The development of a new, ultra-fine, and flexible neuroendoscope for intracranial observation.
A neuroendoscope is a technical advance that allows surgeons to visualize certain regions of the brain that was previously inaccessible through the use of a surgical microscope. Several neuroendoscope designs have been implemented by other neurosurgeons over the past 5 years. The advantage of a neuroendoscope is the addition of a flexible and narrow tip that allows for safe entry into intracranial structures for clinical observation. However, there are some limitations to this approach. Here, we report the use of a modified angioscope as a newly developed neuroendoscope to be employed in observing intracranial structures. We report the use of an angioscope that is 1.8 mm in diameter and has both a thin and flexible tip. In this study, the angioscope was inserted into the lumen of an aspirator tube, and the tip of the device was placed at the intracranial area of intended observation area. Image findings were evaluated using an established in vivo goat brain model. The angioscope was light in weight and maneuverable and could be reached and observed in the blind spot using a surgical microscope. From the cerebellopontine angle, the lower cranial nerves and trigeminal nerve could be observed, and from the cisterna magna, the floor of the fourth ventricle and the aqueduct could be seen. The angioscope is a useful instrument to observe intracranial locations safely and effectively even within a limited surgical field. Further modifications will be required to use the angioscope in various craniotomy procedures.


Macrophage-chemotactic factor-producing T cell hybridomas reactive to phosphorylcholine in I-E-restricted manner.
Macrophage-chemotactic factor (MChF)-producing T cell hybridomas were established. These hybridomas produced MChF upon the specific antigenic stimulation with phosphorylcholine (PC)-conjugated protein in the presence of I-Ed-positive antigen-presenting cells. The hybridomas also secreted MChF after co-culture with concanavalin A in the absence of antigen-presenting cells. The MChF-secreting hybridomas were positive for Kd, Dd, Lyt-1.2 but negative for I-Ad, Lyt-2.2. The molecular weight of MChF produced by the hybridomas was 43000 and the factor was focused at pH 6.6-6.8 in the chromatofocusing procedure. The MChF was protease sensitive but resistant to neuraminidase treatment, and it was stable by heating at 80 degrees C for 15 min. The MChF-producing hybridomas established in this stud did not produce macrophage migration inhibitory factor (MIF), macrophage-activating factor (MAF) or interleukin 2, suggesting molecular nonidentity between MChF and these lymphokines. The MChF-producing T cell hybridomas reactive to specific antigens (PC) will be promising tools for analysis of molecular nature of MChF as well as molecular aspects of antigen recognition mechanism of T cells.


Epo deficiency alters cardiac adaptation to chronic hypoxia.
The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAg(h)) and wild-type (WT) mice. Left (LV) and right ventricular functions were assessed by echocardiography and hemodynamics. HIF-1α, VEGF and Epo pathways were explored through RT-PCR, ELISA, Western blot and immunocytochemistry. Epo gene and protein were expressed in cardiomyocytes of WT mice in normoxia and hypoxia. Increase in blood hemoglobin, angiogenesis and functional cardiac adaptation occurred in CHx in WT mice, allowing a normal oxygen delivery (O2T). Epo deficiency induced LV hypertrophy, increased cardiac output (CO) and angiogenesis, but O2T remained lower than in WT mice. In CHx Epo-TAg(h) mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAg(h) mice could not adapt to CHx despite activation of cardioprotective pathways (increased P-STAT-5/STAT-5). HIF/Epo pathway is activated in the heart of WT mice in hypoxia. Chronic hypoxia induced cardiac adaptive responses that were altered with Epo deficiency, failing to maintain oxygen delivery to tissues.


[Polymer materials for biomedical purposes obtained by radiological methods. I. Review of research trends].
The authors present a review of publications connected with the production of the materials for biomedical purposes using of radiation technology. The general characteristic of the radiation methods and examples of applications of the results of investigations are given.


Nitroprusside abolishes the deleterious effects of surface cooling-induced hypothermia on immature pigs with ventricular septal defects.
The efficacy of systemic hypothermia in combination with cardiopulmonary bypass for the repair of congenital cardiac malformations is established. Surface cooling in infants with ventricular septal defects as a prebypass adjunct has been associated with visceral ischemic complications. Surface cooling in infant pigs with ventricular septal defects results in increased systemic vascular resistance and unchanged pulmonary vascular resistance with increased left-to-right shunting and a maldistribution of blood flow away from the viscera and kidneys. This study was to determine whether nitroprusside ameliorates the deleterious effects of increased systemic vascular resistance during hypothermia in infant pigs with ventricular septal defects. Nine neonatal pigs (4 weeks, 4 kg) had experimental ventricular septal defects resulting in a 2.3 +/- 0.3: 1 shunt. Systemic and pulmonary vascular resistances were determined by the flow probe and microsphere techniques. Systemic and pulmonary blood flow distributions were measured by the microsphere technique. Left-to-right shunt ratios were determined by oximetry, flow probe, and microsphere. The pigs were cooled to 28 degrees C and measurements were made at 37 degrees, 32 degrees, and 28 degrees C. We found that nitroprusside abolishes the deleterious effects of surface cooling by blocking the rise of systemic vascular resistance without significant changes in aortic pressure. As a result, the animals maintained control pulmonary-to-systemic flow levels and maintained control levels of oxygen delivery while showing a decline in oxygen consumption. Additionally, the vasodilatory effect allowed the animals to cool twice as fast as animals without nitroprusside. Regional blood flow distribution as percent cardiac output and absolute tissue flow were protected during surface cooling. This technique may have a role in cardiac operations on infants with left-to-right shunts.


[Time dependence of the shedding of class I and II HLA antigens. Interrelation of the fluctuations of HLA-antigen shedding and 51Cr-labeled macromolecules].
Soluble HLA-A, -B and -DR antigens were determined every 10 min with a rate nephelometry method in supernatants of human mononuclear cells cultured for 3 hrs. The time-dependent oscillations in the quantity of soluble HLA antigens with ultradian (circadian) rhythm characteristics were found. Quantity oscillations of HLA-A antigens were synphase to HLA-B ones and antiphase to HLA-DR antigens. Amplitude characteristics were found to depend on the temperature and cytoskeleton activity.


Cardiovascular outcomes trials with incretin-based medications: a critical review of data available on GLP-1 receptor agonists and DPP-4 inhibitors.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called "incretin-based therapies" (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on various outcomes and inconsistencies observed in the trials is provided. Overall, available data is favourable to the early deployment of GLP-1RAs in clinical practice, fully in line with recommendations from international scientific guidelines, and based on their effects on glucose metabolism parameters, body weight reduction and CV outcomes. Evidence further suggest that the CV benefits of GLP-1RAs may not be a class effect, with GLP-1 analogues having a greater benefit rather than exendin-based agents.


A year with the fear of COVID-19 in multiple sclerosis patients: Examination of depression, sleep quality and quality of life before and after the pandemic.
The COVID-19 outbreak, which has caused great fear and has affected many aspects of life even in healthy individuals, could become more threatening for people with multiple sclerosis (PwMS). The aim of the present study was to evaluate depression, sleep and quality of life before and one year after the COVID-19 pandemic in PwMS and the association between the fear of COVID-19 and these parameters. A total of 89 PwMS and 262 healthy controls were included in this descriptive cross-sectional study. The study compared the data collected before the pandemic with the data collected online approximately one year after the onset of the pandemic. The Fear of COVID-19 Scale (FCV-19S), the Worry and Anxiety Questionnaire (WAQ), the Beck Depression Inventory (BDI), the Pittsburgh Sleep Quality Index (PSQI) and the MS Quality of life scale (MSQoL-54) were used as data collection tools. The mean age of the patients was 41.08 (±10.2) years; 62% were female and half (50.6%) of the patients were not working. The mean EDSS and the mean duration of diagnosis were found to be 1.33(±1.6) and 7.73(±6.1), respectively. The mean age of the control group was 38.08 (±11.4) and 51.5% were female. In both groups, social (PwMS 79.8% vs HC 89.3%) and psychological (PwMS 61.8% vs HC 51.9%) fields were found to have been affected by the COVID-19 pandemic most. Of the patients, 19% reported that the frequency of exacerbations increased during the pandemic. In the patient group, the fear of coronavirus (p=0.808) and the sleep quality (p=0.906) were found not to be different to those in control group; however, the anxiety (p=0.001) and depression (p=0.001) levels were determined to be significantly higher. Compared to the pre-pandemic period, the sleep quality of the patients was seen to be impaired during the pandemic (p<0.05); however, the depression scores were seen not to change (p>0.05). Although there were improvements in energy/vitality (p<0.001) and sexual function (p=0.002) scale scores, compared to the pre-pandemic period, deterioration in many sub-dimensions of quality of life was detected. Multiple regression analysis demonstrated that the anxiety, depression, and the sleep problems were predictors of both the physical health (p<0.001) and the mental health (p<0.001) sub-dimensions. The fear of coronavirus was determined not to have a significant effect on the quality of life (p>0.05). It was determined that PwMS and were psychosocially affected by the COVID-19 pandemic, and had a significant deterioration in sleep quality at the end of a year spent with the pandemic. In addition, there was a deterioration in depression scores, although it was not statistically significant. Considering the fact that many subdimensions of quality of life, especially those associated with mental health, were impaired, it can be said that providing psychosocial support to patients is an important necessity.


The solid component within part-solid nodules: 3-dimensional quantification, correlation with the malignant grade of nonmucinous pulmonary adenocarcinomas, and comparisons with 2-dimentional measures and semantic features in low-dose computed tomography.
There is no consensus on 3-dimensional (3D) quantification method for solid component within part-solid nodules (PSNs). This study aimed to find the optimal attenuation threshold for the 3D solid component proportion in low-dose computed tomography (LDCT), namely the consolidation/tumor ratio of volume (CTRV), basing on its correlation with the malignant grade of nonmucinous pulmonary adenocarcinomas (PAs) according to the 5th edition of World Health Organization classification. Then we tested the ability of CTRV to predict high-risk nonmucinous PAs in PSNs, and compare its performance with 2-dimensional (2D) measures and semantic features. A total of 313 consecutive patients with 326 PSNs, who underwent LDCT within one month before surgery and were pathologically diagnosed with nonmucinous PAs, were retrospectively enrolled and were divided into training and testing cohorts according to scanners. The CTRV were automatically generated by setting a series of attenuation thresholds from - 400 to 50 HU with an interval of 50 HU. The Spearman's correlation was used to evaluate the correlation between the malignant grade of nonmucinous PAs and semantic, 2D, and 3D features in the training cohort. The semantic, 2D, and 3D models to predict high-risk nonmucinous PAs were constructed using multivariable logistic regression and validated in the testing cohort. The diagnostic performance of these models was evaluated by the area under curve (AUC) of receiver operating characteristic curve. The CTRV at attenuation threshold of -250 HU (CTRV- 250HU) showed the highest correlation coefficient among all attenuation thresholds (r = 0.655, P < 0.001), which was significantly higher than semantic, 2D, and other 3D features (all P < 0.001). The AUCs of CTRV- 250HU to predict high-risk nonmucinous PAs were 0.890 (0.843-0.927) in the training cohort and 0.832 (0.737-0.904) in the testing cohort, which outperformed 2D and semantic models (all P < 0.05). The optimal attenuation threshold was - 250 HU for solid component volumetry in LDCT, and the derived CTRV- 250HU might be valuable for the risk stratification and management of PSNs in lung cancer screening.


Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.
Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.


Tumor vascularity predicts recurrence in differentiated thyroid carcinoma.
New prognosticators are necessary for optimizing the extent of thyroidectomy and adjuvant radiotherapy in differentiated thyroid carcinoma. Tumor microvessel density (MVD), expression of thymidine phosphorylase (dThdPase) and CD68 stained macrophages were evaluated in 71 differentiated thyroid carcinomas by an immunohistochemical method. The recurrence-free survival was significantly (P <0.05) shorter in patients with hypervascular tumors but was not related to the dThdPase expression. Significant (R = 0.323, P <0.001) correlation between dThdPase expression score and increment in MVD was documented. Frequent high MVD and dThdPase expression were encountered in tumors >3 cm. Twenty-two of the 27 (82%) patients expressing high dThdPase were also evaluated positive for CD68 (P <0.001). Tumor MVD might be a new prognostic indicator of differentiated thyroid carcinoma, whereas dThdpase expression with high MVD might serve to identify a subgroup of thyroid carcinoma patients as potential candidates for adjuvant radiotherapy.


Routine Lupus Anticoagulant Sensitive aPTT Testing Can Prevent Unnecessary LA Testing.
Even though routine screening of the general hospital population is discouraged, medical laboratories may use a "lupus sensitive" activated partial thromboplastin time test (aPTT) with phospholipid concentrations that are susceptible to inhibition by lupus anticoagulant (LA), to screen for the presence of LA. If deemed necessary, follow-up testing according to ISTH guidelines may be performed. However, LA testing is a laborious and time-consuming effort that is often not readily available due to a lack of automation and/or temporary unavailability of experienced staff. In contrast, the aPTT is a fully automated test that is available 24/7 in almost all medical laboratories and is easily interpreted with the use of reference ranges. In addition to clinical signs, the result of an LA sensitive aPTT may thus be used to lower the suspicion of the presence of LA and reduce costly follow-up testing. In this study, we show that a normal LA sensitive aPTT result may be safely used to refrain from LA testing in the absence of strong clinical suspicion.


Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease.
Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. Thirty-four children with AITD, aged 9.62 +/- 2.35 years, and 31 matched controls, aged 9.24 +/- 2.98 years, were studied. The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, P = 0.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, P = 0.024). No other statistically significant differences were observed in HSV-1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.


Willems I VS Willems II: A comparative study of accuracy in 5-15 year old Indian children.
Studies testing the Willems method of age estimation with gender-specific scores on different population groups have reported consistently more accurate results over other methods. Not enough is known about the validity of Willems non-gender specific scores. The present study aimed to compare the accuracy of the Willems I (gender-specific scores) and Willems II methods (non-gender-specific scores) in the age estimation of 5-15 year-old Indian children. In this cross-sectional observational study, the Willems I and II methods were tested and compared for accuracy in estimating the age of 1200 Indian children aged 5-15 years. The mean differences between dental age calculated by the Willems I method and chronological age were +0.09±0.80 years, +0.08±0.80 years and +0.09±0.80 years for boys, girls and the total sample, respectively. With the Willems II method, the values were -0.06±0.80 years, +0.11±0.79 years and +0.01±0.80 years for boys, girls and the total sample, respectively. Both methods did not show any statistically significant differences between dental and chronological ages for either gender or the total sample (p>0.05). The Willems I method was more accurate in predicting age of boys, while the Willems II method was more accurate in girls in the present study, but not significantly so. Both methods are appropriate for use in this population.


Moving waves and spatiotemporal patterns due to weak thermal effects in models of catalytic oxidation.
We analyze the behavior of a microkinetic model of a catalytic reaction coupled with weak enthalpy effects to show that under fixed gas-phase concentrations it can produce moving waves with an intrinsic length scale, when the underlying kinetics is oscillatory. The kinetic model incorporates dissociative oxygen adsorption, reactant adsorption and desorption, and surface reaction. Three typical patterns may emerge in a one-dimensional system (a long wire or a ring): homogeneous oscillations, a family of moving waves propagating with constant velocities, and patterns with multiple source/sink points. Pattern selection depends on the ratio of the system length to the intrinsic wave length and the governing parameters. We complement these analysis with simulations that revealed a plethora of patterned states on one- and two-dimensional systems (a disk or a cylinder). This work shows that weak long-range coupling due to high feed rates maintains such patterns, while low feed rates or strong long-range interaction can gradually suppress the emerging patterns.


Shear bond strength of visible-light-cured resin relative to heat-cured resin.
One promising clinical application of visible-light-cured (VLC) denture resin is for relining complete and partial dentures. Typically, a VLC resin would be used to reline an existing prosthesis fabricated from heat-cured resin (HCR). This study measured the shear bond strength of a VLC resin bonded to HCR specimens by different bonding agents. For comparison, we measured the shear bond strengths of VLC resin bonded to VLC resin specimens and of autopolymerizing resin (APR) to HCR specimens. Cylindrical specimens of HCR (n = 126) and VLC (n = 24) were thermocycled to simulate aging, and the bonding surfaces were prepared by being sanded to approximate clinical roughness. The specimens were divided into seven groups of approximately 20 each, and test materials were bonded by different bonding agents. Statistical analysis by ANOVA and the Student-Newman-Keuls test showed significant differences (p less than 0.05) among all groups except APR to HCR/no bonding agent, VLC to HCR/VLC bonding agent, or VLC to HCR/VLC and HCR bonding agent. The traditional bond of APR to HCR with HCR bonding agent was significantly stronger (p less than 0.05) than the strongest bond of VLC to HCR with HCR and VLC bonding agents.


Chronic Alcoholism and Its Health Implications: A Case Report.
Individuals with chronic alcohol use can be asymptomatic for a prolonged period of time and then exhibit signs of advanced heart and liver diseases with an abrupt onset. Herein, we present a case of a 60-year-old male with severe alcohol use disorder who presented with newly diagnosed atrial fibrillation (AF) with rapid ventricular response (RVR), dilated cardiomyopathy (DCM), and alcohol-associated cirrhosis following an episode of binge drinking.


Proton pump inhibitor therapy does not increase serum endotoxin activity in patients with cirrhosis.
Proton pump inhibitors (PPIs) are frequently prescribed in patients with cirrhosis, but this therapy entails potential complications. We aimed to investigate the influence of PPI use on intestinal permeability in patients with cirrhosis. We recruited 228 patients with cirrhosis and divided them into four groups. Group (Gp)1 comprised patients receiving a PPI with concurrent neomycin (NEO) (PPI-NEO group, n = 14 [6.1%]), Gp2 and Gp3 comprised those receiving either PPI or NEO (PPI group, n = 91 [39.9%]; and NEO group, n = 11 [4.4%]), and Gp4 comprised those receiving neither of these medications (control group; n = 112 [49.1%]). We assessed the intestinal permeability by measuring endotoxin activity (EA) using a luminol chemiluminescence method. Endotoxin activity levels were significantly higher in patients with Child B cirrhosis than in those with Child A cirrhosis, but we found no significant differences in EA levels between patients with Child C cirrhosis and those with either Child A or B cirrhosis. We observed no significant differences in EA levels among groups 1-4. Patients without antibiotic exposure (n = 203), comprising 91 patients on PPI therapy (Gp2) and 112 no-PPI-therapy controls (Gp4), were subdivided according to Child-Pugh (CP) classification. We found no significant differences in EA levels between Gp2 and Gp4 in either CP class. Our results suggest that PPI usage does not have a significant impact on serum levels of gut-derived endotoxins, which are already elevated because of the increased intestinal permeability in patients with cirrhosis.


Risk to patients, risk to clinicians: a three-site audit of the documentation of counselling in first episode genital herpes.
National guidelines give advice on topics which should be covered when counselling patients with a new diagnosis of genital herpes (HSV) with the aim of reducing transmissions. This three-site UK audit of documentation of counselling for patients with a new diagnosis of genital herpes reviewed the records of 284 patients. Documentation in all areas of counselling was limited and this may result in adverse medico-legal consequences for patients and clinicians.


Detection of foot and mouth disease virus by RT-PCR and microplate hydridization assay using inactivated viral antigens.
A single step RT-PCR was tested for detection of foot and mouth disease virus (FMDV) and immunoenzymatic determination of amplified products in a microplate hybridization assay. Inactivated reference strains (ELISA antigen) of all seven serotypes were used to optimize the test. Oligonucleotide primers were selected from two different genomic regions coding for RNA polymerase and VP1 protein, respectively. The RT-PCR used to amplify the polymerase gene specific RNA detected FMDV strains A, C, O, Asial and SAT1, and the identity of the fragments obtained was confirmed with a specific internal biotin-labelled capture probe. For the amplification of the VP1 genome region, two sets of oligonucleotide primers were used. One primer pair was successfully applied for the detection of serotypes A, C, O and Asial and a second one for serotypes SAT1, SAT2, SAT3. The specific probe enabled the detection of all the amplified products in a PCR ELISA test. By comparison with antigen ELISA, the PCR ELISA method allowed the detection of smaller amounts of FMDV in the inactivated material examined. The application of molecular diagnostic methods to inactivated antigens offers a good alternative procedure for developing and optimizing a sensitive method for detection of FMDV in laboratories that are not allowed to work with viable FMDV.


Automated multivariate measurement of spontaneous motor activity in mice: time course and reliabilities of the behavioral measures.
A variety of automated procedures have been developed to measure certain aspects of spontaneous motor activity in small animals. The present study used a Digiscan Animal Activity Monitor to measure six different aspects of spontaneous motor behavior in male CF-1 mice. The Digiscan system uses infrared beams and computer analysis to quantify various behavioral variables. The mice were tested for 1 hour on 2 different days of the week for 3 consecutive weeks. Both the temporal changes in the measured variables and the test-retest reliabilities were examined in a group of 30 mice. Statistical analysis of the data revealed significantly higher mean values for total movement time, average distance travelled, and horizontal activity on the first test session relative to the second session (p less than 0.01). The other 3 measures, total distance travelled, number of movements, and average speed, did not vary significantly across test sessions. All 6 behavioral variables showed good test-retest reliabilities and these could be increased by aggregating the data on a weekly basis. The present results indicate that the measures obtained from the Digiscan system are reliable and that the animals should first be habituated to the test apparatus in order to obtain stable baseline activity values.


Involvement of specific integrins in apoptosis induced by vascular apoptosis-inducing protein 1.
Hemorrhagic snake venom induces apoptosis in vascular endothelial cells (VEC). In previous reports, we described the purification and cDNA cloning from Crotalus atrox of vascular apoptosis-inducing protein 1 (VAP1) that specifically induces apoptosis in VEC. VAP1 belongs to the metalloprotease/disintegrin family. Yet the mechanism of inducing apoptosis by VAP1 is still not known. Since other various metalloproteases and disintegrins in snake venoms are known to influence extracellular matrix and cell adhesion, we investigated here the involvement of these adhesion molecules in VAP1-induced apoptosis. Consequently, VAP1 induced apoptosis without degrading extracellular matrix or inhibiting adhesion of VEC. However, VAP1-induced apoptosis was inhibited by antibodies for integrin alpha3, alpha6, beta1. Additionally, apoptosis was inhibited by antibody for CD9, an integrin associated protein. These results suggest that integrins are involved in VAP1-induced apoptosis by some specific role rather than that of adhesion to extracellular matrix.


Fission and proliferation of peroxisomes.
Peroxisomes are remarkably dynamic, multifunctional organelles, which react to physiological changes in their cellular environment and adopt their morphology, number, enzyme content and metabolic functions accordingly. At the organelle level, the key molecular machinery controlling peroxisomal membrane elongation and remodeling as well as membrane fission is becoming increasingly established and defined. Key players in peroxisome division are conserved in animals, plants and fungi, and key fission components are shared with mitochondria. However, the physiological stimuli and corresponding signal transduction pathways regulating and modulating peroxisome maintenance and proliferation are, despite a few exceptions, largely unexplored. There is emerging evidence that peroxisomal dynamics and proper regulation of peroxisome number and morphology are crucial for the physiology of the cell, as well as for the pathology of the organism. Here, we discuss several key aspects of peroxisomal fission and proliferation and highlight their association with certain diseases. We address signaling and transcriptional events resulting in peroxisome proliferation, and focus on novel findings concerning the key division components and their interplay. Finally, we present an updated model of peroxisomal growth and division. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease.


Imaging Surveillance of Hypervascular Liver Lesions in Non-Cirrhotic Patients.
A consensus surveillance protocol is lacking for non-cirrhotic patients with hypervascular liver lesions presumed to represent hepatocellular adenomas. Patients with hypervascular liver lesions <5 cm not meeting criteria for focal nodular hyperplasia or hepatocellular carcinoma underwent surveillance with contrast-enhanced magnetic resonance imaging (MRI) 6, 12, and 24 months after baseline imaging. If lesions remained stable or decreased in size, then surveillance imaging was discontinued. Between 2011 and 2014, 116 patients with hypervascular liver lesions were evaluated. Seventy-nine patients were eligible for the surveillance protocol. Median follow-up was 24 months (range, 1-144 months). One patient (1 %) continued oral contraceptive pill (OCP) use and presented with hemorrhage requiring embolization 5 months after initial diagnosis. Ten patients (13 %) underwent elective embolization or surgical resection for size ≥5 cm. The remaining 68 patients (86 %) continued surveillance without hemorrhage or malignant transformation. Risk factors for requiring intervention during the surveillance period included younger age, larger lesion size, and estrogen use (all p < 0.05). Patients with hepatocellular adenomas <5 cm can safely be observed after discontinuing OCP with serial imaging 6, 12, and 24 months after diagnosis. If lesions remain stable or decrease in size, then longer-term surveillance is unlikely to identify patients at risk for complications.


Trypanosome infections of marine fish in the southern Barents Sea and the invasive red king crab Paralithodes camtschaticus.
The red king crab Paralithodes camtschaticus was introduced to the Barents Sea from the North Pacific in the 1960s. A previous study concluded that it may be indirectly responsible for increased transmission of Trypanosoma murmanense to cod Gadus morhua in the southern Barents Sea by promoting an increase in the population of the leech vector Johanssonia arctica. Eleven species of fish, totalling 681 individuals, caught in October 2002 along the coast of Finnmark, were examined for trypanosome infections. The aims were to investigate changes in levels of infection in cod since 1999-2001, and to extend the sampling to other fish species. Relatively high infection levels were found in cod, haddock Melanogrammus aeglefinus and long rough dab Hippoglossoides platessoides, while other species were lightly infected or uninfected. In cod, no significant geographical differences in levels of infection were found, but haddock were significantly more heavily infected in western Finnmark.


The influence of vitamin A status on the response of chickens to aflatoxin B1 and changes in liver lipid metabolism associated with aflatoxicosis.
1 A series of experiments were conducted to investigate the effects of dietary retinol status on chickens ingesting aflatoxin B1. The effects of dietary supplementation with biotin and alpha-tocopherol were also examined. 2. Aflatoxin B1 levels greater than 1 mg/kg diet had a detrimental effect on 'liveability', body-weight gain, food intake and food conversion efficiency. When fed for more than 2 weeks aflatoxin increased relative liver weight and liver lipid concentration. These effects were less pronounced with avitaminotic A chickens. 3. A synergistic effect on hydropericardium development was observed between aflatoxin B1 and retinol. This effect was not observed when the dietary level of alpha-tocopherol was increased tenfold. 4. The specific activities of certain hepatic lipogenic and amino acid-metabolizing enzymes were influenced by aflatoxin ingestion. A reduction in lipogenic enzyme activity was observed before a reduction in the activities of amino acid-metabolizing enzymes. 5. Liver fatty acid composition was significantly influenced by aflatoxin B1. The extent of these changes was reduced by the inclusion of additional dietary biotin.


Correction: Study on ultrasonic leaching and recovery of fluoride from spent cathode carbon of aluminum electrolysis.
[This corrects the article DOI: 10.1039/D3RA02088F.].


[Formation of B12 auxotrophs among spontaneous streptomycin-resistant mutants of Corynebacterium glutamicum].
The spontaneous mutation to streptomycin-resistance (strr) was selective for isolating the definite type of auxotrophs (B12) of grampositive bacteria, Corynebacterium glutamicum ATCC 13032. A correlation between the resistance to the antibiotic and the requirement of vitamin B12 of this culture is suggested.


Multiplex detection of eight different viral enteropathogens in clinical samples, combining RT-PCR technology with melting curve analysis.
Early and accurate identification of infection viruses among children can benefit the personalized medical treatment and management, and reduce the future occurrence of serious symptoms. Thus, it is critical to develop a high-throughput multiplex real-time RT-PCR method to improve the accuracy and efficiency in routine clinical lab tests. We developed a real time RT-PCR combined with melting curve analysis (RRCMC) method for simultaneous detection of rotavirus A, B, C, norovirus GI and GII, adenovirus, astrovirus and sapovirus. Stool samples were collected from 160 children with acute diarrhea and tested by RRCMC assay. A total of 71 patients were tested positive with norovirus, adenovirus or rotavirus. The RRCMC assay has high specificity. There is no internal cross-reaction among the 8 diarrhea viruses and no cross-reaction of other commonly intestinal pathogens and human genome. The limit detection was ranged from 1 × 102 to 1 × 105 nucleic acid copies/ml for each diarrhea virus. The RRCMC method is a suitable rapid clinical test for infectious viruses, with the advantages of high-throughput, low cost, high sensitivity and specificity.


[Technical aspects of phlebography in varicosis of the lower limbs (author's transl)].
Ascending phlebography is a safe and reliable method for preinterventional differential diagnosis of primary and secondary venous insufficiency. With the combined use of fluoroscopy and spot filming, the technique yields functional information on the venous valves and communicating veins. It also permits exact localization of peripheral and proximal varicosis and venous aneurysms. In addition, the plevic and inferior vena cava inflow can be evaluated.


Primary central nervous system lymphoma.
Primary central nervous system lymphoma (PCNSL) is a diffuse large B cell lymphoma in which the brain, spinal cord, leptomeninges and/or eyes are exclusive sites of disease. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Other factors such as T cells, macrophages or microglia, endothelial cells, chemokines, and interleukins, probably also have important roles. Clinical presentation varies depending on the involved regions of the CNS. Standard of care includes methotrexate-based polychemotherapy followed by age-tailored thiotepa-based conditioned autologous stem cell transplantation and, in patients unsuitable for such treatment, consolidation with whole-brain radiotherapy or single-drug maintenance. Personalized treatment, primary radiotherapy and only supportive care should be considered in unfit, frail patients. Despite available treatments, 15-25% of patients do not respond to chemotherapy and 25-50% relapse after initial response. Relapse rates are higher in older patients, although the prognosis of patients experiencing relapse is poor independent of age. Further research is needed to identify diagnostic biomarkers, treatments with higher efficacy and less neurotoxicity, strategies to improve the penetration of drugs into the CNS, and roles of other therapies such as immunotherapies and adoptive cell therapies.


Grommet insertion using a branula.
To develop an easy method of performing myringotomy and grommet insertion, using minimal instruments. An ear speculum and a branula were used. This method was found to be useful. An easy method of performing myringotomy and grommet insertion is proposed.


Trends in cardiovascular risk factors in an urban black population, 1973-74 to 1985: the Minnesota Heart Survey.
Cardiovascular disease mortality rates have fallen dramatically in blacks in the United States. To determine whether this may be due to a decline in cardiovascular risk factors, we compared risk factors in a 1985 urban black population, ages 35 to 69, with those obtained in blacks of the same area in 1973-74. Age-adjusted mean body mass and the prevalence of overweight increased significantly over the 12-year period in both men and women. Mean systolic blood pressures declined significantly in both sexes, diastolic blood pressure declined significantly in men, and the proportion of men and women hypertensives on medication and under control increased. The overall prevalence of cigarette smoking changed very little, but the proportion of heavy smokers decreased significantly in men. No significant changes occurred in resting heart rate. Concurrently with these risk factor trends, age-adjusted heart disease mortality rates in area blacks fell 27% between 1968-73 and 1979-84, and stroke mortality fell 58%. Changing risk factors may be contributing to declining cardiovascular mortality rates in blacks. However, overweight seems to be a worsening problem.


Effect of Xinfeng capsule on nuclear factor Kappa B/tumor necrosis factor alpha and transforming growth factor beta 1/Smads pathways in rats with cardiac injuries induced by adjuvant arthritis.
To investigate effects of Xinfeng capsule (XFC) on cardiac function in rats with adjuvant arthritis (AA) and explore the mechanism of these effects. Forty-eight rats were randomly divided into normal control (NC), model control (MC), methotrexate (MTX) and XFC groups of equal size. In all groups except for the NC group, 0.1 mL Freund's complete adjuvant (FCA) was intracutaneously injected in the right rear vola pedis to induce inflammation. Drugs were applied beginning 19 days after induction of inflammation. Normal saline was administered to the NC and MC groups and 1 mg/ 100 g MTX (weekly) and 0.12 g/100 g XFC (daily) to the MTX and XFC groups, respectively. Rats were sacrificed after 30 day of treatment. Toe swelling degree (TSD), arthritis index (Al), cardiac function and expression of nuclear factor kappa B (NF-κB)/tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1)/Smads pathway proteins were measured. In the MC group, TSD and Al were greatly increased, while parameters of cardiac function were decreased and morphological analysis showed myocardial cell damage. Expression of TNF-α, NF-KB, Smad2, P-Smad2, Smad4 and TGF-β1 proteins were elevated in cardiac tissue, while Smad7 expression was decreased. TSD and Al values closely correlated to parameters of cardiac function and to levels of proteins in the NF-κB/TNF-α and TGF-β1/Smads pathways. Certain correlations were identified among TGF-β1 and NF-KB, Smad2, P-Smad2 and Smad4. With XFC intervention, both TSD and Al were decreased and parameters of cardiac function and ultrastructure of myocardial cells improved. Expressions of NF-κB, Smad2, and Smad4 proteins were greatly decreased and Smad7 expression was elevated, as compared with levels in the MC and MTX groups. XFC regulates expression of proteins in the NF-KB/TNF-α and TGF-β1/Smads pathways, decreases immune complex deposition in cardiac tissue and improves cardiac function in AA rats via upregulation of Smad7.


Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators (Part 2).
γ-Secretase modulators (GSMs), which lower pathogenic amyloid beta (Aβ) without affecting the production of total Aβ or Notch signal, have emerged as a potential therapeutic agent for Alzheimer's disease (AD). A novel series of 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives was discovered and characterized as GSMs. Optimization of substituents at the 8-position of the core scaffold using ligand-lipophilicity efficiency (LLE) as a drug-likeness guideline led to identification of various types of high-LLE GSMs. Phenoxy compound (R)-17 exhibited especially high LLE as well as potent in vivo Aβ42-lowering effect by single administration. Furthermore, multiple oral administration of (R)-17 significantly reduced soluble and insoluble brain Aβ42, and ameliorated cognitive deficit in novel object recognition test (NORT) using Tg2576 mice as an AD model.


Corrigendum to Tumour seeding after a thoracic biopsy for renal cell carcinoma: a case report and a review of the literature.
[This corrects the article DOI: 10.1177/11795549211022261.].


Structural studies of rat cathepsin E: amino-terminal structure and carbohydrate units of mature enzyme.
The amino-terminal structure of rat gastric cathepsin E was identified and compared with the corresponding regions of human procathepsin E and other aspartic proteinases. The alignment revealed that cathepsin E has the most extended amino-terminal structure in aspartic proteinases, thus suggesting that the activation peptide (propeptide) of the human enzyme is 39-residues long. Analysis of oligosaccharide units suggested that rat cathepsin E possesses one N-linked carbohydrate unit, probably of the high mannose type. No evidence was obtained for the presence of O-linked sugars in rat cathepsin E.


3D-tips: user-friendly mesh barrier pipette tips for 3D-spheroid culture.
Three dimensional (3D) cell cultures have been an area of increasing interest and relevance across several research fields including drug discovery, developmental biology and stem cell-based therapies. However, handling 3D structures can be difficult. In particular, the replacement of liquid media and reagents in which liquid is removed using pipettes is difficult to perform as the 3D spheroids can be easily aspirated into the pipette tip. We have developed the 3D-tip, a novel tool that facilitates media change and washing procedures of 3D-spheroid cultures. The 3D-tip contains a mesh with 40-μm pores allowing the aspiration of liquids including media, drugs, buffers and reagents, with the mesh acting as a barrier preventing the spheroids being aspirated into the pipette tip. After aspiration of liquids, the spheroids are gently deposited back into the culture vessel. Our results demonstrate that the 3D-tips offer superior handling of 3D-spheroid cultures in comparison to commonly used methods. We showed that the 3D-tips can easily be used on both fixed and unfixed spheroids and on cancer cell, stem cell and glial cell spheroids.In contrast with the 50/50 media exchange method, the 3D-tips allow a complete media change with minimal loss of spheroids and without damaging their morphology. Our results showed that 86.0% of spheroids remained in the chamber after changing the media using the 3D-tips. In contrast, only 45.0% of spheroids remained using the 50/50 media exchange strategy.In comparison with the centrifugation technique, the 3D-tips preserved spheroids whereas centrifugation led to the loss of spheroids and/or the alteration of the size and shape of the 3D cellular structures. We observed that 87.6 and 84.6% of the fixed and unfixed spheroids remained using the 3D-tip, respectively. In contrast, only 66.3% of the fixed spheroids and 36.4% of the unfixed spheroids were left using the centrifugation method. From a time perspective, the 3D-tips dramatically reduce the time taken for replacing media. This novel pipette tip is suitable for high throughput screening and automation and will revolutionise the techniques used for the production and analysis of 3D spheroids.


The renin-angiotensin-aldosterone system and its suppression.
Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.


Cicerarin, a novel antifungal peptide from the green chickpea.
A peptide designated cicerarin, with an N-terminal amino acid sequence VKSTGRADDDLAVKTKYLPP dissimilar from known proteins and peptides and a molecular mass of 8kDa, was isolated from seeds of the green chickpea Cicer arietinum cv green chickpea. Cicerarin was isolated with a procedure that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, and gel filtration by fast protein liquid chromatography on Superdex 75. Cicerarin was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel in 10mM Tris-HCl buffer (pH 7.3). Cicerarin exerted antifungal activity against Botrytis cinerea, Mycosphaerella arachidicola, and Physalospora piricola. The antifungal activity was preserved after exposure to 100 degrees C for 15min.


Plasma estradiol 17-sulfate and 2-hydroxyestradiol 17-sulfate levels and their metabolic clearance rates in rats.
By using highly specific antisera against estradiol 17-sulfate (E2-17-S) and against 2-hydroxyestradiol 17-sulfate (2-OH-E2-17-S), plasma concentrations of these sulfates in Wistar rats were determined. The plasma levels of E2-17-S and 2-OH-E2-17-S in the male were 23.5 +/- 5.3 and 21.6 +/- 6.2 pg/ml, respectively. During the estrus cycle of the female, the plasma concentration of E2-17-S reached its highest level 69.0 +/- 11.8 pg/ml, during the diestrus stage, and its lowest level 36.9 +/- 6.6 pg/ml, during the proestrus stage. Similar tendencies were observed in the case of 2-OH-E2-17-S. To examine the dynamic behavior of both sulfates, the plasma metabolic clearance rate (MCRp) of E2-17-S and 2-OH-E2-17-S were determined by infusion experiments. MCRp of E2-17-S and 2-OH-E2-17-S in male rats were 102 and 653 ml/h (means), respectively, and in female rats were 115 and 644 ml/h (means), respectively. The low MCRp values of both sulfates imply their slow metabolic turn-over.


Liver weight of adult Japanese, especially recent weight values.
Cases of 445 adult Japanese autopsies of the Tokyo Metropolitan Medical Examiner's Office were used in this study. They were either negative for all hepatitis virus-related markers examined or had little or no histopathological hepatic changes. The maximum liver weight was observed in the fifth decade in both sexes, and after the fifth decade the liver weight decreased markedly with increasing age. The sexual difference in the liver weight was most predominant in the third to fifth decades, but the sexual difference was not marked in the older age groups. The highest liver weight to body weight ratio was observed in the fifth decade of both sexes, and a total decadal pattern of the ratio was similar to a parabola. An interesting finding was that the male liver weights in the third to fifth decades considerably increased in recent years, but the female liver weights in the third decade were almost the same despite the difference in investigation period. We suggest the data of this study may be a standard for Japanese people.


Expression and stability of hypoxia inducible factor 1α in osteosarcoma.
Hypoxia contributes to both physiological and pathological processes and its effects are mainly mediated through the transcription factors hypoxia-inducible factor 1α and 2α (HIF1α and HIF2α). The purpose of this study was to examine the role of these proteins in osteosarcoma progression. We developed a method to isolate primary human osteoblast cell lines. HIF1α and HIF2α expression were then compared in osteoblast and osteosarcoma cell lines under 21% oxygen (normoxia) and 1% oxygen (hypoxia). We also used hypoxia-responsive element (HRE)-driven reporter constructs in conjunction with siRNAs specific to HIF1α or HIF2α to determine the contribution of each protein to HRE-mediated transcription. Finally, we measured HIF1α expression in primary osteosarcoma tumors by immunohistochemistry. We found that mainly HIF1α transcript was significantly higher in osteosarcoma cell lines compared to normal osteoblasts under both normoxia and hypoxia. At the protein level, HIF1α was preferentially stabilized in osteosarcoma cell lines under both conditions. HIF1α expression was required for the observed increases in HRE activity. Finally, nuclear or nucleocytoplasmic HIF1α staining in osteosarcoma cases was associated with high-grade tumors. These findings point to a role for HIF1α in osteosarcoma progression and suggest that the observed differences in HIF1α oxygen dependent degradation may play an important pathophysiological role in this disease. Pediatr Blood Cancer 2012; 59: 1215-1222. © 2012 Wiley Periodicals, Inc.


Synthesis, characterization, and reactivity of a novel μ-η2:η2-diselenidodicopper(II) complex.
The first μ-η(2):η(2)-diselenidodicopper(II) complex has been obtained in the reaction of a copper(I) complex with N,N',N″-tribenzyl-cis,cis-1,3,5-triaminocyclohexane and elemental selenium. The structure and reactivity of the complex is described.


Uncertainty Quantification for Mechanical Properties of Polyethylene Based on Fully Atomistic Model.
This study is to assess the effect of temperature and strain rate on the mechanical properties of amorphous polyethylene (PE) based on fully atomistic model. A stochastic constitutive model using data obtained from molecular dynamics (MD) simulations for the material is constructed. Subsequently, a global sensitivity analysis approach is then employed to predict the essential parameters of the mechanical model. The sensitivity indices show that the key parameter affecting Young's modulus and yield stress is the temperature followed by the strain rate.


Cholinergic and GABAergic neurons in the nucleus basalis region of young and aged rats.
Antibodies directed against choline acetyltransferase and glutamic acid decarboxylase were used in combination with recently developed stereological techniques to quantify changes in cholinergic, GABAergic, and total neuron number (Nissl-stain) within adjacent tissue sections through the horizontal limb/nucleus basalis in young (3 months, n = 6) and aged (27 months, n = 6) Fischer-344 male rats. Unbiased estimates of total neuron number within these regions were produced using a three-dimensional optical probe, the optical disector, in combination with a systematic random sampling scheme. Estimates of cell counts in immunostained tissue sections were conducted throughout the entire horizontal limb/nucleus basalis region. A significant 30% decrease in both cholinergic and total neuron number was detected in the aged animals; GABAergic neuron number remained unchanged. Total neuron number was significantly correlated with both cholinergic (r = 0.94) and glial cell number (r = 0.63), but not with GABAergic cell number. Based on neuron counts within an individual thick tissue section, the cholinergic neurons comprised only 11-15% of all neurons in the nucleus basalis of young and aged animals. Cholinergic neuron loss accounted for only 20% of the total age-related neuron loss within the horizontal limb/nucleus basalis in Fischer-344 male rats. These results indicate that age-related cholinergic neuron loss within the basal forebrain is reflected in reductions in total neuron number; however, GABAergic neurons, many of which project to the cortex, are unaffected by age. The magnitude of the age-related total neuron loss cannot be entirely accounted for by cholinergic cell loss. Therefore, an unidentified non-cholinergic, non-GABAergic component within the basal forebrain is also lost during aging and may contribute to the cognitive deficits previously ascribed to cholinergic dysfunction.


North American historical monthly spatial climate dataset, 1901-2016.
We present historical monthly spatial models of temperature and precipitation generated from the North American dataset version "j" from the National Oceanic and Atmospheric Administration's (NOAA's) National Centres for Environmental Information (NCEI). Monthly values of minimum/maximum temperature and precipitation for 1901-2016 were modelled for continental United States and Canada. Compared to similar spatial models published in 2006 by Natural Resources Canada (NRCAN), the current models show less error. The Root Generalized Cross Validation (RTGCV), a measure of the predictive error of the surfaces akin to a spatially averaged standard predictive error estimate, averaged 0.94 °C for maximum temperature models, 1.3 °C for minimum temperature and 25.2% for total precipitation. Mean prediction errors for the temperature variables were less than 0.01 °C, using all stations. In comparison, precipitation models showed a dry bias (compared to recorded values) of 0.5 mm or 0.7% of the surface mean. Mean absolute predictive errors for all stations were 0.7 °C for maximum temperature, 1.02 °C for minimum temperature, and 13.3 mm (19.3% of the surface mean) for monthly precipitation.


Advances in explosives analysis--part II: photon and neutron methods.
The number and capability of explosives detection and analysis methods have increased dramatically since publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis [Moore DS, Goodpaster JV, Anal Bioanal Chem 395:245-246, 2009]. Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. Part I discussed methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. This part, Part II, will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.


Association study of the A2M and LRP1 Genes with Alzheimer disease in the Han Chinese.
Low-density lipoprotein receptor-related protein 1 (LRP1) and alpha-2-macroglobulin (A2M) are two plausible candidate genes for Alzheimer disease (AD) based on their important biological function and positional information. To date, numerous studies have investigated their possible association with AD but the results are controversial. To investigate the potential genetic contribution of the two genes in the Han Chinese population, we performed a case-control association study using 10 polymorphisms (4 in LRP1 and 6 in A2M) that span approximately the whole corresponding gene. Comparison of allele, genotype, and haplotype frequencies for polymorphisms in A2M revealed no significant differences between patients and control subjects. For the LRP1 gene, however, we found an overrepresentation of the CTCG haplotype in the control group (p = .002). The difference was still of statistical significance in the apolipoprotein E (APOE) epsilon 4 negative subjects (p(CTCG) = .003). Multiple logistic regression analysis did not show any evidence of synergism between A2M, LRP1, and APOE. Our results indicate that the CTCG haplotype of LRP1 may reduce the risk of late-onset AD, but A2M is not associated with this disease in the Han Chinese population.


Light curing in orthodontics; should we be concerned?
Light cured materials are increasingly used in orthodontic clinical practice and concurrent with developments in materials have been developments in light curing unit technology. In recent years the irradiances of these units have increased. The aim of this study was to determine the safe exposure times to both direct and reflected light. The weighted irradiance and safe exposure times of 11 dental curing lights (1 plasma arc, 2 halogen and 8 LED lights) were determined at 6 distances (2-60 cm) from the light guide tip using a spectroradiometer. In addition, using the single most powerful light, the same two parameters were determined for reflected light. This was done at a distance of 10 cm from the reflected light, but during simulated bonding of 8 different orthodontic brackets of three material types, namely stainless steel, ceramic and composite. The results indicate that the LED Fusion lamp had the highest weighted irradiance and the shortest safe exposure time. With this light the maximum safe exposure time without additional eye protection for the patient (at 10 cm), the operator (at 30 cm) and the assistant (at 60 cm) ranged from 2.5 min, 22.1 min and 88.8 min respectively. This indicates a relatively low short term risk during normal operation of dental curing lights. For reflected light at a distance of 10 cm the risk was even lower, but was affected by the material and shape of the orthodontic bracket under test. The short term risks associated with the use of dental curing lights, halogen, LED or plasma, appear to be low, particularly if as is the case adequate safety precautions are employed. The same is true for reflected light from orthodontic brackets during bonding. What is still unclear is the potential long term ocular effects of prolonged exposure to the blue light generated from dental curing lights.


Brief Report: Differential Associations of Interleukin 6 and Intestinal Fatty Acid-Binding Protein With Progressive Untreated HIV-1 Infection in Rakai, Uganda.
The significance of HIV-associated immune activation and microbial translocation in Sub-Saharan African population remains poorly defined. We assessed biomarkers of inflammation, microbial translocation, and cellular activation and found most factors elevated in Ugandan HIV-1 seroconverters compared with community-matched controls. In contrast to previous findings in Western cohorts, C-reactive protein, neopterin, and intestinal fatty acid binding protein were not elevated. Higher T-cell activation and IL-6 were associated with faster disease progression. Surprisingly, intestinal fatty acid binding protein, indicative of enterocyte turnover, was higher in slow than in fast progressors. These data suggest differential relationships among biomarkers of intestinal barrier integrity and innate immune activation between developed countries and Sub-Saharan Africa.


The first images of atopic dermatitis: an attempt at retrospective diagnosis in dermatology.
Atopic dermatitis was defined in 1933. Earlier descriptions have yet not been thoroughly studied. Our purpose was to identify the first images of atopic dermatitis among historical illustrations of skin diseases. We posted 20 selected images on an Internet site and asked experts in pediatric dermatology to decide whether or not they represented atopic dermatitis. By means of the Delphi technique, a consensus could be reached for 19 of the 20 images. The experts' accuracy was good. Thirty-one experts participated. No validated criteria were used for the selection of the images. The first representations of atopic dermatitis are engravings of skin diseases described under the names of strophulus confertus (Willan, 1796), lichen agrius (Willan, 1796), porrigo larvalis (Bateman, 1816), and eczema rubrum (Rayer, 1835). Teledermatology techniques can be reliably applied to retrospective diagnosis.


Curcumin protects sodium nitrite-induced hepatotoxicity in Wistar rats.
In this study, the protective effect of curcumin on sodium nitrite (NaNO2) induced hepatotoxicity was assessed in male Wistar rats. Wistar rats were administered orally daily with 20 mg/kg of curcumin for 28 days and NaNO2 was administered as a single dose of 60 mg/kg on day 28. Lipid profile, liver function biomarkers and C-reactive protein were assessed in the serum; lipid peroxidation, non-enzymatic and enzymatic antioxidants were assessed in the liver. Alanine amino transferases (94.67 U/L), aspartate amino transferases (194.33 U/L), alkaline phosphatases, C-reactive proteins (19.56 ng/L) and lipid peroxidation (8.03 × 10-6 μmol/mg protein) were significantly elevated (P < 0.05), while a significant decrease in lipid profiles (total cholesterol, HDL,LDL, and triglycerides): (0.61,0.37, 0.4 and 0.47 mg/dl respectively), reduced glutathione level (4.16 μmol/mg protein), and decreased catalase, superoxide dismutase and glutathione peroxidase activities with severe histological alterations were observed in the livers of rats exposed to NaNO2. Pre-treatment with curcumin significantly (P < 0.05) prevented these alterations by adjusting the lipid profile, liver function markers, and C-reactive proteins and abrogating the elevated markers of oxidative stress as supported by the liver histology. This suggests that dietary consumption of curcumin is beneficial against NaNO2 induced oxidative stress of the liver via its antioxidant potential.


A novel sensing platform for electrochemical detection of metronidazole antibiotic based on green-synthesized magnetic Fe3O4 nanoparticles.
The spread of antibiotic resistant genes has become a serious global concern. Thus, the development of efficient antibiotic monitoring systems to reduce their environmental risks is of great importance. Here, a potent electrochemical sensor was fabricated to detect metronidazole (MNZ) on the basis of green synthesis of Fe3O4 nanoparticles (NPs) using Sambucus ebulus L. leaves alcoholic plant extract as a safe and impressive reducing and stabilizing agent. Several analyses such as X-ray diffraction (XRD), Fourier transform infrared spectrophotometer (FTIR), thermogravimetric analysis (TGA), field emission scanning electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), and dynamic light scattering (DLS) confirmed the production of homogeneous, monodisperse, regular, and stable magnetite NPs with a spherical morphology. The as-prepared Fe3O4NPs were afterwards applied to evaluate the electrochemical activity of MNZ by merging them with graphene nanosheets (GR NSs) on the glassy carbon electrode (GCE). The GR/Fe3O4NPs/GCE represented extraordinary catalytic activity toward MNZ with two dynamic ranges of 0.05-5 μM and 5-120 μM, limit of detection (LOD) of 0.23 nM, limit of quantification (LOQ) of 0.76 nM, and sensitivity of 7.34 μA μM-1 cm-2. The fabricated sensor was further employed as a practical tool for electrochemical detection of MNZ in real aqueous samples.


HLA-DR-MT matching improves graft survival rate in cadaver kidney transplantation. A prospective multicenter analysis of the South German Cooperative Study Group for Kidney Transplantation.
The influence of prospective HLA-DR matching on the graft survival rate was investigated in a multicenter analysis of 85 transplants. Simultaneously in a retrospective analysis of graft outcome the importance of matching for MT-antigens MT1, MT2 and MT3 as a newly defined B-cell alloantigen system was evaluated. HLA-DR antigens and MT-specificities were determined on B-cells enriched by nylon-wool filtration using locally well characterised HLA-DR antisera and the antiserum set of the 8th International Histocompatibility Workshop ("disease set") which allowed the definition of the HLA-DR specificities HLA-DR 1-9 and of the MT-antigens MT1-3. HLA-DR matching showed a significantly improved graft outcome only in HLA-DR identical donor-recipient combinations. In 11 of 60 patients with one HLA-DR compatibility additional matching for two MT-antigens, however, improved the two year graft survival rate from 60% to 91%. Altogether 17 patients were matched for two MT-specificities with their kidney donor and showed a superior prognosis of 94% at two years compared to 53% or 17% of recipients with one or zero MT compatibility. Graft outcome in this patient group was also superior to that of HLA-DR identical or HLA-AB identical grafts. These data suggested that the MT-system rather than the HLA-DR antigens may be of critical importance in cadaver kidney transplantation. In addition a favorable influence of pretransplant blood transfusions on less HLA-DR matched grafts was confirmed.


[Evaluation of the cell-mediated immune response after administration of Salmonella antigens in patients with multiple myeloma].
Myeloma patients show an impairment of several immunological functions leading to infectious diseases. In this study we evaluated cell-mediated responsiveness in a group of these patients. Six myeloma patients received full doses of I.S.M. Enterovaccino. LIF production by peripheral blood lymphocytes against Salmonella antigens was evaluated after 14 days. All patients studied showed no LIF production.


Sustained mitotic block elicits DNA breaks: one-step alteration of ploidy and chromosome integrity in mammalian cells.
Following prolonged mitotic spindle disruption by microtubule poisons, mammalian cells delay their entry into anaphase, then progressively slip out of mitosis and become tetraploid. Normal cells then stop cycling before S-phase onset, but the mechanisms underlying this arrest are still unclear. Here we show that a double block prevents endo-reduplication. First, cells that exit mitosis without a functional microtubule network are driven toward G0. Reconstitution of the network unmasks a second block that relies on DNA double-strand breaks occurring early in the G1 phase that follows the mitotic block. We propose that a stress signal elicited upon mitotic impairment triggers breakage, which couples the leaky spindle checkpoint to the stringent DNA damage response. Consistent with this finding, cells defective for the damage response continue cycling and acquire, within a single cell cycle, both chromosome rearrangements and abnormal chromosome numbers that remarkably mimic the complex genetic hallmark of tumorigenesis.


Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology.
To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT). This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ2 test and conversion of prenatal to postnatal centiles. A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10th centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90th centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10th centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90th centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3rd centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90th -97th centile and > 97th centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively). Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Change of pupal size of Panolis flammea (Lepidoptera; Noctuidae) and Bupalus piniarius (Geometridae) in response to concentration of industrial pollutants in their food plant.
Larvae of Panolis flammea and Bupalus piniarius were reared in the laboratory on needles of Scots pine affected by industrial air pollutants in Finland. Needles were collected at different distances from a distinctive source of emission along two 9-km-long transects, and from independent control plots. The elemental composition of the needles used as larval food was analysed. Pupal weight, length and width were negatively correlated wiht the distance from the source of emission. The elemental composition of the pine needles explained 24-53% of the variation in pupal weight. Most of the explained variation was assoicated with the concentration of heavy meals in the pine needles.


Intraarticular osteochondroma of shoulder: a case report.
Osteochondroma is a cartilage-capped osseous protrusion that arises from the surface of a bone. Osteochondroma occurs mostly in the metaphysis of long tubular bones such as the femur, tibia, and humerus. Osteochondroma is rare in the diaphysis and in the epiphysis. There was only one case in which a patient had a limited range of motion in the shoulder joint due to an intraarticular osteochondroma of the proximal humerus. We present a rare case of intraarticular osteochondroma involving the proximal humerus with pathologic findings and imaging features on computed tomography and magnetic resonance imaging.


Identification and characterization of yak α-lactalbumin and β-lactoglobulin.
α-Lactalbumin (α-LA) and β-lactoglobulin (β-LG) were isolated from yak milk and identified by mass spectrometry. The variant of α-LA (L8IIC8) in yak milk had 123 amino acids, and the sequence differed from α-LA from bovine milk. The amino acid at site 71 was Asn (N) in domestic yak milk, but Asp (D) in bovine and wild yak milk sequences. Yak β-LG had 2 variants, β-LG A (P02754) and β-LG E (L8J1Z0). Both domestic yak and wild yak milk contained β-LG E, but it was absent in bovine milk. The amino acid at site 158 of β-Lg E was Gly (G) in yak but Glu (E) in bovine. The yak α-LA and β-LG secondary structures were slightly different from those in bovine milk. The denaturation temperatures of yak α-LA and β-LG were 52.1°C and 80.9°C, respectively. This study provides insights relevant to food functionality, food safety control, and the biological properties of yak milk products.


Correction of a CADASIL point mutation using adenine base editors in hiPSCs and blood vessel organoids.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells (PBMCs) of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.


Proposed anti-seizure medication combinations with rufinamide in the treatment of Lennox-Gastaut syndrome: Narrative review and expert opinion.
Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such "rational polytherapy" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.


Extraction, isolation and NMR data of the tetraether lipid calditoglycerocaldarchaeol (GDNT) from Sulfolobus metallicus harvested from a bioleaching reactor.
The successful extraction and isolation of the hydrolysed tetraether lipid calditoglycerocaldarchaeol (GDNT) from Sulfolobus metallicus, a key thermophilic bioleaching archaeon, is described. The archaeal biomass was recovered directly from a thermophilic (68 degrees C) bioleaching tank reactor used to extract nickel from a pentlandite mineral concentrate. The initial Soxhlet extraction method employed was scaled to a bench-scale extraction procedure suitable for the preparation of gram-scale quantities of GDNT. The GDNT so obtained was analysed by 1D- and 2D-NMR techniques, providing the first complete 13C and 2D-NMR data-set for GDNT, including that for the intact underivatised calditol moiety. The study demonstrates the feasibility of recovering high-quality GNDT from thermophilic archaeal-mediated bioleaching reactors. The recovery of these lipids at relatively low cost, as a by-product from bioleaching reactors used in the metals processing industry, has important implications for future tetraether lipid availability and costs.


Evaluation of D2-plus radical resection for gastric cancer with pyloric invasion.
The optimal lymphadenectomy for gastric cancer (GC) with pyloric invasion is controversial because the pattern of lymph node metastasis is different from that of distal GC. The rate of lymph node metastasis into the posterior area of the pancreatic head and hepatoduodenal ligament is high. This study evaluated the estimated benefit of radical gastrectomy with D2-plus lymphadenectomy in patients with pyloric invasion. All patients with GC invading the pylorus who underwent curative surgical resection with D2-plus lymphadenectomy between February 2013 and September 2015 were enrolled in the study. The index of estimated benefit from lymph node dissection (IEBLD) was calculated by multiplying the incidence of metastasis to each lymph node station by the 3-year overall survival (OS) rate of patients with metastasis to that station. In total, 128 patients were eligible. The rate of lymph node metastasis and the 3-year OS rate (and IEBLD) of the patients with metastasis to lymph nodes were 14.3 and 44.4% (5.56) for No. 8p, 10.9 and 35.7% (3.89) for No. 12b, 9.5 and 33.3% (3.13) for No. 12p, 18.8 and 54.2% (10.19) for No. 13, and 21.8 and 53.6% (11.68) for No. 14v, respectively. In radical gastrectomy for GC with pyloric invasion, some survival benefit was observed with dissection of the No. 13 and No. 14 lymph nodes, but there was no survival benefit with dissection of the No. 8p lymph nodes. The No. 12b and No. 12p lymph nodes may be better to dissect in cT3 GC patients with pyloric invasion. http://ClinicalTrials.gov Identifier: NCT01836991. Date of registration: April 17, 2013.


Feasibility of automated target centralization in colonoscopy.
Early detection of colorectal cancer is key to full recovery. This urged governments to start population screening programs for colorectal cancer, often using flexible endoscopes. Flexible endoscopy is difficult to learn and time-consuming. Automation of flexible endoscopes may increase the capacity for the screening programs. The goal of this pilot study is to investigate the clinical and technical feasibility of an assisting automated navigation algorithm for a colonoscopy procedure. Automated navigation (lumen centralization) was implemented in a robotized system designed for conventional flexible endoscopes. Ten novice and eight expert users were asked to perform a diagnostic colonoscopy on a colon model twice: once using the conventional and once using the robotic system. Feasibility was evaluated using time and location data as measures of the system's added value. Automated target centralization (ATC) was turned on by the novices for a median of 4.2% of the time during insertion and 0.3% during retraction. Experts turned ATC on for 4.0% of the time during insertion and 11.6% during retraction. Novices and experts showed comparable times to reach the cecum with the conventional or the robotic setup with ATC. The ATC algorithm combined with the robotized endoscope setup works in an experimental setup that closely resembles the clinical environment and is considered feasible, although ATC use was lower than expected. For novices, it was unclear whether the low usage was due to unfamiliarity with the system or because they did not need ATC. Experts used ATC also during the retraction phase of the procedure. This was an unexpected finding and may indicate an added value of the system.


Simultaneous measurements of ossicular velocity and intracochlear pressure leading to the cochlear input impedance in gerbil.
Recent measurements of three-dimensional stapes motion in gerbil indicated that the piston component of stapes motion was the primary contributor to intracochlear pressure. In order to make a detailed correlation between stapes piston motion and intracochlear pressure behind the stapes, simultaneous pressure and motion measurements were undertaken. We found that the scala vestibuli pressure followed the piston component of the stapes velocity with high fidelity, reinforcing our previous finding that the piston motion of the stapes was the main stimulus to the cochlea. The present data allowed us to calculate cochlear input impedance and power flow into the cochlea. Both the amplitude and phase of the impedance were quite flat with frequency from 3 kHz to at least 30 kHz, with a phase that was primarily resistive. With constant stimulus pressure in the ear canal the intracochlear pressure at the stapes has been previously shown to be approximately flat with frequency through a wide range, and coupling that result with the present findings indicates that the power that flows into the cochlea is quite flat from about 3 to 30 kHz. The observed wide-band intracochlear pressure and power flow are consistent with the wide-band audiogram of the gerbil.


Pre- and postnatal calorie restriction perturbs early hypothalamic neuropeptide and energy balance.
Energy balance is regulated by circulating leptin concentrations and hypothalamic leptin receptor (ObRb) signaling via STAT3 but is inhibited by SOCS3 and PTP1B. Leptin signaling enhances anorexigenic neuropeptides and receptor (POMC, MC3-R, MC4-R) activation while suppressing orexigenic neuropeptides (NPY, AgRP). We investigated in a sex-specific manner the early (PN2) and late (PN21) postnatal hypothalamic mechanisms in response to intrauterine (IUGR), postnatal (PNGR), and combined (IPGR) calorie and growth restriction. At PN2, both male and female IUGR were hypoleptinemic, but hypothalamic leptin signaling in females was activated as seen by enhanced STAT3. In addition, increased SOCS3 and PTP1B supported early initiation of leptin resistance in females that led to elevated AgRP but diminished MC3-R and MC4-R. In contrast, males demonstrated leptin sensitivity seen as a reduction in PTP1B and MC3-R and MC4-R with no effect on neuropeptide expression. At PN21, with adequate postnatal caloric intake, a sex-specific dichotomy in leptin concentrations was seen in IUGR, with euleptinemia in males indicative of persisting leptin sensitivity and hyperleptinemia in females consistent with leptin resistance, both with normal hypothalamic ObRb signaling, neuropeptides, and energy balance. In contrast, superimposition of PNGR upon IUGR (IPGR) led to diminished leptin concentrations with enhanced PTP1B and an imbalance in arcuate nuclear NPY/AgRP and POMC expression that favored exponential hyperphagia and diminished energy expenditure postweaning. We conclude that IUGR results in sex-specific leptin resistance observed mainly in females, whereas PNGR and IPGR abolish this sex-specificity, setting the stage for acquiring obesity after weaning.


[Clinical characteristics of clear cell carcinoma of the ovary].
To study the clinical characteristics of clear cell carcinoma of the ovary. Forty three patients with clear cell carcinoma of the ovary and 51 patients with serous adenocarcinoma of the ovary who were admitted in Peking Union Medical College Hospital between 1984 to 2000 were analyzed retrospectively, and their chemosensitivities and the survival rates were compared. The percentage of early stage patients in the clear cell carcinoma of the ovary and the serous adenocarcinoma of the ovary was 14.4% and 3.8% respectively, the difference was significant (P < 0.005). In the late stage patients who underwent satisfactory cytoreductive surgery, the chemo-resistant rate (88.9%) in the clear cell carcinoma of the ovary was significantly higher than that (57.1%) of the serous adenocarcinoma of the ovary (P < 0.02), the 1-year survival rate (79.0%) in the clear cell carcinoma of the ovary was significantly lower than that (96.2%) of the serous adenocarcinoma of the ovary (P < 0.01). In the late stage patients who underwent unsatisfactory cytoreductive surgery, the chemo-resistant rate and the survival rate had no significant difference between the clear cell carcinoma of the ovary and the serous adenocarcinoma of the ovary (P > 0.05). There are more early stage patients with clear cell carcinoma of the ovary. We should conduct auxiliary therapy and close follow up to them after surgery. Clear cell carcinoma of the ovary is chemo-resistant to platinum-based chemotherapy and has poor prognosis.


[Imaging of brain tumors in children].
Few studies exist in the literature on pediatric brain tumors examined with advances MRI techniques. The aim of this review is to try to find out some specific tissular characteristics of the main cerebral tumors encountered in children, especially through diffusion imaging, perfusion imaging and proton magnetic resonance spectroscopy (MRS). However, hemispheric cerebral tumors are not as common as in the adult population.


Gender differences in Parkinson's disease: focus on plasma α-synuclein.
Among promising biological markers proposed for Parkinson's disease (PD) and other disorders related to Lewy bodies, plasma alpha-synuclein assay has provided conflicting results mainly owing to the various laboratory assay techniques used and protein forms assayed. In this observational and exploratory cross-sectional study, using an immunoenzymatic technique, we assayed and compared total plasma alpha-synuclein concentrations in 69 patients with PD and 110 age-matched healthy control subjects. Two previously unreported findings concerned gender. First, plasma alpha-synuclein concentrations measured in the more advanced parkinsonian disease stages decreased in men, but not in women. Second, again only in men, plasma alpha-synuclein concentration was associated with cognitive impairments, hallucinations, and sleep disorders. These findings underline the gender-related differences in parkinsonian patients and indicate plasma alpha-synuclein expression as a potential biological marker for PD progression in men.


Effectiveness of skin absorption of tincture of I in blocking radioiodine from the human thyroid gland.
Topical application of tincture of iodine (I) was found to be effective in blocking the thyroid uptake of orally administered 131I in humans. Abdominal skin application of tincture of I resulted in an approximately 82% reduction in the uptake of 131I by the thyroid gland. The effectiveness varied among individuals and may have depended on the quantity applied and on the application site. In each study group, elevated levels of serum I were observed.


A labeled guanidine ligand for studying sweet taste.
A synthesis of a biotinylated-, coumarin-substituted-N,N'-diarylguanidine 1 is reported. This ligand has structural features conducive to studying sweet taste including a fluorescent tag to facilitate spectroscopic studies of binding to protein-receptors for sweet ligands and an anchor for affinity purification.


Streptococcus mutans dextransucrase: phosphoglycerides and the detection of inhibitory antibodies in sera.
1) Rabbit and human sera contain high concentrations of phospholipids which can interact with dextransucrase causing enhanced glucan production. 2) Antibody in sera capable of blocking glucan synthesis can be accurately detected by adding excess LPC and dextran to the enzyme prior to incubating with antiserum and assaying with sucrose.


The effect of the method of burial on adipocere formation.
A controlled laboratory experiment was conducted in order to investigate the effect of the method of burial (i.e. the presence of coffin and clothing) on the formation of adipocere. This study follows previous studies by the authors who have investigated the effect of physical conditions on the formation of adipocere present in a controlled burial environment. The study utilises infrared spectroscopy to provide a preliminary lipid profile of the remains following a 12 month decomposition period. Inductively coupled plasma-mass spectrometry was employed as a technique for determining the salts of fatty acids present in adipocere. Gas chromatography-mass spectrometry (GC-MS) was used as the confirmatory test for the identification and determination of the chemical composition of adipocere which formed in the controlled burial environments. The results suggest that coffins will retard the rate at which adipocere forms but that clothing enhances its formation. The results concur with previous observations on adipocere formation in burial environments.


YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner.
Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/β-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.


Antirheumatic drugs in pregnancy and lactation.
To review the toxicity issues of commonly used antirheumatic drugs in pregnancy and lactation. A review of the medical literature using Medline database via Ovid was performed to identify the toxicities of antirheumatic drugs in pregnancy and lactation. Many rheumatologic diseases in women often first present during the childbearing years. In most cases, antirheumatic therapy is required for their disease control. Glucocorticoids may be used during pregnancy; however, first-trimester use should be avoided if possible and breastfeeding should occur 4 hours after the last dosing. Nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors should be discontinued 6 to 8 weeks before delivery. NSAIDs are compatible with lactation, although there is potential risk of jaundice and kernicterus. There is insufficient data on COX-2 inhibitors and lactation. Hydroxychloroquine and sulfasalazine may be continued throughout pregnancy and lactation. Methotrexate and leflunomide are contraindicated during pregnancy and lactation. Cyclophosphamide and mycophenolate mofetil should be avoided during pregnancy and lactation. Azathioprine and cyclosporine A could be used with caution during pregnancy if felt there is a need to suppress disease activity. They are not compatible with breastfeeding. There are insufficient data regarding tumor necrosis factor-antagonists, anakinra, and rituximab in relation to pregnancy and lactation. Male patients should be made aware of the effects methotrexate, leflunomide, sulfasalazine, and cyclophosphamide may have on their fertility. Health care providers should discuss the risks and benefits of antirheumatic therapy during conception, pregnancy, and lactation with their patients. Better maternal and fetal outcomes can be expected if the pregnancy is planned, the rheumatic disease is stable, and if appropriate medication adjustments can be made ahead of time.


Associations of psychological thriving with coping efficacy, expectations for future growth, and depressive symptoms over time in people with arthritis.
Psychological thriving reflects a trajectory of growth over time as opposed to scaling back expectations. Whether thriving is a product, precursor, or process of coping with arthritis-related limitations is unclear. We examined associations between thriving, coping efficacy, and expectations for future growth in individuals with arthritis, and the relations of thriving to depressive symptoms and retrospective perceptions of personal growth over a six-month period. A sample of 423 people with arthritis completed measures of thriving, coping efficacy, depressive symptoms, and expectations for future growth; 168 individuals completed a six-month follow-up survey. Structural equation modeling analyses compared three possible models of psychological thriving, controlling for disease-related variables. Hierarchical regression analyses of the cross-lagged associations of thriving with retrospective perceptions of positive personal change and depressive symptoms were also conducted. Structural equation analyses suggest that the process model in which thriving and coping efficacy jointly predicted expectations for future growth best fit the data. Baseline thriving was also associated with retrospective perceptions of personal growth at follow-up and fewer depressive symptoms at baseline and follow-up, after controlling for disease-related variables. Overall, these findings suggest that psychological thriving is synergistically related to coping efficacy, and to expectations for future growth and less depression, in people with arthritis. Importantly, our findings support the notion that psychological thriving is more than scaling back expectations, and that thriving may be an important quality to cultivate to address the burden of depression in people with arthritis.