A rare anastomosis between the root of common hepatic artery and proper hepatic artery: implications for pancreaticoduodenectomy.
Hepatic artery anomalies are often observed, and the variations are wide-ranging. We herein report a case of pancreatic cancer involving the common hepatic artery (CHA) that was successfully treated with pancreaticoduodenectomy (PD) without arterial reconstruction, thanks to anastomosis between the root of CHA and proper hepatic artery (PHA), which is a very rare anastomotic site. A 78-year-old woman was referred to our department for the examination of a tumor in the pancreatic head. Contrast-enhanced computed tomography (CT) revealed a low-density tumor of 40 mm in diameter located in the pancreatic head. The involvement of the common hepatic artery (CHA), the root of the gastroduodenal artery (GDA), and portal vein was noted. Although such cases would usually require PD with arterial reconstruction of the CHA, it was thought that the hepatic arterial flow would be preserved by the anastomotic site between the root of the CHA and the PHA, even if the CHA was dissected without arterial reconstruction. PD with dissection of the CHA and PHA was safely completed without arterial reconstruction, and sufficient hepatic arterial flow was preserved through the anastomotic site between the CHA and PHA. We presented an extremely rare case of an anastomosis between the CHA and PHA in a patient with pancreatic cancer involving the CHA. Thanks to this anastomosis, surgical resection was successfully performed with sufficient hepatic arterial flow without arterial reconstruction.


A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation.
Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14-3-3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14-3-3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.


Tetra-hedral zinc in tetra-kis-(1-methyl-1H-imidazole-κN)zinc bis-(tetra-fluorido-borate).
In the title compound, [Zn(C(4)H(6)N(2))(4)](BF(4))(2), the Zn(II) ion is in a slightly distorted tetra-hedral coordination geometry, with Zn-N distances in the range 1.980 (2)-1.991 (2) Å. The tetra-hedral angles are in the range 104.93 (9)-118.81 (9)°.


The association between depression during perimenopause and progression of chronic conditions and multimorbidity: results from a Chinese prospective cohort.
The association between perimenopausal depression and many chronic conditions among women has been well-established. However, the role of depression during perimenopause in the progression of multiple chronic conditions (multimorbidity) remains poorly understood. A total of 1,216 community-dwelling women in their perimenopause period between 2010 and 2016 were enrolled in our analysis, and followed up for the progression of multimorbidity. Depression, as well as its severity, was evaluated by the Center for Epidemiologic Studies Depression 10-item scale (CES-D-10). Progression of multimorbidity was defined as the first report of two or more chronic conditions for participants without multimorbidity or the new report of one or more conditions for those with multimorbidity. Univariable and multivariable Cox proportional hazards model and the restricted cubic spline regression model were performed to assess the prospective association between perimenopausal depression and the progression of multimorbidity. A total of 480 (39.5%) women reported depression during perimenopause, and 529 (43.5%) women progressed to multimorbidity. After adjusting for socio-demographic and lifestyle factors, perimenopausal depression was independently associated with the progression of multimorbidity (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.13 to 1.60). Moreover, the severity of depression was positively and linearly associated with the progression of multimorbidity (P < 0.05). Our finding reveals a prospective association between perimenopausal depression and the progression of multimorbidity, indicating interventions targeting perimenopausal depression may reduce the burden of chronic diseases and multimorbidity in women's post-menopausal life.


Drought tolerance of selected bottle gourd [Lagenaria siceraria (Molina) Standl.] landraces assessed by leaf gas exchange and photosynthetic efficiency.
Successful cultivation of bottle gourd in arid and semi-arid areas of sub-Saharan Africa and globally requires the identification of drought tolerant parents for developing superior genotypes with increased drought resistance. The objective of this study was to determine the level of drought tolerance among genetically diverse South African bottle gourd landraces based on leaf gas exchange and photosynthetic efficiency and identify promising genotypes for breeding. The responses of 12 bottle gourd landraces grown in glasshouse under non-stressed (NS) and drought-stressed (DS) conditions were studied. A significant genotype x water regime interaction was observed for gs, T, A, A/Ci, IWUE, WUEins, Fm', Fv'/Fm', ФPSII, qP, qN, ETR, ETR/A and AES indicating variability in response among the studied bottle gourd landraces under NS and DS conditions. Principal component analysis identified three principal components (PC's) under drought stress condition contributing to 82.9% of total variation among leaf gas exchange and chlorophyll fluorescence parameters measured. PC1 explained 36% of total variation contributed by gs, T, F0', Fm', Fv'/Fm' and qN, while PC2 explained 28% of the variation and highly correlated with A, A/Ci, IWUE, WUEins ETR/A and AES. PC3 explained 14% of total variation contributed by ФPSII, qP and ETR. Principal biplot analysis allowed the identification of drought tolerant genotypes such as BG-27, BG-48, BG-58, BG-79, BG-70 and BG-78 which were grouped based on high gs, A, Fm'Fv'/Fm', qN, ETR/A and AES under DS condition. The study suggests that the identified physiological traits could be useful indicators in the selection of bottle gourd genotypes for increased drought tolerance.


The basal nucleus of Meynert revised: the nerve cell number decreases with age.
There is an age-dependent nerve cell loss in some areas of the brain, while other brain regions are stable with aging. The nucleus basalis of Meynert (NbM) is believed to be the source of cholinergic innervation of the cerebral cortex, and loss of its neurons seems to be followed by cognitive deficits. The normal age kinetics of the NbM are, therefore, of considerable importance. Sixteen autoptic human brains were examined, ages ranging from 35th week of gestation to 90 years of age. Blocks containing the NbM in its entirety were cut into 20-mu thick serial sections; every 25th section was cresyl-violet stained and underwent morphometric analysis. Nerve cell counts were slightly but significantly higher in the right hemisphere. The total number of neurons in the 9th decade was 23% below that in newborns. This decrease was statistically significant. We hypothesize that there is a threshold number of nerve cells below which cognitive failure is highly probable.


Latex bead-based artificial antigen-presenting cells induce tumor-specific CTL responses in the native T-cell repertoires and inhibit tumor growth.
Cell-free artificial antigen-presenting cells (aAPCs) were generated by coupling H-2K(b)/TRP2 tetramers together with anti-CD28 and anti-4-1BB antibodies onto cell-sized latex beads and injected intravenously and subcutaneously into naïve mice and antigen-primed mice (B6, H-2K(b)). Vigorous tumor antigen-specific CTL responses in the native T-cell repertoire in each mouse model were elicited as evaluated by measuring surface CD69 and CD25, intracellular IFN-γ, tetramer staining and cytolysis of melanoma cells. Furthermore, the aAPCs efficiently inhibited subcutaneous tumor growth and markedly delayed tumor progression in tumor-bearing mice. These data suggest that bead-based aAPCs represent a potential strategy for the active immunotherapy of cancers or persistent infections.


Angiographic observations 10 years following coronary laser balloon angioplasty.
A patient underwent laser balloon angioplasty (LBA) combined with local intracoronary heparin therapy for treatment of a high grade stenosis of the mid-portion of the left anterior descending (LAD) coronary artery. Sustained patency of the LBA-treated lesion and no new coronary stenoses were found in a 10-year angiographic follow-up study.


Evaluating Spatial, Cause-Specific and Seasonal Effects of Excess Mortality Associated with the COVID-19 Pandemic: The Case of Germany, 2020.
Evaluating mortality effects of the COVID-19 pandemic using all-cause mortality data for national populations is inevitably associated with the risk of masking important subnational differentials and hampering targeted health policies. This study aims at assessing simultaneously cause-specific, spatial and seasonal mortality effects attributable to the pandemic in Germany in 2020. Our analyses rely on official cause-of-death statistics consisting of 5.65 million individual death records reported for the German population during 2015-2020. We conduct differential mortality analyses by age, sex, cause, month and district (N = 400), using decomposition and standardisation methods, comparing each strata of the mortality level observed in 2020 with its expected value, as well as spatial regression to explore the association of excess mortality with pre-pandemic indicators. The spatial analyses of excess mortality reveal a very heterogenous pattern, even within federal states. The coastal areas in the north were least affected, while the south of eastern Germany experienced the highest levels. Excess mortality in the most affected districts, with standardised mortality ratios reaching up to 20%, is driven widely by older ages and deaths reported in December, particularly from COVID-19 but also from cardiovascular and mental/nervous diseases. Our results suggest that increased psychosocial stress influenced the outcome of excess mortality in the most affected areas during the second lockdown, thus hinting at possible adverse effects of strict policy measures. It is essential to accelerate the collection of detailed mortality data to provide policymakers earlier with relevant information in times of crisis.


The validity and utility of the positive presentation management and negative presentation management scales for the Revised NEO Personality Inventory.
Schinka, Kinder, and Kremer developed "validity" scales for the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae) to detect underreporting-the Positive Presentation Management (PPM) Scale and overreporting-the Negative Presentation Management (NPM) Scale. In this investigation, the clinical utility of these scales was examined using the established validity scales from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher et al.) as the referent. The sample was composed of 370 psychiatric patients who completed the NEO PI-R and the MMPI-2 as part of a routine evaluation. Results indicated that response distortion compromised the utility of the NEO PI-R domain scales. Moreover, the PPM and NPM scales and an NPM-PPM index significantly differentiated invalid under-and overreporting groups from a valid responding group. The PPM and NPM-PPM index were adequate in classifying under- and overreporters, respectively.


Sex and seasonal differences in the skin lipids of garter snakes.
1. This study investigates the skin lipids of male and female red-sided garter snakes both in the breeding season and in the non-breeding season. 2. Skin lipids were analyzed by means of thin-layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS). 3. Distinct differences exist in the skin lipids of males and females. 4. Samples obtained during the breeding season were qualitatively different from those acquired during the non-breeding season.


Mosquitocidal Activity of the Pale Brittle Stem Mushroom, Psathyrella candolleana (Agaricomycetes), against Three Vector Mosquitoes.
The aim of the present study was to screen for mosquito larvicidal activity of methanol extract of a wild mushroom Psathyrella candolleana against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi. Larvae and eggs were exposed to four different concentrations (62.5, 125, 250, and 500 ppm) and mortality was assessed 24 and 120 h after treatment. The LC50 and LC90 values of the extract were calculated. Methanol crude extract of P. candolleana showed good larvicidal activity against the third instar larvae of Cx. quinquefasciatus with LC50 and LC90 values of 166.713 and 259.17 ppm, respectively, after 24 h of exposure. No larvicidal activity was observed against Ae. aegypti and An. stephensi. The methanol extract of P. candolleana presented 88% ovicidal activity against Cx. quinquefasciatus at 500 ppm concentration 120 h after treatment. The active methanol extract was tested for toxicity against non-target organism and found was to have no toxicity. Histopathological studies of the treated larvae revealed serious damages to the midgut cells. The mushroom species was confirmed by 5.8S rRNA sequence and phylogenetic tree was constructed. These results suggest that the methanol extract of P. candolleana could be used in Cx. quinquefasciatus control programs as a new eco-friendly larvicide.


[Suture materials in surgery. Significance of basic substance and construction of surgical suture material for utilization in vivo].
The paper is a review of all available suture materials (absorbable and non-absorbable threads). The tissue reaction to the various sutures is discussed and histologically demonstrated, as well as possible complication. It is described which suture material is best suited for the various tissues and suturing techniques.


Computed tomogram prior to prostatectomy. Advantage in defining planning target volumes for postoperative adjuvant radiotherapy in patients with stage C prostate cancer?
To evaluate the influence of a preoperative computed tomogram (CT) on delineation of the planning target volume (PTV) for adjuvant radiation therapy of pT3 pN0 prostate cancer. PTVs of ten patients who had an additional preoperative CT examination were contoured by three independent radiation oncologists. PTV included the former prostatic bed and seminal vesicles with a safety margin. First PTVs were drawn without knowledge of the preoperative CTs and in a second attempt, this procedure was repeated with these CTs available for visual comparison. Changes in PTV dimensions for every patient were analyzed. In 93% of all PTVs there was a decision to increase the PTV after viewing the preoperative CT images. Mean PTV length increased from 7.3 to 8.4 cm and PTV volumes expanded 26% from 244 to 308 cm3. These differences were statistically significant for all three participating radiation oncologists. Planning target volume definition probably is a critical factor in adjuvant radiation therapy after radical prostatectomy. As there is a considerable incertainty in PTV definition a preoperative CT is helpful and therefore may have beneficial influence on results.


Methotrexate compared with placebo in lung cancer.
Two hundred thirty-nine patients with microscopically proven, inoperable bronchogenic carcinoma were allocated at random to receive twice weekly I.M. injections of either methotrexate at "high dose" of 0.06 mg/kg/dose or methotrexate at "low dose" of 0.2 mg/kg or visually indistinguishable placebo in the same volume of 0.1 ml/kg for four months. Twelve patients were invalidated for procedural reasons. Objective response (greater than or equal to 50% tumor regression) was dose-related with 21% of 48 patients with measurable disease on high -ose, 11% of 37 patients on low dose, and 6% of 32 patients on placebo. Corresponding response rates for epidermoid carcinoma were 35% of 23 patients, 9% of 11 patients, and 0 of 13 patients. Responders in the two treatment groups had a three to four fold increase of median survival (p less than .05). Non-responders on high and low dose methotrexate lived as long as patients on placebo. Leukopenic patients in all three treatment groups lived substantially longer than patients without leukopenia less than 4,500/mm3, irrespective of presence or absence of objective response. All three regimens were well tolerated. None of the patients had life-threatening toxicity. It is concluded that methotrexate at "high dose" is a potentially useful drug for temporary palliation of epidermoid carcinoma of the lung.


Molecular analysis of Neorickettsia risticii in adult aquatic insects in Pennsylvania, in horses infected by ingestion of insects, and isolated in cell culture.
Upon ingestion of adult aquatic insects, horses developed clinical signs of Potomac horse fever, and Neorickettsia risticii was isolated from the blood. 16S rRNA and 51-kDa antigen gene sequences from blood, isolates, and caddis flies fed to the horses were identical, proving oral transmission of N. risticii from caddis flies to horses.


Immunostaining images of vitreous transthyretin amyloid.
The purpose of this report is to present the diagnosis of familial amyloid polyneuropathy (FAP) based on vitreous biopsy and to demonstrate immunohistochemical images of transthyretin amyloid protein from vitreous samples. Retrospective case series. Retrospective review of clinical charts of patients with FAP who underwent vitrectomy for vitreous opacities and had immunostaining performed on the vitreous specimens. Three patients were selected for the study: 2 patients had already been diagnosed with FAP, and in 1 of the patients the vitreous sample served to establish the diagnosis of FAP. Pathology examination of the vitreous specimens confirmed the presence of amyloid with positive Congo red staining, and transthyretin was identified with immunolabeling techniques. In this report, we present immunohistochemical staining images of transthyretin deposits in the vitreous tissues. Transthyretin amyloidosis is usually confirmed with positive Congo red staining for amyloid identified by biopsy of peripheral nerves, salivary glands, or abdominal fat. Ocular manifestation of FAP typically appears years after the onset of the disease, and therefore eye tissue specimens usually are not subject to diagnostic biopsies or transthyretin identification. However, in patients with negative systemic tissue biopsies or early ocular involvement, transthyretin identification from samples obtained during vitrectomy may be useful in establishing the diagnosis, and we present the first immunohistochemical images of transthyretin amyloid of vitreous origin, which confirm the elevated deposition of the altered protein in ocular tissues in FAP.


Simultaneous ectopic pregnancy with intrauterine twin gestations after in vitro fertilization and embryo transfer.
A simultaneous ectopic tubal pregnancy with viable intrauterine twin gestations after IVF-ET of five fertilized eggs is presented. Pelvic ultrasound and serial quantitative hCG levels were not helpful in the diagnosis of the tubal pregnancy. The risk of multiple pregnancies and of concomitant intrauterine and extrauterine gestations increases with transfer of a greater number of embryos. Karyotype of the tubal pregnancy was normal (46,XX).


COVID-19 led to a decline in climate and environmental concern: evidence from UK panel data.
A key question in understanding barriers to climate and environmental policy is whether changing economic conditions weaken individuals' support for climate and environmental action. The large body of literature examining this question, however, has come to contradictory results, with studies measuring changes within individuals typically finding no such effect (e.g. Mildenberger and Leiserowitz, Env Polit 26(5):801-824 2017). In this letter, I use the outbreak of the COVID-19 pandemic to provide a stringent test of how economic shocks affect concern for climate change and the environment. Using panel data from the UK, that was collected just before (November 2019) and just after (June 2020) the outbreak of COVID-19, I find that the pandemic caused individuals to significantly deprioritise climate change and the environment in absolute terms, and the environment relative to the economy. These effects significantly vary depending upon individuals' employment trajectories, concerns about the cost of living, and ideological preferences, but do not significantly vary by individuals' prior vote choice. The findings suggest that in times of severe economic distress, unlike smaller economic downturns, climate change and the environment is deprioritised. This has implications for our understanding of the political feasibility of climate and environmental action, when individuals are faced with harsh economic conditions.


Functional differentiation of bmp2a and bmp2b genes in zebrafish.
Bone morphogenetic protein 2 plays an important role in the regulation of osteoblast proliferation and differentiation. Phylogenetic analysis showed that the bmp2 ortholog evolved from the same ancestral gene family in vertebrates and was duplicated in teleost, which were named bmp2a and bmp2b. The results of whole-mount in situ hybridization showed that the expression locations of bmp2a and bmp2b in zebrafish were different in different periods (24 hpf, 48 hpf, 72 hpf), which revealed potential functional differentiation between bmp2a and bmp2b. Phenotypic analysis showed that bmp2a mutations caused partial rib and vertebral deformities in zebrafish, while bmp2b-/- embryos died massively after 12 hpf due to abnormal somite formation. We further explored the expression pattern changes of genes (bmp2a, bmp2b, smad1, fgf4, runx2b, alp) related to skeletal development at different developmental stages (20 dpf, 60 dpf, 90 dpf) in wild-type and bmp2a-/- zebrafish. The results showed that the expression of runx2b in bmp2a-/- was significantly downregulated at three stages and the expression of other genes were significantly downregulated at 90 dpf compared with wild-type zebrafish. The study revealed functional differentiation of bmp2a and bmp2b in zebrafish embryonic and skeletal development.


Risk factors for the occurrence of chronic subdural haematomas after neurosurgical procedures.
Chronic subdural haematoma (CSDH) is a rare clinical complication of neurosurgical procedures. CSDH occurs sporadically after aneurysm clipping surgery and revascularisation surgery but the risk factors are not known. The present study reviewed 6613 consecutive neurosurgical procedures performed from January 1987 to July 2001, and identified 621 cases of CSDH. Fifty of these 621 cases had a past history of neurological disorders treated by neurosurgery. This study evaluated these 50 cases in order to elucidate the clinical and radiological characteristics of CSDH after neurosurgery and to investigate the etiology for identifying in the risk factors of CSDH as a postoperative complication. The incidence of CSDH after neurosurgery was 0.8% (50/6613). Twenty-seven of the 50 patients with a past history of neurosurgery had undergone aneurysm clipping surgery. The incidence after clipping surgery was 2.4%. Twelve of these 27 cases also underwent ventriculoperitoneal shunting. Three patients had postoperative CSDH after arachnoid cyst opening and/or shunting. The incidence was highest at 7.5%. Three patients had postoperative CSDH after brain tumour surgery. The incidence was low at 0.4%. However, the ventricular cerebrospinal fluid (CSF) space was opened during tumour removal in 2 of these 3 patients. Communication of the subarachnoid space to the subdural space is considered to be one of the causative factors and excessive CSF shunting facilitates formation of CSDH after neurological surgery. Repair of arachnoid tearing during neurosurgery and avoidance of excessive CSF shunting may reduce the risk of CSDH after neurosurgery.


POSH regulates assembly of the NMDAR/PSD-95/Shank complex and synaptic function.
Mutation or disruption of the Shank/ProSAP family of genes is a high risk factor for autism spectrum disorders (ASDs) and intellectual disability. N-methyl-D-aspartate glutamate receptor (NMDAR) dysfunction contributes to the development of autism-like behaviors. However, the molecular mechanism of Shank-mediated NMDAR modulation is still not clear. Here, we show that the scaffold protein plenty of SH3s (POSH) directly interacts with two other scaffold proteins, PSD95 and SHANK2/3, at excitatory synapses. In POSH conditional knockout (cKO) mice, normal synaptic clustering of NMDAR/PSD-95/SHANK complex is disrupted, accompanied by abnormal dendritic spine development and glutamatergic transmission in hippocampal neurons. POSH cKO mice display profound autism-like behaviors, including impairments in social interactions, social communication, repetitive behaviors, and deficits in learning and memory. Thus, POSH clusters at the postsynaptic density (PSD) with PSD-95 and SHANK2/3 and plays important roles in the signaling mechanisms of the NMDAR/PSD-95/POSH/SHANK complex as well as in spine development and brain function.


Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial.
We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.


Teleost isotocin receptor: structure, functional expression, mRNA distribution and phylogeny.
A cDNA encoding a receptor for the oxytocin-related peptide isotocin has been identified by screening a lambda gt11 library constructed from poly(A)+ RNA of the hypothalamic region of the teleost Catostomus commersoni. The probe used was obtained by PCR amplification of white sucker genomic DNA using degenerate primers based on conserved sequences in the mammalian receptor counterparts. The full-length cDNA specifies a polypeptide of 390 amino acid residues that displays the typical hydrophobicity profile of a seven transmembrane domain receptor and which exhibits greatest similarity to mammalian oxytocin receptors. Oocytes that express the cloned receptor respond to the application of isotocin by an induction of membrane chloride currents indicating that it is coupled to the inositol phosphate/calcium pathway. The isotocin receptor (ITR) can also be activated by vasotocin, mesotocin, oxytocin and Arg-vasopressin, although these have lower potencies than isotocin. ITR-encoding mRNA has been detected in brain, intestine, bladder, skeletal muscle, lateral line, gills and kidney indicating that this receptor may mediate a variety of physiological functions.


Comparative life cycle assessment of biochar-based lignocellulosic biohydrogen production: Sustainability analysis and strategy optimization.
Lignocellulose has been considered a potential feedstock for biohydrogen production. Recently, a novel closed-loop concept of biochar approach was developed for enhanced lignocellulosic biohydrogen production. This study therefore targets to analyze the environmental impacts of the three existing lignocellulosic biohydrogen production processes, and evaluate the environmental performance of applying biochar in each process at this early stage of technological development. The results suggest that biochar dosing shows better environmental performance for all impact categories, especially in the consolidate bioprocessing case. Electricity consumption was found to be the dominant cause of environmental impact over the life cycle, while by-products generation was also found to have an effect on the life-cycle impacts. Future research focuses on the biohydrogen production scale, the electricity generation scheme transition towards renewable and cleaner energetic systems, and recovery the by-products to the maximum extent, that will make lignocellulosic biohydrogen production more environmentally sustainable.


[Bamifylline. Conditions of its interference in the estimation of urinary 17-oxosteroids. Method of estimation using Zimmermann's reaction (author's transl)].
Bamifylline in therapeutic dosage may markedly disturb the determination of urinary 17-oxosteroids by Zimmermann's reaction, although the conditions of extraction and formation of this chromogenic substance are not always optimal for the metabolites of bamifylline. It is easy to suspect this interference as the chromogenic substance is produced as soon as the reagents are introduced, contrary to 17-oxosteroids, and it presents a more bluish colour. It is possible to separate completely both types of metabolite by washing the chloroform extracts with acid solutions which form salts with bamifylline and thus extract it. From these acid solutions, bamifylline may be recovered and estimated Zimmermann's reaction which is, for this purpose, modified.


Development of a Simultaneous Process of Surface Modification and Pd Nanoparticle Immobilization of a Polymer Substrate Using Radiation.
Pd nanoparticles were immobilized on an acrylonitrile-butadiene-styrene copolymer (ABS) substrate using ionizing radiation. The samples were prepared by irradiating plastic zipper packs containing ABS substrates and a Pd(NO3)2 aqueous solution with a high-energy electron beam (4.8 MeV). Pd nanoparticles immobilized on the ABS substrate surfaces were observed using scanning electron microscopy (SEM). The chemical state of Pd was found to be coordinated to a carbonyl group or a metallic state by X-ray photoelectron spectroscopy (XPS) measurements. The peel strength of the Cu film on the Pd/ABS samples was 0.7 N/mm or higher. This result shows that the prepared Pd/ABS samples have high adhesion strength, despite not undergoing treatments such as etching with chromic acid. This method is expected to immobilize metal nanoparticles, not only on plastic plates but also on various other materials.


Use of complex surgical procedures, patterns of tumor spread, and CA-125 predicts a risk of incomplete cytoreduction: a Korean Gynecologic Oncology Group study (KGOG-3022).
We aimed to develop a risk model to predict a risk of suboptimal cytoreduction in primary surgery of ovarian cancer. The clinical records and computed tomography (CT) data of 358 patients with stages II-IV epithelial ovarian cancer were reviewed. Tumor spread patterns identified by principal component analysis, CA-125, and a newly developed surgical skill index were integrated into a logistic model along with other variables. Internal validation was performed using bootstrapped re-sampling and calibration was assessed by goodness-of-fit test. Among the 358 patients, optimal cytoreduction, which was defined as no residual tumor, was achieved in 145 patients (40.5%). The surgical capacity of an individual institution was estimated by a surgical skill index, which was the frequency of complex surgeries in patients with advanced disease. In a multivariate model, two distinctive CT patterns of tumor spread (diffuse spread pattern and upper abdominal extension pattern), a surgical skill index, and serum CA-125 independently predicted a risk of suboptimal cytoreduction (P=0.006, P=0.013, P=0.031, and P=0.001, respectively). The model showed a C-statistic of .73 (95% confidence interval .67 to .79), which was significantly higher than tumor stage or ascites. Rigorous internal validation by bootstrapped re-sampling successfully confirmed the model. We identified two distinct tumor spread patterns of ovarian cancer, which can be integrated to improve a prediction model. Our model may be useful in patient referral or clinical trials for patient stratification.


Diverse expression of G-proteins in human sarcoma cell lines with different osteogenic potential: evidence for the involvement of Gi2 in cell proliferation.
Previously, it has been shown that the GTP-binding protein Gi2 is implicated in cellular growth [1,2] and differentiation [2,3]. In the present paper we demonstrate that this is also the case for human sarcoma cells. Six human osteosarcoma and three soft tissue sarcoma clonal cell lines were analyzed for levels of G-protein mRNA and polypeptide expression and effector enzyme (i.e., adenylate cyclase and phospholipase C) activation, which were all compared with individual growth rates. Unexpectedly, it appeared that the various strains exhibited large inter-individual variations in G-protein expression and signaling system activation. However, cell doubling time in the exponential phase of growth was inversely correlated (r = 0.71, P < 0.05) to immunodetected levels of intrinsic Gi2 alpha. Furthermore, cells stably transfected with a retroviral (pZipNeo(SV)X) construct containing the activating or inactivating Gi2 alpha-R179E or Gi2 alpha-G204A point mutations consistently reduced or enhanced individual cell strain doubling time, respectively. It appeared that other parameters investigated, including cellular alkaline phosphatase and monoclonal antibody epitope binding, both being markers of the proliferating osteoblast, did not correlate with cell doubling times.


Immunohistochemical expression of fibronectin and C5b-9 in the myocardium in cases of carbon monoxide poisoning.
Even if there is clinical evidence that carbon monoxide poisoning determines cardiac damage, the literature on the cardiac pathomorphology in such cases is scarce. We investigated the immunohistochemical expression of two known markers of fresh cardiac damage, fibronectin and the terminal complement complex C5b-9, in both cardiac ventricles in 26 cases of CO intoxication (study group, 15 ♀, 11 ♂, mean age 47 years, mean COHb level 65.9%, min. 51%, max. 85%) compared to a group of 23 cases of hanging (n = 23, 4♀, 19♂, mean age 42 years) as well as to 25 cases of myocardial infarction (n = 25, 13♀, 12♂, mean age 64 years). Fresh cardiac damage was detected with the antibody fibronectin in cases of CO poisoning and was prevalently localised at the right ventricle.


Toward "Inclusifying" the Underrepresented Minority in STEM Education Research.
Research in undergraduate STEM education often requires the collection of student demographic data to assess outcomes related to diversity, equity, and inclusion. Unfortunately, this collection of demographic data continues to be constrained by socially constructed categories of race and ethnicity, leading to problematic panethnic groupings such as "Asian" and "Latinx." Furthermore, these all-encompassing categories of race and ethnicity exasperate the problematic "underrepresented minority" (URM) label when only specific races and ethnicities are categorized as URMs. We have long seen calls for improved outcomes related to URMs in undergraduate STEM education, but seldom have we seen our own understanding of what it means to be a URM go beyond socially constructed categories of race and ethnicity. If we aim to not only improve diversity outcomes but also make undergraduate STEM education more equitable and inclusive, we must reevaluate our use of the term "URM" and its implications for demographic data collection. The classifications of "underrepresented" and "minority" are more nuanced than simple racial categories. Though there has been development of alternative terms to URM, each with their own affordances, the main goal of this article is not to advocate for one term over another but rather to spark a much-needed dialogue on how we can "inclusify" our collection of racial and ethnic demographic data, particularly through data disaggregation and expanding our definition of what it means to be both "underrepresented" and a "minority" within STEM.


Oxidative phosphorylation in cancer cells.
Evidence suggests that mitochondrial metabolism may play a key role in controlling cancer cells life and proliferation. Recent evidence also indicates how the altered contribution of these organelles to metabolism and the resistance of cancer mitochondria against apoptosis-associated permeabilization are closely related. The hallmarks of cancer growth, increased glycolysis and lactate production in tumours, have raised attention due to recent observations suggesting a wide spectrum of oxidative phosphorylation deficit and decreased availability of ATP associated with malignancies and tumour cell expansion. More specifically, alteration in signal transduction pathways directly affects mitochondrial proteins playing critical roles in controlling the membrane potential as UCP2 and components of both MPTP and oxphos complexes, or in controlling cells life and death as the Bcl-2 proteins family. Moreover, since mitochondrial bioenergetics and dynamics, are also involved in processes of cells life and death, proper regulation of these mitochondrial functions is crucial for tumours to grow. Therefore a better understanding of the key pathophysiological differences between mitochondria in cancer cells and in their non-cancer surrounding tissue is crucial to the finding of tools interfering with these peculiar tumour mitochondrial functions and will disclose novel approaches for the prevention and treatment of malignant diseases. Here, we review the peculiarity of tumour mitochondrial bioenergetics and the mode it is linked to the cell metabolism, providing a short overview of the evidence accumulated so far, but highlighting the more recent advances.


The influence of carbon risk on firm value: Evidence from the European Union Emission Trading Scheme.
This paper examines the impact of carbon risk induced through carbon price uncertainty in cap-and-trade policies on the value of covered firms. Specifically, the study explores the effects of policy adjustments made at the start of the third phase of the European Union Emission Trading Scheme (EU ETS), which aimed to address an oversupply of carbon allowances. Using a difference-in-difference approach, we find that the resulting increase in policy-induced carbon risk led to value discounts for firms with insufficient carbon allowances to offset their emissions, even when carbon prices themselves remained low. The findings highlight the importance of carbon risk exposure and the resulting carbon risk channel that influences firm value in a cap-and-trade scheme.


Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system.
Nanostuctured lipid carriers (NLC) based on mixture of solid lipids with spatially incompatible liquid lipids are a new type of lipid nanoparticles, which offer the advantage of improved drug loading capacity and release properties. In present study, stearic acid (SA) nanostuctured lipid carriers with various oleic acid (OA) content were successfully prepared by solvent diffusion method in an aqueous system. The size and surface morphology of nanoparticles were significantly influenced by OA content. As OA content increased up to 30wt%, the obtained particles showed pronounced smaller size and more regular morphology in spherical shape with smooth surface. Compared with solid lipid nanoparticles (SLN), NLC exhibited improved drug loading capacity, and the drug loading capacity increased with increasing OA content. These results were explained by differential scanning calorimetry (DSC) investigations. The addition of OA to nanoparticles formulation resulted in massive crystal order disturbance and less ordered matrix of NLC, and hence, increased the drug loading capacity. The drug in vitro release behavior from NLC displayed biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards, and the successful control of release rate at the initial stage can be achieved by controlling OA content.


Caspr2 antibodies in herpes simplex encephalitis: an extension of the spectrum of virus induced autoimmunity? - A case report.
Post herpes simplex virus (HSV) autoimmune encephalitis has been reported mainly in association with NMDA receptor antibodies, however, never with Caspr2 antibodies. We report an 82-year old female patient with encephalitis who presented with aphasia, left temporo-mesial hyperintense lesion on MRI, epileptiform discharges on spot electroencephalography, cerebrospinal fluid (CSF) lymphocytic pleocytosis and who showed positive HSV polymerase chain reaction in CSF as well as antibodies against contactin-associated protein-like 2 (Caspr2). This is the first report of a patient with encephalitis who tested positive for HSV as well as for Caspr2 antibodies.


Pediatric neurologic exam.
Although emergency nurses receive education and training in performing comprehensive and rapid assessment, pediatric patients may prove to be challenging due to dynamic growth, development and maturation. If the emergency department (ED) has limited exposure to pediatric patients, performing assessments and prompt interventions may be daunting. Neonates, infants and young children with illness or trauma have unique and often times subtle signs and symptoms that can change rapidly. Although the neurological exam for older children may be similar to that of an adult, there are significant differences based on maturation. The neurologic exam for neonates and infants provides the nurse with even more opportunity to be familiar with developmental differences. Therefore, it is important for ED nurses to become familiar with typical development and early recognition of neurologic insult.


The capsule sensitizes Streptococcus pneumoniae to alpha-defensins human neutrophil proteins 1 to 3.
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Its polysaccharide capsule causes resistance to phagocytosis and interferes with the innate immune system's ability to clear infections at an early stage. Nevertheless, we found that encapsulated pneumococci are sensitive to killing by a human neutrophil granule extract. We fractionated the extract by high-performance liquid chromatography and identified alpha-defensins by mass spectrometry as the proteins responsible for killing pneumococci. Analysis of sensitivity to the commercial alpha-defensins human neutrophil proteins 1 to 3 (HNP1-3) confirmed these findings. We analyzed the sensitivities of different pneumococcal strains to HNP1-3 and found that encapsulated strains are efficiently killed at physiological concentrations (7.5 microg/ml). Surprisingly, nonencapsulated, nonvirulent pneumococci were significantly less sensitive to alpha-defensins. The proposed mechanisms of alpha-defensin resistance in nonencapsulated pneumococci is surface charge modification, e.g., by introduction of positive charge by D-alanylation of surface-exposed lipoteichoic acids. These mechanisms are surmounted by the presence of the capsule, which we hypothesize is masking these charge modifications. Hence, alpha-defensins in the phagolysosome of neutrophils possibly contribute to intracellular killing after antibody-mediated opsonophagocytosis of encapsulated pneumococci.


Rapid screening method for the detection of antimicrobial substances.
Bioluminescence is phenomenon where living organisms produce light and this production is directly dependent on metabolic activity of the organism. Genes encoding enzymes, luciferases, responsible for light production can be cloned into indicator strains, thus allowing sensitive detection of antimicrobial activity. This study utilized bacterial luciferase genes cloned into Staphylococcus aureus, Escherichia coli and Salmonella enterica serovar Typhimurium indicator strains and showed that the detection of antimicrobial activity can be obtained already in 2 h without laborious plate counting and overnight incubation. Indicator strains used in the study harboured luxAB genes responsible of producing light as well as luxCDE genes for synthesis of long-chain fatty aldehyde as substrate for light production. As a consequence, no exogenous aldehyde addition was needed allowing stable light production. Furthermore, the method was used for the detection of antimicrobial activity from lactic acid bacteria after the effect of organic acids was eliminated.


Action comprehension in non-human primates: motor simulation or inferential reasoning?
Some argue that action comprehension is intimately connected with the observer's own motor capacities, whereas others argue that action comprehension depends on non-motor inferential mechanisms. We address this debate by reviewing comparative studies that license four conclusions: monkeys and apes extract the meaning of an action (i) by going beyond the surface properties of actions, attributing goals and intentions to the agent; (ii) by using environmental information to infer when actions are rational; (iii) by making predictions about an agent's goal, and the most probable action to obtain the goal given environmental constraints; (iv) in situations in which they are physiologically incapable of producing the actions. Motor theories are, thus, insufficient to account for primate action comprehension in the absence of inferential mechanisms.


HLA compatibility in couples with children suffering from acute leukemia or aplastic anemia.
The frequency of common HLA-A and -B antigens were determined in 30 couples having a child with acute leukemia (AL), 34 couples having a child with aplastic anemia (AA) and 58 random couples with healthy children. An increased frequency of couples sharing at least two common antigens was observed in parents of both AL and AA children.


Obscure stenosing aortitis and arteritis associated with perivascular lymphadenitis--combined angiographic and lymphographic evaluation.
A series of eleven cases of an obscure occlusive type of aortitis and arteritis is reported. These are characterised by chronic nonspecific perivascular lymphadenitis and fibrosis, constricting the lumen of the vessels. Subsequent spread of the inflammatory process produces irreversible changes in the vessel wall. Timely excision of the nodes, release of fibrous strands and decompression of the vessels may result in a permanent cure; The inflammatory process is nonspecific in nature. The etiology is obscure and is subject to speculation. Tuberculous inflammation of the lymph nodes appears to be unlikely while filarial lymphadenitis is probable. The disease is not a primary panarteritis as observed in Takayusu's disease or allergic vasculitis. Males are predominantly affected and present invariably with clinical signs and symptoms of peripheral vascular obliterative disease of the lower extremities.


The relationship of weight change to changes in blood pressure, serum uric acid, cholesterol and glucose in the treatment of hypertension.
In the Hypertension Detection and Follow-up Program (HDFP), elevated blood pressure (BP) was treated by rigorous, stepped care (SC) therapy among half the participants, while the other half were referred to usual sources of care (referred care, RC). There was no program to reduce weight, however, some participants changed weight voluntarily over the first 2 yr, providing an opportunity to examine the role of weight change in the development of diuretic-induced hyperuricemia, hyperglycemia and hypercholesterolemia. There was a stepwise progression from decreased glucose, uric acid and cholesterol concentrations, and BP associated with maximum weight loss to increased values with maximum weight gain. In SC, systolic BP declined by 22.4% among weight-losers and by 17.1% among weight-gainers; in RC, it was 14.4 and 8.1%, respectively. The pattern in diastolic blood pressure and weight change was similar but not as marked. These findings suggest the potential importance of weight loss in enhancing effectiveness of antihypertensive drug treatment and attenuating increases in glucose, uric acid, and cholesterol associated with diuretic treatment of hypertension. The weight change analyses are based on postrandomization observations and do not reflect experimental changes.


The Occurrence of Postconflict Skills in Captive Immature Chimpanzees (Pan troglodytes).
Conflict management strategies can reduce costs of aggressive competition in group-living animals. Postconflict behaviors such as reconciliation and third-party postconflict affiliation are widely accepted as social skills in primates and have been demonstrated in many species. Although immature primates possess a repertoire of species-specific behaviors, it is thought that they gradually develop appropriate social skills throughout prolonged juvenility to establish and maintain complex social relationships within their group. We examined the occurrence of postconflict skills in five immature chimpanzees (Pan troglodytes) over 15 mo, focusing on interactions that were not with the subject's mother. We observed reconciliation, with conciliatory tendencies comparable to adults, and provide the first evidence that captive immature chimpanzees commonly reconciled using social play. However, immatures were not more likely to reconcile valuable than nonvaluable relationships. We also observed third party postconflict affiliation although at a lower level than reported for adults. Our results provide evidence for postconflict skills in immature chimpanzees but the lack of higher conciliatory tendency with valuable partners and low occurrence of third-party affiliation indicates extended juvenility may be required refine these skills. Further work is needed to investigate whether these behaviors have the same function and effectiveness as those found in adults.


Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial.
Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics. In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 μg kg(-1) dose(-1) of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24 h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24 h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion. A total of 16 patients (median 8.7 years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p = 0.000) in patients that had granisetron at 40 μg/kg and PR interval was shortened in patients that had granisetron at 10 μg/kg dose (p = 0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24 h after granisetron infusion. As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 μg kg(-1) dose(-1) causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 μg kg(-1) dose(-1). However, our results should be supported by prospective randomized studies with larger samples of patient groups.


The putative acceleration of optic neuritis when combined with chronic hepatitis B.
To review the clinical features of optic neuritis (ON) combined with chronic hepatitis B (CHB) retrospectively. Clinical data were reviewed for hospitalized patients diagnosed with isolated ON combined with chronic hepatitis B (CHB-ON) in the Chinese People's Liberation Army General Hospital. The ON diagnosis was confirmed following the criteria of the Optic Neuritis Treatment Trial (ONTT) group. The diagnostic criteria for CHB was serological positivity for hepatitis B surface antigen (HBsAg) for more than 6 months. Other infectious conditions that might lead to bias were excluded. A total of 13 patients (6 female and 7 male, 23 involved eyes) diagnosed with CHB-ON were selected. A total of 12/13 patients presented as atypical ON: 10/13 of the patients exhibited simultaneous or early sequential bilateral eye involvement; 11/13 involved eyes in the acute phase presented with pronounced optic disc edema; and 11/13 patients exhibited corticosteroid resistant. A total of 12/23 affected eyes suffered severe vision loss (<20/200) at the end of the follow-up period, which averaged 13.7 (4-31) months. None of the patients progressed to multiple sclerosis (MS) or neuromyelitis optica (NMO). All blood samples were negative for serological aquaporin 4-antibody using the cell-based assay. CHB-ON usually presented as the atypical form. Chronic hepatitis B virus infection may lead to the tendency for ON exacerbation.


pH dependence of the composition and stability of Mn(III)-bicarbonate complexes and its implication for redox interaction of Mn(II) with photosystemII.
Dependence of the electrochemical potential of oxidation of Mn(II) to Mn(III) on logarithm of bicarbonate concentration at different pH is considered. Slope values of the dependence are equal to -60, -120 and -180mV/log C(HCO)₃ at pH6.20, 6.50 and 8.35 respectively, that corresponds to binding of one, two and three HCO(3)(-) ligands to Mn(III). Extrapolation of these dependences to log C(HCO)₃=0 shows that at pH6.20 complex [Mn(III)HCO(3)](2+) with E(0)=0.99V and K(st)=6.5×10(8)M(-1), at pH6.50 complex [Mn(III)(HCO(3))(2)](+) with E(0)=0.77V and K(st)=3.5×10(12)M(-2), and at pH8.35 complex [Mn(III)(HCO(3))(3)](0) with E(0)=0.67V and K(st)=1.73×10(14)M(-3) are formed. From the dependence of oxidation potential of Mn(II) to Mn(III) on pH at initial concentration of NaHCO(3) equal to 28mM the limits of pH stability of the complexes were determined: pH5.0-6.35 for [Mn(III)HCO(3)](2+), pH6.35-7.0 for [Mn(III)(HCO(3))(2)](+) and pH7.0-8.35 for [Mn(III)(HCO(3))(3)](0). The obtained data may be important for understanding the mechanism of stimulating action of HCO(3)(-) ions on photoinduced electron transfer from Mn(II) to reaction centres of photosystem2 or to reaction centres of anoxygenic photosynthetic bacteria.


Localized cytosolic alkalization and its functional impact in ciliary cells.
Using confocal microscopy we demonstrate that ciliary cells from airway epithelium maintain two qualitatively distinct cytosolic regions in terms of pH regulation. While the bulk of the cytosol is stringently buffered and is virtually insensitive to changes in extracellular pH (pHo), the values of cytosolic pH in the vicinity of the ciliary membrane is largely determined by pHo. Variation of pHo from 6.2 up to 8.5 failed to affect ciliary beat frequency (CBF). Application of NH(4)Cl induced profound localized alkalization near cilia, which did not depress ciliary activity, but resulted in strong and prolonged enhancement of CBF. Calmodulin and protein kinase A (PKA) functionality was essential for the alkalization-induced CBF enhancement. We suggest that the ability of airway epithelium to sustain unusually strong but localized cytosolic alkalization near cilia facilitates CBF enhancement through altering the binding constants of Ca2+ to calmodulin and promotion of Ca2+-calmodulin complex formation. The NH4Cl-induced elevations in cytosolic pH and Ca2+ concentration act synergistically to activate calmodulin-dependent processes, cAMP pathway, and, thereby, stimulate CBF.


The power of women's and men's Social Networks to catalyse normative and behavioural change: evaluation of an intervention addressing Unmet need for Family Planning in Benin.
In Benin, despite good knowledge and availability, modern contraceptive prevalence remains relatively low, and the unmet need for family planning is relatively high. This is partly due to insufficient attention to socio-normative barriers that influence need and method use. Applying social network theory, Tékponon Jikuagou (TJ) aims to reduce socio-normative barriers preventing modern contraceptive use in rural Benin. After community identification, TJ trains influential network actors who encourage critical dialogue about unmet need, family planning, gender, and other social norms within their networks, complemented by radio and services linkages. This paper evaluates TJ's effectiveness and how intervention components affect intermediate and primary FP outcomes. We report findings from pre/post-intervention cross-sectional research with a comparison group conducted at baseline with 1,043 women and 1,030 men, and 14 months later at endline with 1,046 women and 1,045 men. Using sex-stratified models, we assessed balance across intervention and comparison groups on background characteristics using Pearson's chi-square tests of independence; performed bivariate tests of independence to assess differences between baseline to endline on intermediate outcomes and primary FP outcomes; used logistic regression to examine the effect of intervention components on intermediate and primary FP outcomes. Statistically significant improvements in primary outcomes: women's intentions to use modern contraception, achieve met need, and reduce perceived met need. The fourth primary outcome, actual use, showed substantial gains, although not statistically significant. Men's achievement of met FP need and reduced perceived met need were also statistically significant. Assessing intermediate outcomes at individual, couple, normative-network levels, TJ led to statistically significant increases in couple and network communication on fertility desires and family planning use and self-efficacy and confidence to access services. Both women and men showed significant shifts in the acceptability of discussing FP in public. Results for other indicators of norms change were inconsistent. An easy-to-implement, short-duration, gender-equitable social network intervention with a limited set of network actors, TJ effectively decreases social and normative barriers preventing women and men from seeking and using FP services. Results support the broader use of innovative social and behaviour change strategies that diffuse family planning ideas through social networks, diminish normative and communication barriers, and catalyse modern family planning use.


Dietary recommendations to meet both endocrine and autocrine needs of Vitamin D.
In the most recent revision of the dietary recommendations for Americans and Canadians in 1997, a recommended intake for Vitamin D was set in the absence of an estimation of mean requirements. There are now new data to estimate average requirements; however, there must be consideration of factors affecting need in populations and of total body tissue needs including the prevention and treatment of cancer. A recent study provides dietary dose-response data in the absence of sun exposure, and a mean requirement of 12.5microg (500IU) was found for Caucasian men. A seasonal build up (summer) and waning (winter) of Vitamin D stores implies that the requirement of Vitamin D in complete absence of yearly summertime sun exposure would approach levels of intake that mimic Vitamin D gained from sun exposure. High prevalence of Vitamin D insufficiency and the re-emergence of rickets have been observed worldwide. For many countries without mandatory staple food fortification, Vitamin D intake is often too low to sustain healthy circulating levels of 25 hydroxyvitamin D. Even in some countries that require (mandatory) or allow fortification (optional), Vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited or no use of dietary supplements, or changes away from traditional food consumption. Supplement use can significantly increase Vitamin D intakes across all age and gender groups but the benefit is primarily gained in persons whose intakes are close to adequate. African American men and women have greater prevalence of Vitamin D insufficiency, which may be a factor in their susceptibility to certain cancers. New recommendations for Vitamin D should be made for the otherwise healthy populations in greatest need of dietary Vitamin D due to lack of adequate sun exposure.


The effects of dose of elemental mercury and first-pass circulation time on exhalation and organ distribution of inorganic mercury in rats.
The lung plays a major role in the removal of dissolved elemental mercury (Hg0) from the bloodstream. During the first passage through the lung after an intravenous dose of Hg0 dissolved in aqueous buffer, from 10 to 17% was exhaled depending on the dose (0.11 or 1.1 micrograms Hg/rat) and the injection site (jugular versus tail vein). Furthermore, evidence is presented that subsequent exhalation over the next 50 s, before the rats were killed and the mercury determined in the lung at that time, was largely Hg0-extracted during the first pass. The total mercury extracted during the 60 s period was in the range of 40-49% of the dose. The oxidation of Hg0 to Hg2+ in red cells is important in limiting the availability of Hg0 to certain tissues. Thus, after a short residence time in blood (0.6 s after jugular vein injection), 12.9-17% is exhaled in the first pass as compared to 10.4-12.2% with a longer residence time (1.8 s after tail vein injection). Furthermore, there was a general tendency, even at 60 s after dosing, for certain tissues - lung, brain, and heart - to have higher values after dosing from the jugular vein. It was estimated that the half-time for oxidation was 3.3 s. Our results confirm previous observations that the form of inorganic mercury greatly influences the short-term deposition in certain tissues. Thus as compared to Hg2+, administration of Hg0 increases lung levels 5-10-fold; brain, 4-fold; and heart, 3-fold. Blood levels are lower after Hg0, particularly after the higher dose. Such findings are consistent with a model wherein Hg0 is in part oxidized by red blood cells, the remainder rapidly diffusing in tissues where it is also oxidized to Hg2+.


Intravaginal nonablative radiofrequency in the treatment of genitourinary syndrome of menopause symptoms: a single-arm pilot study.
Genitourinary syndrome of menopause (GSM) involves vaginal dryness (VD), pain during sexual activity (SAPain), vaginal itching (VI), burning, pain, and symptoms in the urinary organs. Non-ablative radiofrequency (RF) is a type of current with electromagnetic waves with a thermal effect that generates an acute inflammatory process with consequent neocolagenesis and neoelastogenesis. We aimed to describe the clinical response to VD, SAPain, vaginal laxity (VL), VI, burning sensation, pain in the vaginal opening, urinary incontinence, sexual dysfunction, cytological changes, and adverse effects of non-ablative RF in patients with GSM. This single-arm pilot study included 11 women diagnosed with GSM with established menopause. Patients with hormone replacement initiation for six months, who used a pacemaker, or had metals in the pelvic region, were excluded. Subjective measures (numeric rating scale of symptoms, Vaginal Health Index-VHI) and objective measures (vaginal maturation index-VMI, vaginal pH, sexual function by the FSFI, and urinary function by the ICIQ-SF) were used. A Likert scale measures the degree of satisfaction with the treatment. Five sessions of monopolar non-ablative RF (41°C) were performed with an interval of one week between each application. The entire evaluation was performed before treatment (T0), one month (T1), and three months (T2) after treatment. Adverse effects were assessed during treatment and at T1 and T2. The symptoms and/or signs were reduced after treatment in most patients (T1/T2, respectively): VD 90.9%/81.8%, SAPain 83.3%/66.7, VL 100%/100%, VI 100%/100%, burning 75%/87.5%, pain 75%/75%, and VHI 90.9%/81.9%. Most patients did not show changes in VMI (54.5%) and pH (63.6%) at T1, but there was an improvement in VMI in most patients (54.5%) at T2. Nine patients were satisfied, and two were very satisfied at T1. The treatment was well tolerated, and no adverse effects were observed. There was an improvement in sexual function (72.7%) and urinary function (66.7% in T1 and 83.3% in T2). Intravaginal RF reduced the clinical symptoms of GSM in most patients, especially during T1, and women reported satisfaction with treatment. The technique showed no adverse effects, and there were positive effects on sexual and urinary function. Trial registration This research was registered at clinicaltrial.gov (NCT03506594) and complete registration date was posted on April 24, 2018.


Acute cholestatic hepatitis after exposure to isoflurane.
To report a case of acute cholestatic hepatitis following exposure to the inhalational anesthetic isoflurane. A 70-year-old healthy woman from Iraq developed acute cholestatic hepatitis 3 weeks following repair of the right rotator cuff under general anesthesia. There was no evidence for viral, autoimmune, or metabolic causes of hepatitis. No other medications were involved except for dipyrone for analgesia. The alanine aminotransferase was elevated to a peak concentration of 1533 U/L and the serum bilirubin reached a peak of 17.0 mg/dL. There was slow improvement over 4 months. Accidental reexposure by the patient to dipyrone was uneventful. The clinical and histologic picture of this case resembles halothane hepatitis, which has a significant mortality rate. Isoflurane, a common anesthetic agent, can cause severe cholestatic hepatitis.


Modeling and optimization of chlorophenol rejection for spiral wound reverse osmosis membrane modules.
This study shows an artificial neural network (ANN) model of chlorophenol rejection from aqueous solutions and predicting the performance of spiral wound reverse osmosis (SWRO) modules. This type of rejection shows complex non-linear dependencies on feed pressure, feed temperature, concentration, and feed flow rate. It provides a demanding test of the application of ANN model analysis to SWRO modules. The predictions are compared with experimental data obtained with SWRO modules. The overall agreement between the experimental and ANN model predicted was almost 99.9% accuracy for the chlorophenol rejection. The ANN model approach has the advantage of understanding the complex chlorophenol rejection phenomena as a function of SWRO process parameters.


Clinical Outcome and Recurrence After Meningioma Surgery: An Experience from a Developing Country, Nepal.
Meningioma is the most common primary brain tumor, constituting more than half of all benign central nervous system tumors. This study aims to analyze the clinical outcome and recurrence after surgery of intracranial meningioma in Nepal. This is a retrospective study of newly diagnosed intracranial meningioma patients operated at Nepal Mediciti Hospital between 2007 and 2019. Demographics; clinical, radiologic, and perioperative details; histopathology; and clinical outcome variables were reviewed. Association of independent variables with primary outcome variables: modified Rankin Scale (favorable [≤ 3] vs. unfavorable [>3]) and recurrence was analyzed. Logistic regression model was designed to calculate adjusted odds ratio with 95% confidence interval (CI). Of 233 patients, mean age was 47 years, female individuals were affected twice as much as male individuals. Location was supratentorial in 83.3%, 83.7% had tumor greater than 5 cm in size. Gross total resection (SM 0-III) was achieved in 85.4%. A total of 98.7% had grade I meningioma. Favorable outcome was found in 94.8%. Recurrence rate was 6.9%. Tumor size less than 3 cm (adjusted odds ratio [AOR] 0.024 95% CI 0.001-0.416, P = 0.010), gross total resection (AOR 19.737, 95% CI 4.69-83.063, P < 0.001), and comorbidity (AOR 0.202, 95% CI 0.052-0.785, P = 0.021) were significantly associated with favorable outcome whereas age (AOR 3.491, 95% CI 1.029-11.850, P = 0.045) and WHO grade (AOR 0.024, 95% CI 0.002-0.344, P = 0.006) were independently associated with recurrence. The complication and surgical mortality rates were 30% and 1.72%, respectively. Tumor size, extent of resection, age, tumor grade, and medical comorbidities were significantly associated with postoperative outcome. We recommend a prospective study with standardized follow up protocol to assess the long-term outcome.


Hydrogen exchange kinetics changes upon formation of the soybean trypsin inhibitor-trypsin complex.
The hydrogen exchange kinetics of the complex of trypsin-soybean trypsin inhibitor (Kunitz) have been compared to the calculated sum of the exchange kinetics for the inhibitor and trypsin measured separately. The exchange rates observed for the complex are substantially less than the sum of the exchange rates in the two individual proteins. These results cannot be accounted for by changes in intermolecular or intramolecular hydrogen bonding. The decrease in exchange rates in the complex are ascribed to changes in solvent accessibility in the component proteins.


Predicting the toxicity of metal mixtures.
The toxicity of single and multiple metal (Cd, Cu, Pb, and Zn) solutions to trout is predicted using an approach that combines calculations of: (1) solution speciation; (2) competition and accumulation of cations (H, Ca, Mg, Na, Cd, Cu, Pb, and Zn) on low abundance, high affinity and high abundance, low affinity biotic ligand sites; (3) a toxicity function that accounts for accumulation and potency of individual toxicants; and (4) biological response. The approach is evaluated by examining water composition from single metal toxicity tests of trout at 50% mortality, results of theoretical calculations of metal accumulation on fish gills and associated mortality for single, binary, ternary, and quaternary metal solutions, and predictions for a field site impacted by acid rock drainage. These evaluations indicate that toxicity of metal mixtures depends on the relative affinity and potency of toxicants for a given aquatic organism, suites of metals in the mixture, dissolved metal concentrations and ratios, and background solution composition (temperature, pH, and concentrations of major ions and dissolved organic carbon). A composite function that incorporates solution composition, affinity and competition of cations for two types of biotic ligand sites, and potencies of hydrogen and individual metals is proposed as a tool to evaluate potential toxicity of environmental solutions to trout.


Counterfactual quantum computation through quantum interrogation.
The logic underlying the coherent nature of quantum information processing often deviates from intuitive reasoning, leading to surprising effects. Counterfactual computation constitutes a striking example: the potential outcome of a quantum computation can be inferred, even if the computer is not run. Relying on similar arguments to interaction-free measurements (or quantum interrogation), counterfactual computation is accomplished by putting the computer in a superposition of 'running' and 'not running' states, and then interfering the two histories. Conditional on the as-yet-unknown outcome of the computation, it is sometimes possible to counterfactually infer information about the solution. Here we demonstrate counterfactual computation, implementing Grover's search algorithm with an all-optical approach. It was believed that the overall probability of such counterfactual inference is intrinsically limited, so that it could not perform better on average than random guesses. However, using a novel 'chained' version of the quantum Zeno effect, we show how to boost the counterfactual inference probability to unity, thereby beating the random guessing limit. Our methods are general and apply to any physical system, as illustrated by a discussion of trapped-ion systems. Finally, we briefly show that, in certain circumstances, counterfactual computation can eliminate errors induced by decoherence.


Fate of TLR-1/TLR-2 agonist functionalised pDNA nanoparticles upon deposition at the human bronchial epithelium in vitro.
Plasmid DNA vaccination is a promising approach, but studies in non-human primates and humans failed to achieve protective immunity. To optimise this technology further with focus on pulmonary administration, we developed and evaluated an adjuvant-equipped DNA carrier system based on the biopolymer chitosan. In more detail, the uptake and accompanying immune response of adjuvant Pam3Cys (Toll-like receptor-1/2 agonist) decorated chitosan DNA nanoparticles (NP) were explored by using a three-dimensional (3D) cell culture model of the human epithelial barrier. Pam3Cys functionalised and non-functionalised chitosan DNA NP were sprayed by a microsprayer onto the surface of 3D cell cultures and uptake of NP by epithelial and immune cells (blood monocyte-derived dendritic cells (MDDC) and macrophages (MDM)) was visualised by confocal laser scanning microscopy. In addition, immune activation by TLR pathway was monitored by analysis of interleukin-8 and tumor necrosis factor-α secretions (ELISA). At first, a high uptake rate into antigen-presenting cells (MDDC: 16-17%; MDM: 68-75%) was obtained. Although no significant difference in uptake patterns was observed for Pam3Cys adjuvant functionalised and non-functionalised DNA NP, ELISA of interleukin-8 and tumor necrosis factor-α demonstrated clearly that Pam3Cys functionalisation elicited an overall higher immune response with the ranking of Pam3Cys chitosan DNA NP>chitosan DNA NP=DNA unloaded chitosan NP>control (culture medium). Chitosan-based DNA delivery enables uptake into abluminal MDDC, which are the most immune competent cells in the human lung for the induction of antigen-specific immunity. In addition, Pam3Cys adjuvant functionalisation of chitosan DNA NP enhances significantly an environment favoring recruitment of immune cells together with a Th1 associated (cellular) immune response due to elevated IL-8 and TNF-α levels. The latter renders this DNA delivery approach attractive for potential DNA vaccination against intracellular pathogens in the lung (e.g., Mycobacterium tuberculosis or influenza virus).


In vivo antifungal activity and biocompatibility of Cryptocarya moschata.
The objective of this study was evaluate, in vivo model, the antifungal activity of Cryptocarya moschata extract against Candida albicans and its biocompatibility. The animals (N = 50) were divided into groups (n = 5): CI/CG: candidiasis was induced and treated with C. moschata extract (0.045 g/mL); CI/NG: candidiasis was induced and treated with nystatin; CI/NT: candidiasis was induced and no treated; CI/CG-2: candidiasis was induced and treated with C. moschata extract (0.045 g/mL), reapplied after 24 h; CI/NG-2: candidiasis was induced and treated with nystatin, reapplied after 24 h; NCI/NT: candidiasis was not induced and no treated; NCI/CG: candidiasis was not induced and treated with C. moschata extract (0.045 g/mL); NCI/NG: candidiasis was not induced treated with nystatin; NCI/CG-2: candidiasis was not induced and treated with C. moschata extract (0.045 g/mL), reapplied after 24 h; NCI/NG-2: candidiasis was not induced and treated with nystatin, reapplied after 24 h. The fungi present in the lingual dorsum of mice were collected and analyzed by the count of colony-forming units. In addition, histological analysis was performed. Histologically, there was no cell damage in the mice's tongue, and there was a decrease in Candida biofilm, similar to the use of nystatin. It was concluded that the C. moschata extract was effective against C. albicans and was biocompatible.


The effects of dietary manipulation on blood acid-base status and the performance of high intensity exercise.
The effect of a pattern of exercise and dietary modification, which is normally used to alter muscle glycogen content, upon the acid-base status of the blood and the ability to perform high intensity exercise was studied. Eleven healthy male subjects cycled to exhaustion on an electrically braked cycle ergometer at a workload equivalent to 100% of their maximal oxygen uptake (VO2max) on three separate occasions. The first exercise test took place after a normal diet (46.2 +/- 6.7% carbohydrate (CHO)), and was followed by prolonged exercise to exhaustion to deplete muscle glycogen stores. The second test was performed after three days of a low carbohydrate diet (10.1 +/- 6.8% CHO) and subsequently after three days of a high CHO diet (65.5 +/- 9.8% CHO) the final test took place. Acid-base status and selected metabolites were measured on arterialised venous blood at rest prior to exercise and during the post-exercise period. Exercise time to exhaustion was longer after the normal (p less than 0.05) and high (p less than 0.05). CHO dietary phases compared with the low CHO phase. Resting pre-exercise pH was higher after the high CHO diet (p less than 0.05) compared with the low CHO diet. Pre-exercise bicarbonate, PCO2 and base excess measurements were higher after the high CHO treatment compared with both the normal (p less than 0.01, p less than 0.05, p less than 0.01 respectively) and low CHO phases (p less than 0.001, p less than 0.01, p less than 0.001 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Phytochemical and underlying mechanism of Mikania micrantha Kunth on antibiotic resistance genes, and pathogenic microbes during chicken manure composting.
Chicken manure is a source of antibiotic resistance genes (ARGs) and pathogenic microbes. Mikania micrantha Kunth (MM) is an invasive plant containing phytochemicals as antimicrobial agents. To explore its impacts on ARGs and pathogen-host interactions (PHIs), MM was added to composting mixtures. The findings indicated that compared with control (CK), MM significantly improved the phytochemical abundances, particularly stilbenoids and diarylheptanoids (4.87%), and ubiquinones (2.66%) in the treatment (T) compost. Besides, significant ARGs reduction was noted, where rpoB2, RbpA, FosB1, vatC, and vatB were removed from T compost. PHIs significantly declined in T compost, where the growth of Xanthomonas citri, Streptococcus pneumoniae, Fusarium graminearum, Vibrio cholerae, and Xanthomonas campestris were inhibited. Multiple variable analyses demonstrated that temperature and pH revealed a significant role in ARGs and PHIs decline. Accordingly, this study considerably recommends MM as a promising compost additive in terms of its antimicrobial potential toward pathogenic microbes and ARGs.


IgE and cardiovascular disease. Results from a population-based study.
Because previous reports have suggested that IgE-mediated events may lead to both platelet activation and arterial spasm, a population-based study of 262 men and 315 women, aged 38 to 82, was conducted to investigate the association of serum IgE levels with myocardial infarction, stroke, and noninvasively diagnosed large-vessel peripheral arterial disease. In men with previous myocardial infarction, previous stroke, or current large-vessel peripheral arterial disease, geometric mean serum IgE levels were increased 119 percent, 164 percent, and 78 percent, respectively. These associations were statistically significant (p less than 0.05). Because IgE was positively or inversely correlated with several traditional cardiovascular disease risk factors, logistic regression was used to evaluate the independent association of IgE with any cardiovascular disease (myocardial infarction, stroke, or large-vessel peripheral arterial disease). In a model including age, cigarette smoking, fasting plasma glucose level, diastolic blood pressure, and low-density lipoprotein cholesterol level as covariates, IgE was positively and independently associated with any cardiovascular disease (p = 0.03). Similar evaluations in women revealed no correlation between IgE and cardiovascular disease by either univariate or multivariable analysis. These data indicate that IgE may be an independent marker for cardiovascular disease in men, and thus suggest IgE-mediated events may play a role in the pathogenesis of cardiovascular disease.


Sex differences in the effect of subjective sleep on fear conditioning, extinction learning, and extinction recall in individuals with a range of PTSD symptom severity.
Sleep has been found to play a key role in fear conditioning, extinction learning and extinction recall, and sleep disturbances are linked to many mental disorders including post-traumatic stress disorder (PTSD). Previous studies examining associations between sleep and fear or extinction processes primarily focused on objectively measured sleep architecture. Little research has so far focused on subjective sleep measures and particularly in clinical populations, which often experience subjectively poor sleep, including PTSD. Here we investigated whether subjective sleep disturbance, sleep onset latency, wake after sleep onset or sleep efficiency were related to fear conditioning, extinction learning or extinction recall in a large sample of individuals with a range of PTSD symptom severity (n = 248). Overall, we did not find that subjective sleep was associated with fear conditioning or extinction processes. However, exploratory analyses examining the moderating effect of sex found that shorter sleep onset latency and greater sleep efficiency were associated with improved extinction recall in women with higher PTSD symptom severity. This suggests that less time falling asleep and longer time asleep while in bed may be protective in highly symptomatic women against the commonly observed impaired extinction recall in PTSD. More studies are needed to explore sex-specific effects further.


Diagnostic Yield of Continuous Video EEG for Neonatal Seizures.
Investigators from the University of California, San Francisco studied the yield of continuous video EEG (vEEG) in diagnosing electrographic seizures in their neonatal intensive care unit.


Modifications and insights into a method for the analysis of the nitrogen mustard mechlorethamine by high-performance liquid chromatography.
Previously, a method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA), a stable compound suitable for analysis by HPLC with UV detection [J.C. Reepmeyer, J. Chromatogr. A, 1085 (2005) 262]. Mechlorethamine HCl served as a reference standard and it was derivatized in situ simultaneously with samples of mechlorethamine HCl in ointment preparations. This paper presents the synthesis of PTEMA on a gram scale, synthesis of its picrate salt, bis(2-phenylthioethyl)methylamine picrate (PTEMAP), and isolation of the picrate as a crystalline solid. PTEMAP may serve as a reference standard replacing the toxic mechlorethamine HCl. Insights into the handling, storage, drying, and hygroscopic properties of mechlorethamine HCl and PTEMAP are discussed. In addition, one step following the derivatization procedure in the original method is recognized as a potential for error, and a procedure relating to the order of addition of reagents is presented to avoid this error. The method has been extended to the analysis of mechlorethamine in aqueous solutions.


Safety, Efficiency, and Efficacy of Protocolized Contrast-Enhanced Imaging in Acute Stroke Evaluation.
Computed tomography angiography and perfusion studies have increasingly become a part of acute stroke evaluation. However, the volume, benefit, and scope of need for imaging is sometimes debated. This study evaluated the safety, efficiency, and efficacy of changes to the acute stroke evaluation protocol at our academic institution. Previously, contrast-enhanced imaging was "opt-in" and ordered upon suspicion of large vessel occlusion. This was subsequently transitioned to one where contrast-enhanced imaging was automatically ordered for all patients with "opt-out" of imaging if felt appropriate. We performed a retrospective, case-control study that included patients evaluated for acute stroke management before and after the protocol change. Six hundred forty-seven patients met criteria for study involvement, of which 258 were in the preprotocol and 389 in the postprotocol group. There was no significant difference in rate of acute kidney injury and no delay in door-to-needle time. There was significant improvement in door-to-groin puncture times (49.9 minutes) for typical cases and increase in monthly rate of endovascular therapy (EVT). Protocolization of contrast-enhanced imaging for acute stroke evaluation proved safe with respect to renal function, did not delay door-to-needle time, improved door-to-groin puncture time, and lead to higher rates of EVT.


Superoxide-induced Type I collagen secretion depends on prolyl 4-hydroxylases.
Reactive oxygen species (ROS) including superoxide (O2•-) play an important role in a variety of diseases, including Alzheimer's Disease, cancer, and atherosclerosis. Early reports showed that O2•- is a stimulant for collagen synthesis. However, the mechanism remains incompletely understood. Here we showed that LY83583 (6-anilinoquinoline-5,8-quinone), a substance known to induce O2•- production by smooth muscle cell (SMC), increases Type I collagen secretion. This effect could be blocked by treating the cells with Tiron, a scavenger for O2•-. LY83583-induced Type I collagen secretion required P4HA1 and P4HA2. Knockout of either P4ha1 or P4ha2 greatly reduced LY83583-stimulated Type I collagen maturation whereas silencing of both P4ha1 and P4ha2 completely blocked LY83583-induced Type I collagen maturation. Although significantly more hydroxyproline on purified Type I collagen was detected from LY83583 treated mouse embryonic fibroblast (MEF) cells by mass spectrometry, the level of prolyl 4-hydroxylases was not altered. Thus, LY83583 might increase the enzymatic activity of prolyl 4-hydroxylases to increase Type I collagen maturation. In addition, we found that LY83583 activated prolyl 4-hydrolases differed from ascorbate-activated prolyl 4-hydroxylase in two aspects: (1) LY83583 activated both P4HA1 and P4HA2 involved in collagen maturation whereas ascorbate mainly stimulated P4HA1 in collagen maturation; (2) LY83583 did not induce N259 glycosylation on P4HA1 as ascorbate did. The mechanisms remain to be investigated.


A role for interaction of the RNA polymerase flap domain with the sigma subunit in promoter recognition.
In bacteria, promoter recognition depends on the RNA polymerase sigma subunit, which combines with the catalytically proficient RNA polymerase core to form the holoenzyme. The major class of bacterial promoters is defined by two conserved elements (the -10 and -35 elements, which are 10 and 35 nucleotides upstream of the initiation point, respectively) that are contacted by sigma in the holoenzyme. We show that recognition of promoters of this class depends on the "flexible flap" domain of the RNA polymerase beta subunit. The flap interacts with conserved region 4 of sigma and triggers a conformational change that moves region 4 into the correct position for interaction with the -35 element. Because the flexible flap is evolutionarily conserved, this domain may facilitate promoter recognition by specificity factors in eukaryotes as well.


Assessment of body composition measured by bioelectrical impedance in children.
Bioelectrical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 +/- 4.0% in the junior male group, 14.2 +/- 2.8% in the junior female group, 7.9 +/- 4.7% in the senior male group and 16.1 +/- 2.9% in the senior female group. The %BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.


Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy.
Radiotherapy is used in the treatment of laryngeal carcinoma. The search for biologic parameters that could be used to identify patients who will respond to radiotherapy is crucial. The aim of this study was to determine whether the Ki-67 and p53 indices and the pretreatment apoptotic index would be useful in predicting local control and survival for a group of laryngeal carcinoma patients given postoperative radiotherapy. Fifty-seven patients with laryngeal carcinoma treated between 1988 and 1993 were included in this study. Postoperative radiotherapy was given to a mean dose of 57.7 gray (Gy) (range, 50-68; median, 60) in 2-Gy daily fractions. Ki-67 and p53 immunostaining were performed on paraffin-embedded tissue. Cells were evaluated for apoptosis using hematoxylin and eosin-stained slides. Clinicopathologic tumor characteristics were studied in relation to Ki-67, p53, and apoptotic indices, and as prognostic factors for local control and survival in both univariate and multivariate analysis. The Ki-67, p53, and pretreatment apoptotic indices were not related to any clinicopathologic tumor characteristics. Five-year actuarial local control for the whole group was 47%. Patients with tumors that had low Ki-67 proliferation had better long term local control (P < 0.01). and survival (P < 0.03). p53 expression was not predictive of local control or survival in this study. Patients with tumors that had low pretreatment apoptotic indices had better local control (P < 0.049) and survival (P < 0.056) than patients with highly apoptotic tumors. Tumor extension and the pretreatment apoptotic index were significant predictive factors for local control and survival in multivariate analysis. Ki-67 proliferation measurement and the pretreatment apoptotic index are useful in predicting the clinical outcome of laryngeal carcinoma patients referred for radiotherapy. The role of p53 oncoprotein determination in predicting these outcomes is unclear. Assessment of biologic tumor characteristics could aid in the selection of patients for different treatment strategies.


Low-frequency rTMS over the Parieto-frontal network during a sensorimotor task: The role of absolute beta power in the sensorimotor integration.
Several studies have demonstrated that Repetitive Transcranial Magnetic Stimulation (rTMS) promotes alterations in the Central Nervous System circuits and networks. The focus of the present study is to examine the absolute beta power patterns in the Parieto-frontal network. We hypothesize that rTMS alters the mechanisms of the sensorimotor integration process during a visuomotor task. Twelve young healthy volunteers performed a visuomotor task involving decision making recorded (Catch a ball in a free fall) by Electroencephalography. rTMS was applied on the Superior Parietal Cortex (SPC; Brodmann area [BA] 7) with low-frequency (1 Hz - 15 min - 80% Resting Motor Threshold). For each Frontal and Parietal region, a two-way ANOVA was used to compare the absolute beta power before and after TMS for each condition of the study (Rest 1, Task and Rest 2). The results demonstrated interactions (TMS vs. Condition) for the Frontal electrodes: Fp1, Fp2 and F7 and an effect of TMS (before and after) for F4.The results for the Parietal region showed a main effect of Condition for the P3, PZ and P4 electrodes. Thus, our paradigm was useful to better understand the reorganization and neural plasticity mechanisms in the parieto-frontal network during the sensorimotor integration process.


Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis.
Within the last decade, it became clear that oxygen contributes to the pathogenesis of neonatal brain damage, leading to neurocognitive impairment of prematurely born infants in later life. Recently, we have identified a critical role for receptor-mediated neuronal apoptosis in the immature rodent brain. However, the contribution of the intrinsic apoptotic pathway accompanied by activation of caspase-2 under hyperoxic conditions in the neonatal brain still remains elusive. Inhibition of caspases appears a promising strategy for neuroprotection. In order to assess the influence of specific caspases on the developing brain, we applied a recently developed pentapeptide-based group II caspase inhibitor (5-(2,6-difluoro-phenoxy)-3(R,S)-(2(S)-(2(S)-(3-methoxycarbonyl-2(S)-(3-methyl-2(S)-((quinoline-2-carbonyl)-amino)-butyrylamino)propionylamino)3-methylbutyrylamino)propionylamino)-4-oxo-pentanoic acid methyl ester; TRP601). Here, we report that elevated oxygen (hyperoxia) triggers a marked increase in active caspase-2 expression, resulting in an initiation of the intrinsic apoptotic pathway with upregulation of key proteins, namely, cytochrome c, apoptosis protease-activating factor-1, and the caspase-independent protein apoptosis-inducing factor, whereas BH3-interacting domain death agonist and the anti-apoptotic protein B-cell lymphoma-2 are downregulated. These results coincide with an upregulation of caspase-3 activity and marked neurodegeneration. However, single treatment with TRP601 at the beginning of hyperoxia reversed the detrimental effects in this model. Hyperoxia-mediated neurodegeneration is supported by intrinsic apoptosis, suggesting that the development of highly selective caspase inhibitors will represent a potential useful therapeutic strategy in prematurely born infants.


The African Fusarium/maize disease.
There is a general but rather vague feeling that the use of maize (corn) as a staple foodstuff by black rural Africans is somehow a factor in, or is linked to, chronic disease found in these populations. An attempt is made in this review to consider the evidence for this connection and to identify what is actually the root of the problem. The main thrust of the argument to explain this perception is that maize is routinely contaminated with fungi and of these Fusarium verticillioides is found in maize throughout the world. Evidence is presented to this effect and, further, of the mycotoxins found in maize, the fumonisins are the most common and at the highest levels. Various animal chronic diseases arising from the consumption of contaminated maize are reviewed and possible human conditions listed, in some cases related to the known animal ones. A brief overview of the complicated cellular mechanisms of fumonisin B1 is given and it is concluded that the prime suspect in what might be called "the maize disease" can be attributed to the ingestion of this mycotoxin, sometimes in combination with other synergist mycotoxins and other disease factors, such as smoking and drinking.


Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM. HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases. HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant. Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM.