Size distribution and lung-deposited doses of particulate matter from household exposure to biomass smoke.
Exposure to high concentrations of particulate matter (PM) is associated with a number of adverse health effects. However, it is unclear which aspects of PM are most hazardous, and a better understanding of particle sizes and personal exposure is needed. We characterized particle size distribution (PSD) from biomass-related pollution and assessed total and regional lung-deposited doses using multiple-path deposition modeling. Gravimetric measurements of kitchen and personal PM2.5 (<2.5 µm in size) exposures were collected in 180 households in rural Puno, Peru. Direct-reading measurements of number concentrations were collected in a subset of 20 kitchens for particles 0.3-25 µm, and the continuous PSD was derived using a nonlinear least-squares method. Mean daily PM2.5 kitchen concentration and personal exposure was 1205 ± 942 µg/m3 and 115 ± 167 µg/m3 , respectively, and the mean mass concentration consisted of a primary accumulation mode at 0.21 µm and a secondary coarse mode at 3.17 µm. Mean daily lung-deposited surface area (LDSA) and LDSA during cooking were 1009.6 ± 1469.8 µm2 /cm3 and 10,552.5 ± 8261.6 µm2 /cm3 , respectively. This study presents unique data regarding lung deposition of biomass smoke that could serve as a reference for future studies and provides a novel, more biologically relevant metric for exposure-response analysis compared to traditional size-based metrics.


Amorphous Silk Nanofiber Solutions for Fabricating Silk-Based Functional Materials.
As a functional material, silk has been widely used in tissue engineering, drug release, and tissue regeneration. Increasing subtle control of silk hierarchical structures and thus specific functional performance is required for these applications but remains a challenge. Here, we report a novel silk nanofiber solution achieved through tuning solvent systems used to generate the material. Unlike the β-sheet rich silk nanofibers reported previously, these new silk nanofibers are mainly composed of amorphous structures and maintain a solution state in aqueous environments. The amorphous silk nanofibers are stable enough for storage and also metastable, making them easy to use in the further fabrication of materials through various processes. Silk scaffolds, hydrogels, and films were prepared from these silk nanofiber solutions. These silk materials from amorphous nanofiber solutions show different properties and tunable performance features. Therefore, these amorphous silk nanofibers are suitable units or building blocks for designing silk-based materials.


Origin of the medulloblastoma experimentally induced by human polyomavirus JC.
The origin of the medulloblastoma induced by JC virus (JCV) in golden hamsters was investigated by the in situ hybridization method. After inoculation of JCV into newborn hamsters, a few migrating cells in the cerebellar molecular layer as well as several cells in the internal granular layer hybridized with an antisense mRNA probe of JCV T-antigen on the 10th day. The number of cells positive for this probe decreased on the 15th and 20th days. Moreover, an incipient medulloblastoma consisting of many cells positive for T-antigen mRNA was noticed in the cerebellar internal granular layer 30 days after inoculation. About 6 months post inoculation, 95% of the animals had succumbed to medulloblastoma. Therefore, the origin of the medulloblastoma seemed to be the cells in the cerebellar external granular layer that were infected by JCV, that migrated normally through the molecular layer to the internal granular layer, and that began to proliferate to become medulloblastoma. When 5-day-old hamsters were inoculated, a few cells positive for T-antigen mRNA were detected in the cerebellum within a month. In the long-term observation, the ratio of medulloblastoma induction decreased as the age of the animals at inoculation increased. These results support the idea that JCV infects and transforms the cells in the cerebellar external granular layer, because this layer appears only transiently in newborn hamsters.


How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence.
Community advisory boards (CABs) continue to gain wide use and acceptance in global health research including in HIV clinical trials. They provide means through which community concerns regarding the trial can be considered by the research team, and provide an important platform of communication between the researchers and the community about study goals. Therefore, this systematic review protocol will guide the review of qualitative evidence on the ethical roles of CABs in HIV clinical trials based on the three fundamental ethical principles: respect for the person, beneficence and justice. This systematic review of qualitative evidence will involve searching four medical databases: PubMed, ScienceDirect, CINAHL and Cochrane Library. Additionally, other relevant evidence will be obtained through hand searching and grey literature. Searches will be limited to studies published in the English language from 1989 (the year that CABs were first established in HIV clinical trials) to 2019. Articles searched will be screened by two independent authors based on inclusion and exclusion criteria. Included articles will be appraised for quality using the Critical Appraisal Skills Programme checklist and followed by qualitative data extraction. Findings will be analysed based on the meta-aggregative approach with the aid of EPPI-Reviewer 4 web-based software. Ethical approval does not apply to this review. Data will be disseminated through scientific conferences and peer-reviewed journals to inform policies and stake-holders about the ethical role of CABs. CRD42019133787.


[Risk Assessment of Hematologic Malignancy Treatment of the Elderly].
Along with the aging society in Japan, the number ofelderly cancer patients is increasing, and hematological malignancy is no exception. Treatment ofhematological malignancy is mainly chemotherapy and furthermore it is necessary to keep its dose intensity. In the elderly, adverse events may be strong due to deterioration oforgan function, comorbidity, etc., and it is difficult for individual differences to decide chemotherapy regimen and dose. Geriatric assessment(GA)used in the field of geriatric medicine is reported to be useful for risk assessment of chemotherapy. The usefulness of GA is also shown in hematological malignancy. In non-Hodgkin's lymphoma, attempts have been made to determine the treatment method by stratifying the risk using the results of GA.


Prophylaxis of Candida albicans infection in neutropenic mice with liposome-encapsulated amphotericin B.
The efficacy of liposome-encapsulated amphotericin B in the prophylaxis of disseminated Candida albicans infections in neutropenic mice was studied. The administration of liposome-encapsulated amphotericin B was associated with protection against infection with C. albicans when used at doses of greater than or equal to 2 mg of amphotericin B per kg of body weight. Neither empty liposomes nor free amphotericin B showed prophylactic efficacy.


[Anastomotic Leakage in the Gastrointestinal Tract: Surgical Versus Nonoperative Management].
Most procedures in gastrointestinal (GI) surgery require reconstruction with an anastomosis. Depending on the location within the GI tract, the perfusion and comorbidities of the patients there is a risk for anastomotic leakage. In case of peritonitis with sepsis usually a surgical treatment is required. A stable patient can be treated nonoperatively. In the following overview different treatment options of anastomotic leakage after surgery of the GI tract are described. In case of a leakage of an esophagojejunal or esophagogastric anastomosis after resection of the esophagus or stomach endoscopic treatment can be successful using either clip or stent or negative pressure therapy (NPT). After surgery of the rectum the use of endoluminal NPT has shown good results in case of anastomotic leakage. Nonoperative management of anastomotic leakage can be successful in a stable patient and requires intensive cooperation in an interdisciplinary team with experts in surgery, endoscopy, radiology and intensive care.


Genome-Wide Profiling of Alternative Splicing Signatures Associated with Prognosis and Immune Microenvironment of Hepatocellular Carcinoma.
BACKGROUND The potential roles of alternative splicing (AS) in HCC remain unknown. This study aimed to identify AS signatures associated with the prognosis that influence the immune microenvironment of HCC. MATERIAL AND METHODS The SpliceSeq tool was employed for genome-wide profiling of 7 AS events in 361 HCC patients from The Cancer Genome Atlas (TCGA). A prognostic signature was built by integrating Cox regression and the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) and receiver operating characteristic curve (ROC) were employed to analyze the AS events in the signatures to discriminate the immune microenvironment. RESULTS There were 3546 AS events highly linked to the survival of patients with HCC. The AS signature could effectively stratify HCC patients. Clustering analysis revealed 3 different immune clusters characterized with significantly different prognoses and were significantly correlated with AS signatures. The AS events in the final prognostic signature classified the immune cluster with an average AUC of the ROC (0.88). Moreover, a potential regulatory network of splicing events in HCC is presented. CONCLUSIONS We established the prognostic signature based on AS, which can effectively stratify HCC patients and predict the immune subtypes. Moreover, novel RNA splicing patterns and splicing-regulatory networks involved in HCC were discovered.


[Impact of Cu and Zn pollution on rape growth and soil enzyme activity].
A pot experiment was conducted to study the impact of Cu and Zn pollution on soil enzyme activities and rape seedlings growth. The results showed that Cu had a stronger inhibitory effect than Zn on soil urease activity, while Zn had more obvious impact on soil calatase activity. The damage on the growth and dry mass of rape was more serious under Cu than under Zn pollution. The inhibition of rape seedlings growth was mainly due to the inhibition of root growth and its material accumulation. Factor analysis indicated that root dry mass was more sensitive than other indices, which could be adopted to monitor soil Cu and Zn pollution.


Production of Ultrafine PVDF Nanofiber-/Nanonet-Based Air Filters via the Electroblowing Technique by Employing PEG as a Pore-Forming Agent.
Particles with diameters smaller than 2.5 μm (PM2.5) can penetrate the respiratory system and have negative impacts on human health. Filter media with a porous surface and nanofiber/nanonet structure demonstrate superior filtration performance compared to traditional nano- and microfiber-based filters. In this study, nanostructured filters were produced using the electroblowing method from solutions containing different ratios of poly(vinylidene fluoride) (PVDF) and polyethylene glycol (PEG) polymers for the first time. By increasing the water-soluble PEG ratio in PVDF/PEG blend nanofibers and employing a water bath treatment to the produced mat afterward, a more porous fibrous structure was obtained with a lower average fiber diameter. Notably, the removal of PEG from the PVDF/PEG (3-7) sample, which had the highest PEG content, exhibited clustered nanofiber-/nanonet-like structures with average diameters of 170 and 50 nm at the points where the fibers intersect. Although this process resulted in a slight decrease in the filtration efficiency (-1.3%), the significant reduction observed in pressure drop led to a 3.2% increase in the quality factor (QF). Additionally, by exploiting the polarizability of PVDF under an electric field, the filtration efficiency of the nanostructured PVDF filters enhanced with a ratio of 3.6% after corona discharge treatment leading to a 60% improvement in the QF. As a result, the PVDF/PEG (3-7) sample presented an impressive filtration efficiency of 99.57%, a pressure drop (ΔP) of 158 Pa, and a QF of 0.0345 Pa-1.


A prospective study of associations among helping, health, and longevity.
How does helping behavior contribute to the health and the longevity of older helpers? From an evolutionary perspective, the ultimate cause may be rooted in ancestral parenting and grandparenting. These activities may have generalized to a neural and hormonal caregiving system that also enabled prosocial behavior beyond the family. From a psychological perspective, helping others may be associated with healthy aging, which, in turn, contributes to longevity as a proximate cause. Yet little is known about the extent to which mediating factors such as the health benefits of helping behaviors translate into enhanced longevity, particularly in regard to grandparenting. To fill this gap, we conducted mediation analyses (structural equation models) to examine whether grandparenting and supporting others in the social network contributed directly or indirectly (through better health 5-6 years later) to the longevity of older helpers. We drew on longitudinal data from the Berlin Aging Study (N = 516), in which older adults in Berlin, Germany, were interviewed at baseline (1990-1993, mean age at entry = 85 years) and continuously followed up until 2009. Results suggest that the associations of both grandparenting and supporting others with enhanced longevity are mediated by better prospective health (indirect effect). The effect of helping was not fully mediated, however-helping was also directly associated with increased longevity independently of the health indicators measured. The results were robust against effects of the helper's preexisting health status and sociodemographic characteristics of participants, their children, and grandchildren. We conclude that better prospective health contributes to the link between helping and longevity, but does not fully account for it. Other potential contributing mechanisms remain to be identified. As populations age across the globe, identifying mechanisms that foster health in old age can help to highlight potential targets for public health interventions.


[Alterations in the passive and active performance of cat papillary muscle induced by variation of preload (author's transl)].
In the isolated cat papillary muscle a rapid change in length induces a viscoelastic process of relaxation, during which the diastolic tension attains its new equilibrium after a delay. Its time course may be approximated both after stretching and releasing by a total of four exponential functions being marked by highly diverse time constants. During the stretch-induced relaxation phase the isometrically active papillary muscle shows a marked increase in mechanogram amplitudes, which is preceded in the first seconds by a short-term decrease. An opposite behavior is to be recorded after abrupt releases. The mechanograms of the stationary state prove to be exclusively a function of the degree of stretch, while the contractions in the early relaxation phases are dependent on the speed, direction and scale of the preceding change in length. The higher the stretching step chosen, the more clearly reduced are the mechanogram amplitudes of the early relaxation phase in comparison to the stationary state. This applies especially right of the optimum of force-development and contradicts a viscoelastic interpretation of the systolic phenomena in the poststretch phase. The findings after abrupt stretching point to either an initial decrease of amplitude or to a delayed approach of the contractions to their stationary state. Stretch-induced changes in the time course of the action potentials would constitute an adequate basis for the interpretation of these phenomena.


[Minimal Invasive Fixation of Pelvic Injury: CT-Study of the Pelvic Bone Dimensions].
PURPOSE OF THE STUDY This radiographic study was focused on measuring the dimensions of pelvic bones at sites of minimally invasive screw insertion with the aim to assess the risk of damage to vascular and nervous structures. MATERIAL AND METHODS The group consisted of 77 patients (39 women and 38 men) aged between 19 and 85 years (average, 65; women, 65; men, 64) who underwent CT examination of the pelvis because of reasons other than injury. On the left side, a total of 14 dimensions of the superior pubic ramus, supraacetabular region, retroacetabular region, quadrilateral surface of the acetabulum and lateral foraminal sides of the S1 and S2 vertebral bodies were measured. The results were evaluated using descriptive statistics. RESULTS The inner antero-posterior dimension of the isthmic area of the superior pubic ramus was 8 mm or less in four women (10.3%) and 9 or 10 mm in further 14 women (35.9%). The inner cranio-caudal dimension of the superior pubic ramus was 8 mm or less in 14 women (35.9%) and 9 or 10 mm in further 16 women (41.0%). These dimensions obtained in men were as follows: 8 mm and less in three men (7.9%) (7 mm in one, 8 mm in two), and 9 or 10 mm in nine men. Sizes of the other pelvic bones were large enough to allow for safe insertion of single screws. DISCUSSION Single screws most frequently used in minimally invasive treatment of pelvic fractures are cannulated screws 7.3 mm or 6.5 mm in diameter; less frequently used are 4.5-mm cancellous screws (e.g. in treatment of avulsion injuries) or long 3.5-mm cortical "creeping" screws to be inserted in the superior pubic ramus. The use of "creeping" screws reported by several authors indicates problems associated with placement of standard screws (diameter, 7.3 mm and 6.5 mm) through the isthmus into the superior ramus. In slim high pelvises of some patients with gracile skeletons or in low pelvises of small women, the screws can protrude over the cortical margin. However, the risk of injury to nervous or vascular structures is low when the intraosseous screw is exactly inserted and it is so even in case its thread cuts into cortical bone. Neither the femoral artery nor the femoral nerve is situated too close to the superior pubic ramus. The "corona mortis" may potentially be jeopardised because of its contact with both the superior and posterior cortical bones of the superior ramus, but it usually follows a course more lateral to the isthmus of the ramus. CONCLUSIONS The results of the study showed that the size of the superior pubic ramus in its isthmic area may cause difficulties during insertion of cannulated screws with standard diameters (7.3 mm and 6.5 mm) in the majority of women and in some men. The risk of damage to vascular and nervous structures during screw insertion is associated only with the superior and posterior walls of the superior pubic ramus and with the area of the S2 foramen in case the correct procedure of intraosseous screw insertion is not strictly followed. retrograde pubic screw, iliosacral screw, supraacetabular screw, retrograde posterior column screw.


Genitourinary malignancies in solid organ transplant recipients.
Malignancy is a recognized complication of transplantation. Genitourinary cancers are the second most common tumors in transplant recipients with prostate cancer and renal cell carcinoma the most common. Unlike the more common skin malignancies, genitourinary tumors have a significant impact on both graft and patient survival. Surgical and radiation treatments need to consider the location of heterotopic transplants and administration of chemotherapy may need alteration in light of immunosuppression being used. The major genitourinary malignancies and their management will be reviewed in this article with emphasis on the concerns that arise in a transplant recipient.


Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.
Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level. We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography. Malnutrition was assessed by subjective global assessment (SGA). At basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes mellitus, respectively. At baseline, the mean plasma pentosidine levels were similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19 pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly lower in the patients with carotid plaques than in the patients without carotid plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p < 0.01, respectively). The prevalence of hyperhomocysteinemia (tHcy level > 13.7 micromol/l) was 95%. In univariate analysis, the change in cIM area during the first year of dialysis was significantly correlated with basal plasma pentosidine level (p = 0.31, p = 0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy levels were correlated with cIM area at basal or at 12 months. In a stepwise multiple regression model, age and plasma pentosidine content, but not the tHcy level, associated with changes in the cIM area. Progression of atherosclerosis, as indicated by changes in carotid intima-media area during the course of dialysis treatment, was associated with pentosidine, but not with tHcy, levels at baseline in these CKD patients. This suggests that the accumulation of AGEs in CKD patients may have a role in the pathogenesis of CVD in these patients. Since almost all CKD patients have hyperhomocysteinemia, this finding, however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD patients.


Enhanced Biosynthesis of Fatty Acids Is Associated with the Acquisition of Ciprofloxacin Resistance in Edwardsiella tarda.
Misuse and overuse of antibiotics drive the selection and spread of antibiotic-resistant bacteria. Although genetic mutations have been well defined for different types of antibiotic resistance, ways to revert antibiotic resistance are largely unexplored. Here, we adopted a proteomics approach to investigate the mechanism underlying ciprofloxacin resistance in Edwardsiella tarda, a representative pathogen that infects both economic animal species and human beings. By comparing the protein expression profiles of ciprofloxacin-sensitive and -resistant E. tarda, a total of 233 proteins of differential abundance were identified, where 53 proteins belong to the functional categories of metabolism, featuring a disrupted pyruvate cycle and decreased energy metabolism but increased fatty acid biosynthesis. The altered pyruvate cycle and energy metabolism were confirmed by gene expression and biochemical assays. Furthermore, the role of fatty acid biosynthesis and quinolone resistance were explored. The expression level and enzymatic activity of acetyl coenzyme A (acetyl-CoA) carboxylase, the first step of fatty acid biosynthesis, were increased in ciprofloxacin-resistant E. tarda. Treatment of ciprofloxacin-resistant E. tarda with acetyl-CoA carboxylase and 3-oxoacyl-[acyl carrier protein] synthase II inhibitors, 2-aminooxazole and triclosan, respectively, reduced the expression of fatty acid biosynthesis and promoted quinolone-mediated killing efficacy to antibiotic-resistant bacteria. Similar results were obtained in clinically isolated E. tarda strains. Our study suggests that energy metabolism has been reprogramed in ciprofloxacin-resistant bacteria that favor the biosynthesis of fatty acid, presenting a novel target to tackle antibiotic-resistant bacteria. IMPORTANCE Edwardsiella tarda is the causative agent of edwardsiellosis, which imposes huge challenges on clinics and aquaculture. Due to the overuse of antibiotics, the emergence and spread of antibiotic-resistant E. tarda threaten human health and animal farming. However, the mechanism of ciprofloxacin resistance in E. tarda is still lacking. Here, iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics was performed to identify a differential proteome between ciprofloxacin-sensitive and -resistant E. tarda. The fluctuated pyruvate cycle and reduced energy metabolism and elevated fatty acid biosynthesis are metabolic signatures of ciprofloxacin resistance. Moreover, inhibition of biosynthesis of fatty acids promotes quinolone-mediated killing efficacy in both lab-evolved and clinically isolated strains. This study reveals that a ciprofloxacin resistance mechanism is mediated by the elevated biosynthesis of fatty acids and the depressed pyruvate metabolism and energy metabolism in E. tarda. These findings provide a novel understanding for the ciprofloxacin resistance mechanism in E. tarda.


Elastofibroma in the Rearfoot: A Case Report of a Rare Soft Tissue Tumor.
An elastofibroma is a rare, benign, slow-growing, progressive soft tissue neoplasm with distinct histopathological features consisting of collagen and coarse elastic fibers. When it occurs, it has a propensity for the subscapular region in elderly female patients. It can occur less commonly at other anatomical sites, and its exact etiology is unclear. The incidence of elastofibroma, especially in the foot, has been sporadically reported; however, the presentation of elastofibroma in the rearfoot has not been previously described in the literature. We present the first report of a 79-year-old female presenting with plantar heel pain secondary to an elastofibroma found at the insertion of the plantar fascia into the calcaneal tuberosity. The patient underwent surgical excision, and pathological analysis revealed the diagnosis of elastofibroma. We discuss the peculiar manifestation of elastofibroma in this case, the pathological diagnosis, and a review of the literature.


How often should computed tomographic scans following cross-table lateral cervical films be performed?
In patients with blunt trauma, a cross-table lateral cervical (CTLC) film is followed by a focused computed tomographic (CT) scan of the cervical spine to assess an area inadequately delineated by common techniques and suspected injuries, based on recent guidelines in the United States. The purpose of this study was to calculate the frequency of such supplemental CT scans and to evaluate the efficacy of the recent guidelines describing the use of CTLC films as an indicator of supplemental focused CT scanning in Japan. A review of CTLC films was performed. 100 initial CTLC films with injuries and another 100 films without injuries were evaluated for the lowest vertebra visualised on the CTLC film. The frequency of abnormal signs on the CTLC films was then examined. Technically adequate CTLC films that showed the upper border of the T1 vertebra were not obtained from 70 patients with injuries and 63 patients without injuries. 88 patients with injuries and 28 patients without injuries had abnormal findings on CTLC films. Overall, 97 patients with injuries and 74 patients without injuries should have received supplemental CT scans. CTLC films require frequent supplemental use of CT, even for patients without cervical spine injuries. Thus, the guidelines that consider CTLC film as an indicator of the necessity for CT scanning are not efficient and need revision.


Feasibility of withholding antibiotics in selected febrile neutropenic cancer patients.
To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of 471 (US $572) for every potentially low-risk patient. This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.


Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats.
The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to be pregnant in the control, low-, mid-, and high-dose group, respectively. The NHDC treatment was well tolerated and all animals survived till the end of the study. Body weights (bw) and body weight gains did not differ between controls and NHDC treatment groups. The intake of NHDC was 0.8-0.9, 1.6-1.7, and 3.1-3.4 g/kg bw/day for the low-, mid-, and high-dose group, respectively. Except for cecal enlargement, there were no changes observed at necropsy which could be related to the NHDC treatment. All dams had viable fetuses. The fecundity and gestation index, the number of corpora lutea, implantation sites, live and dead fetuses, early and late resorptions, pre- and post-implantation losses, and sex-ratio were not affected by the treatment. There were no differences for the mean weight of the gravid and empty uterus, ovaries, and placenta between the NHDC treatment groups and the controls. Examination of the fetuses for external, visceral, and skeletal changes did not reveal any fetotoxic, embryotoxic or teratogenic effects of NHDC. In conclusion, no adverse effects were observed at NHDC levels of up to 5% of the diet, the highest dose level tested, at which the rats consumed about 3.3g/kg body weight/day. The observed cecal enlargement is a well-known physiological, adaptive response to the ingestion of high doses of a low-digestible substance and is generally accepted to lack toxicological relevance.


Adenoma of the retinal pigment epithelium: a report of 3 cases.
To report the clinical manifestations and pathologic features of adenoma of the retinal pigment epithelium (RPE). Retrospective study. Three patients with an initial clinical diagnosis of choroidal melanoma. Routine eye examinations, including visual acuity, intraocular pressure, slit-lamp examination, and ophthalmoscopy, were performed. Auxiliary examinations included fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), B-scan ultrasonography, colour Doppler imaging (CDI), and MRI. Endoresection of the tumours was performed, and the specimens underwent pathological examination. The tumours were of yellow-pink or brown colour and all located in the right eye. On FFA and ICGA, the tumours demonstrated hypofluorescence in the early phase and hyperfluorescence with prominent leakage in the late phase. CDI showed arterial blood signals in the tumour, and MRI showed hyperintensity in the T1-weighted image and hypointensity in the T2-weighted image. On pathological examination all the tumours were positive with periodic acid-Schiff, S-100, neurone-specific enolase, synaptophysin, epithelial membrane antigen, and vimentin staining but negative with melanoma-specific antigen HMB45, and cytokeratin. After 3 years of follow-up, there was no tumour recurrence and the retinas remained attached. RPE-derived adenoma is difficult to diagnose clinically. In most cases, pathological confirmation is needed. Local resection is a favorable alternative treatment for some patients.


An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.
During the last 10 years, three European phase II studies were performed to investigate the treatment of elderly patients with myelodysplastic syndrome (MDS) with low-dose 5-aza-2'-deoxycytidine (decitabine, DAC). All these European trial data were reviewed on the basis of the International Prognostic Scoring System (IPSS) risk criteria and the response criteria as recently published by an international working group. To investigate the results in a larger cohort of patients and to determine risk factors, all data were pooled with some observations from the PCH 95-06 US phase II study. The response rate in the 177 patients evaluated (median age 70 years) was 49%. The median response duration was 36 weeks, and the median survival was 15 months. Analysis of the data according to sex, age, French-American-British classification, percentage of blasts in the bone marrow, IPSS risk group, lactate dehydrogenase and cytogenetics did not reveal any factor predictive of response. Overall, 69% of patients benefited, including those with stable disease during therapy. Response duration was significantly shorter with increasing risk (according to the IPSS classification). Haemoglobin level and neutrophil count showed an inverse correlation to the IPSS classification. Univariate analysis showed a significantly inferior survival for elderly patients (>75 years of age) and for those with high levels of serum lactate dehydrogenase (LDH) (more than two times the normal values). Patients with high-risk cytogenetic abnormalities according to the IPSS risk criteria showed better overall survival than those with intermediate-risk abnormalities. When analysed according to the IPSS risk classification, high-risk patients had worse survival prospects following decitabine therapy than those with intermediate risk; however, compared to the originally reported IPPS outcomes for high-risk patients, they probably showed better survival. During the treatment period, 18% of the patients progressed towards acute leukaemia. Decitabine showed a rather low toxicity profile in this elderly patient group. In conclusion, low-dose decitabine is an active drug for the treatment of MDS patients, even for those older than 75 years with bad prognostic characteristics.


IL-4 receptor signaling in Clara cells is required for allergen-induced mucus production.
Excessive mucus production is an important pathological feature of asthma. The Th2 cytokines IL-4 and IL-13 have both been implicated in allergen-induced mucus production, inflammation, and airway hyperreactivity. Both of these cytokines use receptors that contain the IL-4Ralpha subunit, and these receptors are expressed on many cell types in the lung. It has been difficult to determine whether allergen-induced mucus production is strictly dependent on direct effects of IL-4 and IL-13 on epithelial cells or whether other independent mechanisms exist. To address this question, we used a cell type-specific inducible gene-targeting strategy to selectively disrupt the IL-4Ralpha gene in Clara cells, an airway epithelial cell population that gives rise to mucus-producing goblet cells. Clara cell-specific IL-4Ralpha-deficient mice and control mice developed similar elevations in serum IgE levels, airway inflammatory cell numbers, Th2 cytokine production, and airway reactivity following OVA sensitization and challenge. However, compared with control mice, Clara cell-specific IL-4Ralpha-deficient mice were nearly completely protected from allergen-induced mucus production. Because only IL-13 and IL-4 are thought to signal via IL-4Ralpha, we conclude that direct effects of IL-4 and/or IL-13 on Clara cells are required for allergen-induced mucus production in the airway epithelium.


Septic hip presenting with dislocation as a source of occult infection in a burn patient.
An 11-year-old boy was transferred to a regional burn center after sustaining 53% TBSA burns. Initial wound cultures grew multiple organisms. Multiresistant Klebsiella was cultured from the patient's blood. When the patient indicated worsening hip pain, radiographs revealed a spontaneous hip dislocation. Immediate arthrotomy revealed left hip synovial fluid infected with Klebsiella. The patient remained afebrile and was discharged home 6 months after admission.


Synthesis of the t [beta-D-Gal-(1 goes to 3)-alpha-D-GalNAc]-antigenic determinant in a form useful for the preparation of an effective artificial antigen and the corresponding immunoadsorbent.
The T antigenic determinant was synthesized in the form 8-methoxycarbonyloctyl 2-acetamido-2-deoxy-3-O-(beta-D-galactopyranosyl)-alpha-D-galactopyranoside (6) (beta-D-Gal-(1 goes to 3)-alpha-D-GalNAcO(CH2)8CO2Me). This T-hapten was used to prepare a T-BSA artificial antigen (7) and an immunoadsorbent (8), which were shown to possess the expected immunological properties. Nuclear Overhauser enhancements of the signals for anti-periplanar H-2' and the syn-axial H-3' of the beta-D-galactopyranosyl group were observed on saturation of H-1'. The signal for H-3 of the 2-acetamido-2-deoxy-alpha-D-galactopyranoside residue was also enhanced.


Risk of viral transmission via bone marrow progenitor cells versus umbilical cord blood hematopoietic stem cells in bone marrow transplantation.
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for children and certain adults with malignant and nonmalignant hematologic disease. Since viral infections are the major problem, this study examined those that might potentially be transmitted to HSCT recipients via bone marrow (BM) versus umbilical cord blood (UCB). BM progenitor cells, peripheral blood leukocytes, and plasma samples were collected from 30 allogenic BM donors. Umbilical cord blood hematopoietic stem cells and plasma samples were also collected from 34 UCB donors. Viral DNA extracted and purified from collected specimens was processed using nested polymerase chain reactions (PCR) to detect human parvovirus B19 (HPV B19), human herpesvirus-6 (HHV-6), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and Epstein-Barr virus (EBV). The prevalences of HCMV DNA in collected BM progenitor cells versus UCB hematopoietic stem cells were 73% versus 23%, respectively. Conversely, HHV-6 DNA was not detected in any collected specimen by simple PCR. Distribution of the other investigated virus DNAs except EBV DNA was similar in specimens collected from both groups. EBV DNA was not determined in UCB hematopoietic stem cells. The results indicate that the risk of viral transmission to BM transplant recipients via UCB hematopoietic stem cells is less than that with BM progenitor cells.


The S. cerevisiae Yap1 and Yap2 transcription factors share a common cadmium-sensing domain.
Towards elucidating the function of Yap2, which remains unclear, we have taken advantage of the C-terminal homology between Yap1 and Yap2. Swapping domains experiments show that the Yap2 C-terminal domain functionally substitutes for the homologous Yap1 domain in the response to Cd, but not to H2O2. We conclude that specificity determinants of the Cd response are encoded within both Yap1 and Yap2 C-terminus, whereas those required for H2O2 response are only present in the Yap1 C-terminus. Furthermore, our results identify FRM2 as Cd-responsive Yap2 target and indicate a possible role of this protein in regulating a metal stress response.


Refinements in the Techniques of Venous Surgery.
The surgery of venous disease falls into two distinct categories, the removal of malfunctioning unsightly superficial veins and the restoration of the function of the deep veins by repairing or replacing valves or bypassing obstructions. During the past decade surgical advances have mainly been concerned with the refinement of techniques to reduce the cost of surgery and its outward and visible manifestation - the scars, rather than the introduction of new principles or objectives.


Higher ultra-processed food intake was positively associated with odds of NAFLD in both US adolescents and adults: A national survey.
The effect of ultra-processed foods (UPF) on NAFLD remains unclear. Related evidence for adult NAFLD is limited and no study has yet evaluated UPF's impact on NAFLD in adolescence. We used data from the National Health and Nutrition Examination Survey (2017-2018) with 806 adolescents and 2734 adults. UPF intake was estimated using dietary data from two 24-hour dietary recalls. NAFLD was defined by transient elastography. Logistic regression was used to estimate the multivariable OR and 95% CI for associations between UPF and NAFLD with survey weight adjustments. The mean UPF intake was 812 g/d in adolescents and 823 g/d in adults. A total of 12.4% of the adolescents and 35.6% of the adults had NAFLD. Higher UPF intake was associated with higher odds of NAFLD in both adolescents (OR Quintile 5 vs. Quartile 1 = 2.34, 95% CI, 1.01, 5.41; ptrend = 0.15) and adults (OR Quintile 5 vs. Quintile 1 = 1.72, 95% CI, 1.01, 2.93; ptrend = 0.002). In adults, ~68% and 71% of the association between UPF intake and NAFLD was mediated by body mass index and waist circumference (all p-values < 0.001), respectively. The results were similar for adolescents but not statistically significant. A higher UPF intake was associated with lower levels of serum albumin and higher levels of C-reactive protein in adults. Higher UPF intake was linked to higher NAFLD odds in both adolescents and adults, mainly because of elevated body fatness. If confirmed, reducing UPF intake may help prevent NAFLD in both adolescents and adults.


Analysis of trap distribution of a red persistent luminescent materials using thermoluminescence.
Trap distribution plays a crucial role in deciding the applicability of a material. The thermoluminescence (TL) parameter that describes trap distribution is η, which has never been discussed in TL analysis so far. TL analysis of a commercially available red persistent luminescent material (CaSrS:Eu) was performed using computerized glow curve deconvolution (CGCD) in the new general order kinetics. CGCD results showed that the red persistent luminescent material in the temperature range 300-600º K was comprised of nine peaks. Activation energy ranged from 0.66-1.27 eV. Frequency factor was in the range 109 to 1011 sec-1 . The major peaks of the red persistent luminescent material had lesser empty traps. The most important information provided by the analysis was that the major peaks of the red persistent luminescent material had 30-60% of the empty traps close to the filled traps, and this accounted for retrapping of thermally released electrons. This finding suggests that the occurrence of 30-60% empty traps close to the filled traps is a necessary requisite for a persistent luminescent material.


[Revisiting bipolar disorder].
According to the theory of evolution of Charles Darwin which is an author of The Origin of Species, human being evolves after long time to be profitable to "prosperity of a kind", and it is thought that there is the adaptive meaning. In other words, man stand on various creatures in number, and it may be said that human being building a high civilized society is the creature which was able to have an element of chosen mind and body in natural selection. However, a disease does not disappear from our daily life and tends to consider us to be "the misfortune" even if we human being is easy to suffer from a disease. "Evolution medicine" (Darwinian medicine) drop hint of meaning/the significance in aging and the process of the pathology. This paper refers to such a conception of bipolar disorder.


A potential therapeutic pitfall in the treatment of venous reflux due to variant planar anatomy of varicose segments.
Purpose To elaborate on a planar anatomic variant of great saphenous vein as a potential therapeutic pitfall in the treatment of venous reflux. Materials and methods Lower extremity veins in 568 limbs with great saphenous vein insufficiency were sonographically mapped. A rather overlooked variation, the saphenous bow, was studied with emphasis on anatomic clarification and its involvement in venous insufficiency. Results This variation, observed in 5.1% (n = 29) of limbs, comprised two segments; one uninterrupted great saphenous vein proper coursing throughout saphenous compartment and one extra-compartmental segment originating distally from and proximally fusing with it. Venous arch remains within compartment only briefly during take-off and re-entry. Extra-compartmental venous arch had reflux either alone (10.3%) or together with intra-compartmental segment (75.9%). Conclusion This variation, part of saphenous segmental aplasia/hypoplasia complex, is associated with venous insufficiency. Meticulous mapping of great saphenous vein territory and identification of such variants during planning stage is indispensable for optimal clinical outcomes of treatment.


A technique and some results of meteorite microbiological investigations.
The possibility of the introduction of living organisms on earth with meteorites is a question of interest for scientists. It is quite possible that bacterial spores can remain in an anabiotic state for a long time, thus there is no reason to refuse the possibility of microorganisms present in meteorite. A special box was constructed in order to take samples from meteorites under sterile conditions because penetration of a soil microflora inside meteorites upon their fall on the earth surface is quite possible. The sterilized rock pieces were put into soil, samples were removed at intervals and subjected to microbiological assay. In all cases different soil microorganisms were found in the central parts of the samples tested. In another study a canal was drilled in the sterile rock and meteorite samples and a bacterial culture was poured into this canal, the sample being submerged into a liquid growth medium. Cell penetration through the rock took place and bacterial growth was found in the liquid growth medium. Therefore meteorites extracted from soil not at once after their fall are hardly suitable for microbiological assay.


Genomics of sleep-disordered breathing.
The technologies of genomics and proteomics are powerful tools for discovering novel gene and protein expression responses to disease. Considerable evidence indicates that a genetic basis exists to the causes of sleep-disordered breathing, in particular its most common form of obstructive sleep apnea (OSA), which is characterized by periods of intermittent hypoxia and disrupted sleep. However, the genetic contribution to the pathogenesis of OSA has largely been determined using traditional genetic approaches of family, twin, and linkage studies in clinical populations and quantitative trait loci and targeted gene procedures in animal models of OSA. In contrast to the pathogenesis of OSA, the consequences or sequelae of OSA are highly amenable to genomic and proteomic approaches. Animal studies have assessed changes in gene and protein expression in multiple organ systems in response to intermittent hypoxia and sleep deprivation and uncovered novel gene activation paradigms. The first tentative steps have been made toward applying proteomic analyses of blood and urine from patients with OSA as a potential screening tool for diagnosis in the clinical setting. It is anticipated that genomic and proteomic technologies will become increasingly used in the area of OSA with the unprecedented access to tissue in procedures such as bariatric surgery. OSA represents a severe insult to the oxygenation of tissues and the homeostasis of sleep, and genomic and proteomic approaches hold promise for defining previously unexplored mechanisms and pathways that lead to downstream pathologies, including hypertension, insulin resistance, and neurocognitive dysfunction.


Tracking Study About Adenovirus 36 Infection: Increase of Adiposity.
This study investigated the cross-sectional and longitudinal association between adenovirus 36 (Ad36) and obesity in 79 Korean adolescent boys over 1 year. We analyzed the changes in body composition and metabolic risk factors according to the presence of Ad36 antibodies. Ad36 antibodies in serum were detected using the constant virus-decreasing serum method. We found that the fat percentage and fasting insulin in the Ad36-seropositive group were greater than the Ad36-seronegative group. These results suggest that Ad36 infection is associated with an increase of adiposity, and the experience of Ad36 infection may affect the future fat gain of adolescents.


Behavioral responses and Fos activation following painful stimuli in a rodent model of Parkinson's disease.
In Parkinson's disease (PD), the motor dysfunction caused by degeneration of the nigrostriatal pathway is often associated with alterations of pain perception. This is likely related to the role that the nigrostriatal system may play in the processing of noxious, somatosensory stimuli. To further address this issue, we used a rodent model of PD, based on the unilateral, intrastriatal injection of neurotoxin 6-hydroxydopamine (6-OHDA). We investigated the effects of the nigrostriatal lesion on behavioral responses to pain tests designed to explore different aspects of nociception, such as the formalin test and the tail flick test; we also explored modifications in the expression of Fos protein, a marker of neuronal activation, in supraspinal nuclei involved in the integration of pain perception and stress-related behavior. Rats bearing the nigrostriatal lesion showed complex alterations in pain perception, including hyperalgesic responses to the tonic, inflammatory pain elicited by formalin injection, but only when the stimulus was delivered ipsilaterally to the lesion. This phenomenon was associated with delayed responses to the phasic, thermal stimulus induced by the tail flick test. The hyperalgesic response to the formalin test was accompanied by reduced Fos expression in the paraventricular nucleus of the hypothalamus, which is part of a network (the medial pain system) that mediates motivational-affective aspects of pain. Our results confirm that a unilateral alteration of central dopaminergic transmission disrupts the neural mechanisms underlying proper integration of painful stimuli, particularly in the hemibody ipsilateral to the dopaminergic denervation.


Robust ultrafine ruthenium nanoparticles enabled by covalent organic gel precursor for selective reduction of nitrobenzene in water.
Metal nanoparticles (NPs) supported on nitrogen-doped porous carbon (NPC) are one type of promising heterogeneous catalysts. The tuning and understanding of metal-support interactions are crucial for the design and synthesis of highly durable and efficient heterogeneous catalytic systems. Here, we present an effective strategy to integrate ultrafine metal NPs into NPC via utilizing a covalent organic gel (COG) as the precursor for the first time. The ruthenium (Ru) NPs were uniformly dispersed in NPCs with the average size as low as 1.90 ± 0.4 nm. Irrespective of their ultrafine size, Ru NPs showed unprecedented stability and recyclability in Ru-catalyzed reduction of nitrobenzene and were greatly superior to commercial Ru/C and NPC-supported Ru NPs synthesized by the traditional post-loading method. This synthetic strategy can be extended to the synthesis of other metal or alloy NPs for a variety of advanced applications.


A new method for E-government procurement using collaborative filtering and Bayesian approach.
Nowadays, as the Internet services increase faster than ever before, government systems are reinvented as E-government services. Therefore, government procurement sectors have to face challenges brought by the explosion of service information. This paper presents a novel method for E-government procurement (eGP) to search for the optimal procurement scheme (OPS). Item-based collaborative filtering and Bayesian approach are used to evaluate and select the candidate services to get the top-M recommendations such that the involved computation load can be alleviated. A trapezoidal fuzzy number similarity algorithm is applied to support the item-based collaborative filtering and Bayesian approach, since some of the services' attributes can be hardly expressed as certain and static values but only be easily represented as fuzzy values. A prototype system is built and validated with an illustrative example from eGP to confirm the feasibility of our approach.


Non-classical Helices with cis Carbon-Carbon Double Bonds in the Backbone: Structural Features of α,γ-Hybrid Peptide Foldamers.
The impact of geometrically constrained cis α,β-unsaturated γ-amino acids on the folding of α,γ-hybrid peptides was investigated. Structure analysis in single crystals and in solution revealed that the cis carbon-carbon double bonds can be accommodated into the 12-helix without deviation from the overall helical conformation. The helical structures are stabilized by 4→1 hydrogen bonding in a similar manner to the 12-helices of β-peptides and the 310 helices of α-peptides. These results show that functional cis carbon-carbon double bonds can be accommodated into the backbone of helical peptides.


Effect of glucose-6-phosphate dehydrogenase deficiency on neutrophil function.
The bactericidal activity of neutrophils depends primarily on free oxygen radicals released by the activation of NADPH oxidase when neutrophils are stimulated by microorganisms. Severe glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with decreased NADPH production. Increased susceptibility to recurrent bacterial infections in children with severe neutrophil G6PD deficiency as a consequence of decreased NADPH production has been reported earlier. In this study, the in vitro activity of neutrophils from normal and G6PD-deficient individuals was assessed by measuring the [14C]CO2 released via the hexose monophosphate shunt from radiolabeled [1-14C]-glucose and the nitroblue tetrazolium (NBT) dye reduction test. Our results show that the G6PD activity of neutrophils from 48 individuals, identified as severely erythrocyte (RBC) G6PD deficient (< 2 U/10(12) RBC) was 23% of the enzyme activity of neutrophils from 53 individuals with normal RBC G6PD levels (98.8 U/10(12) RBC). However, the results of functional assays of neutrophils as measured by hexose monophosphate shunt and the NBT test were comparable in G6PD-deficient and normal individuals, suggesting that a reduced activity of G6PD to as low as 23% of normal does not affect neutrophil function.


Stabilization of substilisin E in organic solvents by site-directed mutagenesis.
Subtilisin E was rationally engineered to improve its stability in polar organic solvents such as dimethylformamide (DMF). A charged surface residue, Asp248, was substituted by three amino acids of increasing hydrophobicity, Asn, Ala, and Leu; all three variants were stabilized with respect to wild type in 80% DMF. This stabilization was only observed in the presence of high concentrations of the organic solvent: no stability enhancements were observed in 40% DMF. In contrast, the mutation Asn218 --> Ser alters internal hydrogen bonding interactions and stabilizes subtilisin E in both 40% and 80% DMF. This study provides additional evidence that substitution of surface-charged residues is a generally useful mechanism for stabilizing enzymes in organic media and that the stabilizing effects of such substitutions are unique to highly altered solvent environments. The effects of the single amino acid substitutions on free energies of stabilization are additive in the Asp248 --> Asn + Asn218 --> Ser combination variant, yielding an enzyme that is 3.4 times more stable than wild type in 80% DMF.


A comparative study on bioactive constituents in different parts of Lonicera japonica determined by HPLC-ESI-MS(n).
Lonicera japonica Thunb. is a well-known traditional herbal medicine in most East Asian countries. In China, the flower bud and stem of this plant are used for various clinical therapies, while the leaf is not officially recognized as an active part. Due to the similarities in their chemical constituents but great differences in their commercial values, the flower bud has been found to be adulterated with leaf and/or stem during the production of formulations by some drug manufactures. In order to identify adulteration in products and enable quality control, it is necessary to chemically discriminate these three parts of L. japonica. In the current study, an HPLC-ESI-MS(n) method was developed and validated for the quantitative analysis of 18 bioactive compounds: 7 organic acids, 6 iridoids, and 5 flavonoids, in batches of flower bud, stem, and leaf samples. Subsequently, chemometric analyses, such as one-way analysis of variance, principal component analysis, and hierarchical clustering analysis, were performed based on the quantitative data. The results indicated that there were remarkable differences in the distribution of the investigated compounds among the three parts of L. japonica, and that they could be straightforwardly and reliably distinguished according to their chemical profiles. Twelve compounds were selected as potential differential metabolites, which would be useful for quality control of L. japonica. As the content of caffeic acid was low in the flower bud but much higher in the stem and leaf, it could be used as a chemical marker to identify adulteration.


Atmospheric input of carbon dioxide from burning wood.
The atmospheric input of carbon dioxide from burning wood, in particular from forest fires in boreal and temperate regions resulting from both natural and man-made causes and predominantly from forest fires in tropical regions caused by shifting cultivation, is estimated to be 5.7 x 10(15) grams of carbon per year as gross input and 1.5 x 10(15) grams of carbon per year as net input. This is a significant amount as compared to the fossil fuel carbon dioxide produced from the utilization of oil, gas, coal, and limestone, and bears on the hypothesis of the enhanced sedimentation of marine detritus as a removal mechanism of excess atmospheric carbon dioxide.


Methodology and Characterization of Isolation and Preconcentration in a Gas-Filled Digital Linear Ion Guide.
Digital operation of linear ion guides allows them to operate as traps and mass filters by modulating the duty cycles of the two driving waveforms. A gas-filled (5 mTorr) digitally driven quadrupole ion guide was used to demonstrate ion isolation and preconcentration. These abilities allow ion trapping mass spectrometers to be filled to capacity with only ions in the range of interest at essentially any value of m/z. Due to the unique performance characteristics of digitally operated quadrupoles, isolation with purely duty cycle enhanced waveforms was developed with three increasingly sophisticated isolation methods. First, the guide was used as a gas-filled transmission mass filter using the waveform duty cycle to generate a narrow mass window. The second method used broadband trapping to collect ions and translationally cool along the transmission axis before shifting the duty cycle to filter the trapped ions. A subsequent duty cycle change axially ejected the filtered population for measurement. The third method improved resolution by shifting the operating frequency during isolation. The resolving power was optimized with the shift frequency to yield a device limited resolving power of 400 (m/Δm). It is the temporal control of the duration of the isolation process that sets digital waveform based isolation apart from the current technology and that minimizes ion loss even when the mass is very large. Preconcentration by repeated trapping and isolation of an individual charge state was also demonstrated to saturate the ion guide with that charge state. These digital isolation and preconcentration techniques will permit the same isolation resolution (m/Δm) at any value of mass or m/z without significant ion loss as long as the secular frequencies do not significantly overlap while in the trapping mode. It is therefore ideal for the isolation and preconcentration of single charge states of large proteins and complexes.


Technostress and academic motivation: direct and indirect effects on university students' psychological health.
Research has well demonstrated that the pandemic entailed several implications among university students worldwide in terms of increased use of Information and Communication Technologies (ICTs), technostress, disruptions in academic goals and motivation processes, and growing psychological suffering. Responding to the new research need to go in-depth into the processes linking technostress and motivation dimensions to inform current research/interventions, the present study aimed to explore the direct effects of perceived Technostress dimensions (Techno-Overload, Work-Home Conflict, Pace of Change, Techno-Ease, Techno-Reliability, and Techno-Sociality) and Academic Motivation dimensions (Amotivation, Intrinsic, and Extrinsic Motivation dimensions) on students' perceived levels of Anxiety/Depression and test the potential indirect effect (mediating role) of Academic Motivation dimensions in the associations between Technostress and psychological health conditions. Overall, 1,541 students from five European countries (Czech Republic, Greece, Italy, Serbia, United Kingdom) completed a survey comprising a Background Information Form, the Technostress Scale, the Academic Motivation Scale-College, and the Hospital Anxiety and Depression Scale. Hayes' PROCESS tool was used to test direct and indirect (mediating) effects. Data revealed that Techno-Overload, Work-Home Conflict, Amotivation, and Extrinsic Motivation-Introjected had a direct negative effect, whereas Techno-Ease, Techno-Reliability, Techno-Sociality, all Intrinsic Motivation dimensions, and Extrinsic Motivation-Identified had a direct protective role for students' psychological health. The significant indirect role of motivation dimensions in the associations between Technostress dimensions and Anxiety/Depression was fully supported. Findings allow gaining further insight into the pathways of relationships between technostress, motivation, and psychological health, to be used in the current phase, featured by the complete restoration of face-to-face contacts, to inform the development of tailored research and interventions, which address lights and shadows of the technology use, and which take into account the necessity to enhance its potentials yet without impairing students' motivation and psychological health.


How much misoprostol is safe? - First reported case of second-trimester uterine rupture after a single low dose.
With the rising rate of caesarean births, the scenario of fetal demise occurring in a woman with previous caesarean births is becoming more prevalent. The optimal mode of management of intrauterine fetal demise in women with multiple caesarean births presents a challenge for the obstetricians due to absence of a definite protocol with good efficacy, safety and acceptability in these women. The risks of hysterotomy have to be balanced against the risk of uterine rupture with induction. Misoprostol is one of the most common drugs being used in mid-trimester miscarriage but with variable doses. The reports of uterine rupture with previous caesarean scar are rare and have occurred with different doses, making it difficult to counsel women regarding maternal risks. It is difficult to conduct a randomised control trial to address this issue due to limited number of patients and therefore no drug or dosage can be recommended with certainty. We present a unique and first case of second-trimester uterine rupture in a woman with three previous caesarean births and intrauterine fetal demise, after a single low dose of 25 μg vaginal misoprostol. This highlights the need for further research in context of misoprostol dosage in women with more than two previous caesarean births having second-trimester induction of labour.


Pretreatment of murine thymocytes by phytohemagglutinin inhibits the binding of H-concanavalin A.
The binding of H-concanavalin A (Con A) to cortisone-resistant and normal mouse thymocytes, which greatly differ in mitogenic responsiveness, was compared. Almost equal numbers of 3H-Con A molecules (7 x 10(5) molecules per cell) were found to bind to both cell types, and the rates of H-Con A binding were nearly identical. The binding capacity of thymocytes for H-Con A decreased rapidly after removal from the thymus and incubation in protein free synthetic medium. Similarly, mitogenic responsiveness droped rapidly after cells were exposed to this medium. H-Con A molecules bound to cells were dissociated from them after a brief incubation, about 30 percent of radioactivity being lost in 2 hr with increasing radioactivity being found in the supernatant. When cells were pretreated with PHA-P, which is a T cell mitogen, their mitogenic responsiveness to Con A was suppressed along with H-Con A binding to the cells. In contrast, a B cell mitrogen, LPS, that has a synergistic effect on the Con A mitogenic response in thymocytes had no effect on binding of H-Con A to thymocytes.


Measles in Saudi Arabia: from control to elimination.
This article describesthe tremendous efforts made in the field of measles immunization in Saudi Arabia in the past 20 years, from the control phase to the elimination phase. Mandatory measles vaccination with one-dose Schwartz vaccine was introduced in 1982 by a royal decree, a step aimed at increasing vaccine coverage. In 1991, a two-dose schedule was implemented using Edmonston-Zagreb measles vaccine, with a first dose at 6 months to protect children younger than 9 months and a second dose of MMR at 12 months of age to protect those who did not respond to the first dose. A marked reduction in the epidemic peak and a shift of infection to older age were noticed. But the same data showed that 50% of measles cases in the 1- to 4-year age group occurred in vaccinated children. In 1998, with the start of elimination phase, an MMR campaign was launched in two phases, targeting school children in 1998 (secondary schools) and in 2000 (primary and intermediate schools). Evaluation of the MMR campaign and surveillance data was reflected in the measles immunization policy by shifting the age of measles immunization to 12 months and to preschool using the two-dose MMR schedule.


Risk factors for hearing loss in neonates: a prospective study.
To identify potential risk factors for neonatal hearing loss that are not included in the current variables recognized by the Joint Committee on Infant Hearing (JCIH). A series of consecutively born neonates with risk factors for hearing loss based on the 1994 JCIH registry were screened prospectively. There were 110 subjects with hearing loss and 636 subjects without hearing loss. Data collected as potential risk factors for infant hearing loss included not only those on the JCIH list but also others that we believed to be possibly significant. The infant hearing screening was performed on each subject using auditory brain stem testing. Statistical analysis of data was performed using the chi-square test. In addition to the variables listed by the JCIH, we identified 11 additional risk factors that were associated with hearing loss in our neonatal population. These are: length of stay in the intensive care unit, respiratory distress syndrome, retrolental fibroplasia, asphyxia, meconium aspiration, neurodegenerative disorders, chromosomal abnormalities, drug and alcohol abuse by the mother, maternal diabetes, multiple births, and lack of prenatal care. This study identifies 11 risk factors in addition to those currently on the high-risk registry published by the JCIH for neonatal hearing loss. The inclusion of these additional risk factors in neonatal screening programs may improve the detection rate of neonates with hearing loss. Further study will be needed to determine whether inclusion of these additional risk factors in a hearing screening program can provide an efficacious alternative to the use of universal infant screening.


Two-dimensional pattern recognition methods for rapidly recording and interpreting high resolution coherent three-dimensional spectra.
High resolution coherent multidimensional spectroscopy has the ability to reduce congestion and automatically sort peaks by species and quantum numbers, even for simple mixtures and molecules that are extensively perturbed. The two-dimensional version is relatively simple to carry out, and the results are easy to interpret, but its ability to deal with severe spectral congestion is limited. Three-dimensional spectroscopy is considerably more complicated and time-consuming than two-dimensional spectroscopy, but it provides the spectral resolution needed for more challenging systems. This paper describes how to design high resolution coherent 3D spectroscopy experiments so that a small number of strategically positioned 2D scans may be used instead of recording all the data required for a 3D plot. This faster and simpler approach uses new pattern recognition methods to interpret the results. Key factors that affect the resulting patterns include the scanning strategy and the four wave mixing process. Optimum four wave mixing (FWM) processes and scanning strategies have been identified, and methods for identifying the FWM process from the observed patterns have been developed. Experiments based on nonparametric FWM processes provide significant pattern recognition and efficiency advantages over those based on parametric processes. Alternative scanning strategies that use synchronous scanning and asynchronous scanning to create new kinds of patterns have also been identified. Rotating the resulting patterns in 3D space leads to an insight into similarities in the patterns produced by different FWM processes.


Expression of sodium-dependent purine nucleoside carrier (SPNT) mRNA correlates with nucleoside transport activity in rat liver.
The expression of sodium-dependent purine nucleoside transport (SPNT) mRNA has been studied in physiological situations in which Na+-dependent nucleoside uptake in plasma membrane vesicles from rat liver was induced. Sodium-dependent uridine transport rates were induced in genetically obese Zucker rats, during liver regeneration after partial hepatectomy, and under euglycemic-hyperinsulinemic clamp. A PCR-generated fragment, based on a published SPNT sequence cloned from rat liver, was used as a probe in Northern blot analysis. We show that the hepatic mRNA levels of the putative sodium-dependent transport system SPNT correlate with the sodium-dependent uridine transport rates in plasma membrane vesicles from rat liver. These results suggest that the induction of the sodium-dependent nucleoside transport expressed in liver parenchymal cells involves regulation of SPNT gene expression.


Computed tomography in Alexander's disease.
Computed tomography demonstrated contrast-enhancing lesions in the periventricular frontal regions, caudate nuclei, and thalami in an infant with Alexander's disease. The distribution of the enhancing lesions corresponded to the areas in which Rosenthal fibers were most prominent. These radiological findings have not been described in other white matter diseases; thus, they may help to distinguish Alexander's disease from Canavan's disease and decrease the necessity for diagnostic brain biopsy.


Debris retention and wear in three different nickel-titanium rotary instruments.
The aim of this in vitro study was to compare three nickel-titanium (Ni-Ti) rotary instruments: EndoWave, K3 and ProFile, with respect to their debris retention and wear. Thirty simulated root canal models made from resin blocks with 40 degrees canal curvature were used. They were divided into three groups of 10 samples each; EndoWave, K3 and ProFile were used in Groups A, B and C respectively. They were prepared with four serial size files. The weight of each file was measured to evaluate debris retention and wear at four representative time points: prior to root canal preparation (W1), immediately after root canal preparation (W2), after ultrasonic cleaning (W3), after further additional cleaning (W4). The weight of debris on each file after root canal instrumentation and ultrasonic cleaning was calculated as D1: (W2 - W4) and D2: (W3 - W4) respectively. Also, wear of the file was calculated as WF: (W1 - W4). There was a significant difference in the amount of debris remaining on the file among the three files; EndoWave retained more debris (D1) than K3 and ProFile (P < 0.001, one-way anova). ProFile had the largest amount of debris (D2) remaining after ultrasonic cleaning (P < 0.001). Wear was not detectable in this study. Under the conditions of this study, immediately after root canal preparation, EndoWave retained the largest amount of debris, while ProFile retained the most debris even after ultrasonic cleaning.


Prediction of chronicity in psychiatric patients.
In order to determine the best combination of variables for predicting which patients would be released from state mental hospitals and which would be retained, the 1,500 patients examined in the course of a cross-sectional survey of the residental population of Texas state mental hospitals in 1966 were followed up in 1971. Eighteen variables were selected for discriminant analysis, comparing the patients nerver released from the hospital with those known to be current extrainstitutional residents. The stepwise program selected four variables: (1) length of prior stay; (2) relatives' attitudes toward release; (3) social adequacy; and (4) conceptual disorganization. Applying this model to the study groups, 79% were correctly classified with regard to their in hospitals/not in hospital status, suggesting that early identification of chronicity in future studies is feasible.


Social rhythm in anxiety disorder patients.
The social rhythm metric (SRM) is a self report diary instrument which generates a numerical measure of rhythmicity of daily life behaviors. Depression researchers have proposed that life events cause disruption of social rhythmicity and this leads to disturbance in the sense of well-being and to disruption of physiologic rhythmicity known to be related to depressive episodes. We hypothesized that low rhythmicity of daily activities might also be characteristic of anxiety disorder patients. Forty-eight patients who met DSM III-R criteria for an anxiety disorder were recruited and compared with 41 previously monitored normal controls. All patients and controls completed at least two weeks of daily monitoring with the SRM. Anxiety patients underwent structured diagnostic assessment and completed demographic and clinical rating scales. SRM was analyzed according to a previously developed algorithm. Anxiety disorder patients report significantly lower regularity of daily activities than normal controls. The low SRM scores were not accounted for by the presence of comorbid affective disorder. We identify a new type of abnormality in anxiety disorder patients which has potential clinical as well as theoretical interest.


Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk.
Glioblastoma multiformes (GBMs) are extensively heterogeneous at both cellular and molecular levels. Current therapeutic strategies include targeting of key signaling molecules using pharmacological inhibitors in combination with genotoxic agents such as temozolomide. In spite of all efforts, the prognosis of glioma patients remains dismal. Therefore, a proper understanding of individual molecular pathways responsible for the progression of GBM is necessary. The epidermal growth factor receptor (EGFR) pathway is probably the most significant signaling pathway clinically implicated in glioma. Not surprisingly, anti-EGFR therapies mostly prevail for therapeutic purposes. The Wnt/β-catenin pathway is well implicated in multiple tumors; however, its role in glioma has only recently started to emerge. We give a concise account of the current understanding of the role of both these pathways in glioma. Last, taking evidences from a limited literature, we outline a number of points where these pathways intersect each other and put forward the possibility of combinatorially targeting them for treatment of glioma.


Expression of Long-chain Fatty Acyl-CoA Synthetase 4 in Breast and Prostate Cancers Is Associated with Sex Steroid Hormone Receptor Negativity.
Previous studies have shown that key enzymes involved in lipid metabolic pathways are differentially expressed in normal compared with tumor tissues. However, the precise role played by dysregulated expression of lipid metabolic enzymes and altered lipid homeostasis in carcinogenesis remains to be established. Fatty acid synthase is overexpressed in a variety of cancers, including breast and prostate. The purpose of the present study was to examine the expression patterns of additional lipid metabolic enzymes in human breast and prostate cancers. This was accomplished by analysis of published expression databases, with confirmation by immunoblot assays. Our results indicate that the fatty acid-activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), is differentially expressed in human breast cancer as a function of estrogen receptor alpha (ER) status. In 10 separate studies, ACSL4 messenger RNA (mRNA) was overexpressed in ER-negative breast tumors. Of 50 breast cancer cell lines examined, 17 (89%) of 19 ER-positive lines were negative for ACSL4 mRNA expression and 20 (65%) of 31 ER-negative lines expressed ACSL4 mRNA. The inverse relationship between ER expression and ACSL4 expression was also observed for androgen receptor status in both breast and prostate cancers. Furthermore, loss of steroid hormone sensitivity, such as that observed in Raf1-transfected MCF-7 cells and LNCaP-AI cells, was associated with induction of ACSL4 expression. Ablation of ACSL4 expression inMDA-MB-231 breast cancer cells had no effect on cell proliferation; however, sensitivity to the cytotoxic effects of triacsin C was increased three-fold in the cells lacking ACSL4.


Delineating Conformation Control in the Photophysical Behaviour of a Molecular Donor-Acceptor-Donor Triad.
Mechanochromic luminescent materials, exhibiting a change in luminescence behavior under external stimuli have emerged as one of the promising candidates for upcoming efficient OLEDs. Recently mechanochromic luminescence was reported in a donor-acceptor-donor (D-A-D) triad featuring two phenothiazine units separated by a dibenzo[a,j]phenazine motif. The triad follows different emissive routes ranging from phosphorescence to TADF based on the conformational switching of the D units. In this article, we investigate such conformation-dependent photophysical behavior of this triad through theoretical calculations. By analyzing the nature of ground state, excited state and factors determining the reverse ISC crossing rates associated with the relative orientation of the D and A units, we delineate the effect of the conformational changes on their photophysical properties. Our findings reveal that axial orientation of both the donor groups enhances the overlap between HOMO and LUMO leading to a large singlet-triplet gap ( ΔEST ) which drives phosphorescence emission. On the contrary, the equatorial orientation of the donor groups minimizes ΔEST to facilitate rISC making the conformers TADF active. The role of several geometric factors affecting the photophysical properties of the conformers is also highlighted. Finally, we show how to regulate the population difference among the conformers by functionalizing the triad to harvest the maximum TADF efficiency.


Intraventricular craniopharyngiomas: topographical classification and surgical approach selection based on an extensive overview.
This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome. Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared. For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome. Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.


The effects of human insulin on antibody formation in pregnant diabetics and their newborns.
We studied the immunogenicity of human insulin in 11 diabetic mothers and their newborns. Serum antibody formation was assayed by two different methods. Upon switching four patients from beef/pork insulin to human insulin, we found that elevated baseline antibody levels in three women decreased, in two to undetectable levels at term. The fourth patient had undetectable antibody levels at baseline and borderline levels at term. Only one of their four newborns had antibodies. Upon initiation of insulin treatment in another five diabetics without detectable antibodies at baseline, only two developed antibodies, and only one of their newborns developed antibodies. Two other patients, initially not on insulin, had baseline elevations of antibody that decreased with administration of human insulin; both of their newborns had antibodies. Overt diabetes evolved subsequently in both mothers after pregnancy. We conclude the following: 1) Upon transfer from beef/pork insulin to human insulin, mothers and their newborns show a decrease in insulin antibodies; 2) new patients initiated on insulin develop low levels of antibodies, if any, and their newborns also have low levels of antibodies if any; and 3) the decreased or absent immunogenicity of human insulin supports its use in pregnant diabetics.


Ophthalmologic Complications Associated With Oculofacial Plastic and Esthetic Surgeries.
To assess the ophthalmologic complications after oculofacial plastic and esthetic surgeries, including their incidence and management. A retrospective study was performed on 110 patients who presented with ocular complications followed by oculofacial plastic and esthetic surgeries from January 2014 to December 2015. The incidence and management of complications after each surgery or procedure were analyzed. For lower eyelid blepharoplasty, the common complications were chemosis and lower eyelid ectropion. There was also a case of canalicular laceration. Exposure keratitis and corneal abrasion were the most common complications after upper eyelid blepharoplasty. Chemosis frequently occurred after lateral cathoplasty, but other complications, such as ectropion, trichiasis, and lacrimal fistula, were also seen. Nasolacrimal duct obstruction occurred in some cases of orthognathic surgery, and was managed with endonasal dacryocystorhinostomy. Inflammatory lipogranuloma was a common complication after autologous fat transplantation. Complications after oculofacial plastic and esthetic surgeries are not rare. Ophthalmologists must be aware of not only common complications but also rare and possibly serious conditions that may occur after such surgeries.


Enzymatic mechanism of RNA translocation in double-stranded RNA bacteriophages.
Many complex viruses acquire their genome by active packaging into a viral precursor particle called a procapsid. Packaging is performed by a viral portal complex, which couples ATP hydrolysis to translocation of nucleic acid into the procapsid. The packaging process has been studied for a variety of viruses, but the mechanism of the associated ATPase remains elusive. In this study, the mechanism of RNA translocation in double-stranded RNA bacteriophages is characterized using rapid kinetic analyses. The portal complex of bacteriophage 8 is a hexamer of protein P4, which exhibits nucleotide triphosphatase activity. The kinetics of ATP binding reveals a two-step process: an initial, fast, second-order association, followed by a slower, first-order phase. The slower phase exhibits a high activation energy and has been assigned to a conformational change. ATP binding becomes cooperative in the presence of RNA. Steady-state kinetics of ATP hydrolysis, which proceeds only in the presence of RNA, also exhibits cooperativity. On the other hand, ADP release is fast and RNA-independent. The steady-state rate of hydrolysis increases with the length of the RNA substrate indicating processive translocation. Raman spectroscopy reveals that RNA binds to P4 via the phosphate backbone. The ATP-induced conformational change affects the backbone of the bound RNA but leaves the protein secondary structure unchanged. This is consistent with a model in which cooperativity is induced by an RNA link between subunits of the hexamers and translocation is effected by an axial movement of the subunits relative to one another upon ATP binding.


Phylogenetic beta diversity in bacterial assemblages across ecosystems: deterministic versus stochastic processes.
Increasing evidence has emerged for non-random spatial distributions of microbes, but knowledge of the processes that cause variation in microbial assemblage among ecosystems is lacking. For instance, some studies showed that deterministic processes such as habitat specialization are important, while other studies hold that bacterial communities are assembled by stochastic forces. Here we examine the relative influence of deterministic and stochastic processes for bacterial communities from subsurface environments, stream biofilm, lake water, lake sediment and soil using pyrosequencing of the 16S ribosomal RNA gene. We show that there is a general pattern in phylogenetic signal in species ecological niches across recent evolutionary time for all studied habitats, enabling us to infer the influences of community assembly processes from patterns of phylogenetic turnover in community composition. The phylogenetic dissimilarities among-habitat types were significantly higher than within them, and the communities were clustered according to their original habitat types. For communities within-habitat types, the highest phylogenetic turnover rate through space was observed in subsurface environments, followed by stream biofilm on mountainsides, whereas the sediment assemblages across regional scales showed the lowest turnover rate. Quantifying phylogenetic turnover as the deviation from a null expectation suggested that measured environmental variables imposed strong selection on bacterial communities for nearly all sample groups. For three sample groups, spatial distance reflected unmeasured environmental variables that impose selection, as opposed to spatial isolation. Such characterization of spatial and environmental variables proved essential for proper interpretation of partial Mantel results based on observed beta diversity metrics. In summary, our results clearly indicate a dominant role of deterministic processes on bacterial assemblages and highlight that bacteria show strong habitat associations that have likely emerged through evolutionary adaptation.


Blood pressure variability and ambulatory monitoring.
The inherent variability of blood pressure means that the accuracy of a small number of clinic readings in estimating the true blood pressure is limited. In many patients, a clinic visit provokes an increase in blood pressure such that they may be misclassified as being hypertensive (white coat hypertension). This applies to about 20% of hypertensives. Ambulatory monitoring has the potential to overcome these limitations. The white coat effect may still occur in patients taking antihypertensive medications, although in some cases medication may lower the clinic pressure without affecting the ambulatory pressure. The diurnal rhythm of blood pressure is another major source of variability and is influenced by both extrinsic and intrinsic factors. Its pathologic significance is unclear. Antihypertensive medication generally lowers the set point of blood pressure but has relatively little effect on variability.


[Study on Chemical Constituents of Peanut Hull].
To investigate the chemical constituents of peanut hull. Several chromatography methods such as silica gel and Sephadex LH-20 combined with recrystallization were applied to isolate the compounds. Based on spectrum technologies (MS,1H-NMR and 13C-NMR) and physico-chemical methods, structures of isolated compounds were identified. Twelve compounds were isolated and elucidated as luteolin (1), diosmetin (2), 5,7,3',4'-tetrahydroxy-8-prenyflavone (3),5,7,3'-trihydroxy-4'- methoxy-8-prenylflavone(4), eriodicrtyol (5), racemoflavone (6), hydnocarpin (7), 5,7-dihydroxy chromone (8), 5-hydroxy-chromone- 7-O-β-D-glucoside (9), ferulic acid (10), β-sitosterol (11) and daucosterol(12). Except compounds 1, 5 and 8, all compounds are obtained from peanut hull for the first time.


Functional CT imaging of prostate cancer.
The purpose of this paper is to investigate the distribution of blood flow (F), mean capillary transit time (Tc), capillary permeability (PS) and blood volume (vb) in prostate cancer using contrast-enhanced CT. Nine stage T2-T3 prostate cancer patients were enrolled in the study. Following bolus injection of a contrast agent, a time series of CT images of the prostate was acquired. Functional maps showing the distribution of F, Tc, PS and vb within the prostate were generated using a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The precision of the maps was assessed using covariance matrix analysis. Finally, maps were compared to the findings of standard clinical investigations. Eight of the functional maps demonstrated regions of increased F, PS and vb, the locations of which were consistent with the results of standard clinical investigations. However, model parameters other than F could only be measured precisely within regions of high F. In conclusion functional CT images of cancer-containing prostate glands demonstrate regions of elevated F, PS and Vb. However, caution should be used when applying a complex tracer kinetic model to the study of prostate cancer since not all parameters can be measured precisely in all areas.


Changes in the proteomic profile during the differential polarization status of the human monocyte-derived macrophage THP-1 cell line.
Macrophages are heterogeneous and plastic populations that are an essential component of inflammation and host defense. To understand how macrophages respond to cytokine signals, we used 2DE to identify protein profiles in macrophages stimulated with interleukin 4 (M2) and those stimulated with lipopolysaccharide and interferon γ (M1). In total, 32 differentially expressed proteins in THP-1 cells were identified by MALDI-TOF MS/MS analysis. The different proteins were mainly involved in cellular structure, protein metabolism, stress response, oxidative response, and nitric oxide production during macrophage polarization. In particular, proteins playing important roles in production of nitric oxide (NO) were downregulated in M2 macrophages. Many antioxidant and heat shock proteins, which are related to oxidative response, were upregulated in M2 macrophages. More importantly, a remarkable decrease in intracellular ROS and NO production were detected in M2 macrophages. Our results provide a proteomic profile of differentially polarized macrophages and validate the function of the identified proteins, which may indicate possible mechanism of macrophage polarization process.


Effect of optical transformation order on design of arbitrary polygonal invisible cloak.
The design of an arbitrary polygonal invisible cloak is introduced in this paper by considering the different transformation orders. The transformation order is considered as a design variable to achieve the allowable constitutive parameters for a practical cloak with the optimum performance. In the proposed method, a thin layer is removed from the inner cloak boundary to avoid the inevitable singularity at this boundary. Then the transformation order is optimized to achieve the best performance in this truncated cloak. Also, the effect of transformation order in choosing the cloak shield thickness is investigated to design a truncated cloak with better performance.


Chemical composition of Greek avgotaracho prepared from mullet (Mugil cephalus): nutritional and health benefits.
Crude composition, lipid composition, and tocopherols, ascorbic acid, cholesterol, phytosterols, and squalene content together with fatty acids and antiplatelet activities of total, neutral, and polar lipids of avgotaracho (wax-covered, dried, and salted Mugil cephalus roe) were studied and compared with those of similar products. Wax and steryl esters accounted for 63.7% of roe lipids followed by phosphatidylcholine (PC), which comprised 20.3%. Wax esters were rich in saturated fatty alcohols, monounsaturated fatty acids, and long chain omega3 highly unsaturated fatty acids (HUFA). The fatty acid distribution in roe total and neutral lipids was similar to that of wax esters, while in polar lipids, the omega3 HUFA predominated. Avgotaracho provides significant amounts of protein, fat, alpha-tocopherol, ascorbic acid, and PC, certain amounts of squalene and phytosterols, and cholesterol at levels comparable to hens' eggs. Total, polar, and neutral lipids of avgotaracho exhibited a strong inhibition of platelet activating factors and thrombin, with polar lipids being more active. The results obtained indicate that avgotaracho is a food of high nutritive value, rich in protein and lipids with a healthy lipid profile in terms of omega3/omega6 ratio and major fatty acid classes, while the antiplatelet activity of its oil indicates a putative antithrombotic potential.


Supplementary physicians' fees: a sustainable system?
In Belgium and France, physicians can charge a supplementary fee on top of the tariff set by the mandatory basic health insurance scheme. In both countries, the supplementary fee system is under pressure because of financial sustainability concerns and a lack of added value for the patient. Expenditure on supplementary fees is increasing much faster than total health expenditure. So far, measures taken to curb this trend have not been successful. For certain categories of physicians, supplementary fees represent one-third of total income. For patients, however, the added value of supplementary fees is not that clear. Supplementary fees can buy comfort and access to physicians who refuse to treat patients who are not willing to pay supplementary fees. Perceived quality of care plays an important role in patients' willingness to pay supplementary fees. Today, there is no evidence that physicians who charge supplementary fees provide better quality of care than physicians who do not. However, linking supplementary fees to objectively proven quality of care and limiting access to top quality care to patients able and willing to pay supplementary fees might not be socially acceptable in many countries. Our conclusion is that supplementary physicians' fees are not sustainable.