CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.
Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.


[Use of alpha-tocopherol acetate in the treatment of hemodynamic disorders in patients with pulmonary tuberculosis].
Examination of 101 patients with pulmonary tuberculosis established the impact of specific intoxication on central hemodynamics in 51 patients. Specific treatment was found to have a certain positive effect on impaired hemodynamics. However, there were no significant changes in patients with severe tuberculosis. Hemodynamics substantially improved when alpha-tocopherol acetate was supplemented to antibacterial therapy.


The mammalian red nucleus and its role in motor systems, including the emergence of bipedalism and language.
The human red nucleus consists of the well-developed parvicellular red nucleus (pNr) and the rudimentary magnocellular red nucleus (mNr). It is believed that the human pNr is separated from the nucleus accessorius medialis of Bechterew (NB), which, generally speaking, is located in the ventral central gray. It was initially suggested that the "rolled sheet" model of the human pNr that we proposed included the view that the human NB does not occupy the ventral central gray but is placed in the dorsomedial part of the red nucleus. It is perhaps more appropriate to state that the NB, the origin of the medial tegmental tract (MTT), over time became displaced from the ventral central gray and was in part shifted to the adjacent reticular formation. The majority of the MTT tract however remained in its established location. Evolutionarily speaking, this separation of the NB and the nucleus of Darkschewitsch (ND), and the translocation of the position of the NB just referred to, might have begun within the lineage of the apes prior to the emergence of man. Furthermore it is generally believed that the human mNr consists of a scattered few groups of giant-to-large neurons situated among the fiber bundles of the superior cerebellar peduncle at the level of the oculomotor nerve fibers. It has long been considered impossible to clearly draw an outline of the human mNr such that it could be seen as a self-contained structural entity. However, we now demonstrate just such an outline of the rudimentary human adult mNr through employment of the concepts of the so-called "Mannen's closed nucleus" and "Ogawa's human mNr": descriptions that exclude the associated area that contains neurons which possess melanin pigment. Interestingly, recent studies have shown that the human fetus and newborns have a well-developed semilunar mNr, and this observation raises the possibility that the associated transient but well-developed rubrospinal tract seen in the perinatal state might have had an important role for the development of upright bipedalism in hominids. The well-developed human prefrontal-NB-olivo-lateral cerebellar circuit might possibly have resulted in the emergence of language.


Energy drink use frequency among an international sample of people who use drugs: Associations with other substance use and well-being.
The study aims were to identify: i.) energy drink (ED), caffeine tablet, and caffeine intranasal spray use amongst a sample who report drug use, and ii.) the association between ED use frequency and demographic profile, drug use, hazardous drinking, and wellbeing. Participants (n=74,864) who reported drug use completed the online 2014 Global Drug Survey. They provided data on demographics, ED use, and alcohol and drug use, completed the Alcohol Use Disorders Identification Test (AUDIT) and Personal Wellbeing Index (PWI), and reported whether they wished to reduce alcohol use. Lifetime ED, caffeine tablet and intranasal caffeine spray use were reported by 69.2%, 24.5% and 4.9%. Median age of ED initiation was 16 years. For those aged 16-37, median years using EDs increased from 4 to 17 years of consumption, where it declined thereafter. Greater ED use frequency was associated with: being male; under 21 years of age; studying; and past year caffeine tablet/intranasal spray, tobacco, cannabis, amphetamine, MDMA, and cocaine use. Past year, infrequent (1-4days) and frequent (≥5days) past month ED consumers reported higher AUDIT scores and lower PWI scores than lifetime abstainers; past month consumers were less likely to report a desire to reduce alcohol use. ED use is part of a complex interplay of drug use, alcohol problems, and poorer personal wellbeing, and ED use frequency may be a flag for current/future problems. Prospective research is required exploring where ED use fits within the trajectory of other alcohol and drug use.


The association between fetal head position prior to vacuum extraction and pregnancy outcome.
To estimate the association of fetal head position prior to vacuum extraction (VE) and pregnancy outcome. A retrospective cohort study of singleton pregnancies who underwent VE. Pregnancy outcome of occipito-anterior (OA) position of the fetal head was compared to those with occipito-posterior (OP) position. Amongst overall 12,063 women undergoing trial of labor, there were 1118 (9.2%) VE deliveries. Of them, 871 (77.9%) had OA and 247 (22.1%) had OP position of the fetal head. Except for a higher rate of nulliparity in the OA group, no significant differences between the groups regarding pregnancy complications and birthweight were noted. In the OP group, there were higher rates of prolonged 2nd-stage of labor as an indication for VE (49.8 vs. 36.5%, p < 0.001) and single detachment of vacuum cup (11.3 vs. 6.7%, p = 0.02) without any increased risk of failed extraction. Higher risks for sub-galeal hematoma (aOR = 4.36, p = 0.03) and low 5-min Apgar score (aOR = 4.63, p = 0.02) were observed in the OP group with otherwise similar rates of adverse maternal and neonatal outcomes. Among women undergoing VE, OP position is associated with higher rate of vacuum cup detachment, low 5-min Apgar score and increased risk for sub-galeal hematoma with otherwise similar rates of adverse maternal and neonatal outcomes.


Mortality of inherited arrhythmia syndromes: insight into their natural history.
For most arrhythmia syndromes, the risk of sudden cardiac death for asymptomatic mutation carriers is ill defined. Data on the natural history of these diseases, therefore, are essential. The family tree mortality ratio method offers the unique possibility to study the natural history at a time when the disease was not known and patients received no treatment. In 6 inherited arrhythmia syndromes caused by specific mutations, we analyzed all-cause mortality with the family tree mortality ratio method (main outcome measure, standardized mortality ratio [SMR]). In long-QT syndrome (LQTS) type 1, severely increased mortality risk during all years of childhood was observed (1-19 years), in particular during the first 10 years of life (SMR, 2.9; 95% CI, 1.5-5.1). In LQTS type 2, we observed increasing SMRs starting from age 15 years, which just reached significance between age 30 and 39 (SMR, 4.0; 95% CI, 1.1-10.0). In LQTS type 3, the SMR was increased between age 15 and 19 years (SMR, 5.8; 95% CI, 1.2-16.9). In the SCN5A overlap syndrome, excess mortality was observed between age 10 and 59 years, with a peak between 20 and 39 years (SMR, 3.8; 95% CI, 2.5-5.7). In catecholaminergic polymorphic ventricular tachycardia, excess mortality was restricted to ages 20 to 39 years (SMR, 3.0; 95% CI, 1.3-6.0). In Brugada syndrome, excess mortality was observed between age 40 and 59 (SMR, 1.79; 95% CI, 1.2-2.4), particularly in men. We identified age ranges during which the mortality risk manifests in an unselected and untreated population, which can guide screening in these families.


Utility of TL-201 SPECT in clarifying false-positive FDG-PET findings due to osteoradionecrosis in head and neck cancer.
This study aimed to determine whether Tl-201 single photon emission CT (SPECT) is potentially useful in differentiating false-positive fluorodeoxyglucose positron emission tomography (FDG-PET) findings caused by osteoradionecrosis (ORN) from recurrent head and neck cancer after radiotherapy. Five patients were recruited. Dual-phase FDG-PET and dual-phase Tl-201 SPECT were performed for each patient. All 5 patients proved to have ORN without recurrent cancer. By visual interpretation, the results were 4 positive versus 1 negative for PET, and 4 negative versus 1 positive for Tl-201 SPECT. The Tl-201 SPECT clarified 3 of the 4 false-positive PETs to be ORN. Dual-phase semiquantitative studies showed decreased standardized uptake value (SUV) over time in 3 of the 4 false-positive PETs and decreased lesion/background ratio over time in the false-positive Tl-201 SPECT. The Tl-201 SPECT may help clarify suspected false-positive FDG uptake caused by ORN. Dual-phase FDG-PET and dual-phase Tl-201 SPECT may also have some value.


Exact random-walk models in crystallographic statistics. IV. P.d.f.'s of [E] allowing for atoms in special positions.
The effect of scatterers, located in variable special positions, on the probability density function of the magnitude of the normalized structure factor has been investigated. Exact characteristic functions have been obtained for all the statistically different variable special positions in triclinic, monoclinic and ortho-rhombic space groups except in Fdd2 and in the space groups based on the point group 222, and the probability density functions have been evaluated from their Fourier or Fourier-Bessel series expansions. It is seen that the effect of heavy scatterers, located in the special positions investigated, is very marked and should be accounted for in cases of space-group ambiguities.


Outcomes of hemi- versus whole liver transplantation in patients from mainland china with high model for end-stage liver disease scores: a matched analysis.
Adult hemiliver transplantation (AHLT) is an important approach given the current shortage of donor livers. However, the suitability of AHLT versus adult whole liver transplantation (AWLT) for recipients with high Model for End-Stage Liver Disease (MELD) scores remains controversial. We divided patients undergoing AHLT and AWLT into subgroups according to their MELD scores (≥ 30: AHLT, n = 35; AWLT, n = 88; and < 30: AHLT, n = 323; AWLT, n = 323). Patients were matched by demographic data and perioperative conditions according to propensity scores. A cut-off value of 30 for MELD scores was determined by comparing the overall survival data of 735 cases of nontumor liver transplantation. Among patients with an MELD score ≥ 30 and < 30, AHLT was found to be associated with increased warm ischemia time, operative time, hospitalization time, and intraoperative blood loss compared with AWLT (P < 0.05). In the MELD ≥ 30 group, although the 5-year survival rate was significantly higher for AWLT than for AHLT (P = 0.037), there was no significant difference between AWLT and AHLT in the MELD < 30 group (P = 0.832); however, we did not observe a significant increase in specific complications following AHLT among patients with a high MELD score (≥ 30). Among these patients, the incidence of complications classified as Clavien-Dindo grade III or above was significantly higher in patients undergoing AHLT than in those undergoing AWLT (25.7% vs. 11.4%, P = 0.047). For the MELD < 30 group, there was no significant difference in the incidence of complications classified as Clavien-Dindo grade III or above for patients undergoing AHLT or AWLT. In patients with an MELD score < 30, AHLT can achieve rates of mortality and overall survival comparable to AWLT. In those with an MELD score ≥ 30, the prognosis and incidence of complications classified as Clavien-Dindo III or above are significantly worse for AHLT than for AWLT; therefore, we may need to be more cautious regarding the conclusion that patients with a high MELD score can safely undergo AHLT.


Reflection health means hope: 2013 is the year of the children.
Serious mental illnesses often have their onset before age 20. Early identification and treatment is critical in minimizing the long-term effects of mental illness. We have made great strides in our understanding of children's behavioral health difficulties and how to treat them. But many challenges remain-from gaps in insurance coverage to inadequate public understanding of children's behavioral health-and not all youth who need services are able to access them in a timely fashion. The National Council for Behavioral Health offers many programs to address the challenges.


The use of ketoconazole in the emergency management of disseminated intravascular coagulation due to metastatic prostatic cancer.
The disseminated intravascular coagulation syndrome is an untoward side effect of metastatic adenocarcinoma of the prostate. In addition to appropriate replacement of blood, platelets and clotting factors, prompt treatment of the prostatic carcinoma is required to correct the underlying pathophysiological defect. Ketoconazole is the ideal method for hormonal manipulation for patients with life-threatening complications of prostatic carcinoma (disseminated intravascular coagulation and acute paraparesis/paraplegia) because of its prompt onset of action in decreasing circulating concentrations of androgens to castrate levels. Serum testosterone levels are castrate within 48 hours of the initiation of therapy with ketoconazole as opposed to a minimum of 10 to 14 days with estrogens. A patient with spontaneous bleeding from disseminated intravascular coagulation was treated with 400 mg. ketoconazole every 8 hours and bleeding stopped within 48 hours. Ketoconazole is particularly valuable when a prompt therapeutic response is needed and orchiectomy is contraindicated because of bleeding diathesis (as in disseminated intravascular coagulation), delay in histological confirmation (as in acute paraparesis/paraplegia) or patient reluctance to undergo castration.


Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.
The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.


Tricuspid annular plane systolic excursion is a robust outcome measure in systemic sclerosis-associated pulmonary arterial hypertension.
The tricuspid annular plane systolic excursion (TAPSE) strongly reflects right ventricular (RV) function and predicts survival in idiopathic pulmonary arterial hypertension (PAH). But its role in systemic sclerosis (SSc)-associated PAH has not been established. Our objective was to validate the TAPSE in the assessment of RV function and prediction of survival in SSc-PAH. Fifty consecutive patients with SSc-PAH who underwent echocardiography with TAPSE measurement within 1 h of clinically indicated right heart catheterization were followed prospectively. The relationship between TAPSE and measures of RV function and measures of survival was assessed. The majority of the cohort were women in New York Heart Association class III/IV with severe PAH (mean cardiac index 2.4 ± 0.8 l/min/m(2)). RV function was significantly impaired (mean cardiac index 2.1 ± 0.7 vs 2.9 ± 0.8 l/min/m(2); p < 0.01) and RV afterload was significantly greater (mean pulmonary vascular resistance 11.1 ± 5.1 vs 5.8 ± 2.5 Wood units; p < 0.01) in subjects with a TAPSE ≤ 1.7 cm. The proportion surviving in the low TAPSE group was significantly lower [0.56 (95% CI 0.37-0.71) and 0.46 (95% CI 0.28-0.62) vs 0.87 (95% CI 0.55-0.96) and 0.79 (95% CI 0.49-0.93), 1- and 2-year survival, respectively]. TAPSE ≤ 1.7 cm conferred a nearly 4-fold increased risk of death (HR 3.81, 95% CI 1.31-11.1, p < 0.01). TAPSE is a robust measure of RV function and strongly predicts survival in patients with PAH-SSc. Future studies are needed to identify the responsiveness of TAPSE to PAH-specific therapy and to assess its diagnostic utility in PAH-SSc.


Identification of lymph node metastasis in pre-operation cervical cancer patients by weakly supervised deep learning from histopathological whole-slide biopsy images.
Lymph node metastasis (LNM) significantly impacts the prognosis of individuals diagnosed with cervical cancer, as it is closely linked to disease recurrence and mortality, thereby impacting therapeutic schedule choices for patients. However, accurately predicting LNM prior to treatment remains challenging. Consequently, this study seeks to utilize digital pathological features extracted from histopathological slides of primary cervical cancer patients to preoperatively predict the presence of LNM. A deep learning (DL) model was trained using the Vision transformer (ViT) and recurrent neural network (RNN) frameworks to predict LNM. This prediction was based on the analysis of 554 histopathological whole-slide images (WSIs) obtained from Qilu Hospital of Shandong University. To validate the model's performance, an external test was conducted using 336 WSIs from four other hospitals. Additionally, the efficiency of the DL model was evaluated using 190 cervical biopsies WSIs in a prospective set. In the internal test set, our DL model achieved an area under the curve (AUC) of 0.919, with sensitivity and specificity values of 0.923 and 0.905, respectively, and an accuracy (ACC) of 0.909. The performance of the DL model remained strong in the external test set. In the prospective cohort, the AUC was 0.91, and the ACC was 0.895. Additionally, the DL model exhibited higher accuracy compared to imaging examination in the evaluation of LNM. By utilizing the transformer visualization method, we generated a heatmap that illustrates the local pathological features in primary lesions relevant to LNM. DL-based image analysis has demonstrated efficiency in predicting LNM in early operable cervical cancer through the utilization of biopsies WSI. This approach has the potential to enhance therapeutic decision-making for patients diagnosed with cervical cancer.


Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis.
Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.


Genome sequencing of cold-adapted Planococcus bacterium isolated from traditional shrimp paste and protease identification.
Psychrophiles have evolved to adapt to freezing environments, and cold-adapted enzymes from these organisms can maintain high catalytic activity at low temperature. The use of cold-adapted enzymes has great potential for the revolution of food and molecular biology industries. In this study, four different strains producing protease were isolated from traditional fermented shrimp paste, one of which, named Planococcus maritimus XJ11 by 16S rRNA nucleotide sequence analysis, exhibited the largest protein hydrolysis clear zone surrounding the colonies. Meanwhile, the strain P. maritimus XJ11 was selected for further investigation because of its great adaptation to low temperature, low salinity and alkaline environment. The enzyme activity assay of P. maritimus XJ11 indicated that the optimum conditions for catalytic activity were pH 10.0 and 40 °C. Moreover, the enzyme also showed an increasing activity with temperatures from 10 to 40 °C and retained more than 67% activity of the maximum over a broad range of salinity (50-150 g L-1 ). Genome sequencing analysis revealed that strain XJ11 possessed one circular chromosome of 3 282 604 bp and one circular plasmid of 67 339 bp, with a total number of 3293 open reading frames (ORFs). Besides, 21 genes encoding protease, including three serine proteases, were identified through the NR database. Cold-adapted bacterium P. maritimus XJ11 was capable of producing alkaline proteases with high catalytic efficiency at low or moderate temperatures. Furthermore, the favorable psychrophilic and enzymatic characters of strain P. maritimus XJ11 seem to have a promising potential for industrial application. © 2020 Society of Chemical Industry.


Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression.
G protein-coupled receptor 56 (GPR56) is highly expressed in acute myeloid leukemia (AML) cells with high EVI1 expression (EVI1high AML). Because GPR56 is a transcriptional target of EVI1 and silencing of GPR56 expression induces apoptosis, we developed a novel drug to suppress GPR56 expression in EVI1high AML cells. For this purpose, we generated pyrrole-imidazole (PI) polyamides specific to GPR56 (PIP/56-1 or PIP/56-2) as nuclease-resistant novel compounds that interfere with the binding of EVI1 to the GPR56 promoter in a sequence-specific manner. Treatment of EVI1high AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56-1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of EVI1 to its promoter, leading to suppression of cell growth with increased rates of apoptosis. Moreover, intravenous administration of PIP/56-1 into immunodeficient Balb/c-RJ mice subcutaneously transplanted with UCSD/AML1 cells significantly inhibited tumor growth and extended survival. Furthermore, organ infiltration by leukemia cells in immunodeficient Balb/c-RJ mice, which were intravenously transplanted using UCSD/AML1 cells, was successfully inhibited by PIP/56-1 treatment with no apparent effects on murine hematopoietic cells. In addition, PIP treatment did not inhibit colony formation of human CD34+ progenitor cells. Thus, PI polyamide targeting of GPR56 using our compound is promising, useful, and safe for the treatment of EVI1high AML.


Characterization of double-stranded RNA genetic elements associated with biological control of chestnut blight: organization of terminal domains and identification of gene products.
We have determined the organization within the terminal domains of the major large double-stranded RNA genetic elements associated with the hypovirulent strain EP713 of the chestnut blight pathogen Cryphonectria (Endothia) parasitica. Only the polyadenylated strand contained long open reading frames. Furthermore, only RNA of the same polarity as the polyadenylated strand was detectable in a single-stranded form, indicating that the polyadenylated strand is the coding or plus strand. The organization of the 5'-proximal portion of the plus strand consisted of a 495 nucleotide non-coding leader sequence followed by two overlapping open reading frames. The first, ORF1, extended 957 nucleotides while the second, ORF2, began 68 nucleotides upstream of the ORF1 termination codon and extended at least 1412 nucleotides. No open reading frames of significant size were detected within 0.8 kb of the poly(A) tail. In vitro translation of synthetic transcripts containing ORF1 yielded a polypeptide of Mr 29 kd. The ORF1 product was also detected in lysates of the hypovirulent strain but was absent in lysates of the isogenic virulent strain. It represents the first protein to be identified as a gene product encoded by a hypovirulence-associated double-stranded RNA genetic element.


Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or Obese Otherwise Healthy Adults: A Pilot Randomized Trial.
Adipokines play an important role in the regulation of glucose metabolism. We have previously shown that carnosine supplementation in overweight or obese non-diabetic individuals improves glucose metabolism but does not change adiponectin concentrations. However, its effect on other adipokines has not been investigated. Herein we further determined the effect of carnosine supplementation on serum adipsin, resistin and leptin. Twenty-two overweight or obese otherwise healthy adults were randomly assigned to receive either 2 g of carnosine (n = 13) or identically looking placebo (n = 9) for 12 weeks. Serum adipsin, leptin and resistin were analyzed using a bead-based multiplex assay. Carnosine supplementation decreased serum resistin concentrations compared to placebo (mean change from baseline: -35 ± 83 carnosine vs. 35 ± 55 ng/mL placebo, p = 0.04). There was a trend for a reduction in serum leptin concentrations after carnosine supplementation (-76 ± 165 ng/mL carnosine vs. 20 ± 28 ng/mL placebo, p = 0.06). The changes in leptin and resistin concentrations were inversely related to the change in concentration for urinary carnosine (r = -0.72, p = 0.0002; r = -0.67, p = 0.0009, respectively), carnosine-propanal (r = -0.56, p = 0.005; r = -0.63, p = 0.001, respectively) and carnosine-propanol (r = -0.61, p = 0.002; r = -0.60, p = 0.002, respectively). There were no differences between groups in change in adipsin concentrations. Our findings show carnosine supplementation may normalize some, but not all, of the serum adipokine concentrations involved in glucose metabolism, in overweight and obese individuals. Further clinical trials with larger samples are needed to confirm these results.


Magnifying endoscopy is useful for tumor border diagnosis in ulcerative colitis patients.
Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC. We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes. We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99). ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.


MR images restoration with the use of fuzzy filter having adaptive membership parameters.
A new fuzzy adaptive median filter is presented for the noise reduction of magnetic resonance images corrupted with heavy impulse (salt and pepper) noise. In this paper, we have proposed a Fuzzy Adaptive Median Filter with Adaptive Membership Parameters (FAMFAMP) for removing highly corrupted salt and pepper noise, with preserving image edges and details. The FAMFAMP filter is an improved version of Adaptive Median Filter (AMF) and is presented in the aim of noise reduction of images corrupted with additive impulse noise. The proposed filter can preserve image details better than AMF while suppressing additive salt and pepper or impulse type noise. In this paper, we placed our preference on bell-shaped membership function with adaptive parameters instead of triangular membership function without variable coefficients in order to observe better results.


Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study.
Practice guidelines for the initial treatment of bipolar II (BP II) major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial AD monotherapy would be superior to MS monotherapy for BP II MDE with a low hypomanic switch rate. Bipolar II MDE patients were randomized to a 12-week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium carbonate monotherapy (n = 40). The primary outcome measure was the 28-item Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures included the Young Mania Rating Scale (YMRS), clinical global impressions severity and change ratings, and the proportion of patients classified as responder (with > or = 50% reduction in baseline HAM-D score) or as remitter (final HAM-D score, < or = 8). Thirty-four venlafaxine-treated patients (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005). Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18) (P = 0.017) between treatment conditions. There was a greater proportion of venlafaxine-treated (vs lithium-treated) patients classified either as treatment responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS scores over time in the venlafaxine (vs lithium) treatment condition, and no significant increase in mean YMRS scores at any study visit compared with baseline for either treatment. Results from this study suggest that AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE with a low hypomanic switch rate.


Long-term efficacy of immunoadsorbent plasmapheresis in a patient with Budd-Chiari syndrome due to antiphospholipid syndrome: case report with nine-year follow-up.
We describe the safety and efficacy of long-term immunoadsorbent plasmapheresis (IAPP) with dextran sulfate-cellulose bead columns in antiphospholipid syndrome (APS). IAPP was administered to a 38-year old male Japanese patient with APS with Budd-Chiari syndrome (BCS), who had presented with refractory lower leg skin ulcers and arterial and venous thromboses including BCS. After hepatic vein transluminal angioplasty was performed, the combination of corticosteroid, aspirin and IAPP was administered because of an underlying bleeding tendency related to liver dysfunction. From February 1994 to February 2003, a total of 228 procedures were performed. No further thrombosis-related symptoms or bleeding have occurred for more than nine years, suggesting that IAPP with dextran sulfate cellulose columns is safe and effective for APS in preventing additional thrombotic events. This IAPP supplements anticoagulation, antiplatelet, corticosteroid and immunosuppressant therapies.


The clinical appearance of the lamina cribrosa as a function of the extent of glaucomatous optic nerve damage.
The authors evaluated the shapes of the largest clinically visible pores on the surface of the lamina cribrosa in 87 eyes of 52 glaucoma patients and found an apparent progression in pore shape as a function of the extent of glaucomatous optic nerve head damage. Small, round pores predominated in eyes with mild field loss, oval pores were more common in eyes with moderate field loss, and striate or slit-shaped pores were most frequent in eyes with advanced field loss. If the pores of the lamina cribrosa elongate as a function of increasing glaucomatous optic atrophy, and if large pore size is associated with an increased risk for pressure-related axonal damage, then the threshold for ganglion cell atrophy may drop as the damage to the optic nerve progresses.


Categorization of biologically significant objects, food and gender, in rhesus monkeys. I. Behavioral study.
Macaque monkeys have a highly evolved visual system comparable to that of humans. One of the important visual functions is performing discriminations among biologically significant objects such as food or heterosexual partners. In the present study, we examined whether rhesus monkeys could categorize two-dimensional images related to food or gender using a visual discrimination task. Three rhesus monkeys were trained to make distinctions of food from non-food items, and between male and female monkeys, using 60 or more different pictures of each category. After more than 9 months of training, the monkeys discriminated a variety of foods from non-food and different males from females with more than 80% accuracy, even when the stimuli were used for the first time or presented only once in a session. The proportion of correct responses and response latencies showed better performance in discrimination of food/non-food than that of gender. The results suggest that rhesus monkeys are able to perform visual discrimination of highly abstract biologically significant categories with better performance in a food-related category than a gender-related one, using two-dimensional visual information.


Use of tree bark for comparing environmental pollution in different sites from Buenos Aires and Montevideo.
Multi-elemental profiles in bark of green ash trees collected in three representative areas of Buenos Aires, Argentina and Montevideo, Uruguay, were assessed as potential air pollution indicators. Ten elements: Al, Ba, Cr, Cu, Fe, Mg, Mn, Ni, Pb, and Zn, were measured using inductively coupled plasma optical emissions spectrometry from 70 samples collected in different environments: central, residential and rural (reference site), in order to compare spatial patterns of metal concentration. The samples used as a control were collected from a nature reserve situated far away from any significant influences, not even a nearby road. The reference site (RF) exhibited the lowest concentrations of Al, Cr, Fe, Ni, Pb, and Zn. However, Ba and Mn showed similar concentrations in all measured sites. Magnesium is the only element that had a greater concentration in RF than at the other sites. Copper did not show any clear pattern. The Centre of Montevideo (MVD) showed higher concentrations of Al, Ba, Cr, Fe, Pb and Zn than the Centre of Buenos Aires (BA). In the A sectors, Montevideo (SAMVD) showed higher concentrations of Al, Cu, Mg, Ni, and Zn and lower concentrations of Ba, Cr, Fe, Mn, and Pb than Buenos Aires (SABA). In the B sectors, Montevideo (SBMVD) showed higher concentrations of Al, Ba, Cu, Fe, Pb, and Zn and lower concentrations of Cr and Mg than Buenos Aires (SBBA), but similar concentrations of Mn and Ni. The use of bark for biomonitoring metals allowed us to detect concentration differences related to the urban fabric and the different kinds of vehicles and their fuels. In the cities, the differences in metal concentrations detected in bark were more striking between the sectors than between centers, despite CBA being much larger than CMVD in population, extension and vehicular traffic.


Multifunctional cationic polyurethanes designed for non-viral cancer gene therapy.
Nano-polyplexes from bioreducible cationic polymers have a massive promise for cancer gene therapy. However, the feasibility of cationic polyurethanes for non-viral gene therapy is so far not well studied. In this work, a linear cationic polyurethane containing disulfide bonds, urethane linkages and protonable tertiary amino groups was successfully generated by stepwise polycondensation reaction between 2,2'-dithiodiethanol bis(p-nitrophenyl carbonate) and 1,4-bis(3-aminopropyl)piperazine (BAP). We confirmed that the cationic polyurethane (denoted as PUBAP) displayed superior gene delivery properties to its cationic polyamide analogue, thus causing higher in vitro transfection efficiency in MCF-7 and SKOV-3 cells. Besides, further folate-PEGylation and hydrophobic deoxycholic acid (DCA) conjugation to amino-containing PUBAP can be conducted to afford multifunctional polyurethane gene delivery system. After optimization, folate-decorated nano-polyplexes from the PUBAP conjugated with 8 folate-PEG chains and 12 DCA residues exhibited superb colloidal stability under physiological conditions, and performed rapid uptake via folate receptor-mediated endocytosis, efficient intracellular gene release and nucleus translocation into SKOV-3 cells in vitro and in vivo. Importantly, PUBAP based polyplexes possess low cytotoxicity as a result of PUBAP biodegradability. Therefore, marked growth inhibition of SKOV-3 tumor xenografted in Balb/c nude mice was achieved with negligible side effects on the mouse health after intravenous administration of PUBAP based polyplexes with a therapeutic plasmid encoding for TNF-related apoptosis-inducing ligand. This work provides a new insight into biomedical application of bio-responsive polyurethanes for cancer therapy. In this study, we have confirmed that disulfide-based cationic polyurethane presents a new non-viral vector for gene transfer and cancer gene therapy. The significance of this work includes: (1) design and synthesis of a group of novel disulfide-based cationic polyurethane by non-isocyanate chemistry; (2) comparative study of transfection activity between cationic polyurethanes and cationic polyamides; (3) feasibility of bioreducible cationic polyurethanes for in vivo cancer gene therapy.


Detection of tip-enhanced fluorescence from loop-mediated isothermal amplification of hepatitis B virus by two-photon microscopy.
Tip-enhanced fluorescence of localized DNA replication by loop-mediated isothermal amplification (LAMP) is a potential way to observe real-time biological reaction confined in nanometer scale. We successfully coated Bst polymerase on the apex (~100 nm) of an atomic force microscope (AFM) tip and performed localized LAMP reaction of hepatitis B virus (HBV). By using this tip-based reaction, the replicated HBV DNA can be directly imaged to be 400~500 nm spots by using two-photon excitation fluorescence microscopy.


Orientation of molecular groups of fibers in nonoriented samples determined by polarized ATR-FTIR spectroscopy.
A method based on polarized attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is proposed for determining the infrared dichroic absorption ratio of a single fiber from a sample deposited flat on a germanium crystal without the requirement of fiber orientation. The method shows its efficiency on cellulose fibers of paper and has been applied to protein fibers (type I collagen and β-amyloid) and polysaccharide fibers (cellulose and starch). The method gives access to the dichroic ratio of strong absorptions bands, which is not easily accessible with conventional absorption techniques. Then, the orientation of the molecular groups of organic fibers can be easily determined by polarized ATR-FTIR spectroscopy. By extension, this method will be useful to determine the molecular orientation of fibers in structured complex samples, such as biological tissues and plants. Spatially resolved information on the organization of the fiber network will be easily extracted by utilizing a focal plane array detector for imaging measurements.


Determination of field size limitations in stereotactic and intensity modulated radiotherapy.
For dose measurement in small photon fields, different detectors are currently in use: TLD, semiconductor, diamond-detector, film, etc. But for absolute dosimetry, ionization chambers show the most advantages. To meet the basic dosimetrical requirements for lateral electron equilibrium the field size F must not remain under specified values: i.e. 5.2 x 5.2 cm2 for 15 MeV X-bremsstrahlung. As well as increasing the focus-chamber-distance, changing the physical density of the build-up material in the close vicinity of the chamber will be helpful to determine the output factor OF for smaller fields. By means of a correction factor, k(mat), this is taken into account. For a 6 MeV X and a 15 MeV X-bremsstrahlung of linear accelerators the lower limit of the field size F is determined: F > or = 0.8 cm. This value is mainly dependent on the diameter of the focal-spot (phi = 3 mm) of the treatment unit including design characteristics of the treatment head. Beside the dosimetrical aspects, some geometrical parameters have to be considered, when accuracy of dose application should remain on the same level as in medium and large field treatment (4 cm < or = F < or = F(max)). To keep dose-volume errors as low as +/- 10 % (diameter of PTV: 20 mm), the mean total error delta of CT-scanning (delta(p)), planning (delta(pl)), patient positioning (delta(x)), and treatment unit instabilities (delta(m)) should not exceed +/- 0.8 mm.


Role of the purinergic system in patients with cervical intraepithelial neoplasia and uterine cancer.
Cervical cancer remains the second leading cause of death among women. Intraepithelial neoplasias and uterine invasive cancer are frequently associated with disturbances in coagulation and changes in the concentrations of adenine nucleotides. This work intended to analyze changes in extracellular adenine nucleotide hydrolysis and blood platelet aggregation in patients diagnosed for cervical intraepithelial neoplasia in different stages as well as uterine invasive cancer. NTPDase, E-NPP, 5'-nucleotidase, total ADA and its isoforms (ADA1 and ADA2), as well as the platelet aggregation from patients with different stages of cervical intraepithelial neoplasia (NICs I, NIC II, NIC III) and uterine invasive cancer were verified. Neither ATP hydrolysis nor E-NPP activity was changed by the neoplasia stage. On the other hand, ADP and AMP hydrolysis as well as ADA activity were enhanced in NIC I group. AMP hydrolysis was also increased in the cancer group. ADA 1 was the ADA isoform found in platelets from both control and patient groups. Our results showed for the first time that NTPDase, 5'-nucleotidase, E-NPP and ADA are not sensible regarding the grade of neoplasia development, since no significant difference was found between the groups studied. Only ADP hydrolysis and ADA activity showed a significant enhancement in NIC I group related to the other stages possibly as a result of the beginning of the neoplasic transformation. This increase could be reflecting a body's reaction against the probable high adenosine levels. We propose for the first time that the ADA isoform present in platelets is ADA 1.


Fructose 2,6-bisphosphate in developing rat brain.
Fructose 2,6-bisphosphate (Fru-2,6-P2) levels and 6-phosphofructo-1-kinase and 6-phosphofructo-2-kinase activities have been studied in rat brain during development from embryonal to adult state. Fru-2,6-P2 increases slightly from day 16 of gestation, reaching a maximum 24 h after birth, remaining quite constant during postnatal development. In contrast with 6-phosphofructo-1-kinase, which increases progressively after the first week of age, 6-phosphofructo-2-kinase remains unaltered throughout the period studied. The role of Fru-2,6-P2 in controlling cerebral glycolysis is discussed.


Mechanical ventilation and acute respiratory distress syndrome in older patients.
As the population of the United States ages, an increasing number of elderly adults will be cared for in intensive care units. An understanding of how aging affects the respiratory system is important for patient care and ongoing research. The incidence rates of acute respiratory failure and of acute respiratory distress syndrome increase dramatically with age, and therefore understanding the relationship between age and ARDS is important. This article focuses on the age-specific changes in respiratory function. We present a discussion of the management of acute lung injury and acute respiratory distress syndrome with a focus on the role of mechanical ventilation. We conclude with what is known about age and its impact on mortality and functional outcomes after mechanical ventilation.


Impact of different tongue cleaning methods on the bacterial load of the tongue dorsum.
To assess the extent and duration of the effect of tongue cleaning procedures on bacterial load on the dorsal surface of the tongue. 19 subjects participated in this blinded crossover study. Subjects abstained from oral hygiene, eating and drinking from 22:00 h the previous evening. Tongue samples were collected at baseline and within 15 minutes of one of three procedures: teeth brushing alone; teeth brushing plus tongue scraping; teeth brushing plus tongue cleaning using a high speed vacuum ejector and irrigation with 20 ml antibacterial mouthwash. Subjects then brushed twice daily for 3 days apart from the second group who additionally scraped their tongue twice daily. On day 4, baseline and post-treatment samples were collected as per day 1. Bacteria (total anaerobes, Gram-negative anaerobes, VSC-producing bacteria and Streptococcus saliuarius) were enumerated using appropriate selective media. The tongue dorsum was colonized by all 4 bacterial categories (log(10) 6-8 cfu/sample). For subjects who brushed their teeth only, there was a significant reduction from baseline for S. saliuarius only. In contrast, tooth brushing plus tongue scraping resulted in statistically significant reductions from baseline for all bacterial categories (range log(10) 0.11-0.40 cfu/sample). Highly statistically significant reductions (log(10) 1.11-1.96 cfu/sample) were observed for subjects who underwent thorough tongue cleaning with the saliva ejector/mouthwash. To determine longevity of treatment effects, baseline bacterial loads for days 1 and 4 were compared. Only daily tongue scraping resulted in statistical significant reduction in baseline microbial loads on day 4. While mechanical tongue cleaning with or without chemical intervention can reduce bacterial load on the tongue, this effect is transient, and regular tongue cleaning is required to provide a long lasting (overnight) reduction in bacterial numbers. Nevertheless, tongue cleaning is an oral hygiene procedure that is little practiced due to discomfort and/or lack of awareness on the part of dental professionals and their patients.


High-speed spline fitting, with application to boundary tracing in low-contrast digital images.
The practical implementation of a rapid Catmull-Rom (cardinal) spline is described, and its advantages with respect to speed and ease of use are discussed. Consideration is also given to interactive tensioning of the curve, and how the spline may be used to contour the boundary in digital images prior to segmentation. For this purpose the spline control points are positioned by the user and automatically optimized by means of a local, two dimensional edge detector.


Ureteroileal fistulas.
Of the fistulas that involve the urinary and intestinal tracts vesicointestinal fistulas are the most common and nephrointestinal fistulas are infrequent. Ureteroileal fistulas are extremely rare, with only 6 previously reported cases. Three recent cases are presented to highlight current management. In all 3 patients the ureteroileal fistula developed postoperatively, including 1 after radical pelvic surgery for advanced ovarian carcinoma, 1 following failed transureteroureterostomy and 1 after a repeat left ureteral reimplant with a pelvic abscess. Infection and/or urinary leakage had a major role in these cases, similar to the previously reported fistulas. In contrast to the previously reported patients, all of whom underwent surgical excision or revision, the 3 patients described herein were managed successfully with percutaneous nephrostomy or indwelling ureteral stents. Although successful management today may bypass operative intervention in these rare fistulas most are preventable operative complications.


Prognostic factors vs. outcome in male-to-female transsexualism. A follow-up study of 13 cases.
Thirteen male-to-female transsexuals were investigated 6 to 25 years after surgery. Thirty-five prognostic items were compared with each of three outcome variables. Traumatic loss of both parents in infancy was connected with repentance at follow-up. A childhood family of an overprotective mother and a distant father, on the other hand, was prognostically favourable. Contrary to most previous reports, high sexual activity and bisexual experience was associated with fair sexual adjustment and with non-repentance after sex change. The repenting individuals, on the other hand, had been a-sexual or hyposexual before surgery. Completed military service, a history of typically masculine, hard jobs, and a comparatively late (more than 30 years of age) first request for surgery, were found to be negative prognostic factors in sex-reassignment evaluations. The phenomenon of ambivalence or hesitance during the trial period is discussed. Both too much and too little ambivalence may suggest a poor prognosis.


Readmission to the intensive care unit after "fast-track" cardiac surgery: risk factors and outcomes.
The introduction of "fast-track" management into cardiac surgery has significantly shortened the intensive care unit (ICU) length of stay. Readmission to the ICU, traditionally used as a quality index, has not been investigated in these patients. The aim of this study was to assess the causes, risk factors, and outcomes associated with readmission to the ICU. All patients undergoing open-heart surgery in a tertiary care, university-affiliated center were included in this prospective observational study. Preoperative and intraoperative data as well as ICU outcome were noted in all patients. Over the 27-month study period,1,613 patients were targeted for fast track management (discharge from ICU on the first postoperative day). The readmission rate was 3.29% (53 patients). Forty-three percent of readmissions occurred within 24 hours of discharge usually because of pulmonary problems (43%) or arrhythmias (13%). Readmission was associated with a prolonged ICU stay (105 +/- 180.0 versus 19.2 +/- 2.4 hours of initial ICU stay) and worse outcome: the only patients who died (6 of 53, 11.3%) were in this group. On multivariate analysis, a Bernstein-Parsonnet risk estimate more than 20 strongly predicted readmission (odds ratio, 3.08; 95% confidence interval, 1.43 to 6.69). Among a homogeneous group of patients targeted for fast-track management after cardiac surgery, readmission although uncommon is associated with a longer second ICU stay and significant mortality. The recognition of specific risk factors may allow for appropriate modification of the postoperative course.


Molecular mapping of general anesthetic sites in a voltage-gated ion channel.
Several voltage-gated ion channels are modulated by clinically relevant doses of general anesthetics. However, the structural basis of this modulation is not well understood. Previous work suggested that n-alcohols and inhaled anesthetics stabilize the closed state of the Shaw2 voltage-gated (Kv) channel (K-Shaw2) by directly interacting with a discrete channel site. We hypothesize that the inhibition of K-Shaw2 channels by general anesthetics is governed by interactions between binding and effector sites involving components of the channel's activation gate. To investigate this hypothesis, we applied Ala/Val scanning mutagenesis to the S4-S5 linker and the post-PVP S6 segment, and conducted electrophysiological analysis to evaluate the energetic impact of the mutations on the inhibition of the K-Shaw2 channel by 1-butanol and halothane. These analyses identified residues that determine an apparent binding cooperativity and residue pairs that act in concert to modulate gating upon anesthetic binding. In some instances, due to their critical location, key residues also influence channel gating. Complementing these results, molecular dynamics simulations and in silico docking experiments helped us visualize possible anesthetic sites and interactions. We conclude that the inhibition of K-Shaw2 by general anesthetics results from allosteric interactions between distinct but contiguous binding and effector sites involving inter- and intrasubunit interfaces.


Prostaglandins, steroids and human mammary cancer.
PGE2 and PGF2 alpha secretion in vitro were measured from tissues of patients with breast tumours and examined in relation to oestrogen receptor status. Prostaglandin secretion was significantly greater from malignant breast tumours than from 'normal' breast tissue or benign tumours. Synthesis of PGE2 by oestrogen-positive and malignant tumours was significantly higher than by oestrogen-negative tumours, suggesting a correlation between prostaglandin E2 and receptor status. Synthesis of PGF2 alpha by the malignant tumour tissues also occurred, but only at relatively low levels and with no significant difference between oestrogen-positive and negative tissues. Exogenous oestrogen in vitro had a significant stimulatory effect on both PGE2 and PGF2 alpha secretion by oestrogen-positive malignant tumour tissues but did not influence oestrogen-negative tumour tissues. Progesterone, on the other hand, had no statistically significant effect on PG secretion by either type of tumour tissue, although the increased levels of PGE2 secreted by oestrogen-positive tumour tissue in the presence of progesterone are unlikely to have arisen by chance. The results support the concept of steroidal influence on excess production of prostaglandins by human malignant breast tumour tissues.


[The combined use of traditional acupuncture and microacupuncture therapy in treating bronchial asthma patients].
The attacks of bacterial asthma in 100 patients were treated by standard acupuncture, microacupuncture and by combined use of the modalities. The comparative analysis revealed the highest efficiency for the combined treatment, the less for microacupuncture. The disease of moderate severity, light severity and that free of attacks should be treated, as the authors believe, with acupuncture plus microacupuncture, standard acupuncture, and microacupuncture, respectively.


A comparative study of the binding of Graves' immunoglobulins by the patients own and other thyroid membranes.
Thyroid membrane preparations from six patients with active Graves' disease were tested in an assay which detects the thyroid interactive immunoglobulins of Graves' disease by their inhibition of binding of [125I]-thyroid stimulating hormone (TSH). With all preparations inhibition of binding of 125I-TSH by excess TSH could be demonstrated (specific binding). The patients' own immunoglobulins were assayed against their own thyroid membranes and against each other's under exactly comparable conditions. Inhibition of binding by IgGs from the patients varied between membrane preparations: with one preparation 5/6 IgGs were inhibitory but with another none were effective. Of the six patients, their own IgG inhibited binding of 125I-TSH to their own thyroid membrane preparation in only four instances, and when interaction did occur this did not reliably predict that the membrane preparation would interact with IgGs from other patients with Graves' disease. The selection of a membrane preparation for this assay cannot be made solely on ability to specifically bind TSH but the measure of the specific interaction with a Graves' IgG of proven potency must also be considered. Moreover, because of the variability between different membrane preparations, sequential clinical studies on individual patients, of the changes in concentration of Graves' IgG, must be performed using the same selected thyroid membrane preparation. We infer from these observations that the membrane structure in the vicinity of the TSH binding site is an important determinant of the interaction of Graves' IgGs with the TSH receptor, and that the configuration of this area is variable between individuals of the same species. The distinction between 'human-specific' and 'non-species-specific' thyroid stimulating antibodies is therefore probably not valid. The observation that the patient's own IgG was not often the most potent IgG inhibitor of binding of TSH also suggests that the Graves' IgG binding site is not identical or restricted to the TSH binding site; alternative explanations are discussed.


Effects of high-intensity interval training (HIIT) on skeletal muscle atrophy, function, and myokine profile in diabetic myopathy.
Diabetes is a metabolic disorder characterized by chronic hyperglycemia due to insulin deficiency and/or loss of its action. Diabetic myopathy causes functional limitations in diabetic patients. The beneficial effects of high-intensity interval training (HIIT) are widely reported. We have hypothesized that HIIT application would prevent the development of diabetic myopathy. Male, Wistar albino rats (10 W) were randomly divided into four groups (1)Control(C), (2)Diabetes(DM), (3)Training(HIIT), and (4)Diabetes + Training(DM + HIIT). Streptozotocin(60 mg/kg) was injected for the induction of diabetes. The maximum exercise capacity(MEC) of animals was determined by an incremental load test. HIIT protocol (4 min 85-95 % MEC, 2 min 40-50 % MEC, 6 cycles, 5 days/week) was applied for 8 weeks. In the end, functional parameters, atrophy, and resistance to fatigue in soleus and EDL muscles were evaluated. IL-6, FNDC5, and myonectin levels were measured in EDL, soleus, and serum. We observed atrophy, fatigue sensitivity, and proinflammatory alterations (IL-6 increase) in the EDL samples due to diabetic myopathy which were not observed in the soleus samples. HIIT application prevented the aforementioned detrimental alterations. Both force-frequency response and parallelly the twitch amplitude increased significantly in the DM + HIIT group. Half relaxation time (DT50) increased in both exercising and sedentary diabetics. FNDC5 was significantly higher in the exercising animals in soleus samples. Myonectin was significantly higher in the soleus muscle only in the DM + HIIT group. Current findings show that diabetic myopathy develops earlier in glycolytic-fast-twitch fibers(EDL) than in oxidative-slow-twitch fibers(soleus). Furthermore, HIIT application prevents atrophy in skeletal muscle, increases resistance to fatigue, and has an anti-inflammatory effect. The current study analyzes the myokine profile and skeletal muscle function under the effect of diabetes HIIT-type exercise. We also measured maximal exercise capacity and tailored the exercise program individually according to the result. Diabetic myopathy is an important complication of diabetes yet still, it is not understood completely. Our results show that HIIT-type training would be beneficial in diabetic myopathy but further investigation is needed to understand the whole molecular mechanism.


Age Differences in Expression of Generalized and Social Anxiety Among Youth with Autism Spectrum Disorder.
This study examined differences in generalized and social anxiety symptoms across two age groups of children with autism spectrum disorder (ASD) while accounting for overall anxiety level, gender, and intellectual functioning. Older children (12-18 years) expressed more overall and social anxiety symptoms than younger children (6-11 years), and social anxiety symptoms were predominant in the older group. Younger children expressed more generalized anxiety symptoms than the older youth, and there was a trend for generalized anxiety symptoms to be more dominant in the younger group. Findings are consistent with theory of differential expression of specific anxiety symptoms across different ages seen with typically developing children, yet social evaluative concerns may be even stronger for adolescents with ASD.


Responses to moisture stress in male and female plants of Rumex acetosella L. (Polygonaceae).
Male and female plants of Rumex acetosella were grown on a moisture gradient to measure possible differences in the drought tolerance of the sexes. The growth of both sexes declined under water stress but males were significantly more drought tolerant. This could not be explained by greater water use efficiency in the male plants; measured rates of both photosynthesis and leaf conductance did not differ significantly between the sexes. Multiple discriminant analysis showed that the sexes differed at all moisture regimes in their overall patterns of biomass allocation. Males had proportionately greater investment in root and leaf tissue which could explain their growth advantage over females under water stress. Despite essentially equal water use efficiencies, on a per plant basis males, with more leaf and root biomass, could fix more carbon and more rapidly exploit the local water resource than females. Thus the pattern of biomass allocation rather than intrinsic physiological differences appears to explain the greater drought tolerance of male plants of Rumex acetosella.


Human alpha 2-macroglobulin: a major serum factor cytotoxic for tumor cells.
Human alpha 2-macroglobulin (alpha 2M) was established here as a major serum factor which inhibits the DNA synthesis of a mouse ovarian tumor cell line in culture. This inhibitory activity was species non-specific, dose-dependent and unaffected by serum concentrations in culture. alpha 2 M was cytotoxic to both murine and human tumor cell lines in culture, as determined by 2 different viability staining techniques, morphological observation and long-term in vitro culture. This report implicates alpha 2 M or an alpha 2 M-associated substance as a major cytotoxic serum factor that may be involved in endogenous cancer control processes in mammalian species.


Combined administration in a single injection of a feline multivalent modified live vaccine against FHV, FCV, and FPLV together with a recombinant FeLV vaccine is both safe and efficacious for all four major feline viral pathogens.
Nobivac Tricat, a lyophilised trivalent modified live attenuated vaccine is routinely used to protect cats against three commonly diagnosed feline viral pathogens namely herpesvirus, calicivirus and panleukopenia virus. The recognition of feline leukaemia virus (FeLV) as an important viral pathogen has prompted the development of an efficacious liquid recombinant subunit FeLV vaccine (p45 envelope protein). Lyophilised Tricat vaccine was dissolved in the liquid FeLV vaccine and no detectable deleterious effect on the titre of any of the live virus components was observed after 2h incubation. In vivo studies where the vaccines were mixed in the same syringe prior to inoculation showed no alteration to the safety profile assessed by repeat and overdose studies. Serological comparisons of the modified live viral antibody titres showed no evidence of reduced responses following administration of the mixed products. Challenge studies using pathogenic herpesvirus and FeLV revealed no difference in the degree of clinical protection. This paper shows that neither safety nor efficacy is adversely affected as a result of mixing the two vaccines.


Catecholamine contents of rabbit gingiva and dental pulp.
The contents of endogenous noradrenaline (NA) in rabbit gingiva and dental pulp were approximately 15-fold greater than either adrenaline (A) or dopamine (DA). Whereas catecholamine contents of maxillary incisor pulps were similar to those in mandibular incisor pulps, variations existed between gingiva excised from different regions. Both reserpine pretreatment and chronic sympathetic denervation greatly decreased the NA contents. These findings support the view that NA is the sympathetic neurotransmitter in dental pulp and gingiva.


Small-scale batch crystallization of proteins revisited: an underutilized way to grow large protein crystals.
Growth of high-quality crystals is a major obstacle in many structural investigations. In recent years, the techniques for screening crystals have improved dramatically, whereas the methods for obtaining large crystals have progressed more slowly. This is an important issue since, although many structures can be solved from small crystals with synchrotron radiation, it is far easier to solve and refine structures when strong data is recorded from large crystals. In an effort to improve the size of crystals, a strategy for a small-scale batch method has been developed that in many cases yields far larger crystals than attainable by vapor diffusion.


Matchmaker of Marriage between a Li Metal Anode and NASICON-Structured Solid-State Electrolyte: Plastic Crystal Electrolyte and Three-Dimensional Host Structure.
The marriage between a Li metal anode and the solid-state electrolyte is expected to limit the safety risk of secondary batteries. However, dendrites and interfacial stability hinder the combination of Li metal anode and solid-state electrolyte. Herein, a plastic crystal electrolyte (PCE) and three-dimensional (3D) host structure played the role of a matchmaker in combining the solid-state electrolyte and Li metal anode. Succinonitrile cooperated with Li salt and Li6.4La3Zr1.4Ta0.6O12 nanosize powder and built a PCE interphase, which enhanced the interfacial stability between Li1.5Al0.5Ge1.5(PO4)3 and Li metal anode. To protect the soft PCE from the dendrite penetration, commercially sold Super P, carbon nanotube, KS6, and Ketjen black were co-heated with the melted Li metal. However, only KS6 built a 3D host in Li metal successfully because of its high graphitization and layered structure. Benefitting from the matchmakers, the solid-state batteries exhibited enhanced cycling stability.


Functional characterization of human T cells immortalized by oncogene transfection.
We have succeeded in immortalizing human lymphocytes derived from the peripheral blood of a healthy donor and of an atopic patient, and from the lymph node of a cancer patient by oncogene transfection (Alam et al., 1996). All immortalized human lymphocytes were shown to be CD3+ and CD19-, indicating that these immortalized human lymphocytes were all T cells. We established 317, 154 and 692 individual immortalized human T cell lines derived from the healthy donor, the atopic patient and the cancer patient, respectively. The ratios of CD4+ and CD8+ subpopulations within the set containing immortalized T cells derived from the healthy donor were shown to be varied depending on the combinations of transfected oncogenes used. However, CD8+ cells were found to be the dominant subpopulation of immortalized T cells derived from the atopic patient and the cancer patient. These immortalized T cells showed different proliferative responses in the presence of exogenous human IL-2 depending on their origin, and was consistent with the surface expression of the IL-2 receptor. Furthermore, the cytokine secretion patterns of these immortalized T cells stimulated with mitogen were investigated. The results showed that the immortalized T cells from the healthy donor is able to secrete various kinds of cytokines such as IL-2, IL-10, β-IFN and GM-CSF. However, immortalized T cells from the cancer patient was shown to only secrete IL-2 and GM-CSF. These results suggest that depending on the origin, the immortalized T cells came from different subsets or from cells in different activated states. Mixed lymphocytes reactions demonstrated that these immortalized T cells are able to proliferate in the presence of allogenic or xenogenic stimulator cells, suggesting that they maintain the ability to recognize specific antigens on the stimulator cells and can proliferate even after the immortalization. Furthermore, immortalized T cells derived from the healthy donor and the cancer patient strongly responded to K562 cells, suggesting that MHC-nonrestricted killer T cells were also immortalized.Abbreviations IL-2R - interleukin 2 receptor; MLR - mixed lymphocyte reaction.


Boron perturbed click reactions prompt aromatic C-H activations.
The reaction of boron alkynes and boron azides leads to rare N3BC heterocycles resulting from aromatic C-H activation of benzene and toluene. While subsequent treatment with PMe3 gave the P-B adduct with the exocyclic boron, reaction with PtBu3 effected deprotonation of the heterocycle to give the corresponding phosphonium salt.


Midazolam reduces the selective activation of the rhinal cortex by contextual fear stimuli.
Independent brain circuits appear to underlie different forms of conditioned fear, depending on the type of conditioning used, such as a context or explicit cue paired with footshocks. Several clinical reports have associated damage to the medial temporal lobe (MTL) with retrograde amnesia. Although a number of studies have elucidated the neural circuits underlying conditioned fear, the involvement of MTL components in the aversive conditioning paradigm is still unclear. To address this issue, we assessed freezing responses and Fos protein expression in subregions of the rhinal cortex and ventral hippocampus of rats following exposure to a context, light or tone previously paired with footshock (Experiment 1). A comparable degree of freezing was observed in the three types of conditioned fear, but with distinct patterns of Fos distribution. The groups exposed to cued fear conditioning did not show changes in Fos expression, whereas the group subjected to contextual fear conditioning showed selective activation of the ectorhinal (Ect), perirhinal (Per), and entorhinal (Ent) cortices, with no changes in the ventral hippocampus. We then examined the effects of the benzodiazepine midazolam injected bilaterally into these three rhinal subregions in the expression of contextual fear conditioning (Experiment 2). Midazolam administration into the Ect, Per, and Ent reduced freezing responses. These findings suggest that contextual and explicit stimuli endowed with aversive properties through conditioning recruit distinct brain areas, and the rhinal cortex appears to be critical for storing context-, but not explicit cue-footshock, associations.


The role of circulating miRNAs in multiple myeloma.
Multiple myeloma (MM) is a common malignant hematological disease. Dysregulation of microRNAs (miRNAs) in MM cells and bone marrow microenviroment has important impacts on the initiation and progression of MM and drug resistance in MM cells. Recently, it was reported that MM patient serum and plasma contained sufficiently stable miRNA signatures, and circulating miRNAs could be identified and measured accurately from body fluid. Compared to conventional diagnostic parameters, the circulating miRNA profile is appropriate for the diagnosis of MM and estimates patient progression and therapeutic outcome with higher specificity and sensitivity. In this review, we mainly focus on the potential of circulating miRNAs as diagnostic, prognostic, and predictive biomarkers for MM and summarize the general strategies and methodologies for identification and measurement of circulating miRNAs in various cancers. Furthermore, we discuss the correlation between circulating miRNAs and the cytogenetic abnormalities and biochemical parameters assessed in multiple myeloma.


Peripheral enhancement in computerized cranial tomography: a non-specific finding.
Peripheral enhancement of intracranial lesions on CT examination is still being considered by some radiologists as specific for an abscess or a cystic tumor. A review of the last 4,000 scans at this institution has demonstrated that it is neither specific nor, in many cases, of much help in the differential diagnosis of the lesions. Examples of the various types of lesions that can demonstrate peripheral enhancement are shown. It is suggested that many if not all types of pathology would demonstrate this effect if the cranial CT scans were done at a fortuitous time or sequentially. Some differential diagnostic suggestions are also made.


From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials.
Usually, a clinical trial in rheumatoid arthritis and psoriatic arthritis aiming to demonstrate that a new antirheumatic drug treatment can inhibit progression of structural damage has a 'superiority design': The new treatment is compared to placebo or to another active treatment. Currently, many new drug treatments have shown to be able to completely suppress progression (progression rates close to zero). For largely unknown reasons, during the last 10 years, radiographic progression rates in clinical trials have gradually decreased, so that progression rates in the comparator groups are often too low to demonstrate meaningful inhibition, and thus superiority of the new treatment. We here propose an alternative framework to demonstrate that new treatments have the ability to 'preserve structural integrity' rather than to 'inhibit radiographic progression'. Anno 2013, preserving structural integrity is conceptually more realistic than inhibiting radiographic progression.


Proliferation of Schwann cells in a developing feline lumbar ventral spinal root.
Schwann cell proliferation in the L6 ventral spinal root of cat fetuses and young kittens was studied by light microscopical autoradiography and electron microscopy. The proliferative activity reached a maximum 35 days after mating. This is about one week before the immature alpha-axons begin to myelinate and about one month before birth (63 days after mating) when the myelination of the immature gamma-axons starts. The proliferative activity was already quite low 45 days after mating and ceased completely after birth. Calculations based on the observed number of Schwann cell nuclei per 100 axons showed that the number of Schwann cells already present 45 days after mating was equal to or even a little higher than the observed adult number. Necrotic nucleated Schwann or endoneurial cells were not observed. I conclude that Schwann cell proliferation in the L6 ventral spinal root is already nearly finished when the first immature alpha-axons begin their myelination and that myelination of the immature gamma-axons begins without a preceding increase in Schwann cell proliferative activity.


Model of hospital's inflow.
To be accepted as an inpatient in the Geneva Hospital one must proceed through a registration post. Data collecting sessions were set up there to study its working. Since many random components enter the registration procedure a stochastic queuing process is the appropriate model. The process main characteristics are determined by rather involved statistical and mathematical means. The values reckoned for the most relevant parameters (to both medical staff and general public) are found quite plausible.


The reassuring role of music associated with the personality traits of children during dental care: a randomized clinical trial.
The objective of this study was to analyze the reassuring role of music associated with the personality traits of children during dental care. The study involved a randomized crossover clinical trial with 34 children, aged from 4 to 6 years, who exhibited two carious lesions on the occlusal surfaces of the molars. The children were divided into two groups: (G1) first tooth restoration intervention session with music, second session without music; and (G2) first tooth restoration intervention session without music, second session with music. The first consultation was to perform a clinical examination, and the second and third to perform modified Atraumatic Restorative Treatment (mART). Symphony No. 40 by Mozart was played via headphones. Pulse rate (PR) was measured using a pulse oximeter. The Brazilian version of the Eysenck Personality Questionnaire-Junior (EPQ-J) was used to measure the children's personality. For statistical analysis, descriptive, Chi-square, and Wilcoxon tests were carried out. The G1 group exhibited a lower PR at the time of the intervention during the second consultation compared to the third consultation (p = 0.012). The G2 group exhibited a lower PR at the time of the intervention during the third consultation compared to the first consultation (p = 0.002). The majority of the children with a low level of extraversion presented with higher PR (p = 0.005). Music could reduce the PR among children during dental intervention. Children with low extraversion showed a tendency towards a higher PR without music during dental care.


Alterations in the mucosa-associated bacterial composition in Crohn's disease: a pilot study.
Changes in the intestinal bacterial composition seem to play a major role in the pathogenesis and in the clinical course of inflammatory bowel diseases (IBD), which consist of Crohn's disease (CD), and ulcerative colitis (UC). Mutations in the NOD2 gene are the most important genetic risk factors for the development of CD. In this study, the association between mucosal biopsies and the mucosa-associated bacterial composition from CD and UC patients regarding their genetic risk factors (mutations in the NOD2 gene), their endoscopic activity, and their medical therapy (TNF-α blocking therapy) was examined. Seventy biopsies from routine colonoscopies from 33 IBD patients (26 CD and 7 UC) were obtained. Disease activity and clinical characteristics were assessed. Seven different bacterial strains (Bacteroides fragilis, Escherichia coli, Prevotella melaninogenica, Clostridium coccoides, Clostridium difficile, Bifidobacterium bifidum, and Faecalibacterium prausnitzii) were quantified using real-time PCR. NOD2 genotyping from patients with CD was performed. Five of the 24 patients were positive for at least one mutation in the NOD2 gene. The bacterial composition was different in CD compared to UC, in macroscopic healthy compared to macroscopic inflamed biopsies, in NOD2 mutated compared to NOD2 wildtype patients, and in patients receiving TNF-α blocking therapy compared to patients without this treatment. This study further characterizes the mucosa-associated bacteria in IBD patients. Different clinical situations lead to an altered mucosa-associated bacterial composition. The analyzed bacteria could be promising targets for cost-effective surveillance or therapies in IBD patients.


The noncatalytic regions of the tyrosine kinase Tnk1 are important for activity and substrate specificity.
Human Tnk1 (thirty-eight negative kinase 1) is a member of the Ack family of nonreceptor tyrosine kinases. Tnk1 contains a sterile alpha motif, a tyrosine kinase catalytic domain, an SH3 (Src homology 3) domain, and a large C-terminal region that contains a ubiquitin association domain. However, specific physiological roles for Tnk1 have not been characterized in depth. Here, we expressed and purified Tnk1 from Sf9 insect cells and established an in vitro assay system using a peptide substrate derived from the Wiskott-Aldrich Syndrome Protein (WASP). By Tnk1 expression in mammalian cells, we found that the N-terminal SAM domain is important for self-association and kinase activity. We also studied a fusion protein, originally discovered in a Hodgkin's Lymphoma cell line, that contains an unrelated sequence from the C17ORF61 gene fused to the C-terminus of Tnk1. Cells expressing the fusion protein showed increased tyrosine phosphorylation of cellular substrates relative to cells expressing WT Tnk1. A truncated Tnk1 construct (residues 1-465) also showed enhanced phosphorylation, indicating that the C17ORF61 sequence was dispensable for the effect. Additionally, in vitro kinase assays with the WASP peptide substrate showed no increase in intrinsic Tnk1 activity in C-terminally truncated constructs, suggesting that the truncations did not simply remove an autoinhibitory element. Fluorescence microscopy experiments demonstrated that the C-terminus of Tnk1 plays an important role in the subcellular localization of the kinase. Taken together, our data suggest that the noncatalytic regions of Tnk1 play important roles in governing activity and substrate phosphorylation.


Notes on the early development of pediatric surgery in the United States.
This lecture addresses the leadership roles in American surgery.


Time distortion associated with smartphone addiction: Identifying smartphone addiction via a mobile application (App).
Global smartphone penetration has brought about unprecedented addictive behaviors. We report a proposed diagnostic criteria and the designing of a mobile application (App) to identify smartphone addiction. We used a novel empirical mode decomposition (EMD) to delineate the trend in smartphone use over one month. The daily use count and the trend of this frequency are associated with smartphone addiction. We quantify excessive use by daily use duration and frequency, as well as the relationship between the tolerance symptoms and the trend for the median duration of a use epoch. The psychiatrists' assisted self-reporting use time is significant lower than and the recorded total smartphone use time via the App and the degree of underestimation was positively correlated with actual smartphone use. Our study suggests the identification of smartphone addiction by diagnostic interview and via the App-generated parameters with EMD analysis.


[Method of determination of hydrogen and chloride ions in the air].
The turbidimetric method of determination of hydrogen chloride and chloride ions has been elaborated. The determination range of the method is 20--100 microgram Cl-in solution. The precision error is +/- 3.28%.


Analysis of planar acintigraphic images using the Li-Ma technique.
A statistics-based approach to comparison of planar scintigraphic images is introduced to provide additional information to subtraction method. The proposed procedure leads to parametric images with better noise properties allowing subsequent statistical analysis. An example of an application of the technique is given using parathyroid scintigrams. The presented technique is not intended to replace the image subtraction method but offers a tool that may help during a diagnosis-making process.


Feature Aggregation and Refinement Network for 2D Anatomical Landmark Detection.
Localization of anatomical landmarks is essential for clinical diagnosis, treatment planning, and research. This paper proposes a novel deep network named feature aggregation and refinement network (FARNet) for automatically detecting anatomical landmarks. FARNet employs an encoder-decoder structure architecture. To alleviate the problem of limited training data in the medical domain, we adopt a backbone network pre-trained on natural images as the encoder. The decoder includes a multi-scale feature aggregation module for multi-scale feature fusion and a feature refinement module for high-resolution heatmap regression. Coarse-to-fine supervisions are applied to the two modules to facilitate end-to-end training. We further propose a novel loss function named Exponential Weighted Center loss for accurate heatmap regression, which focuses on the losses from the pixels near landmarks and suppresses the ones from far away. We evaluate FARNet on three publicly available anatomical landmark detection datasets, including cephalometric, hand, and spine radiographs. Our network achieves state-of-the-art performances on all three datasets. Code is available at https://github.com/JuvenileInWind/FARNet .


Potential treatment of aged cow manure using spare capacity in anaerobic digesters treating a mixture of food waste and pig manure.
With the increasing production of cow manure (CM) and the continuing decrease in the demand for manure compost, CM management has become an urgent and challenging task in Korea. In most cattle farms in Korea, CM mixed with bedding materials is left in pens exposed to the open air for several months before treatment, which makes CM an unsuitable feedstock for anaerobic digestion. This study examined the co-digestion of aged CM with a mixture of food waste and pig manure as the base substrate to assess the possibility of treating and valorizing CM using spare capacity in existing anaerobic digesters dealing with other wastes. The duplicate digesters initially fed with the base substrate were subjected to the addition of increasing amounts of CM (3-10% in the feed, w/v) over nine months. Co-feeding CM up to 5% in the feed (w/v) did not compromise the methanogenic degradation of the substrates, but adding more CM led to a significant performance deterioration likely related to the buildup of inhibitory free ammonia and H2S. Adding CM substantially influenced the digester microbial communities, especially methanogenic communities, and induced a dominance shift from aceticlastic Methanothrix to hydrogenotrophic methanogens as the CM fraction increased. The overall results suggest that the CM fraction should not exceed 5% in the feed (w/v) for its stable treatment with the base substrate in the experimental digesters. Although further studies are needed, anaerobic treatment using spare capacity in existing digesters can be a useful strategy for the management of aged CM.


Photosynthesis in dynamic light: systems biology of unconventional chlorophyll fluorescence transients in Synechocystis sp. PCC 6803.
Photosynthetic organisms live in a dynamic environment where light typically fluctuates around a mean level that is slowly drifting during the solar day. We show that the far-from-equilibrium photosynthesis occurring in a rapidly fluctuating light differs vastly from the stationary-flux photosynthesis attained in a constant or slowly drifting light. Photosynthetic organisms in a static or slowly drifting light can be characterized by a steady-state quantum yield of chlorophyll fluorescence emission F' that is changing linearly with small and slow variations of the incident irradiance I+DeltaI(t): F'(I+DeltaI(t)) approximately Fmean '(dF)/(dI).DeltaI(t). In Synechocystis sp. PCC 6803, the linear approximation holds for an extended interval covering largely the static irradiance range experienced by the cyanobacteria in nature. The photosynthetic dynamism and, consequently, the dynamism of the chlorophyll fluorescence emission change dramatically when exposing the organism to a fluctuating irradiance. Harmonically-modulated irradiance I+DeltaI . sin(2pit/T), T approximately 1-25 s induces perpetual, far-from-equilibrium forced oscillations that are strongly non-linear, exhibiting significant hysteresis with multiple fluorescence levels corresponding to a single instantaneous level of the incident irradiance. We propose that, in nature, the far-from-equilibrium dynamic phenomena represent a significant correction to the steady-state photosynthetic activity that is typically investigated in laboratory. Analysis of the forced oscillations by the tools of systems biology suggests that the dynamism of photosynthesis observed in fluctuating light can be explained by a delayed action of regulatory agents.


Early and midterm outcomes after off pump coronary artery bypass surgery.
There has been debate whether off pump coronary artery bypass surgery (OPCAB) has results comparable to conventional on pump bypass surgery. This has led to the low uptake of OPCAB in the West. In India, OPCAB is the default mode of coronary revascularization. However, there is scarce data on mid-term outcomes of OPCAB in our patients. This study aims to evaluate both short and mid-term mortality and analyze factors associated with mortality. This is a single center study of all consecutive patients undergoing isolated OPCAB from October 2014 to December 2019. Patient data was collected from hospital records and follow-up was from the hospital electronic medical records and telephone interviews. Mortality and factors contributing to survival were analyzed. Operative mortality was 2.3%. Mid-term mortality was 5.5%. Preoperative renal dysfunction, post-operative renal failure, use of the intra-aortic balloon pump (IABP), re-exploration for bleeding, postoperative stroke, ventilation > 24 h, and postoperative atrial fibrillation were associated with operative mortality. Factors associated with mid-term mortality were age > 62 years, postoperative renal failure, IABP usage, ventilation time > 24 h, and postoperative atrial fibrillation. The mean survival time was 2343.55 + / - 15.27 days and 6-year survival was 88.7%. OPCAB can safely be performed with satisfactory short and mid-term outcomes. Further corroborative studies from different regions of the country or a multi-center study will help to establish the suitability of the technique in Indian patients.


Mandibular condyle morphology among patients with mucopolysaccharidosis: An observational study of panoramic radiographs.
Mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by a wide spectrum of symptoms including progressive condylar resorption. The aim of this study was to quantify the severity of condylar involvement in MPS I individuals in comparison with a group of non-MPS individuals and to describe how condylar changes may vary among the different types of MPS. Fifty panoramic radiographs of MPS patients (13.4 ± 6.2 years) with MPS I (n = 14), MPS II (n = 2), MPS IV (n = 8) and MPS VI (n = 2) were compared with forty panoramic radiographs of non-MPS individuals. The severity of condylar resorption was evaluated using a qualitative score (grades 0-3) and using the ratio of condylar height to ramus height (CH: RH). All MPS I and VI individuals showed pronounced bilateral degenerative condylar resorption. In contrast, individuals with MPS II and IV exhibited heterogeneous findings. The quantification of condylar height to ramus height revealed that CH: RH was significantly decreased in MPS I as compared to that of non-MPS individuals (P < .001). In contrast, the CH: RH ratios of MPS II and IV showed great variability. Mucopolysaccharidoses subtypes differ with regard to the severity of condylar resorption.


Effects of isoproterenol and propranolol on pharmacologically induced depression of intraventricular conduction.
The cardiac adrenergic system is known to have practically no influence on conduction velocity in the ventricles under normal conditions. The effects of isoproterenol and propranolol were investigated on depression of intraventricular conduction induced by a class IC antiarrhythmic drug, cibenzoline, in anaesthetized, closed-chest dogs. In addition to electrocardiogram for measurement of QRS duration in sinus rhythm, conduction time was measured in the ventricular contractile tissue between an electrode advanced to the apex and a pacing electrode near the base, at 400- and 200-ms pacing periods. Effective refractory period (ERP) was measured concurrently according to the extrastimulus method. After intraventricular conduction had been slowed down by cibenzoline IV administered (loading dose of 3 mg/kg plus infusion of 0.2 mg/kg/min over 15 min), isoproterenol was infused or propranolol injected by the intravenous route also (0.5 mn/micrograms/kg/min over 5 min and 0.4 mg/kg, respectively). When conduction time has been raised by 75/150% (depending on the pacing rate), isoproterenol appears to attenuate and propranolol to aggravate substantially the impairment of conduction, whereas the reduction undergone by ERP does not differ from usual. Thus, reentrant arrhythmias might be prevented by isoproterenol and triggered by propranolol. Intraventricular conduction, when depressed, therefore, is sensitive to adrenergic drugs, probably because of the enhanced influence of polarization of the fibres in the presence of a sodium conductance impairment.


Establishment of rat-mouse T cell hybridomas that constitutively produce a soluble factor that is needed for the generation of cytotoxic cells: biochemical and functional characterization.
Spleen cells from Lewis rats were cultured with 4 micrograms/ml Con A. These cells were then fused with BW 5147 mouse T lymphoma cells. Two hybrid clones (6B2-B8 and 6B2-E6) obtained by fusion formed CGF effectively. It was found that hybrid cells can be boosted to produce higher levels of CGF upon stimulation with Con A. 6B2-B8 express rat T cell markers. CGF formed by 6B2-B8 had a m.w. of 23,000 and 40,000. CGF was eluted from a Mono Q anion-exchange column with an FPLC system at 0.4 to 0.6 M NaCl as a major peak and at 0.8 M NaCl as a minor peak. CGF was eluted as three peaks with pH 4.1, 4.8, and 5.2 from a Mono P chromatofocusing column. CGF from 6B2-B8 does not contain IL-1, IL-2, IL-3, or CSF.


Identification of potential blood biomarkers for early diagnosis of Alzheimer's disease through immune landscape analysis.
Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer's disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37, in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.


[Mobile soundproof booth for audiometric industrial testing].
The authors modified a caravan for the purpose of audiometric testing in the neighbourhood of industrial workplaces. The sound insulation of the caravan increased due to the use of double glasses in the windows, special tightening of the doors and covering the walls with sound absorbing material. The gained insluation enables the testing of the threshold of hearing in a surrounding where the ambient noise does not exceed foolowing octave-band noise levels: 49 dB--125 Hz, 59 dB--250 Hz, 57 dB--500 Hz, 74 dB--1000 Hz, 81 dB--2000 Hz, 91 dB--4000 Hz, and 100 dB--8000 Hz.


Fatty alcohol oxidase 3 (FAO3) and FAO4b connect the alcohol- and alkane-forming pathways in Arabidopsis stem wax biosynthesis.
The alcohol- and alkane-forming pathways in cuticular wax biosynthesis are well characterized in Arabidopsis. However, potential interactions between the two pathways remain unclear. Here, we reveal that mutation of CER4, the key gene in the alcohol-forming pathway, also led to a deficiency in the alkane-forming pathway in distal stems. To trace the connection between the two pathways, we characterized two homologs of fatty alcohol oxidase (FAO), FAO3 and FAO4b, which were highly expressed in distal stems and localized to the endoplasmic reticulum. The amounts of waxes from the alkane-forming pathway were significantly decreased in stems of fao4b and much lower in fao3 fao4b plants, indicative of an overlapping function for the two proteins in wax synthesis. Additionally, overexpression of FAO3 and FAO4b in Arabidopsis resulted in a dramatic reduction of primary alcohols and significant increases of aldehydes and related waxes. Moreover, expressing FAO3 or FAO4b led to significantly decreased amounts of C18-C26 alcohols in yeast co-expressing CER4 and FAR1. Collectively, these findings demonstrate that FAO3 and FAO4b are functionally redundant in suppressing accumulation of primary alcohols and contributing to aldehyde production, which provides a missing and long-sought-after link between these two pathways in wax biosynthesis.