and this proportion appeared to correlate inversely with damage to organ systems containing the branched-chain keto acid dehydrogenase. With high protein intake, the proportion decarboxylated rose to 44 to 53%. Thse results confirm that the decarboxylation of KIV in man varies under different conditions of dietary intake and metabolic disease. The 14CO2 brewth excretion test is applicable to other related analyses of carboxylic acid metabolism in human subjects.


Recall bias in a case-control surveillance system on the use of medicine during pregnancy.
It is important to study possible teratogenic effects of drugs used during pregnancy. Many studies of this type rely upon case-control designs in which drug intake is recalled by the mothers after having given birth. Recall bias in this situation may lead to spurious associations. We looked for indicators of recall bias by comparing self-reported drug intake with medically notified intake for specific diseases in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, which includes 22,865 cases with congenital abnormalities and 39,151 controls. Recall error was present, especially for drugs used for a short time period. Furthermore, the timing of drug intake was reported slightly closer to the time of interview for cases compared than for controls. Severe or visible congenital abnormalities did not appear to be more conducive to recall bias than other abnormalities under study. A case-control surveillance system of this type may frequently cause spurious associations, with biased odds ratios up to a factor of 1.9.


Associations between family history of cardiovascular disease, knowledge of cardiovascular disease risk factors and health behaviours.
The objective of the study was to examine associations between family history of premature cardiovascular disease (CVD), knowledge of CVD risk and protective factors, and health behaviours. The design was via administration of a questionnaire to 307 participants from four general practice centre waiting rooms in the Sydney West area. The most recognised CVD risk factor was smoking (97.7%) and the most recognised CVD protective factor was omega-3 fatty acids (78.5%). After adjustment for age, sex, education attainment and personal history of CVD, a strong family history of premature CVD was associated with being more likely to interpret a blood pressure of 130/85 as a CVD risk factor (OR 2.77, 95% CI 1.07-7.14), but less likely to identify being an ex-smoker (compared with never having smoked before) as a risk factor (OR 0.32, 95% CI 0.12-0.90). Those with a strong family history of premature CVD, on average, had smoked 0.82 pack years more than those with an average family history of premature CVD (s.e. 4.22, P=0.04). In conclusion, there continues to be both strengths and deficits in the community's overall knowledge of CVD risk and protective factors, and a strong family history of premature CVD appears to be an independent risk factor for smoking.


A salty cause of cough in a 24-year-old man.
With improvement in the diagnosis and treatment of cystic fibrosis cases in recent years, the survival of these cases has been increased. On the other hand, an increasing number of cases are presented during adulthood. Here we report a 24-year-old man with a history of productive cough, bilateral paranasal sinusitis and polyps, and recurrent abdominal pain. Thoracic computed tomography revealed a bilateral scattered tree in bud pattern and some bronchiectatic changes. Semen analysis showed azoospermia. A sweat chloride test was >60 mEq/l in two occasions.


[Improvement of legal and regulatory framework of epidemic control measures in bureau of forensic medicine].
The study objective is to improve epidemic control measures in the bureau of forensic medicine by reviewing current local regulatory documents, formulating proposals for their modification, and updating issues related to infectious safety and diagnostic accuracy of infectious diseases. Specific proposals have been provided for modifications of statistical forms for infectious disease recording, regulatory documents, and internal instructions.


[Medicine of yore in the Moesano].
Through a series of walks with former colleagues and investigations in archives the author succeeded in reconstructing the medical past of the Moesano, a remote region of the italian speaking Grisons comprising the valleys of Calanca and Mesolcina. His analysis illustrates and reviews the demographic movements in a district of which certain parts are on the way of depopulation, the medical practitioners who followed one another during the last century, their daily activities under circumstances totally different from ours, the means at their disposal in particular the therapeutical possibilities an overview of the popular medicines of that time and a short historical report about the health resort of San Bernardino.


ALDH3A2, ODF2, QSOX2, and MicroRNA-503-5p Expression to Forecast Recurrence in TMPRSS2-ERG-Positive Prostate Cancer.
Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail. Between 40 and 50% of PCa cases belong to the TMPRSS2-ERG subtype that is a sufficiently homogeneous group for high-precision prognostic marker search to be possible. This study includes two independent cohorts and is based on high throughput sequencing and qPCR data. As a result, we have been able to suggest a perspective-trained model involving a deep neural network based on both qPCR data for mRNA and miRNA and clinicopathological criteria that can be used for recurrence risk forecasts in patients with TMPRSS2-ERG-positive, locally advanced PCa (the model uses ALDH3A2 + ODF2 + QSOX2 + hsa-miR-503-5p + ISUP + pT, with an AUC = 0.944). In addition to the prognostic model's use of identified differentially expressed genes and miRNAs, miRNA-target pairs were found that correlate with the prognosis and can be presented as an interactome network.


Photocycle of dried acid purple form of bacteriorhodopsin.
The photocycle of dried bacteriorhodopsin, pretreated in a 0.3 M HCl solution, was studied. Some properties of this dried sample resemble that of the acid purple suspension: the retinal conformation is mostly all-trans, 15-anti form, the spectrum of the sample is blue-shifted by 5 nm to 560 nm, and it has a truncated photocycle. After photoexcitation, a K-like red-shifted intermediate appears, which decays to the ground state through several intermediates with spectra between the K and the ground state. There are no other bacteriorhodopsin-like intermediates (L, M, N, O) present in the photocycle. The K to K' transition proceeds with an enthalpy decrease, whereas during all the following steps, the entropic energy of the system decreases. The electric response signal of the oriented sample has only negative components, which relaxes to zero. These suggest that the steps after intermediate K represent a relaxation process, during which the absorbed energy is dissipated and the protein returns to its original ground state. The initial charge separation on the retinal is followed by limited charge rearrangements in the protein, and later, all these relax. The decay times of the intermediates are strongly influenced by the humidity of the sample. Double-flash experiments proved that all the intermediates are directly driven back to the ground state. The study of the dried acid purple samples could help in understanding the fast primary processes of the protein function. It may also have importance in technical applications.


[Neopterine and ige during respiratory-syncytial virus infection in infants].
The number of studies confirms the correlation between IgE and neopterine levels. One of the forms of revelation of the immune answer of T-cells is the activation of T-cell system, that in its turn results in secretion of IL-2 and INF-gamma by Th-1 subtype cells. Activation of macrophages by INF-gamma the human organism. The target of our research was the evaluation of the role of the marker of macrophage activation -- neopterine in children with recurrent wheezing developed during onset of RSV infection and possible connection with IgE level. In the study 52 children of age from 1 to 12 months having RS-virus infection were included. Two groups were determined as controls -- group of healthy children and children with wheezing of non RSV etiology. Determination of neopterine was performed by enzyme immunoassay method (ELISA). During the RS-virus induced acute respiratory infection the rate of neopterine in the blood serum was significantly decreased in the group of patients with recurrent wheezing in comparison with the I group (first episode of wheezing). At the same time the significant difference between the group with wheezing of non -- RSV etiology and the control group was not observed. Decreasing of neopterin was significant in the II and III groups. IgE levels were elevated significantly in the second group of patients with recurrent wheezing. In this group negative correlation between neopterin and IgE was found.


The art and science of guessing.
This research examined how one affectively reacts to others' guesses at a value one cares about, such as one's income. Conventional wisdom suggests that people will feel happier upon receiving more favorable guesses (e.g., higher income) than less favorable guesses. We found the opposite pattern. We propose a model to explain the effect and identify its boundaries and report experimental evidence for the model. This research enriches existing literature on self-enhancement and yields practical implications for how to approach guessing in interpersonal communications.


Effects of chronically administered atrial natriuretic factor in aldosterone-infused hypertensive rats.
To assess the pathophysiological role of atrial natriuretic factors in mineralocorticoid hypertension, we studied the effects of chronic infusion of synthetic atrial natriuretic factor on blood pressure and sodium-water excretion in rats with aldosterone salt-induced hypertension. Administration of synthetic atrial natriuretic factor (150 micrograms/kg/day) to rats made hypertensive by 7-day infusion of aldosterone (100 micrograms/kg/day) and sodium loading with 1% NaCl as drinking water returned the blood pressure to control levels, and the antihypertensive effect was not associated with any changes in urine volume and urinary sodium excretion. These results indicate that atrial natriuretic factors may be involved in the regulation of blood pressure in mineralocorticoid hypertension, independent of the renal effects of these substances.


Facultative heterochromatin: is there a distinctive molecular signature?
The Latin word "facultas" literally means "opportunity." Facultative heterochromatin (fHC) then designates genomic regions in the nucleus of a eukaryotic cell that have the opportunity to adopt open or compact conformations within temporal and spatial contexts. This review focuses on the molecular and functional aspects of fHC that distinguish it from constitutive heterochromatin (cHC) and euchromatin (EC) and discusses various concepts regarding the regulation of fHC structure. We begin by revisiting the historical developments that gave rise to our current appreciation of fHC.


Francis Galton on twins, heredity and social class.
In 1875 Francis Galton was the first to study twins as a test of the relative strenght of heredity and environment. This paper examines Galton's work on twins, using his surviving working papers. It shows that his enquiry was larger and more systematic than previously realized. Galton issued several hundred questionnaires to parents of twins, with the aim of establishing how far the similarities and differences between twins were affected by their life experiences. The paper also discusses Galton's study in relation to his understanding of the physiology of twinning and his theory of heredity. The modern concept of monozygotic twins had not yet been established, and the similarity between Galton's work and modern twin studies should not be overstated. While Galton's work was important as a pioneering study, in some respects his conclusions went beyond his evidence. The paper finally examines whether Galton's twin studies influenced his position on the links between social class, heredity and social mobility, and surveys the evidence for his views on these issues.


Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project.
The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision referrals increased coverage and decreased incidence over ∼29 months of follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population. Rural and periurban communities in Botswana. We used the Cost-Effectiveness of Preventing AIDS Complications model to estimate lifetime health impact and cost of (1) earlier ART initiation and (2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio [US$/quality-adjusted life-years (QALY)] for CP vs. standard of care. In CP, 1418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an incremental cost-effectiveness ratio of $79 per QALY. Enhanced HIV testing, linkage, and early ART initiation improve life expectancy, reduce transmission, and can be cost-effective or cost-saving in settings like Botswana.


[Changes in autonomic nerve function during the normal menstrual cycle measured by the coefficient of variation of R-R intervals].
The purpose of this study was to determine if there is a change in autonomic nerve function during the menstrual cycle. The subjects were 20 females (average age 26.1 years +/- 4.6) with a normal menstrual cycle. The coefficient of variation of R-R intervals (CV R.R) was measured to investigate autonomic function in the menstrual, follicular, ovulatory, luteal, and premenstrual phases. Average CV R-R for all phases was 5.2 +/- 1.9%. And the CV R-R tended to be lower in those in their 30s than in those in their 20s. And no noticeable difference was seen in the CV R-R among the 5 phases of the menstrual cycle. On the other hand, the CV R-R of 11 females with premenstrual syndrome was low in the ovulatory, luteal and premenstrual phases. These results, which provide basic data for clinical use, suggest the following. (1) The age of subjects should be taken into consideration. (2) Changes in the CV R-R during the menstrual cycle are negligible. (3) However, in those showing symptoms associated with the menstrual cycle such as premenstrual syndrome, changes during the menstrual cycle should be taken into account. At the same time psychological changes in the subjects were evaluated by the following tests: Cornell Medical Index, Taylor's manifest anxiety scale, and Zung's self-rating depression scale. The results of these tests did not vary significantly during the menstrual cycle.


Inter-Individual Variation in Cancer and Cardiometabolic Health Outcomes in Response to Coffee Consumption: A Critical Review.
Coffee is associated with a lower risk of cancer, cardiovascular disease, and type 2 diabetes at the population level. However, individual susceptibility to the effects of coffee consumption will cause heterogeneity in health responses between individuals. In this critical review determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption are systematically evaluated. Embase and MEDLINE are searched for observational studies and clinical trials that examined variation in the response to coffee consumption. A total of 74 studies meet the inclusion criteria, which report variation in cancer (n = 24) and cardiometabolic health (n = 50) outcomes. The qualitative analysis shows that sex, BMI, smoking, alcohol intake, menopausal status, and genetic polymorphisms are probable or possible determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption, albeit the majority of studies have insufficient statistical power to detect significant interaction between these factors and coffee consumption. Several genetic and non-genetic determinants of inter-individual variability in the responses to coffee and caffeine consumption are identified, indicating that some of the health benefits of coffee may only occur in a subgroup of subjects.


Magnetic resonance imaging in plantar heel pain.
Magnetic Resonance Imaging (MRI) is generally only indicated in patients with plantar heel pain who have atypical symptoms or who do not improve with appropriate management. This study retrospectively reviewed the MRI findings of 112 patients with heel pain divided into two groups consisting of 50 patients with persistent pain despite appropriate treatment and 62 patients with atypical heel pain. Of the 50 patients with persistent heel pain, 38 (76%) of MRIs confirmed the diagnosis of plantar fasciitis. Of the 62 patients who had presented with atypical symptoms or signs, 21 patients had presented with night pain and the remaining 41 had presented with acute pain, tenderness of the lateral or medial aspect of the heel, significant swelling, neurological features or pain posterior to the insertion of the plantar fascia. Patients with night pain were shown to have plantar fasciitis associated with calcaneal marrow edema in 15 (71.4%) cases (p < 0.05). One patient presenting with night pain was found to have a plantar arterio-venous malformation. Acute pain was associated with plantar fascia tears in 4 out of 9 (p < 0.05). MRI may provide reassurance in cases of persistent heel pain but rarely changes the management. In cases of atypical heel pain, MRI may demonstrate other pathology such as plantar fascia tearing, calcaneal edema or arteriovenous malformation.


Colon cancer and gene alterations: their immunological implications and suggestions for prognostic indices and improvements in biotherapy.
Studies have shown that changes occur in c-Ki-ras, p53, and Bcl2 gene structure and function during the various stages of human colon carcinogenesis. Alterations of these genes are responsible for the establishment of a state of continuous stimulus for cell division and apoptotic inhibition at physiological and pharmacological levels. This paper focuses on the results of our research aimed at investigating how these gene alterations influence tumoral mechanisms on an immunological level and how immunological parameters can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. Overall, our data suggest that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response, determining an impairment of immune cell activation at both antigen- presenting-cell and T-cell levels. c-Ki-ras gene mutations, p53 deletions, and Bc12 expression, on the other hand, can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. The p53 oncogene does not appear to impair patients' immunological response further. In conclusion, an evaluation of c-Ki-ras, rather than p53 gene alterations, would seem to be more relevant in colon cancer prevention programs and biotherapy improvement.


Imaging with chemical analysis: adsorbed structures formed during surface chemical reactions.
Imaging surfaces and interfaces with structural and chemical specificity has been essential for understanding a variety of phenomena occurring in adsorbed layers during surface chemical reactions. A recent achievement of chemical imaging with spectroscopic analysis is the experimental proof of theoretically predicted spontaneous formation of regular patterns of metal adatoms during surface chemical reactions. An attractive feature of this finding is that the reaction rate and adlayer coverage can be employed to precisely control the morphology of the structures. The mechanisms of these self-organisation phenomena, driven by the interplay between energetic principles and kinetics, opens a conceptually novel route to creating a wide range of surface-supported functional structures at the micro- and nanometre length scales.


Evolution of gait abnormalities in SOD1(G93A) transgenic mice.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the loss of upper and lower motoneurons. Clinically, it is manifested by weakness, muscle atrophy and progressive paralysis and ends up with patients' death 2-5 years after diagnosis. Although these symptoms lead in many cases to gait deficits in patients, an exhaustive locomotor profile of animal models mimicking the disease has not been assessed yet. In this work we evaluated the locomotor performance of the SOD1(G93A) mouse model of ALS using computerized treadmill gait analysis. SOD1(G93A) mice presented early (8 weeks of age) gait abnormalities, evidenced by an increase in the time of the propulsion phase of hindlimb stance. The alterations progressed during the disease until a complete disturbance of normal gait. This finding is meaningful to the field because the identification of a significant difference in a functional endpoint as early as 8 weeks might be a step forward resolving the debate about treatment of mice prior to the symptomatic phase in efficacy studies. These results also point out that digitizing analysis of treadmill locomotion may be useful to evaluate whether new therapeutic approaches are improving functional outcome of the animals.


Sequential docetaxel and vinorelbine for patients with advanced breast cancer previously treated with anthracyclines: a phase II study.
With respect to their association, sequential non-cross-resistant cytostatics could be better tolerated and allow a similar antitumor effect. From January, 1998 to July, 1999, 42 consecutive patients with metastatic breast cancer (MBC) previously treated with anthracyclines as adjuvant- or first-line therapy entered a phase II multicenter study where docetaxel (TXT, 100 mg/m2/3 weeks/4 times) was followed by vinorelbine (VNR, 25 mg/m2/10 days/8 times). Median follow-up is 21 months and 22/42 patients have died. Four patients did not complete therapy due to early death, grade 3-4 gastrointestinal mucosytis (2 patients) and grade 3 neurotoxicity during TXT therapy. Overall response rate was 57%, and 5% of patients had stable disease. There were 38% of therapy failures due to non-evaluability (10%) or progressive disease (28%). Median time to progression and survival are 10.1 and 17.1 months. Sequential TXT-VNB is a suitable strategy for MBC patients previously treated with anthracyclines. It avoids haematologic toxicity and allows a good antitumor effect. Careful monitoring of intestinal mucosytis is required.


Modeling of the As (III) adsorption using Fe impregnated polyethylene terephthalate char matrix: A statistical approach.
The present research aimed to analyse the impact of economical Fe impregnated polyethylene terephthalate (PET) char (PETC-Fe) for adsorption of As (III) through series of column experiments. For an inlet arsenite concentration of 1,000 μg/L, PETC-Fe exhibits excellent uptake capacity of 1,892 μg/g. Central composite design (CCD) in response surface methodology (RSM) was used to evaluate the influence of various process variables on the response function (breakthrough time) for optimization and assessment of interaction effects. The breakthrough time is more responsive to influent As (III) concentration and bed height than inlet flow rate, according to the perturbation plot. Adams-Bohart, Bed Depth Service Time (BDST) model, and Thomas models were used to model the dynamics of the adsorption system. The BDST model suited the experimental data well in the early part of the breakthrough curve, but there were minor variations over the breakpoints. Despite the fact that the experimental values and the data sets estimated using the Adams-Bohart model followed a similar pattern, they differed slightly. The PETC-Fe was found to be a sustainable and highly economical adsorbent, with a desorption performance of more than 97%, indicating the adsorbent's reusability. This adsorbent's excellent As (III) uptake capacity and regeneration performance imply that it might be used in industrial/domestic applications, and the information obtained could aid in future scaling up of the adsorption system.


Complete remission of pure white cell aplasia associated with thymoma, autoimmune thyroiditis and type 1 diabetes.
Pure white cell aplasia (PWCA) is a rare disorder of unknown origin, often associated with thymoma, characterized by selective neutropenia or pure agranulocytosis, and absence of granulocyte precursors in the bone marrow, but with normal erythroblasts and megakaryocytes. We report a case of PWCA associated with thymoma. Unusual findings in this case report included simultaneous presence of autoimmune thyroiditis, type 1 diabetes, anti-striated muscle antibodies, and the presence in the peripheral blood of CD8+ T cells that expressed a homogeneous naive phenotype. Neutrophil count became normal on immunosuppressive therapy after thymectomy.


The Prevalence and Risk Factors of Latent Tuberculosis Infection among Health Care Workers Working in a Tertiary Hospital in South Korea.
The risk of tuberculosis (TB) infection among health care workers (HCWs) is higher than as noted among workers in the general population. The prevalence and risk factors of TB infection among HCWs were assessed in a tertiary hospital in South Korea, resulting in a conclusion of an intermediate TB burden within the country. This cross-sectional study enrolled HCWs who underwent a QuantiFERON-TB Gold In-Tube (QFT-GIT) test to detect the presence of a latent TB infection (LTBI), in patients admitted to a tertiary hospital in South Korea in 2017. The departments of the hospital were divided into TB-related and TB-unrelated departments, which were based on the risk of exposure to TB patients. In this sense, the risk factors for LTBI, including current working in the TB-related departments, were analyzed. In this case, a total of 499 HCWs (54 doctors, 365 nurses and 80 paramedical personnel) were enrolled in this study. The median age of the subjects was 31 years (range, 20-67 years), 428 (85.8%) were female, and 208 (41.7%) were working in the TB-related departments. The prevalence of LTBI was 15.8% based on the QFT-GIT. Additionally, the prevalence of experience of exposure to pre-treatment TB patents was higher among HCWs working in the TB-related departments, than among HCWs working in the TB-unrelated departments (78.8% vs. 61.9%, p<0.001). However, there was no significant difference in the prevalence of LTBI between the two groups (17.3% vs. 14.8%, p=0.458). On a review of the multivariate analysis, only the factor of age was independently associated with an increased risk of LTBI (p=0.006). Broadly speaking, the factor of age was associated with an increased risk of LTBI among the HCWs in South Korea. However, those workers current working in the TB-related departments was not associated with an increased risk of LTBI.


Association of Cytokine Gene Polymorphism with Peri-implantitis Risk.
To investigate whether polymorphisms of cluster of differentiation 14 (CD14), tumor necrosis factor alpha (TNFα), interleukin (IL)6, IL10, and IL1ra genes are associated with the risk of peri-implantitis susceptibility in patients with dental implants in the Serbian population. Isolated DNA from the blood was used for IL10-1082, TNFα-308, IL6-174, CD14-159, and interleukin 1 receptor antagonist (IL1ra) genotyping using polymerase chain reaction (PCR)-based methodology. Clinical parameters included: peri-implant pocket depth (PPD), Plaque Index (PI), Gingival Index (GI), bleeding on probing (BOP), and radiologic bone loss. The study included 98 patients with dental implants in function for at least 1 year, divided into peri-implantitis (34) and healthy peri-implant tissue (64) groups. The percentage distribution of smokers was significantly different between patients who developed peri-implantitis and patients with healthy peri-implant tissue (71% vs 42%, respectively) and associated with increased peri-implantitis risk (OR: 3.289, 95% CI: 1.352 to 8.001; P = .007). A positive history of periodontitis was more frequent in the peri-implantitis group (62%) than in the healthy peri-implant tissue (20%) group and associated with increased peri-implantitis risk (OR: 6.337, 95% CI: 2.522 to 15.927; P = .0001). Frequencies of CD14-159, TNFα-308, IL10-1082, and IL6-174 genotypes were significantly different between patients with and without peri-implantitis. However, logistic regression revealed only TNFα-308 polymorphic GA/AA genotypes (OR: 8.890, 95% CI: 2.15 to 36.7; P = .003) and smoking (OR: 6.2, 95% CI: 1.44 to 26.7; P = .014) as independent factors associated with increased peri-implantitis risk, while CD14-159 polymorphic CT/TT genotypes were associated with decreased risk for peri-implantitis (OR: 0.059, 95% CI: 0.009 to 0.355; P = .002). The findings suggest that smoking and the presence of TNFα-308 GA/AA genotypes may increase the risk for peri-implantitis, while CD14-159 polymorphic CT/TT genotypes decrease the risk. The results also indicate significant association of CD14-159, TNFα-308, and IL6-174 genotypes and clinical parameters in the Serbian population. However, future studies in larger patient groups are necessary to confirm these observations.


The Competitive Endogenous RNA (ceRNA) Regulation in Porcine Alveolar Macrophages (3D4/21) Infected by Swine Influenza Virus (H1N1 and H3N2).
H1N1 and H3N2 are the two most common subtypes of swine influenza virus (SIV). They not only endanger the pig industry, but are also a huge risk of zoonotic diseases. However, the molecular mechanism and regulatory network of pigs (hosts) against influenza virus infection are still unclear. In this study, porcine alveolar macrophage cell (3D4/21) models infected by swine influenza virus (H1N1 and H3N2) were constructed. The expression profiles of miRNAs, mRNAs, lncRNAs and circRNAs after H1N1 and H3N2 infected 3D4/21 cells were revealed in this study. Then, two ceRNAs (TCONS_00166432-miR10391-MAN2A1 and novel_circ_0004733-miR10391-MAN2A1) that regulated H1N1 and H3N2 infection in 3D4/21 cells were verified by the methods of bioinformatics analysis, gene overexpression, gene interference, real-time quantitative PCR (qPCR), dual luciferase activity assay and RNA immunoprecipitation (RIP). In addition, the important candidate molecules (miR-10391, TCONS_00166432, and novel_circ_0004733) were identified by qPCR and enzyme linked immunosorbent assay (ELISA). Finally, the regulatory effect and possible molecular mechanism of the target gene MAN2A1 were identified by the methods of gene interference, qPCR, Western blot and ELISA. The results of this study suggested that TCONS_00166432 and novel_circ_0004733 could competitively bind miR-10391 to target the MAN2A1 gene to regulate swine influenza virus infecting 3D4/21 cells. This study reported for the first time the ceRNA networks involved in the regulation of the swine influenza virus infecting 3D4/21 cells, which provided a new insight into the molecular mechanism of 3D4/21 cells against swine influenza virus infection.


Placebo-controlled trial of valproic Acid versus risperidone in children 3-7 years of age with bipolar I disorder.
The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children, 3-7 years of age, with bipolar I disorder (BPD), during a mixed or manic episode. Forty-six children with Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode, were recruited over a 6 year period from two academic outpatient programs for a double-blinded, placebo-controlled trial in which subjects were randomized in a 2:2:1 ratio to risperidone solution, valproic acid, or placebo. After 6 weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores change, adjusted for baseline YMRS scores, from baseline by treatment group was: Valproic acid 10.0±2.46 (p=0.50); risperidone 18.82±1.55 (p=0.008); and placebo 4.29±3.56 (F=3.93, p=0.02). The mixed models for repeated measure (MMRM) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects (p=0.008) but not for valproic acid-treated subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone over 6 weeks led to increased prolactin levels, liver functions, metabolic measures, and weight/body mass index (BMI). Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit. In this small sample of preschool children with BPD, risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did not. The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics, and that, therefore, frequent laboratory and weight monitoring are warranted.


Click modification of helical amylose by poly(l-lysine) dendrons for non-viral gene delivery.
Although amylose as a naturally-occurring helical polysaccharide has been widely used for biomedical applications, few studies have dealt with its chemical modification for non-viral gene delivery. In this work, the click modification of amylose by poly(l-lysine) dendrons was carried out and then characterized by Fourier transform infrared spectroscopy, wide-angle X-ray diffraction and elemental analyses. Such a modified polysaccharide exhibited excellent ability to condense plasmid pMSCV-GFP-PARK2 into compact and spherical nanoparticles. Moreover, it displayed much lower cytotoxicity when compared to branched polyethylenimine (bPEI, 25kDa), a commercially available gene vector. Similar to bPEI, it had a dose-dependent gene transfection activity in human embryonic kidney 293T cells, as observed by confocal laser scanning microscopy and flow cytometry. At each optimized N/P ratio, the percentage of transfected cells by this modified polysaccharide was found to be comparable to that by bPEI. Western blot and cell apoptosis analyses confirmed its effectiveness for the delivery of plasmid pMSCV-GFP-PARK2 to 293T cells.


A durable surface-enhanced Raman scattering substrate: ultrathin carbon layer encapsulated Ag nanoparticle arrays on indium-tin-oxide glass.
The application of Ag nanostructures to surface-enhanced Raman scattering (SERS) is hindered by their chemical instability. Fabrication of durable Ag-based SERS substrates is therefore of great significance in practical applications. In this work, ultrathin C-layer-encapsulated Ag nanoparticle arrays (UCL-Ag-NAs) are successfully fabricated on the surface of indium-tin-oxide (ITO) glass, using a hydrothermal method, for use as durable SERS substrates. The problem of Ag nanoparticles dissolving during the hydrothermal process is solved by using ZnO powder as a pH-buffering reagent. The SERS signal intensity of UCL-Ag-NAs decreases, accompanied by an improvement in Raman signal stability, as the C-layer thickness increases. Raman spectra show that the SERS signal intensities obtained from UCL-Ag-NAs with C-layers of 4.5 nm and 7.3 nm stored for 180 days are 64.9% and 77.8% of those obtained from as-prepared counterparts. The SERS intensity of the UCL-Ag-NA (C-layer of 4.5 nm) is 152.7% that of the bare Ag NA after 180 days of storage. XPS spectra confirm that the C-layer effectively suppresses the oxidation of the Ag NA. This methodology can be generalized to improve the durability of other dimensional Ag nanostructures for SERS applications.


Results from percutaneous drainage of Hinchey stage II diverticulitis guided by computed tomography scan.
Percutaneous abscess drainage guided by computed tomography scan is considered the initial step in the management of patients presenting with Hinchey II diverticulitis. The rationale behind this approach is to manage the septic complication conservatively and to follow this later using elective sigmoidectomy with primary anastomosis. The clinical outcomes for Hinchey II patients who underwent percutaneous abscess drainage in our institution were reviewed. Drainage was considered a failure when signs of continuing sepsis developed, abscess or fistula recurred within 4 weeks of drainage, and emergency surgical resection with or without a colostomy had to be performed. A total of 34 patients (17 men and 17 women; median age, 71 years; range, 34-90 years) were considered for analysis. The median abscess size was 6 cm (range, 3-18 cm), and the median duration of drainage was 8 days (range, 1-18 days). Drainage was considered successful for 23 patients (67%). The causes of failure for the remaining 11 patients included continuing sepsis (n = 5), abscess recurrence (n = 5), and fistula formation (n = 1). Ten patients who failed percutaneous abscess drainage underwent an emergency Hartmann procedure, with a median delay of 14 days (range, 1-65 days) between drainage and surgery. Three patients in this group (33%) died in the immediate postoperative period. Among the 23 patients successfully drained, 12 underwent elective sigmoid resection with a primary anastomosis. The median delay between drainage and surgery was 101 days (range, 40-420 days). In this group, there were no anastomotic leaks and no mortality. Drainage of Hinchey II diverticulitis guided by computed scan was successful in two-thirds of the cases, and 35% of the patients eventually underwent a safe elective sigmoid resection with primary anastomosis. By contrast, failure of percutaneous abscess drainage to control sepsis is associated with a high mortality rate when an emergency resection is performed. The current results demonstrate that percutaneous abscess drainage is an effective initial therapeutic approach for patients with Hinchey II diverticulitis, and that emergency surgery should be avoided whenever possible.


Morphine-induced regional and dose-response differences on unit impulse activity in decerebrate rats.
Previous studies have indicated that morphine alters nerve impulse activity differently in various brain areas of intact animals. Because morphine has profound effects on visceral organs and on the spinal cord, cervically transected preparations, in which hypothermia was prevented, were used for recording spontaneous impulse activity before and for 30 min after morphine simultaneously from six regions of the brain: caudate (Cau), midbrain reticular formation (MBRF), central grey (CG), cingulate cortex (CC), hippocampus (Hip), and substantia nigra (SN). Morphine (5 and 15 mg/kg, i.p.) caused a naloxone-preventable depression of impulse activity in most brain areas. The depression was, however, especially pronounced in the CG, more so with the lower than the higher dose; naloxone completely blocked the low-dose effect. The MBRF responded with increased impulse activity after 5 mg/kg, but with depression after 15 mg/kg; naloxone blocked both responses. Activity in both the Hip and CC was depressed by the low dose of morphine, but not by the high dose; naloxone blocked the depression. Both doses of morphine generally depressed the variance in impulse activity, with a clear preferential depression of CG variance; naloxone blocked the CG variance effect, but not that of other brain areas.


Molecular free energy optimization on a computational graph.
Free energy is arguably the most important property of molecular systems. Despite great progress in both its efficient estimation by scoring functions/potentials and more rigorous computation based on extensive sampling, we remain far from accurately predicting and manipulating biomolecular structures and their interactions. There are fundamental limitations, including accuracy of interaction description and difficulty of sampling in high dimensional space, to be tackled. Computational graph underlies major artificial intelligence platforms and is proven to facilitate training, optimization and learning. Combining autodifferentiation, coordinates transformation and generalized solvation free energy theory, we construct a computational graph infrastructure to realize seamless integration of fully trainable local free energy landscape with end to end differentiable iterative free energy optimization. This new framework drastically improves efficiency by replacing local sampling with differentiation. Its specific implementation in protein structure refinement achieves superb efficiency and competitive accuracy when compared with state of the art all-atom mainstream methods.


"Oxidatively induced" reductive elimination of dioxygen from an eta2-peroxopalladium(II) complex promoted by electron-deficient alkenes.
The first example of associative displacement of dioxygen from a peroxopalladium(II) complex is reported. Electron-deficient alkenes, p-X-trans-beta-nitrostyrene (X = OCH3, CH3, H, F, Br, CF3, NO2), react quantitatively with (bc)Pd(eta2-O2) (bc = bathocuproine) in dichloromethane at room temperature to form the corresponding palladium(0)-alkene complexes. Mechanistic studies indicate that ligand substitution proceeds through an associative mechanism, and the electronic characteristics of the reactions are consistent with an "oxidatively induced" reductive elimination pathway.


[Clinical Characteristics, Treatment and Prognosis of PTLD after allogeneic Hematopoietic Stem Cell Transplantation].
To study the clinical characteristics of patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic peripheral blood hematopoietic stem cell transplantation, and to improve the understanding and diagnosis of PTLD. The clinical data of 244 patients underwent allogeneic hematopoietic stem cell transplantation in the General Hospital of PLA from May 2014 to April 2017 were analyzed retrospectively. The follow-up time was up to November 30, 2017. The incidence, risk factors, treatment and survival of patients with PTLD were statistically analyzed. Among the 244 cases the PTLD occurred in 22 cases, the incidence rate was 9.02%, 5 of them were diagnosed by pathology, and 17 were diagnosed clinically. All of them had EB virus infection. They were all ATG user, either underwent related haploidentical hematopoietic stem cell transplantation or unrelated hematopoietic stem cell transplantation, 20 cases were treated with rituximab or rituximab combined with γ-globulin, glucocorticoid, ERV+CTL, chemotherapy and 17 showed the effective response, with a total effective rate of 85%. The median follow-up time was 122 days, the median survival time was 5 months (1-22 months) and the total survival rate was 50%. The incidence of PTLD after allogeneic peripheral blood hematopoietic stem cell transplantation closely relates with EB virus infection. The application of ATG in the preconditioning scheme is a high risk factor for the onset of PTLD. In the case of no pathological diagnosis, clinical and laboratory examinations should be actively combined so as to define clinical diagnosis. The riturimab should be used more and more for patients with PTLD.


Detection of hepatocellular carcinoma by tissue resonance interaction method (TRIM).
Diagnosis of hepatocellular carcinoma (HCC) is considerably delayed, being frequently done in the non-curative stage of disease. The reason for delayed diagnosis is indolent course in early stages and/or unspecific symptoms indistinguishable from underlying cirrhosis. Hitherto methods used for screening of HCC have important limitations. TRIMprob is a non-invasive method, which showed utility in detection of cancers located in prostate, breast, or urinary bladder. To determine the diagnostic accuracy of TRIMprob in detecting HCC in cirrhotic liver. Forty-five patients were prospectively enrolled according to final clinical diagnosis into a group of cirrhosis and HCC or a group of cirrhosis without HCC. A control group consisted of 33 healthy subjects. Hepatocellular carcinoma was diagnosed by computed tomography (CT) or magnetic resonance (MR) and guided biopsy. The TRIMprob examination was performed in each patient. Three wave frequencies were used: 465, 930, and 1395 MHz. In patients with HCC the intensity of return signal using wave a frequency of 465 MHz was significantly reduced in patients with HCC in comparison to healthy subjects (p < 0.0005), but not to cirrhotic patients without HCC. Moreover, cirrhosis was associated with significantly decreased TRIMprob signal in comparison to healthy liver (p < 0.002). In ROC analysis an optimal cut-off value for detection of HCC was 106 units, which yielded 80% sensitivity. TRIMprob identifies HCC with good sensitivity; however, the accuracy of this method to identify HCC in screening circumstances may be hindered by attenuation of the resonance interaction signal by cirrhosis itself.


Assessing mental health literacy of primary health care workers in Kenya: a cross-sectional survey.
To assess mental health literacy of health workers in primary health care services in Kenya. Mental illness is common in Kenya, yet there are fewer than 500 specialist mental health workers to serve Kenya's population of over 50 million. The World Health Organization recommends the integration of mental health care into primary health care services to improve access to and equity of this care, especially in low and middle-income countries. An important step to integrating mental health care into primary health care services is to determine mental health literacy levels of the primary health care workforce. A cross-sectional survey using Jorm's Mental Health Literacy Instrument (adapted for the Kenyan context) was administered to 310 primary health care workers in four counties of Kenya. Of the 310 questionnaires distributed, 212 (68.3%) were returned. Of the respondents, 13% had a formal mental health qualification, while only 8.7% had received relevant continuing professional development in the five years preceding the survey. Just over one third (35.6%) of primary health care workers could correctly identify depression, with even fewer recognising schizophrenia (15.7%). This study provides preliminary information about mental health literacy among primary health care workers in Kenya. The majority of respondents had low mental health literacy as indicated by their inability to identify common mental disorders. While identifying gaps in primary health care workers' mental health knowledge, these data highlight opportunities for capacity building that can enhance mental health care in Kenya and similar low and middle-income countries.


Running Biomechanics of Adolescents With Autism Spectrum Disorder.
Research examining gait biomechanics of persons with autism spectrum disorder (ASD) has grown significantly in recent years and has demonstrated that persons with ASD walk at slower self-selected speeds and with shorter strides, wider step widths, and reduced lower extremity range of motion and moments compared to neurotypical controls. In contrast to walking, running has yet to be examined in persons with ASD. The purpose of this study was to examine lower extremity running biomechanics in adolescents (13-18-year-olds) with ASD and matched (age, sex, and body mass index (BMI)) neurotypical controls. Three-dimensional kinematics and ground reaction forces (GRFs) were recorded while participants ran at two matched speeds: self-selected speed of adolescents with ASD and at 3.0 m/s. Sagittal and frontal plane lower extremity biomechanics and vertical GRF waveforms were compared using two-way analyses of variances (ANOVAs) via statistical parametric mapping (SPM). Adolescents with ASD ran with reduced stride length at self-selected speed (0.29 m) and reduced vertical displacement (2.1 cm), loading-propulsion GRFs (by 14.5%), propulsion plantarflexion moments (18.5%), loading-propulsion hip abduction moments (44.4%), and loading knee abduction moments (69.4%) at both speeds. Running at 3.0 m/s increased sagittal plane hip and knee moments surrounding initial contact (both 10.4%) and frontal plane knee angles during midstance (2.9 deg) and propulsion (2.8 deg) compared to self-selected speeds. Reduced contributions from primarily the ankle plantarflexion but also knee abduction and hip abduction moments likely reduced the vertical GRF and displacement. As differences favored reduced loading, youth with ASD can safely be encouraged to engage in running as a physical activity.


[Delivering bad news: How to improve communication with relatives].
Communicating bad news, e.g. the message of the death of a close relative, is not a straight forward task for physicians. Typical common inter-speaking attitudes often fail in this difficult situation. Even simple rules and cooking recipes are seldom helpful. Medical training unfortunately does not cover this topic sufficiently. Hence physicians have to learn from trial and error. However, this trial-and-error-method may provoke an unfavourable course of conversation. Training and knowledge of evidence-based rules can improve communicative faculties and facilitate delivering bad news.


Radiotherapy after surgical resection for head and neck mucosal melanoma.
To present our single-institution experience with postoperative radiotherapy for mucosal melanoma of the head and neck. Between 1992 and 2007, 27 patients with mucosal melanoma of the head and neck underwent surgical resection followed by postoperative radiotherapy. Median age was 68 years (range: 45-89 years). Sites included were sinonasal in 24 patients, oral cavity in 2, and oropharynx in 1. All but 2 patients had stage I disease. Twenty-two patients received hypofractionated radiation. Radiation techniques were intensity-modulated radiation therapy in 13, 3-dimensional conformal in 4, and conventional in 10. The median follow-up for living patients was 45 months (range: 24-122 months). The 3- and 5-year estimates of local progression-free, loco-regional progression-free, distant metastasis-free, and overall survival were: 47% and 35%; 34% and 22%; 30% and 24%; and 40% and 33%, respectively. Median time to local failure and distant metastasis was 32 and 14 months, respectively. Acute toxicities included 19% with grade 2 or higher mucositis. No late complications related to the optic structures were seen. Modern radiotherapeutic techniques including intensity-modulated radiation therapy appear feasible and well-tolerated in the postoperative treatment of head and neck mucosal melanoma. Unusual or serious late complications have not been observed despite extensive use of hypofractionated regimens. However, rates of local and distant failure remain high.


Inter-relationships of Salmonella status of flock and grow-out environment at sequential segments in broiler production and processing.
In this study, we investigated how the likelihoods of Salmonella presence in various samples from broilers and their grow-out environment throughout one production cycle were related. Sixty-four broiler flocks from 10 complexes of two companies in the southern United States were included in the study. Samples from the gastrointestinal tracts of chicks, transport tray pads and litter and drag swabs from the house were collected on the day of placement of each flock. Approximately, 1 week before harvest, whole bird carcass rinses, caecum and crop samples were collected from birds from these same flocks. On the day of harvest, litter and drag swab samples were also taken from the house after the birds were removed. Upon arrival of the flocks at the processing plant, whole carcass rinses, caecum and crop samples were collected. As the flocks were processed, carcass rinses were collected just before the carcasses entered the immersion chill tank and as they exited the chill tank. Logistic regression was used to model the relationships between the likelihood of Salmonella in samples of each type collected at each sampling point and Salmonella frequencies in all the samples taken from the flock and grow-out environment at preceding production stages. The analysis demonstrated that increased likelihood of Salmonella contaminated carcasses entering the immersion chill tank was associated with higher contamination of the exteriors and crops of birds at arrival for processing as well as house environmental samples at the time of harvest and prior to placement. The best predictors of post-chill broiler carcass Salmonella status were the frequencies of Salmonella in the litter on the day of harvest and prior to placement. The immersion chilling appeared to disrupt some of the relationships between the processing plant and pre-harvest samples.


High-resolution 1H NMR spectroscopy in a live mouse subjected to 1.5 Hz magic angle spinning.
It is demonstrated that the resolution of the (1)H NMR metabolite spectrum in a live mouse can be significantly enhanced by an ultraslow magic angle spinning of the animal combined with a modified phase-corrected magic angle turning (PHORMAT) pulse sequence. Proton NMR spectra were measured of the torso and the top part of the belly of a female BALBc mouse in a 2 T field while spinning the animal at a speed of 1.5 Hz. It was found that even in this relatively low field, with PHORMAT an isotropic spectrum is obtained with line widths that are a factor of 4.6 smaller than those obtained in a stationary mouse. It is concluded that in vivo PHORMAT has the potential to significantly increase the utility of (1)H NMR spectroscopy for biochemical and biomedical animal research.


Microvascular invasion as a prognostic indicator in renal cell carcinoma: a systematic review and meta-analysis.
Microvascular invasion (MVI), an omen of potential hematogenous spread of tumor cells, has been identified as an accepted risk factor for poor prognosis in some solid tumors. But its prognostic value in renal cell carcinoma (RCC) remains disputable. In order to address this question rigorously, we performed a systematical review of the published literature on MVI and RCC prognosis. According to the PRISMA statement, we searched PubMed, Web of science, and Cochrane Library database and identified 33 cohort articles that met the eligibility criteria and involved 14,946 patients (48-2596 per study) in this meta-analysis. Using the random effects model, the association between MVI and four generally recognized end points were estimated, including cancer-specific survival (CSS), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS). The presence of MVI was detected in 14.4% of the pathological specimens. A higher incidence of MVI was associated with some acknowledged prognostic risk factors such as higher pathological TNM stages and higher tumor grades. Statistical significance of the combined hazard ratio (HR) was detected for CSS (HR, 2.090; 95% CI, 1.530-2.857), RFS (HR = 2.749; 95% CI, 1.974-3.828), MFS (HR = 1.621; 95% CI, 1.095-2.400). However, the association between MVI and worse overall survival did not address statistical significance (HR = 1.371; 95% CI, 0.978-1.923). These findings suggest that the presence of MVI has a detrimental effect on clinicopathological features of RCC and could serve as a poor prognostic factor for patient with RCC.


In vivo observation of cerebral microcirculation after experimental subarachnoid hemorrhage in mice.
Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.


Orientation Preferences and Motion Sickness Induced in a Virtual Reality Environment.
Astronauts' orientation preferences tend to correlate with their susceptibility to space motion sickness (SMS). Orientation preferences appear universally, since variable sensory cue priorities are used between individuals. However, SMS susceptibility changes after proper training, while orientation preferences seem to be intrinsic proclivities. The present study was conducted to investigate whether orientation preferences change if susceptibility is reduced after repeated exposure to a virtual reality (VR) stimulus environment that induces SMS. A horizontal supine posture was chosen to create a sensory context similar to weightlessness, and two VR devices were used to produce a highly immersive virtual scene. Subjects were randomly allocated to an experimental group (trained through exposure to a provocative rotating virtual scene) and a control group (untrained). All subjects' orientation preferences were measured twice with the same interval, but the experimental group was trained three times during the interval, while the control group was not. Trained subjects were less susceptible to SMS, with symptom scores reduced by 40%. Compared with untrained subjects, trained subjects' orientation preferences were significantly different between pre- and posttraining assessments. Trained subjects depended less on visual cues, whereas few subjects demonstrated the opposite tendency. Results suggest that visual information may be inefficient and unreliable for body orientation and stabilization in a rotating visual scene, while reprioritizing preferences for different sensory cues was dynamic and asymmetric between individuals. The present findings should facilitate customization of efficient and proper training for astronauts with different sensory prioritization preferences and dynamic characteristics.Chen W, Chao J-G, Zhang Y, Wang J-K, Chen X-W, Tan C. Orientation preferences and motion sickness induced in a virtual reality environment. Aerosp Med Hum Perform. 2017; 88(10):903-910.


[Effects of Pinus massoniana plantation stand density on understory vegetation and soil properties].
By using plot investigation and sampling analysis methods, the understory vegetation and soil properties of Pinus massoniana plantations with different stand density in subtropical area were studied in Daqingshan, Guangxi Province. In the P. massoniana plantations after 14-year natural growth, the understory species diversity index of shrub layer increased with the increase of stand density from 1050 trees x hm(-2) to 1800 trees x hm(-2), but decreased when the stand density further increased to 2250 trees x hm(-2). Herb species diversity index was not sensitive to the stand density change. With increasing stand density, shrub biomass had the same variation trend as that of shrub species diversity index, while herb biomass decreased with increasing stand density. Significant differences (P < 0.05) were observed in the soil (0-20 cm) physical and chemical properties between the plantations with different stand density. The soil nutrient contents except those of total P and available K and P had the same variation trend with that of the understory species diversity index of shrub layer. Soil available K and P contents fluctuated with stand density, whereas soil total P content was higher when the stand density was 2100 trees x hm(-2). In the plantations with moderate stand density (1800 trees x hm(-2)) , soil water-holding capacity and soil porosity were higher, and soil bulk density was lower.