Fatigue and apathy in patients on chronic hemodialysis.
This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD). One hundred thirty-nine chronic HD patients underwent the assessment of fatigue, apathy, depression, and their functional status, with the fatigue severity scale (FSS), the Apathy Evaluation Scale (AES), the beck depression inventory (BDI), the activity of daily living (ADL), and instrumental activity of daily living (IADL). Patients with high FSS had a significantly lower ADL and IADL score, higher BDI, Charlson Comorbidity Index, and AES score, and lower serum levels of creatinine, compared to low FSS patients. FSS was highly correlated with the AES, as well as with the BDI and the AES correlates with the BDI. At multiple regression analyses, only apathy and IADL were independent predictor variables of fatigue in HD population. Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients.


Circumstances surrounding gun violence with youths in an urban setting.
Our pediatric trauma center has noted an increase in the occurrence of gunshot wounds in children. We aimed to understand the circumstances surrounding these injuries in order to provide targeted injury prevention methodologies. A retrospective review was performed on patients who presented with a gunshot wound to our Level I Pediatric Trauma Center and two neighboring Adult Trauma Centers between 2013 and 2017. Three hundred twenty-six patients (6 months to 18 years) were treated for gunshot wounds. Patients were African American (86%), Caucasian (9%), and other races (5%). Eight zip-codes were identified as high-risk, accounting for 52% of patients. Most injuries (86%) were from powder firearms. Known circumstances (n = 275) included drive-by shootings (47%), unlocked guns (19%), crime related (13%), altercation between adolescents (7%), cross-fire from adult altercation (6%), home invasion (6%), and suicide attempts (2%). There was a progressive increase of 50% over the last 4 years. The increase in incidence was predominantly from an increase in drive-by shootings; however, the incidence of injuries from unlocked guns has remained relatively constant per year. Mortality was 6%. Identifying high-risk zones for drive-by shootings and other crimes is critical for developing system-focused interventions. Zip-code data stratified by age and circumstances, will allow for targeted community outreach on gun safety education, in an effort to reduce the incidence of injuries from unlocked guns. Prognostic and Epidemiologic study, Level III.


Globalization, health and foreign policy: emerging linkages and interests.
A discussion of the growing links between the issues of globalization, health and foreign policy. This article examines the effect this has on health, development and foreign policy communities in the UK and internationally and considers what steps the policy community must take to address the challenges and opportunities of this new relationship.


The advantages of microfluidics to study actin biochemistry and biomechanics.
The regulated assembly of actin filaments is essential in nearly all cell types. Studying actin assembly dynamics can pose many technical challenges. A number of these challenges can be overcome by using microfluidics to observe and manipulate single actin filaments under an optical microscope. In particular, microfluidics can be tremendously useful for applying different mechanical stresses to actin filaments and determining how the physical context of the filaments affects their regulation by biochemical factors. In this review, we summarize the main features of microfluidics for the study of actin assembly dynamics, and we highlight some recent developments that have emerged from the combination of microfluidics and other techniques. We use two case studies to illustrate our points: the rapid assembly of actin filaments by formins and the disassembly of filaments by actin depolymerizing factor (ADF)/cofilin. Both of these protein families play important roles in cells. They regulate actin assembly through complex molecular mechanisms that are sensitive to the filaments' mechanical context, with multiple activities that need to be quantified separately. Microfluidics-based experiments have been extremely useful for gaining insight into the regulatory actions of these two protein families.


The role of the left putamen in multilingual language production.
Subcortical structures are a key component of bilingual language processing. For instance, there is now evidence that the head of the left caudate is involved in controlling languages in bilingual individuals. On the other hand, the left putamen is hypothesized to be involved in articulatory processes but little is known on its engagement in bilingual language processing. Here, our hypothesis was that the left putamen of multilinguals is engaged when producing words in the less proficient language. We investigated this issue with event-related functional Magnetic Resonance (er-fMRI) in a group of multilinguals (n = 14) and in monolinguals (n = 14) during a picture-naming task. Further, we hypothesized increased grey matter density in the left putamen as an effect of experience since multilinguals constantly face a major articulatory load (i.e., speaking multiple languages) during life. To test these hypotheses we measured structural differences between multilinguals and monolinguals using voxel-based morphometry (VBM). Our results indicate that multilinguals have increased activation in the left putamen for a non-native language, but only if they are not highly proficient in that language. In addition, we found increased grey matter density in the left putamen of multilinguals compared to monolinguals. These findings highlight that the multilingual brain handles a complex articulatory repertoire (i.e., dealing with multiple languages) by inducing structural plasticity in the left putamen.


SBD, a novel structural subunit of the Drosophila nicotinic acetylcholine receptor, shares its genomic localization with two alpha-subunits.
Nicotinic acetylcholine receptors (nAChRs) display marked heterogeneity in both vertebrates and invertebrates. Here we describe the structure of a cDNA from Drosophila melanogaster which encodes a novel nAChR beta-type subunit (SBD or beta 2). The deduced amino acid sequence of SBD displays remarkable similarity to the Drosophila alpha-subunits, ALS and SAD, while homology to the Drosophila beta-subunit ARD is less pronounced. The temporal expression of sbd transcripts during Drosophila development is similar to that of other nAChR subunit mRNAs, with high levels being found during late embryonic and late pupal stages. In embryos, sbd and als transcripts are localized in the central nervous system. The sbd gene maps cytogenetically in proximity to the als and sad genes at position 96A of chromosome 3R, suggesting the existence of a nAChR gene cluster in invertebrates.


Polycyclic aromatic hydrocarbons suppress meiosis in primordial germ cells via the AHR signaling pathway.
Numerous studies have demonstrated that polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy is associated with negative reproductive consequences in adulthood, such as reduced sperm production and oocyte destruction in human and laboratory animals. However, the mechanism(s) underlying these epidemiological findings is still unclear, largely due to the lack of an in vitro model of gametogenesis. Here we established an in vitro model of gametogenesis through retinoic acid (RA)-induced differentiation of chicken primordial germ cells (PGCs) that progressed through meiosis to generate 55% of haploid cells. Using this system, we demonstrated that PAH exposure directly suppressed meiotic initiation and completion in chicken PGCs and promoted the apoptosis of PGCs, eventually leading to reduction of haploid cell formation by 66.9%. Furthermore, knockdown experiments suggested that AHR was essential for the adverse effects of PAH on PGC differentiation. Collectively, these findings offer novel insight into the dynamic mechanism by which PAH affects gametogenesis, suggesting that AHR-dependent inhibition of meiosis might be the cause of reduced gamete production. This study also provides a novel model for direct examination of the molecular and genetic pathways of environmental toxicants on gametogenesis.


Iodine-Induced Hyperthyroidism and Long-term Risks of Incident Atrial Fibrillation and Flutter.
Although iodine-induced hyperthyroidism is a potential consequence of iodinated radiologic contrast administration, its association with long-term cardiovascular outcomes has not been previously studied. To investigate the relationships between hyperthyroidism observed after iodine contrast administration and incident atrial fibrillation/flutter. Retrospective cohort study of the U.S. Veterans Health Administration (1998-2021) of patients age ≥18 years with a normal baseline serum thyrotropin (TSH) concentration, subsequent TSH <1 year, and receipt of iodine contrast <60 days before the subsequent TSH. Cox proportional hazards regression was employed to ascertain the adjusted hazard ratio (HR) with 95% CI of incident atrial fibrillation/flutter following iodine-induced hyperthyroidism, compared with iodine-induced euthyroidism. Iodine-induced hyperthyroidism was observed in 2500 (5.6%) of 44 607 Veterans (mean ± SD age, 60.9 ± 14.1 years; 88% men) and atrial fibrillation/flutter in 10.4% over a median follow-up of 3.7 years (interquartile range 1.9-7.4). Adjusted for sociodemographic and cardiovascular risk factors, iodine-induced hyperthyroidism was associated with an increased risk of atrial fibrillation/flutter compared with those who remained euthyroid after iodine exposure (adjusted HR 1.19, 95% CI 1.06-1.33). Females were at greater risk for incident atrial fibrillation/flutter than males (females, HR 1.81, 95% CI 1.12-2.92; males, HR 1.15, 95% CI 1.03-1.30; P for interaction = .04). Hyperthyroidism following a high iodine load was associated with an increased risk of incident atrial fibrillation/flutter, particularly among females. The observed sex-based differences should be confirmed in a more sex-diverse study sample, and the cost-benefit analysis of long-term monitoring for cardiac arrhythmias following iodine-induced hyperthyroidism should be evaluated.


Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not.
Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain. Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5' exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded. Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48+/-2.49 days; BMI 22-25 (n=70), 6.09+/-2.40; BMI 25-30 (n=113), 6.76+/-3.61; BMI >30 (n=46), 8.50+/-5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8+/-12.1 mg; BMI 22-25 (n=70), 25.9+/-11.4 mg; BMI 25-30 (n=113), 29.6+/-25.2; BMI >30 (n=46), 35.8+/-19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability. Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.


Modification of ilmenite surface chemistry for enhancing surfactants adsorption and bubble attachment.
In this study, microwave irradiation is used to modify ilmenite surface chemistry to enhance the adsorption of surfactants and the air bubble attachment. The results indicate that microwave irradiation can increase ilmenite flotation recovery by 20%. A positron emission particle tracking technique is used to study the dynamic behaviour of ilmenite particles in a Denver cell. The data shows that the poor flotation recovery of ilmenite is not only due to the reduce probability of ilmenite being captured by air bubbles, but also the short residence time of the particles remaining in the froth phase. The ilmenite particles can be frequently captured by air bubbles, but dropped to the bulk liquid from the froth phase, normally over 15 s. Microwave irradiation changes the ilmenite flow pattern in the Denver cell. The average time of ilmenite remaining in froth phase is increased from 11.5 to 29.1 s.


Development of a patient-reported outcome measure for the foot affected by rheumatoid arthritis.
To develop an idiographic and nomothetic patient-reported outcome measure (PROM) for the assessment and evaluation of patients with feet affected by rheumatoid arthritis (RA). The development of the Salford Rheumatoid Arthritis Foot Evaluation (SAFE) Instrument PROM was divided into four stages: establishment of the PROM's conceptual basis and content generation, following a descriptive phenomenological study; clinimetric instrument development; instrument pretesting, involving expert reviews and cognitive interviews; and demonstration of instrument measurement properties, including convergent validity and test-retest reliability of the nomothetic scale. A total of 123 items were initially generated for the SAFE, with 25 of them clinimetrically selected for nomothetic scale (SAFE-Part A) and 80 items initially included in the idiographic scale (SAFE-Part B). The pretesting strategy proved effective for improving and refining the SAFE, with the final draft consisting of 19 items in Part A and 42 items in Part B. The SAFE-Part A has strong evidence for convergent validity and test-retest reliability. The SAFE features a nomothetic and idiographic assessment strategy that, with further development, will prove to be a valuable tool for clinicians involved in managing the foot health problems associated with RA.


[The diagnosis and treatment procedure in nonopaque foreign bodies in the stomach and intestines].
For 10 years, 26 patients underwent treatment for complications caused by presence in the stomach and intestine of the foreign bodies with low radio-opacity and echogenicity. All the patients were operated on. At operation, a cause of the disease was established: in 17 cases--a fish bone, in 5--a small chicken bone, in 1--a conifer needle, in 2--a wooden chip, in 1--a home-made toothpick.


Inhibition of prostate cancer-meditated osteoblastic bone lesions by the low-calcemic analog 1alpha-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D3.
Prostate cancer metastasizes almost exclusively into the bone whereby it induces primarily an osteoblastic response. Non-calcemic vitamin D analogs have been shown to inhibit proliferation of prostate cancer cells in culture and inhibit their growth as subcutaneous xenografts in mice. However, their effect on prostate cancer cell growth in the bone has not been examined. In the present study, we inoculated the osteoblastic prostate cancer cell line MDA-PCa 2b into the bone of male SCID mice and examined the effect of the low-calcemic hybrid analog 1alpha-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D(3) (JK-1626-2) on their ability to induce bone lesions. We found that 7 weeks after inoculation of MDA-PCa 2b cells, 90% of the mice in the vehicle-treated group had significant bone lesions that were detectable by micro-computed tomography and characterized by thickening of the cortical bone and ossification of the epiphysis. Only 30% of the mice in the analog-treated group (daily injections of 4microg/kg, 5 days/week for up to 7 weeks) had detectable bone lesions. Histological examination of the decalcified tumor-bearing bones has shown that tumor cells completely replaced the bone marrow in the diaphysis, and destroyed the trabecular bone in the metaphysis in 90% of the vehicle-treated mice. In contrast, the metaphysis of 60% of analog-treated mice appeared normal, although tumor cells were still found in the diaphysis of 70% of the bones in the analog-treated group. There was no evidence of hypercalcemia in any of the analog-treated mice. In a co-culture, MDA-PCa 2b cells induced a profound mitogenic response in osteoblasts followed by enhanced differentiation. However, in the presence of the analog the mitogenic response of the osteoblasts to the malignant cells was significantly attenuated. These experiments led to the hypothesis that, in vivo, JK-1626-2 prevented the metastatic bone lesions by inhibiting the mitogenic response of osteoblasts to growth factors produced by MDA-PCa 2b cells.


Evaluation of the measurement of children's blood pressure in an epidemiological multicentre study.
Reliability and repeatability of blood pressure (BP) measurements performed by both a local nurse and a control nurse visiting all five study areas in the Finnish Multicentre Study were analysed. As an objective control, Rose's tape recordings were played at least three times during the study period to each nurse. It was found that the nurses differed from each other with variations of 2.5 mm Hg, 54.6 mm Hg and 17.9 mm Hg in the recordings of systolic, diastolic Korotkoff's IV (KIV) phase and diastolic KV phase sounds respectively, in assessing the tape. Correlation coefficients between the systolic BP and diastolic BP measurements made by the local and control nurses in 3-year-old children varied from 0.10 to 0.72 and from -0.16 to 0.46 respectively. Correlation coefficients in 6-18-year-old subjects between systolic, diastolic KIV and diastolic KV BP measurements made by the control and local nurses varied from 0.69 to 0.81, from 0.42 to 0.63 and from 0.38 to 0.58 respectively. All of the nurses had a significant terminal digit preference and it was pronounced in two of them. Because of these findings it was concluded that comparisons of BP values in different areas should be done cautiously.


Association of cartilage defects, and other MRI findings with pain and function in individuals with mild-moderate radiographic hip osteoarthritis and controls.
To evaluate the relationship of hip radiographic osteoarthritis (ROA) and MRI findings of cartilage lesions, labral tears, bone marrow edema-like lesions (BMELs) and subchondral cysts with self-reported and physical function. Eighty five subjects were classified as controls (n = 55, Kellgren-Lawrence (KL) 0, 1) or having mild-moderate ROA (n = 30, KL 2, 3). T2 weighted MRI images at 3-T were graded for presence of cartilage lesions, labral tears, BMELs and subchondral cysts. Posterior wall sign, cross-over sign, center-edge angle and alpha angle were also recorded. Function was assessed using Hip dysfunction and Osteoarthritis Outcome Score (HOOS), Timed-Up and Go (TUG) test and Y-Balance Test (YBT). Analysis compared function between subjects with and without ROA and those with and without femoral or acetabular cartilage lesions, adjusted for age. Non-parametric correlations were used to assess the relationship between radiographic scores, MRI scores and function. Subjects with acetabular cartilage lesions had worse HOOS (Difference = 5-10%, P = 0.036-0.004), but not TUG or YBT, scores. Acetabular cartilage lesions, BMELs and subchondral cysts were associated with worse HOOS scores (ρ = 0.23-0.37, P = 0.041-0.001). Differences in function between subjects with and without ROA or femoral cartilage lesions were not significant. Other radiologic findings were not associated with function. Acetabular cartilage defects, but not femoral cartilage defects or ROA, were associated with greater self-reported pain and disability. BMELs and subchondral cysts were related to greater hip related self-reported pain and disability. None of the radiographic or MRI features was related to physical function.


Limitations of the cholecystogram.
There is a little doubt that the spontaneous passage of gallstones occurs sometimes without pain or jaundice. This is probably more frequent than is realised. While the cholecystogram is a reliable investigation and of great assistance to the clinician, occasionally a normal gallbladder will be demonstrated, when it has previously been the resting place of small gallstones. Four cases are described in which patients suffering clinically from cholelithiasis are shown to have a normal cholecystogram, but on repeat examinations gallstones are demonstrated in each case over intervals of one or two years. It is suggested that gallstones had been present in all these cases at the time of the initial symptoms, but could well have passed prior to the first examination.


Inter- and intrarater reliability of short-term measurement of heart rate variability on rest in chronic obstructive pulmonary disease (COPD).
Individuals with COPD have an imbalance of cardiac autonomic control. In this context, HRV is considered an important tool for assessing cardiac sympathetic and parasympathetic balance, however it is a dependent evaluator measure and subject to methodological biases that may compromise the interpretation of results. This study examines the inter- and intrarater reliability of HRV parameters derived from short-term recordings in individuals with COPD. Fifty-one individuals of both genders with COPD clinical diagnosis confirmed by the pulmonary function test and aged ≥50 years were included. The RR interval (RRi) were recorded during a 10 min period on supine position using a portable heart rate monitor (Polar® H10 model). The data were transferred into Kubios® HRV Standard analysis software and analyzed within the stable sessions containing 256 sequential RRi. The intraclass correlation coefficient (ICC) ranged from 0.942 to 1.000 according to the intrarater analysis by Researcher 01 and 0.915 to 0.998 to the intrarater by Researcher 02. The interrater ICC ranged from 0.921 to 0.998. The coefficient of variation was up to 8.28 for Researcher 01 intrarater analysis, 9.06 for Researcher 02 intrarater analysis and 13.07 for interrater analysis. The measurement of HRV using a portable heart rate device in individuals with COPD present acceptable values of intra- and interrater reliability, supporting the use of HRV in the clinical and scientific scenario. Furthermore, it is important that the data analysis be performed by the same experienced evaluator.


Resistance to cisplatin in human lung adenocarcinoma cells: effects on the glycophenotype and epithelial to mesenchymal transition markers.
The characteristics that grant the most malignancy to cancer cells are the ability to evade apoptotic mechanisms and the capacity to migrate beyond the boundaries of the original tissue. Studies by our own group and others show that changes in glycosylation are now considered hallmarks of cancer cells and are also able to impact tumor malignancy. This study aims to evaluate changes in the glycosylation profile of the A549 lung cancer cells brought about by the induction of a MDR phenotype as well as investigate the relationship between drug resistance, the cell glycophenotype and EMT. We induced resistance by employing a continuous treatment with cisplatin. Our results demonstrate overexpression of ABC transporters as well as anti-apoptotic members of the Bcl-2 family, leading to a MDR phenotype. The cells also undergo a classic EMT process, displaying the iconic cadherin switch and increased of both total and oncofetal fibronectin, coupled with increased cell motility. We also managed to show changes in the expression of both glycosyltransferases and the glycan epitopes they are responsible for building. We also suggest that perhaps not only changes in cell sialylation are common during resistance induction but are essential to it.


Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors.
Current tumor targeted drug and diagnostic delivery systems suffer from a lack of selectivity for tumor cells. Here, we propose a two-step tumor targeting strategy based on mesenchymal stem cells (MSCs), which actively traffic to tumors. We developed glycoengineering protocols to induce expression of non-natural azide groups on the surface of MSCs without affecting their viability or tumor homing properties. Glycoengineered MSCs demonstrated active tumor homing in subcutaneous and orthotopic lung and ovarian tumor models. Subsequent systemic administration of dibenzyl cyclooctyne (DBCO)-labeled fluorophores or nanoparticles to MSC pretreated mice resulted in enhanced tumor accumulation of these agents through bio-orthogonal copper-free click chemistry. Further, administration of glycoengineered MSCs along with paclitaxel-loaded DBCO-functionalized nanoparticles resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in an orthotopic metastatic ovarian tumor model. These results provide evidence for the potential of MSC-based two-step targeting strategy to improve the tumor specificity of diagnostic agents and drugs, and thus potentially improve the treatment outcomes for patients diagnosed with cancer.


Sclerostin in periodontal ligament: Homeostatic regulator in biophysical force-induced tooth movement.
To study the role of sclerostin in periodontal ligament (PDL) as a homeostatic regulator in biophysical-force-induced tooth movement (BFTM). BFTM was performed in rats, followed by microarray, immunofluorescence, in situ hybridization, and real-time polymerase chain reaction for the detection and identification of the molecules. The periodontal space was analysed via micro-computed tomography. Effects on osteoclastogenesis and bone resorption were evaluated in the bone-marrow-derived cells in mice. In vitro human PDL cells were subjected to biophysical forces. In the absence of BFTM, sclerostin was hardly detected in the periodontium except in the PDL and alveolar bone in the furcation region and apex of the molar roots. However, sclerostin was up-regulated in the PDL in vivo by adaptable force, which induced typical transfiguration without changes in periodontal space as well as in vitro PDL cells under compression and tension. In contrast, the sclerostin level was unaffected by heavy force, which caused severe degeneration of the PDL and narrowed periodontal space. Sclerostin inhibited osteoclastogenesis and bone resorption, which corroborates the accelerated tooth movement by the heavy force. Sclerostin in PDL may be a key homeostatic molecule in the periodontium and a biological target for the therapeutic modulation of BFTM.


The role of blood vessels in the bioconversion of leukotrienes in the pig.
Porcine pulmonary artery has the ability to convert leukotriene C4 (LTC4) to LTD4 and then to LTE4. In this vessel, there appears to be no further metabolism beyond LTE4. LTC4 (1 nM) is converted rapidly to LTD4, whereas the conversion of LTD4 to LTE4 is somewhat slower. The conversion of LTC4 to LTD4 is inhibited by the gamma-glutamyl transpeptidase inhibitor, serine-borate (45 mM). The conversion of LTD4 to LTE4 is inhibited by the aminopeptidase inhibitor, L-cysteine (10 mM). LTB4 did not appear to be metabolized by porcine pulmonary artery. These results suggest that the vessel wall may play a role in the early stages of leukotriene metabolism.


Novel method of intraoperative liver tumour localisation with indocyanine green and near-infrared imaging.
Fluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection. From 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0-3 or Day 4-7. Among 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0-3 and Day 4-7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events. ICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis.


Assessment of third trimester choline phosphotransferase activity in uncomplicated human pregnancies.
CDP--choline:1,2-diglyceride choline phosphotransferase (CPT; EC 184.108.40.206) undergoes a marked surge in activity in human amniotic fluid when assayed from 30 weeks of gestation to term. The activity of this enxyme, plotted against gestational age, follows a highly significant regression correlation from which an equation can be obtained for the prediction of gestational age.


Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases.
The objective of this study was to examine the effects of alendronate on the expression and activity of matrix metalloproteinases (MMPs) and the expression of the tissue inhibitors of MMPs (TIMPs) from human osteoblast-like MG63 cells. MG63 cells were exposed to various concentrations of alendronate. Cell proliferation and cytotoxicity were evaluated by water-soluble tetrazolium-1 and lactate dehydrogenase, respectively. MG63-mediated collagen degradation was assessed utilising Type I collagen assays. Conditioned media and membrane extracts were collected for Western blot analyses of select MMPs and TIMPs. Gelatin zymography gels were incubated with alendronate to assess its effects on MMP-2 activity. Alendronate affected MG63 proliferation and cytotoxicity at concentrations equal to/or greater than 10(-5) M (all p < 0.05). There were no significant differences in the collagen degrading ability of treated cells at non-toxic levels vs. untreated cells. Alendronate had no effects on the expression of MMP-2 or MT1-MMP (membrane type-1 MMP) in the conditioned media or membrane extracts, and of MMP-1 or TIMP-2 in the conditioned media. TIMP-2 in the membrane extracts was not detectable. MMP-2 activity in the zymograms was inhibited by 10(-3) and 10(-2) M alendronate. Alendronate at 10(-5) M or higher was toxic to the cells. Alendronate at 10(-8) to 10(-6) M did not alter the expression of MMP-1, MMP-2, MT1-MMP or TIMP-2, as well as did not alter collagen degradation. Alendronate inhibited MMP-2 activity at 10(-3) and 10(-2) M in the zymograms. In conclusion, non-toxic levels of alendronate (10(-8) to 10(-6) M) did not alter MMP expression in MG63 cells or inhibit MMP-2 activity.


A cost-benefit analysis of the downstream impacts of e-waste recycling in Pakistan.
This paper presents downstream cost-benefit analysis for electronic waste (e-waste) recycling workers in Pakistan, a country that both generates large quantities of e-waste domestically and imports a significant amount from developed countries. Financial cost-benefit elements - reduction in productive capacity, lost wages, medical expenses, wages (and meals) and non-financial cost-benefit elements - opportunity cost, cost of illiteracy and value of life have been quantified. Primary data collected on site was analyzed using quantitative and qualitative methods. The estimated total net economic cost to recycling workers is between Rs.34,069 and Rs.85,478 (US$ 203-5101) per month or an average of Rs.50,363 (US$ 300) per worker. This main finding suggests that cost exceeds by 2.6-4.7 times the estimated economic benefits derived by these workers. Related qualitative data suggests government and owners of recycling businesses are largely blind to many of the less visible costs of this industry, while recycling workers and their families appear trapped in a vicious cycle of poverty. Understanding that what can be measured can be managed and improved, a systematic assessment of informal recycling based on identified impact factors may help mitigate and ideally also motivate a shift towards formal processing that would reduce the downstream negative impacts, both visible and hidden.


Effect of human fibroblast interferon on natural killer cell activity: stimulation in vitro and inhibition in vivo.
This paper describes the influence of human fibroblast interferon (IFN-beta) on the cytotoxic activity of natural killer cells (NK) in vitro and in vivo using the blood of healthy donors and myeloma patients. IFN-beta stimulates NK activity against all target cells tested in vitro in a dose-dependent way up to 250% of pretreatment values. At higher IFN concentrations, stimulation returned to baseline values. Stimulation was most pronounced in the lowest lymphocyte to target cell ratio. 1- to 2-h preincubation of effector cells with IFN was enough to achieve maximal stimulation. The effector cells of IFN-treated myeloma-patients, or patients with herpes zoster, showed a clear reduction of toxicity against all cells tested during the first infusion, as compared to the pretreatment values.


The diagnosis of old and new gastrointestinal parasites.
For the foreseeable future, light microscopy will continue to be the method of choice for diagnosing gastrointestinal parasites. However, in selected circumstances, the use of commercially available immunofluorescent kits will supersede the use of routine light microscopy for diagnosis of Giardia lamblia and Cryptosporidium parvum. These techniques may used to diagnose invasive amebic infections caused by E. histolytica in the future. Pooling stool samples from the same or even different patients may offer a means to process specimens in a more efficient and cost-effective manner without lowering the predictive value of an ova and parasite examination. Although we suggest that, with some exceptions, stools for ova and parasite examination should not be accepted past the fourth day of hospitalization, we cannot recommend the use of a single stool sample for diagnosis without extensive studies in individual parasitology laboratories. Techniques have still not been developed for the optimum methods of concentration of stool for diagnosis of coccidian infections. For most laboratories, the diagnosis of microsporidian infections remains problematic because of the lack of a commercial source for oocysts to provide positive control material. (Note: There is now a commercial source for oocysts available.)


Ovine interleukin-2: partial purification and assay in normal sheep and sheep with ovine progressive pneumonia.
Interleukin-2 (IL-2), a T cell derived lymphokine, acts in nonspecific hormone-like fashion to maintain proliferation of activated lymphocytes in vitro and is believed to play a key role in cell-mediated immune function in vivo. The parameters of induction and assay of factors with IL-2 activity were examined in a group of clinically normal sheep seronegative for antibodies to ovine progressive pneumonia virus (OPPV-). Supernatants from cultures of Concanavalin A (Con A) stimulated mononuclear leukocytes (ML) derived from peripheral blood and lymph nodes contained factors with the capacity to maintain continued proliferation in Con A stimulated lymphoblasts. This activity was localized by gel chromatography to fractions containing proteins of 17,000-20,000 daltons. In a group of sheep seropositive for antibodies to OPPV (OPPV+), decreased levels of IL-2 activity were found in ML culture supernatants derived from the posterior mediastinal lymph nodes of sheep with clinical and pathological evidence of OPP, when compared to OPPV+ sheep with no lesions and sheep with visceral caseous lymphadenitis. This decrease in IL-2 activity appeared not to be associated directly with levels of prostaglandin E2 in these supernatants. These findings may correlate with virus induced alterations in cell mediated immune function in lymphoproliferative lesions of OPP.


TNFAIP3, TNIP1, and MyD88 Polymorphisms Predict Septic-Shock-Related Death in Patients Who Underwent Major Surgery.
In many immune-related diseases, inflammatory responses and several clinical outcomes are related to increased NF-κB activity. We aimed to evaluate whether SNPs related to the NF-κB signaling pathway are associated with higher susceptibility to infection, septic shock, and septic-shock-related death in European patients who underwent major surgery. We performed a case-control study on 184 patients with septic shock and 212 with systemic inflammatory response syndrome, and a longitudinal substudy on septic shock patients. Thirty-three SNPs within genes belonging to or regulating the NF-κB signaling pathway were genotyped by Agena Bioscience's MassARRAY platform. No significant results were found for susceptibility to infection and septic shock in the multivariate analysis after adjusting for multiple comparisons. Regarding septic-shock-related death, patients with TNFAIP3 rs6920220 AA, TNIP1 rs73272842 AA, TNIP1 rs3792783 GG, and TNIP1 rs7708392 CC genotypes had the highest risk of septic-shock-related death in the first 28 and 90 days. Also, the MyD88 rs7744 GG genotype was associated with a higher risk of death during the first 90 days. Haplotype analysis shows us that patients with the TNIP1 GAG haplotype (composed of rs73272842, rs3792783, and rs7708392) had a lower risk of death in the first 28 days and the TNIP1 AGC haplotype was associated with a higher risk of death in the first 90 days. The SNPs in the genes TNFAIP3, TNIP1, and MyD88 were linked to the risk of septic-shock-related death in patients who underwent major surgery.


Photosensitivity in South Africa. III. Ovine hepatogenous photosensitivity caused by the plant Athanasia trifurcata L. (Asteraceae).
Hepatogenous photosensitivity was experimentally induced in 1 out of 4 sheep dosed with milled Athanasia trifurcata. This is an unpalatable aromatic shrub commonly found along the south-western and south-eastern Cape coast on overgrazed, recently burnt or disturbed veld, up to an altitude of 1 300m. The liver lesions ranged from a few small multifocal areas of necrosis in 1 animal to various zonal patterns of necrosis (centrizonal, midzonal and peripheral) in each of the other 3. Botanical, toxicological and clinical data are given.


[A comparison of lanthanum contained rinse on acid resistant abilities to human enamel and root surface].
To compare the effect of different does of lanthanum-contained rinse solution on carious-resistance, and to investigate the acid-resistant abilities of dental enamel and root surface that treated with lanthanum-contained rinse solution. Human dental root surfaces were treated in vitro with various doses (100 x 10(-6) - 2000 x 10(-6)) of lanthanum-contained rinse solution under the pH cycle environment that mimic the normal pH change curve of oral cavity. The qualitative and quantitative analysis was carried out on dental cementum according to their mineralized degrees. The best effective dose for carious-resistance was set for further investigation in vitro. Dental enamel and root surfaces were treated with the rinse for 1 hour each day, total for five days. The rinse solution containing 500 x 10(-6) lanthanum or more than it showed a obvious carious-resistant effect and there was no significant difference between root surfaces and dental enamel while treated with 500 x 10(-6) lanthanum-contained rinse solution. To compare demineralized degrees between enamel and root surfaces before or after treatment, enamel showed severer demineralization than root surfaces. 500 x 10(-6) lanthanum-contained rinse solution is considered to be the lowest effective dose for carious-resistance, and lanthanum-contained rinse solution is especially suitable for the treatment and prevention of dental root caries.


Organic solvent tolerance of an alkaline protease from salt-tolerant alkaliphilic Streptomyces clavuligerus strain Mit-1.
A salt-tolerant alkaliphilic actinomycete, Mit-1 was isolated from Mithapur, coastal region of Gujarat, India. The strain was identified as Streptomyces clavuligerus and based on 16S rRNA gene sequence (EU146061) homology; it was related to Streptomyces sp. (AY641538.1). The organism could grow with up to 15% salt and pH 11, optimally at 5% and pH 9. It was able to tolerate and secrete alkaline protease in the presence of a number of organic solvents including xylene, ethanol, acetone, butanol, benzene and chloroform. Besides, it could also utilize these solvents as the sole source of carbon with significant enzyme production. However, the organism produced spongy cell mass with all solvents and an orange brown soluble pigment was evident with benzene and xylene. Further, the enzyme secretion increased by 50-fold in the presence of butanol. With acetone and ethanol; the enzyme was highly active at 60-80 degrees C and displayed optimum activity at 70 degrees C. The protease was significantly stable and catalyzed the reaction in the presence of xylene, acetone and butanol. However, ethanol and benzene affected the catalysis of the enzyme adversely. Crude enzyme preparation was more stable at 37 degrees C in solvents as compared to partially purified and purified enzymes. The study holds significance as only few salt-tolerant alkaliphilic actinomycetes are explored and information on their enzymatic potential is still scares. To the best of our knowledge this is the first report on organic solvent tolerant protease from salt-tolerant alkaliphilic actinomycetes.


Co-fabrication of chitosan and epoxy photoresist to form microwell arrays with permeable hydrogel bottoms.
Microfabrication technology offers the potential to create biological platforms with customizable patterns and surface chemistries, allowing precise control over the biochemical microenvironment to which a cell or group of cells is exposed. However, most microfabricated platforms grow cells on impermeable surfaces. This report describes the co-fabrication of a micropatterned epoxy photoresist film with a chitosan film to create a freestanding array of permeable, hydrogel-bottomed microwells. These films possess optical properties ideal for microscopy applications, and the chitosan layers are semi-permeable with a molecular exclusion of 9.9 ± 2.1 kDa. By seeding cells into the microwells, overlaying inert mineral oil, and supplying media via the bottom surface, this hybrid film permits cells to be physically isolated from one another but maintained in culture for at least 4 days. Arrays co-fabricated using these materials reduce both large-molecular-weight biochemical crosstalk between cells and mixing of different clonal populations, and will enable high-throughput studies of cellular heterogeneity with increased ability to customize dynamic interrogations compared to materials in currently available technologies.


Glassy carbon electrodes modified with reduced graphene oxide-MoS2-poly (3, 4-ethylene dioxythiophene) nanocomposites for the non-enzymatic detection of nitrite in water and milk.
The detrimental effect of (NO2-) on environment, a sensitive and selective detection of nitrite (NO2-) ions with point-to-care device is need to be fabricated. Herein, we report the non-enzymatic nitrite sensor using a novel reduced graphene oxide/molybdenum disulfide/poly (3, 4-ethylene dioxythiophene) (rGO/MoS2/PEDOT) nanocomposite electrode. The rGO/MoS2/PEDOT nanocomposite was synthesized using facile and cost-effective hydrothermal and polymerization approaches. The characteristics of rGO-MoS2-PEDOT nanocomposite was investigated by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Raman, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analyses. The rGO-MoS2-PEDOT nanocomposite modified glassy carbon electrode (GCE) was directly used for electrocatalytic detection of nitrite ions present in the solution. TEM images show the PEDOT nanoparticles with an average size of 100-120 nm are uniformly covered on the outer face of rGO-MoS2 nanosheets. The interaction between the PEDOT and rGO-MoS2 is evidenced in the FTIR, XRD and XPS studies, and they produced synergistic effect, resulting enhanced electrocatalytic performance activity towards oxidation of nitrite. Under optimized conditions, the fabricated electrode exhibited remarkably good sensitivity (874.19 μA μM-1 cm-2), low detection limit (LOD) (0.059 μM, S/N = 3), wide linear range (0.001-1 mM) of nitrite with desirable selectivity, long-term stability and reproducibility. Furthermore, the practical feasibility of the fabricated sensor is validated by the successful detection of nitrite ion in some water and milk samples with excellent correlation. Thus, feasible easier synthesis method was adopted first time to fabricate rGO-MoS2-PEDOT nanocomposite nitrite sensor in the milk and water samples with enhanced selectivity, sensitivity and LOD.


A new pre-gelatinized starch preparing by spray drying and electron beam irradiation of oat starch.
As a green and safe physical technology, irradiation is increasingly used to improve starch properties. In the study, oat starch was pre-gelatinized at 70 °C followed by spray drying. Subsequently, the spray-dried starch (SDS) was exposed to electron beam (e-beam) irradiation at different doses to obtain new pre-gelatinized starch. Spray drying caused a decrement in the ratio of long B3 chains and the molecular weight of starch. Spray-dried starch (SDS) slightly increased solubility and swelling power than native starch. When SDS was subjected to e-beam irradiation, its solubility and swelling power increased dramatically, but the pasting viscosities, gelatinization temperatures, apparent viscosity, storage modulus (G') and lost modulus (G″) reduced. The depolymerization of starch molecules and the breakage of amylopectin chains might be responsible for changing the physicochemical properties of e-beam irradiated starch. These results showed that spray drying combined with e-beam irradiation would potentially produce new pre-gelatinized starch.


Patterns of enzyme activities and gene expressions in sucrose metabolism in relation to sugar accumulation and composition in the aril of Litchi chinensis Sonn.
Sucrose metabolism enzymes, including invertase (EC 184.108.40.206), sucrose synthase (SS, EC 126.96.36.199), and sucrose phosphate synthase (SPS, EC 188.8.131.52), are key factors that determine fruit sugar accumulation and composition. Sugar concentration and sugar composition in the arils of 42 litchi cultivars were determined at maturity. The cultivars were grouped into three types according to their hexose/sucrose ratio. Five cultivars of each type were selected to monitor the activities and gene expressions of enzymes related to sucrose metabolism. Pattern changes in the arils of four cultivars with different sugar concentrations and compositions were traced from around 40 d after anthesis to full maturity. Highly significant positive correlations were observed between hexose/sucrose ratios and the activities and expression levels of soluble acid invertase (SAI) and SS among the 15 cultivars tested. The increase in hexose/sucrose ratio was accompanied by enhanced acid invertase (AI) and SS activities and the expression of their genes in Feizixiao (FZX) and Heiye (HY). By contrast, no significant correlation was observed between hexose/sucrose ratio and SPS. These results indicate that the sugar composition in litchi aril depends mainly on the sucrose cleavage enzymes AI and SS and not on the sucrose synthetic enzyme SPS. The cultivar Nuomici, which had the highest sugar content among the cultivars studied, displayed significantly lower activities of cell wall acid invertase, SAI, neutral invertase, and SS and lower expression levels of SAI and SS compared with HY, the cultivar with the lowest sugar content. The inconsistent patterns of sugar accumulation and activities and expressions of sucrose metabolism enzymes suggest that these sucrose metabolism enzymes are not necessarily related to sugar accumulation.


Etiology and perinatal outcome of polyhydramnios.
To determine causes of polyhydramnios and the respective perinatal outcome. We retrospectively analyzed cases with polyhydramnios at the Medical University Graz, Austria from 2003 - 2011. Inclusion criteria were single deepest pocket ≥ 8 cm, amniotic fluid index ≥ 25 cm, each of the latter parameters > 95th percentile or subjective impression. Etiologies, including TORCH infection, diabetes and congenital malformations, as well as perinatal outcome were evaluated. Out of 860 singleton pregnancies with polyhydramnios, 2.9 % had positive TORCH serology, 8.5 % had congenital anomalies, 19.8 % had maternal diabetes, and 68.8 % were idiopathic. The most common fetal anomalies were cardiac defects (32.9 %). Elective caesarean sections were more common in the groups with malformations and maternal diabetes. Low birth weight combined with severe polyhydramnios or maternal diabetes was associated with malformations. Diagnosis of polyhydramnios should prompt glucose-tolerance testing, detailed sonography including fetal echocardiography, and TORCH serology. Especially pregnancies with polyhydramnios and small fetuses as well as those with maternal diabetes should be carefully evaluated for malformations.


Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis.
Functional disruption and neuronal loss followed by progressive dysfunction of the nervous system underlies the pathogenesis of numerous disorders defined as "neurodegenerative diseases". Multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system resulting in serious neurological dysfunctions and disability, is one of the most common neurodegenerative diseases. Recent studies suggest that disturbances in mitochondrial functioning are key factors leading to neurodegeneration. In this review, we consider data on mitochondrial dysfunctions in multiple sclerosis, which were obtained both with patients and with animal models. The contemporary data indicate that the axonal degeneration in multiple sclerosis largely results from the activation of Ca2+-dependent proteases and from misbalance of ion homeostasis caused by energy deficiency. The genetic studies analyzing association of mitochondrial DNA polymorphic variants in multiple sclerosis suggest the participation of mitochondrial genome variability in the development of this disease, although questions of the involvement of individual genomic variants are far from being resolved.


Moxifloxacin in experimental Streptococcus pneumoniae cerebritis and meningitis.
Rifampin, a protein synthesis inhibitor, reduced mortality in a mouse model of meningitis compared to bacteriolytic cephalosporin standard therapy. To assess whether moxifloxacin (known to cause a less rapid bacteriolysis than cephalosporins) can similarly reduce mortality, mice infected with Streptococcus pneumoniae by deep intracerebral injection were treated subcutaneously with either 200 mg/kg of moxifloxacin or ceftriaxone every 8 hours for 5 days (n = 49 each). They were then observed for an additional 8 days. Overall mortalities were 35 and 29 in moxifloxacin- and ceftriaxone-treated mice, respectively (p = 0.29). Kaplan-Meier survival analysis also revealed no statistically significant differences (p = 0.32). Moxifloxacin failed to reduce mortality compared to cephalosporin standard therapy.


Effect of the visible light irradiation of fullerene-containing composites on the ROS generation and the viability of tumor cells.
To study the effect of fullerene-containing composites, irradiated by visible light, on the radical oxygen species (ROS) generation in thymocytes, ascitic cells from Erlich's tumor and leukemia cells L1210; to investigate viability of these cells in the presence of fullerene-containing composites under irradiation conditions. The viability of cells was evaluated by staining with 0.4% solution of the trypan blue; ROS were detected with the use of electron paramagnetic resonance (EPR) spectroscopy and spin traps; solutions of fullerene-containing composites were irradiated with mercury-vapor lamp. We demonstrated that under irradiation conditions fullerene-containing composites increase the rate of ROS generation and decrease the number of viable tumor cells. The obtained data allow to consider the fullerene-containing composites as potential agents for photodynamic therapy.


Association of intra- and extradural developmental venous anomalies, so-called venous angioma and sinus pericranii.
We report a case of cerebellar venous angioma and parietal sinus pericranii. Venous angioma is classified as a developmental venous anomaly (DVA) because it is not a neoplasm but a variant that develops during embryogenesis. Sinus pericranii should be classified as extradural-type DVA. Although there have been few reports of association between these conditions, both are suspected to have the same pathogenesis, i.e., transient venous hypertension in the late embryonic period influencing venous development.


Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.
The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein we describe the properties of metreleptin, its use in patients, which includes the administration of the drug and how it may be acquired by medical professionals as well as its safety, tolerability, and properties. Finally, we speculate on future uses and development of metreleptin.


Transcriptomic analysis of placenta affected by antiphospholipid antibodies: following the TRAIL of trophoblast death.
Antiphospholipid antibodies, a maternal risk factor for preeclampsia, increase shedding of necrotic trophoblast debris from the placenta, leading to endothelial dysfunction. Using Affymetrix HGU133 Plus 2 microarrays we found changes in the transcriptome of placental explants treated with antiphospholipid antibodies, including mRNAs BCL2L1, MCL1, PDCD2L, FASLG, SEMA6A, PRKCE and TRAIL that are involved in the regulation of apoptosis. Quantitative real-time RT-PCR and immunohistochemistry confirmed a reduction in TRAIL expression in response to antiphospholipid antibodies. These results may help to understand how antiphospholipid antibodies affect trophoblast cell death and how the antibodies could contribute to the pathogenesis of preeclampsia.


The effect of masker interaural time delay on the masking level difference in children with history of normal hearing or history of otitis media with effusion.
To determine the relation between the masking level difference (MLD) and the interaural time delay of the stimulus in children with a history of normal hearing and with a history of otitis media with effusion (OME). MLDs for a 500 Hz pure tone presented in a 100 Hz-wide masking noise were determined as a function of the interaural delay of the masker (six interaural delays between -726 microsec and +998 microsec were examined). For the masker with zero interaural delay, the signal was presented either interaurally in-phase or 180 degrees out of phase. For the masker delay conditions, the signal was given the same interaural delay as the masker and then was inverted interaurally. All children had normal audiograms at the time of testing. Ten children had a history of normal hearing and seven children had a history of OME. Similar to what has been found previously in adults, children with a history of normal hearing showed the maximum MLD (approximately 16 dB) for an interaural time delay of 0 microsec, with the MLD decreasing as a function of interaural time delay (by as much as 4 to 5 dB for the extreme delays). Children with a history of OME had significantly smaller MLDs than normal for the three smallest interaural delays but did not differ significantly from normal at the three largest interaural delays. The form of the function relating masker interaural time delay to MLD magnitude is adult-like by age 6 yr. The function indicates a binaural advantage for the processing of sound near auditory midline. This advantage is less apparent in children having a history of OME.


Hepatitis C services and individuals with serious mental illness.
Although individuals with serious mental illness have been shown to be at increased risk for hepatitis C viral (HCV) infection, there is growing concern regarding limited dissemination of recommended HCV related services to this population. This paper presents rates of receipt of HCV prevention services among a cohort of seriously mentally ill adults and reports rates of recommended follow-up care among the subset who tested HCV positive in a pilot study. Previous HCV screening was low and indicated medical follow-up among those who tested positive was also limited. Results stress the need for increased screening and counseling and delivery of preventive and follow-up medical services.


Designing an evaluation framework for WFME basic standards for medical education.
To create an evaluation plan for the World Federation for Medical Education (WFME) accreditation standards for basic medical education. We conceptualized the 100 basic standards from "Basic Medical Education: WFME Global Standards for Quality Improvement: The 2012 Revision" as medical education program objectives. Standards were simplified into evaluable items, which were then categorized as inputs, processes, outputs and/or outcomes to generate a logic model and corresponding plan for data collection. WFME standards posed significant challenges to evaluation due to complex wording, inconsistent formatting and lack of existing assessment tools. Our resulting logic model contained 244 items. Standard B 5.1.1 separated into 24 items, the most for any single standard. A large proportion of items (40%) required evaluation of more than one input, process, output and/or outcome. Only one standard (B 3.2.2) was interpreted as requiring evaluation of a program outcome. Current WFME standards are difficult to use for evaluation planning. Our analysis may guide adaptation and revision of standards to make them more evaluable. Our logic model and data collection plan may be useful to medical schools planning an institutional self-review and to accrediting authorities wanting to provide guidance to schools under their purview.


The effect of caffeine on cisplatin-induced apoptosis of lung cancer cells.
Cisplatin is an important DNA-damaging anticancer drug that has been used to treat many cancer types. However, the effectiveness of cisplatin treatment diminishes quickly as cancer cells develop resistance to the drug, which eventually results in treatment failure. Caffeine is an ingredient contained in many food sources. Caffeine can inhibit activities of both ATM and ATR, two important protein kinases involved in DNA damage-induced cell cycle arrest and apoptosis. The effect of caffeine on cisplatin-based cancer treatment is not well known. Caspase-3 activation and cell growth inhibition assays were used to determine the effect of caffeine on cisplatin-induced apoptosis and cell growth in lung cancer cells. Real time PCR, immunoblotting, and flow cytometry assays were used determine a mechanism through which the presence of caffeine increased cisplatin-induced apoptosis of the lung cancer cells. Our caspase-3 activation studies demonstrated that the presence of caffeine increased the cisplatin-induced apoptosis in both HTB182 and CRL5985 lung cancer cells. Our cell growth inhibition studies indicated that the presence of caffeine caused a more increase for cisplatin-induced cell growth inhibition. The results obtained from our real time PCR and western blot studies revealed that the presence of caffeine increased cisplatin-induced expression of the PUMA pro-apoptotic protein in these lung cancer cells. The results of our protein phosphorylation studies indicated that the presence of caffeine caused a decrease in CHK1 phosphorylation at Ser(317)/Ser(345) but an increase in ATM phosphorylation at Ser(1981) in the lung cancer cells treated with cisplatin. In addition, our flow cytometry studies also revealed that the presence of caffeine caused an increase in G1 cell population but a decrease for cisplatin-induced cell cycle arrests at the S and the G2 checkpoints in HTB182 and CRL5985 cells respectively. Our results suggest that the presence of caffeine increases the cisplatin-induced lung cancer cell killings by inhibiting ATR but inducing ATM activation, resulting in an increase in expression of PUMA protein and an increase in apoptosis.


Ecosystem health. IV. The National Animal Poison Information Network database as a tool for ecological risk assessment.
Toxicology is a unique discipline in human and veterinary medicine because there are orders of magnitude more toxicants available to man and animals than all known pathogenic microorganisms and parasites. The study of toxicologic responses of ecosystems to contaminants, ecoepidemiology, and the specific study of animal populations in this context, epizootiologic ecotoxicology, are concerned with identifying chemically induced causes and determining effects on and links among populations, communities, and ecosystems. Necessary activities implied by the term "epizootiologic ecotoxicology" are the systematic compilation and analysis of "health" data for ecosystem components. This concept paper describes the value and limitations of adapting methods used by the National Animal Poison Information Network (NAPINet) for epizootiologic ecotoxicology studies. It is concluded that NAPINet methodology, as part of an innovative use of population statistics and clinical measurements, could eventually be adapted into a valuable component of a standardized approach to epizootiologic ecotoxicology.


Valproate activates phosphodiesterase-mediated cAMP degradation: relevance to C6 glioma G1 phase progression.
Forskolin, a diterpene activator of adenylate cyclase, stimulates the production of cyclic adenosine monophosphate (cAMP) in a wide variety of cell types. In C6 glioma, used in this study, the anticonvulsant agent valproic acid (VPA) inhibited forskolin-stimulated cAMP accumulation in intact cells in a concentration-dependent manner. Kinetic studies indicated this valproate effect not to be mediated by direct inhibition of adenylate cyclase activity. The valproate-induced inhibition of cAMP accumulation was partially reversed by the phosphodiesterase (PDE) inhibitor isobutylmethyl xanthine (IBMX). Degradation of cAMP over time was more rapid in valproate-treated cells than in controls, and this effect was also reversed by IBMX. In synchronised C6 glioma, phosphodiesterase type IV (PDE4A1) expression was selectively upregulated during the G1 phase, in tandem with temporal biphasic peaks of cAMP. However, the expression of PDE4 isoforms was not affected by a 48-h exposure to valproate. These findings suggest inhibition of forskolin-stimulated cAMP levels in C6 glioma by valproate to be mediated by increased activation of PDE in the G1 phase. Since the degree of cell cycle arrest induced by valproate is intimately associated with its teratogenic potency, it appears that PDE-mediated inhibition of cAMP may contribute to the molecular mechanisms of valproate-induced teratogenicity.


Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the type A and B syndromes.
Acanthosis nigricans and hyperandrogenism are commonly found in patients with extreme target cell resistance to insulin, as in the type A and B syndromes of insulin resistance. However, the significance of concurrent acanthosis nigricans and hyperandrogenism in other clinical settings is not clear. We observed acanthosis nigricans to be present in 5% (15 of 300) of patients being evaluated for hyperandrogenism, and carried out studies of insulin binding and action in a group (7) of these women. Although none were diabetic, all were insulin resistant as assessed by hyperinsulinemia when fasting and after oral glucose administration. All patients were obese (mean IBW, 169%). However, when matched to hyperandrogenized women of similar body weight, patients with acanthosis nigricans were clearly more hyperinsulinemic. Insulin binding to monocytes and red cells was decreased in patients with acanthosis, and the extent of decrease was predicted by the fasting insulin level. There was also marked resistance to exogenous insulin during euglycemic insulin clamp studies in the two patients so tested. Anti-insulin receptor antibodies were not detectable, ruling out the type B syndrome. Unlike the type A syndrome, insulin binding to monocytes of these patients increased after acute (2/2) and chronic (1/1) caloric restriction. In the latter patient, acanthosis nigricans remitted as insulin resistance and the insulin binding defect improved. We conclude that acanthosis nigricans is present in as many as 5% of women with clinically significant hyperandrogenism. These women, although not diabetic, have fairly marked insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)


Female sex hormones and periodontal health-awareness among gynecologists - A questionnaire survey.
Sex hormones play an important role in periodontal health and disease. For example, puberty, menses, pregnancy, menopause, and oral contraceptive use influence a woman's periodontal health. Periodontal infection has also been associated with adverse pregnancy outcomes. Subsequently, it is important that gynecologists are educated about hormonal effects on women's oral health. The current study assessed gynecologist's awareness regarding the effect of female sex hormones on periodontal health, preterm delivery, and maternal periodontal disease. Gynecologists from the Bagalkot district of the Karnataka state, India, completed a questionnaire regarding female hormonal and periodontal health. Respondents were divided into two groups: Group A (doctors that practiced at a medical college or hospital) and Group B (doctors that practiced at private hospitals). Out of 73 gynecologists, 62 (85%) completed the survey, with 19 (30.6%) participants in Group A and 43 (69.4%) participants in Group B. Survey responses were collected in the presence of the investigator, and data between the groups were statistically compared. Our findings showed that most gynecologists were aware and concerned about female patient's oral health during various hormonal phases. However, gynecologists practicing at medical colleges and hospitals (Group A) had significantly greater health awareness than doctors practicing at private hospitals (Group B). Women have special periodontal health care considerations, and there is a need for better oral health education among caregivers. Our results suggest that increasing dental health awareness among gynecologists would significantly improve women's health and pregnancy outcomes.


Changes in the gamma chain heterogeneity of hemoglobin F of the baboon (Papio cynocephalus) postnatally and after partial switching to hemoglobin F production by various stimuli.
The postnatal switch from hemoglobin (Hb) F to Hb A in the baboon (Papio cynocephalus) occurs somewhat more rapidly than in humans. Minor components which are related to Hb F and Hb A are also present and show reciprocal rise and fall. The baboon produces two types of gamma chain presumably from nonallelic genes. These have either an isoleucyl (I gamma) or a valyl (V gamma) residue in position 75. As in the human case with G gamma and A gamma chains, the ratio I gamma to V gamma chains changes during the postnatal switch. Production of Hb F in the baboon may be stimulated by phenylhydrazine or more effectively by 5-azacytidine. With phenylhydrazine, the ratio of I gamma to V gamma chains in the Hb F is the same as in the traces of Hb F in the juvenile or adult baboon. However, with 5-azacytidine, at least some of the Hb F that is produced probably has been synthesized with an I gamma to V gamma ratio that is present prenatally and in the newborn baboon.


Experimental and modeling studies on microwave-assisted extraction of mangiferin from Curcuma amada.
Mangiferin, a bioactive compound having potent nutraceutical, strong antioxidant and pharmacological significance has been extracted using microwave-assisted extraction (MAE) technique from Curcuma amada, commonly known as mango ginger. The extraction solvent ethanol is eco-friendly, nontoxic and reduces the risk of environmental hazards. The influence of several independent variables such as microwave power, ethanol concentration, extraction (irradiation) time and pre-leaching time has been studied under varying conditions using one-factor-at-a-time analysis to obtain an optimal extraction ratio. The maximum mangiferin content of 1.1156 mg/g is obtained at microwave power of 550 W and extraction time of 50 s with 80 % ethanol as a solvent and pre-leaching time of 20 min. The results indicate that microwave power and ethanol concentration have the most significant effect on the yield of mangiferin content. The presence of mangiferin in final Curcuma amada extract is confirmed through high-performance liquid chromatography and the functional groups are identified through Fourier transform infrared spectroscopy analyses using standard mangiferin. The experimental profiles are fitted into a two-parameter modified first-order kinetic model and a three-parameter modified logistic model and checked using the goodness-of-fit criterion. The Curcuma amada retained its antioxidant activity after MAE treatment and the antioxidant activity of mangiferin obtained after extraction using DPPH free radical scavenging assay is studied.


Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics.
The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the "cytokine storm" underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.


Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis.
The insulin-like growth factor-I receptor (IGF-IR) is frequently overexpressed and constitutively activated in pancreatic cancer, thus representing a promising target for therapy. We investigated the impact of a novel inhibitor of IGF-IR (NVP-AEW541) on signalling and growth of pancreatic cancer. Human pancreatic cancer cells and endothelial cells were employed, and effects of NVP-AEW541 on signalling pathways investigated by Western blotting. NVP-AEW541 diminished the activation of IGF-IR, IRS-1, Erk, Akt and STAT3. Furthermore, NVP-AEW541 reduced cancer cell proliferation and abrogated migratory effects of IGF-I. NVP-AEW541 elicited a direct effect on endothelial cells in terms of reducing endothelial cell migration. In vivo, treatment of mice with NVP-AEW541 significantly reduced orthotopic pancreatic tumour growth, vascularisation, and VEGF expression. Interestingly, NVP-AEW541 lowered serum levels of IGF-binding-protein-3 (IGFBP-3). In conclusion, the IGF-IR inhibitor NVP-AEW541 effectively disrupts IGF-I signalling and reduces pancreatic tumour growth. Hence, blocking IGF-IR could prove valuable for targeted therapy of pancreatic cancer.


Posterior cingulate cortex mediates outcome-contingent allocation of behavior.
Adaptive decision making requires selecting an action and then monitoring its consequences to improve future decisions. The neuronal mechanisms supporting action evaluation and subsequent behavioral modification, however, remain poorly understood. To investigate the contribution of posterior cingulate cortex (CGp) to these processes, we recorded activity of single neurons in monkeys performing a gambling task in which the reward outcome of each choice strongly influenced subsequent choices. We found that CGp neurons signaled reward outcomes in a nonlinear fashion and that outcome-contingent modulations in firing rate persisted into subsequent trials. Moreover, firing rate on any one trial predicted switching to the alternative option on the next trial. Finally, microstimulation in CGp following risky choices promoted a preference reversal for the safe option on the following trial. Collectively, these results demonstrate that CGp directly contributes to the evaluative processes that support dynamic changes in decision making in volatile environments.


Ghosts: A travel barrier to tourism recovery.
This study aims to assess whether or not beliefs in ghosts really deter tourists from traveling to disaster-hit destinations. To many it may appear that cultural differences do play a role in travel decision making between Asian and Western tourists. However, it is vital to provide empirical evidence of the impact of cultural differences in beliefs through a case study of the tsunami-hit destinations. Thus, this study aims to examine tourist barriers associated with tsunami-hit destinations, and also to assess cultural differences regarding such beliefs between Asians tourists from China and Thailand and Western tourists from Britain, Germany, and the United States and also across demographic profile.


[Results of integrating pharmaceutical care in an Acute Geriatric Unit].
To evaluate whether the integration of pharmaceutical care in an acute geriatric unit can promote the detection of potentially inappropriate drug prescriptions (PIP) and adverse drug events (ADE), and if this can improve patient and caregiver information at hospital discharge. Descriptive prospective study in older patients admitted for acute care in the Geriatric Department of a university hospital. On admission, a pharmacist recorded a comprehensive drug history from the patient, caregiver and other available sources, and reviewed preadmission treatments in order to detect adverse drug events (using the 3(rd) Granada consensus criteria) and potentially inappropriate prescriptions (using STOPP-START criteria). At hospital discharge, the pharmacist informed patients and caregivers about the treatment and gave them computer generated written information for all drugs prescribed. In a 9 month period 189 patients (84.7% of all admissions) were included in the pharmaceutical care program (71.9% women, mean age 87.2±5.5 years). After analysing 1523 prescriptions (mean drugs/patient 8.1±3.3), 356 (23.4%) potentially inappropriate prescriptions and 580 (38.1%) adverse drug events were detected (1.9 PIP and 3.2 ADE per patient). Almost three-quarters (74.2%) of the patients had at least one PIP: STOPP (48.9%) and START (26.9%). The most frequent adverse drug event was an untreated health problem. The pharmacist offered verbal and written information to 74.7% of the discharged patients. Adding pharmaceutical care to the multidisciplinary activity of an acute geriatric care unit enables a great number of potentially inappropriate prescriptions and adverse drug events to be detected, and increases patient and caregiver information at hospital discharge.


Bilaterally symmetric Fourier approximations of the skull outlines of temnospondyl amphibians and their bearing on shape comparison.
Present work illustrates a scheme of quantitative description of the shape of the skull outlines of temnospondyl amphibians using bilaterally symmetric closed Fourier curves. Some special points have been identified on the Fourier fits of the skull outlines, which are the local maxima, or minima of the distances from the centroid of the points at the skull outline. These points denotes break in curvature of the outline and their positions can be compared to differentiate the skull shapes. The ratios of arc-lengths of the posterior and lateral outline of 58 temnospondyl skulls have been plotted to generate a triaguarity series of the skulls. This series grades different families, some of their genera and species as well as some individuals according to their posterior and lateral skull length ratios. This model while comparing different taxa, takes into account the entire arc-length of the outline of the temnospondyl skulls, and does not depend on few geometric or biological points used by earlier workers for comparing skull shapes.


Managing Complications Related to Peripheral Nerve Surgery: Selected Illustrative Cases.
Peripheral nerve surgery mostly involves elective procedures; thus, the associated complications are of great clinical, social, and medicolegal importance. Apart from the general perioperative morbidity, complications during interventions on peripheral nerves are extremely rare. However, iatrogenic peripheral nerve injuries during unrelated surgical procedures performed by those not specialised in peripheral nerve surgery remain the most significant group of complications, accounting for up to approximately 17% of all cases. The aims of this review are to provide better insight into the multifaceted nature of complications related to peripheral nerve surgery-from the perspective of their causes, treatment, and outcome-and to raise surgeons' awareness of the risks of such morbidity. It should be emphasized that intraoperative complications in peripheral nerve surgery are largely "surgeon-related" rather than "surgery-related"; therefore, they have great potential to be avoided.


Historical biogeography of the North American glacier ice worm, Mesenchytraeus solifugus (Annelida: Oligochaeta: Enchytraeidae).
North American ice worms are the largest glacially-obligate metazoans, inhabiting coastal, temperate glaciers between southcentral Alaska and Oregon. We have collected ice worm specimens from 10 new populations, completing a broad survey throughout their geographic range. Phylogenetic analyses of 87 individuals using fragments of nuclear 18S rRNA, and mitochondrial 12S rRNA and cyctochrome c oxidase subunit 1 (CO1) identified 18 CO1 haplotypes with divergence values up to ~10%. Phylogeographic interpretations suggest a St. Elias Range, Alaskan ancestry from an aquatic mesenchytraeid oligochaete during the early-Pliocene. A gradual, northward expansion by active dispersal from the central St. Elias clade characterizes a northern clade that is confined to Alaska (with one exception on Vancouver Island, British Columbia), while a distinct southern clade representing worms from British Columbia, Washington and Oregon was likely founded by a passive dispersal event originating from a northern ancestor. The geographic boundary between central and southern clades coincides with an ice worm distribution gap located in southern Alaska, which appears to have restricted active gene flow throughout the species' evolutionary history.


[Genetic deafness].
The aim of this study was to review the different types of genetic deafness. We describe syndromic and isolated sensorineural deafness and transmission deafness. Genetic sensorineural syndromic deafness represents 30% of cases of genetic deafness. A frequent cause is Pendred syndrome, which associates congenital sensorineural deafness with goitre and malformations of the inner ear which can be identified on computed tomography scan. Isolated deafness which is responsible for 70% of cases of genetic deafness is then outlined. Among the different types of isolated deafness, 80% are autosomal recessive disorders. A frequent form of autosomal recessive deafness is due to mutations in the connexin 26 gene. Lastly, we detail transmission deafness dominated by aplasia. Major aplasia is characterized by a malformation of the external ear associated with malformations of the middle ear whereas, minor aplasia corresponds to a malformation of the middle ear, sometimes associated with minor external ear malformations. For each type of deafness we propose a systematic assessment.


A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma.
Sunitinib is a multi-target tyrosine kinase inhibitor (TKI) that inhibits VEGF receptor 1, 2, 3 (VEGFRs), platelet-derived growth factor receptor (PDGFR), colony-stimulating factor receptor (CSFR), and the stem cell factor receptor c-KIT. Temsirolimus inhibits mammalian target of rapamycin (mTOR) through binding to intracellular protein FKBP-12. Both agents are approved for the treatment of metastatic renal cell carcinoma (mRCC), have different anticancer mechanisms, and non-overlapping toxicities. These attributes form the scientific rationale for sequential combination of these agents. The primary objective of the study was to investigate the efficacy of alternating sunitinib and temsirolimus therapy on progression-free survival (PFS) in mRCC. We undertook a phase II, multi-center, single cohort, open-label study in patients with mRCC. Patients were treated with alternating dosing of 4 weeks of sunitinib 50 mg PO daily, followed by 2 weeks rest, then 4 weeks of temsirolimus 25 mg IV weekly, followed by 2 weeks rest (12 weeks total per cycle). The primary endpoint was PFS. Secondary endpoints included clinical response rate and characterization of the toxicity profile of this combination therapy. Nineteen patients were enrolled into the study. The median observed PFS (n = 13 evaluable for PFS) was 8.8 months (95% CI 6.8-25.2 months). Best responses achieved were five partial response, nine stable disease, and three disease progression according to RECIST 1.1 guidelines (two non-evaluable). The most commonly observed toxicities were fatigue, platelet count decrease, creatinine increased, diarrhea, oral mucositis, edema, anemia, rash, hypophosphatemia, dysgeusia, and palmar-plantar erythrodysesthesia syndrome. Alternating sunitinib and temsirolimus did not improve the PFS in patients with mRCC.


[Communicating uteri; a rather uncommon but important malformation (author's transl)].
A rare genital double malformation is dealt with in short. Including the four cases, which are reported, the number of the known cases in the literature amounts to only 31. The characteristic feature of the malformation is a communication of embryological origin between two uterine cavities. Diagnostic difficulties and clinical peculiarities can arise. Very often the genital malformation is accompanied by unilateral agenesis of kidney and ureter. Some clinical symptoms cannot be recognized and treated without knowledge about the existence of communication uteri, but the knowledge that malformations of the urinary tract may coexist is not less important. Indeed, it may be crucial for the patient's destiny.


[Study on expression and methylation of caveolin 1 gene in non-small cell lung cancers].
To study the methylation of CpG islands in the promoter region, expression of caveolin 1 (Cav-1) gene and their clinical significance in non-small cell lung cancers (NSCLC). Immunohistochemistry and quanta Qd600 staining were used to detect the expression of Cav-1 in tissues from benign lung lesions (n = 17) and NSCLC (n = 123). DNA was treated with sodium bisulfite and the Cav-1 promoter region was screened using methylation-specific polymerase chain reaction for the possible methylation sites. Cav-1 protein was highly expressed in cytoplasm and cell membrane of normal bronchial epithelium, alveolar epithelium, endothelial cells, fibroblasts and smooth muscle cells. The expression rates of Cav-1 protein were 100% (17/17) in the control group and 43.1% (53/123) in the NSCLC group (P = 0.001). Amongst the NSCLC group, there was no statistically significant difference in Cav-1 protein expression in different histologic types (P = 0.552) and tumor grades (P = 0.160). On the other hand, Cav-1 protein immunoreactivity was remarkably higher in advanced tumor stage: 72.7% in stage III A + III B, compared with 9.4% in stage I A + I B and 38.3% in stage II A + II B (P = 0.001). The expression rate of Cav-1 protein in the NSCLC cases with lymph node metastasis was 53.6%, compared with 20.5% in those without nodal involvement (P = 0.001). DNA from 40 NSCLC cases with negative Cav-1 protein expression and 12 cases of peritumoral lung tissues were extracted. Methylation in the promoter region of Cav-1 gene was not detected in lung cancer or peritumoral tissues. High expression of Cav-1 protein is respected of the aggressive clinical behavior and advanced tumor stage. Loss of Cav-1 protein expression seems not correlated to the methylation status in the promoter region of Cav-1 gene.


Long-term fencing can't benefit plant and microbial network stability of alpine meadow and alpine steppe in Three-River-Source National Park.
A great number of fencing facilities has been established in Three-River-Source National Park. However, with the transformation of wild animals into the main consumers of grassland ecosystem and the increasing years of fence (>15 years), whether the fence still has a positive effect on grassland ecosystem has become controversial. Therefore, taking the alpine steppe and alpine meadow in Three-River-Source National Park as the case study, this study focused on the effects of long-term enclosure on different ecological components by investigating plant communities, soil physical and chemical characteristics and soil microbial characteristics (16S, ITS). Furthermore, we evaluated the ecological benefits of long-term fencing based on the stability of plant communities and microbial networks. We found that fencing did not significantly promote the stability of plant community in different grassland types. The analysis of bacteria-fungal symbiotic network indicated that fencing significantly reduced the stability of soil microbial network in alpine meadows. The results of structural equation showed that the microbial community was indirectly affected by the changes of soil moisture content (SMC) and soil total nutrient content in the alpine steppe, and the stability of microbial network was significantly correlated with the diversity of fungal community. In alpine meadows, fencing indirectly affected soil microbial community by changing SMC and pH. High SMC was not conducive to microbial network stability, while high plant community stability was beneficial to microbial network stability. Network stability was remarkably related to bacterial community composition and diversity, as well as fungal community diversity. Therefore, in Three-River-Source National Park, the positive effects of long-term fencing on various components in different grassland types are weak, especially the negative effects on the stability of soil microbial community in alpine meadows may also weaken the stability of the ecosystem, which is not conducive to the ecological protection of grassland ecosystem.


Bioaccessibility by perspiration uptake of minerals from two different sulfurous peloids.
The risks associated with the use of peloids in thermal centers, spas, or at home, must be tested to develop appropriate safety guidelines for peloids formulations and the release of substances of high concern. Additionally, the beneficial effects of some elements on human health should be assessed to aid in interpreting the therapeutic action and effectiveness of pelotherapy on dermatological or osteomuscular disorders. Therefore, a methodology was developed to better understand the biogeochemical behavior of the elements in formulated peloids. Two peloids were formulated with the same clay and two different sulfurous mineral-medicinal waters for 90 days, with light stirring every 15 days. Bentonite clay, with a high content of smectite and Ca and Mg as the main exchangeable cations, and high heat capacity, was used. The selected mineral-medicinal waters were collected from two Portuguese thermal centers with recognized therapeutic efficacy for rheumatic, respiratory and dermatological pathologies. The peloids were used without drying and withdrawn directly from the maturation tank, and a mixture of bentonite and demineralized water was prepared as a reference sample. A stabilized, ready-to-use, artificial perspiration test was used to simulate the peloids' interaction with skin. Thirty-one elements extracted from the two prepared peloids were analyzed using ICP-MS. The data were analyzed and related to the mineralogical composition of the original clay and supernatant composition of the maturation tanks. The content of some potentially toxic elements and metals' bioaccessibility by perspiration showed very low solubility and undetectable amounts extracted from the studied samples. This analytical method provided reliable information on dermal exposure and the identification of some elements that may enter the systemic circulation, requiring implementation of surveillance and control measures.


MRI-Guided Derivation of the Input Function for PET Kinetic Modeling.
Blood samples obtained by arterial cannulation are the gold standard to measure the input function for PET pharmacokinetic modeling. There is interest in less invasive methods, such as image-derived input functions (IDAIF). MRI can be used to segment and correct partial volume effects of the PET images, improving IDAIF extraction. Preclinical studies have shown that the input function of PET tracers, namely fluorodeoxyglucose and [(18)F]fluoroethyl-l-tyrosine, can be derived from the Gd-DTPA input function. Noninvasive, MRI-guided, PET input function derivation is a promising avenue to reduce or eliminate the need for arterial plasma samples in preclinical and clinical settings.


[³H]serotonin release assay using antigen-stimulated rat peritoneal mast cells.
The concentration of nerve growth factor (NGF) is elevated in a number of inflammatory and autoimmune states in conjunction with increased accumulation of mast cells. Mast cells, which are of hematopoietic lineage, and NGF appear to be involved in neuroimmune interactions and tissue inflammation. Mast cells themselves are capable of producing and responding to NGF. Here we describe a protocol for the isolation and culture of peritoneal-derived rat mast cells, together with a [(3)H]serotonin release assay which is useful in assessing the effects of antigens and neurotrophic factors on mast-cell activation.


Decision-making in pediatric blunt solid organ injury: A deep learning approach to predict massive transfusion, need for operative management, and mortality risk.
The principal triggers for intervention in the setting of pediatric blunt solid organ injury (BSOI) are declining hemoglobin values and hemodynamic instability. The clinical management of BSOI is, however, complex. We therefore hypothesized that state-of-art machine learning (computer-based) algorithms could be leveraged to discover new combinations of clinical variables that might herald the need for an escalation in care. We developed algorithms to predict the need for massive transfusion (MT), failure of non-operative management (NOM), mortality, and successful non-operative management without intervention, all within 4 hours of emergency department (ED) presentation. Children (≤18 years) who sustained a BSOI (liver, spleen, and/or kidney) between 2009 and 2018 were identified in the trauma registry at a pediatric level 1 trauma center. Deep learning models were developed using clinical values [vital signs, shock index-pediatric adjusted (SIPA), organ injured, and blood products received], laboratory results [hemoglobin, base deficit, INR, lactate, thromboelastography (TEG)], and imaging findings [focused assessment with sonography in trauma (FAST) and grade of injury on computed tomography scan] from pre-hospital to ED settings for prediction of MT, failure of NOM, mortality, and successful NOM without intervention. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were used to evaluate each model's performance. A total of 477 patients were included, of which 5.7% required MT (27/477), 7.2% failed NOM (34/477), 4.4% died (21/477), and 89.1% had successful NOM (425/477). The accuracy of the models in the validation set was as follows: MT (90.5%), failure of NOM (83.8%), mortality (91.9%), and successful NOM without intervention (90.3%). Serial vital signs, the grade of organ injury, hemoglobin, and positive FAST had low correlations with outcomes. Deep learning-based models using a combination of clinical, laboratory and radiographic features can predict the need for emergent intervention (MT, angioembolization, or operative management) and mortality with high accuracy and sensitivity using data available in the first 4 hours of admission. Further research is needed to externally validate and determine the feasibility of prospectively applying this framework to improve care and outcomes. III STUDY TYPE: Retrospective comparative study (Prognosis/Care Management).


Educational technologies and the teaching of ethics in science and engineering.
To support the teaching of ethics in science and engineering, educational technologies offer a variety of functions: communication between students and instructors, production of documents, distribution of documents, archiving of class sessions, and access to remote resources. Instructors may choose to use these functions of the technologies at different levels of intensity, to support a variety of pedagogies, consistent with accepted good practices. Good pedagogical practices are illustrated in this paper with four examples of uses of educational technologies in the teaching of ethics in science and engineering. Educational technologies impose costs for the purchase of hardware, licensing of software, hiring of support personnel, and training of instructors. Whether the benefits justify these costs is an unsettled question. While many researchers are studying the possible benefits of educational technologies, all instructors should assess the effectiveness of their practices.


The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence.
Nephrotoxicity remain a major life-threatening complication in cancer patients on cisplatin chemotherapy. In this study, we investigated the protective effect and possible cellular mechanism of the hesperetin, a naturally-occurring bioflavonoid against cisplatin-induced renal injury in rats. Hesperetin was administered at a dose of 50mg/kg and 100mg/kg orally for 10days and cisplatin (7.5mg/kg, ip) was administered on the 5th day of experiment. Cisplatin induced nephrotoxicity was evidenced by alteration in the level of markers such as blood urea nitrogen, creatinine, serum albumin and severe histopathological changes in kidney. Cisplatin administration also resulted in significant increase in the tissue oxidative stress and inflammatory cytokines. The level of antioxidants enzymes were decreased significantly in the cisplatin administered rats. Hesperetin treatment (50mg/kg and 100mg/kg) normalized the renal function by attenuation of the cisplatin-induced oxidative stress, lipid peroxidation, and inflammatory cytokines and histopathological alterations. On the basis of these experimental findings our present study postulate that co-administration of hesperetin with cisplatin chemotherapy may be promising preventive approach to limit the major mortal side effect of cisplatin.


The use of portfolios in the assessment of learning and competence.
Portfolios have been used to incorporate accreditation of prior learning into nursing and midwifery assessment. This article aims to review the available literature on the use of portfolios. There needs to be a thorough evaluation of portfolios to determine their effectiveness as assessment tools in relation to the curriculum.


Prenatal diagnosis of de novo distal 5q duplication associated with hygroma colli, fetal oedema and complex cardiopathy.
We report the first prenatal diagnosis of de novo distal 5q duplication after the echographic findings of hygroma colli and complex cardiopathy in a female fetus of 16 weeks' gestation. Cytogenetic studies on amniocytes showed a de novo inverted distal 5q duplication: karyotype: 46,XX, inv dup(5) (pter-->q3.53::q3.53-q3.33::q3.53-->qter). Based on the findings in the literature, a review of the malformative syndrome associated with partial distal 5q trisomy is given.