Metabolic fingerprinting reveals extensive consequences of GLS hyperactivity.
High glutaminase (GLS;EC188.8.131.52) activity is an important pathophysiological phenomenon in tumorigenesis and metabolic disease. Insight into the metabolic consequences of high GLS activity contributes to the understanding of the pathophysiology of both oncogenic pathways and inborn errors of glutamate metabolism. Glutaminase catalyzes the conversion of glutamine into glutamate, thereby interconnecting many metabolic pathways. We developed a HEK293-based cell-model that enables tuning of GLS activity by combining the expression of a hypermorphic GLS variant with incremental GLS inhibition. The metabolic consequences of increasing GLS activity were studied by metabolic profiling using Direct-Infusion High-Resolution Mass-Spectrometry (DI-HRMS). Of 12,437 detected features [m/z], 109 features corresponding to endogenously relevant metabolites were significantly affected by high GLS activity. As expected, these included strongly decreased glutamine and increased glutamate levels. Additionally, increased levels of tricarboxylic acid (TCA) intermediates with a truncation of the TCA cycle at the level of citrate were detected as well as increased metabolites of transamination reactions, proline and ornithine synthesis and GABA metabolism. Levels of asparagine and nucleotide metabolites showed the same dependence on GLS activity as glutamine. Of the nucleotides, especially metabolites of the pyrimidine thymine metabolism were negatively impacted by high GLS activity, which is remarkable since their synthesis depend both on aspartate (product of glutamate) and glutamine levels. Metabolites of the glutathione synthesizing γ-glutamyl-cycle were either decreased or unaffected. By providing a metabolic fingerprint of increasing GLS activity, this study shows the large impact of high glutaminase activity on the cellular metabolome.


Adipose stromal cell and sarpogrelate orchestrate the recovery of inflammation-induced angiogenesis in aged hindlimb ischemic mice.
Aging population displays a much higher risk of peripheral arterial disease (PAD) possibly due to the higher susceptibility, poor prognosis, and fewer therapeutic options. This study was designed to examine the impact of combined multipotent adipose-derived stromal cells (mADSCs) and sarpogrelate treatment on aging hindlimb ischemia and the mechanism of action involved. mADSCs (1.0 × 10(7)) constitutively expressing enhanced green fluorescent protein (eGFP) or firefly luciferase (Fluc) reporter were engrafted into the hindlimb of aged Vegfr2-luc transgenic or FVB/N mice subjected to unilateral femoral artery occlusion, followed by a further administration of sarpogrelate. Multimodality molecular imaging was employed to noninvasively evaluate mADSCs' survival and therapeutic efficacy against aging hindlimb ischemia. Aged Tg(Vegfr2-luc) mice exhibited decreased inflammatory response, and downregulation of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR2) compared with young ones following hindlimb ischemia induction, resulting in angiogenesis insufficiency and decompensation for ischemia recovery. Engrafted mADSCs augmented inflammation-induced angiogenesis to yield pro-angiogenic/anti-apoptotic effects partly via the VEGF/VEGFR2/mTOR/STAT3 pathway. Nonetheless, mADSCs displayed limited survival and efficacy following transplantation. Sarpogrelate treatment with mADSCs further upregulated mammalian target of rapamycin (mTOR)/STAT3 signal and modulated pro-/anti-inflammatory markers including IL-1β/TNF-α/IFN-γ and IL-6/IL-10, which ultimately facilitated mADSCs' survival and therapeutic benefit in vivo. Sarpogrelate prevented mADSCs from hypoxia/reoxygenation-induced cell death via a mTOR/STAT3-dependent pathway in vitro. This study demonstrated a role of in vivo kinetics of VEGFR2 as a biomarker to evaluate cell-derived therapeutic angiogenesis in aging. mADSCs and sarpogrelate synergistically restored impaired angiogenesis and inflammation modulatory capacity in aged hindlimb ischemic mice, indicating its therapeutic promise for PAD in the elderly.


Computed tomographic evaluation of the thoracic prevertebral and paravertebral spaces.
The thoracic prevertebral and paravertebral spaces are defined by the vertebrae and fascial planes. Many important structures lie within these spaces, for example, the intercostal arteries, descending aorta, the azygos and hemiazygos veins, sympathetic nerve trunk, thoracic duct, and lymph nodes. Computed tomography has been notably successful in evaluating the mediastinum and specifically the prevertebral and paravertebral spaces. Computed tomography of the normal anatomy and some examples of pathology involving these specific areas are presented. Computed tomography is strongly indicated to evaluate pathology in this area.


Functional brain asymmetry and attentional modulation in young and stabilised schizophrenic patients: a dichotic listening study.
Impaired functional brain asymmetry has been shown in schizophrenic patients, in addition to attentional deficits related to this laterality impairment. However, it has usually been shown in older patients with frequent positive symptoms. This is a matter of concern because previous studies have suggested that such deficits interact with subgroup characteristics, especially positive symptoms like hallucinations and age/duration of the illness. Thus, in this study, we tested a homogeneous group of young and stabilised schizophrenic patients. We used a verbal dichotic listening test with consonant-vowel syllables to study brain asymmetry and attentional modulation. Nineteen patients were compared with healthy subjects with the same age, handedness and gender distribution. All subjects were tested during a divided and two focused attention conditions. The patient and reference group showed the same performance pattern. This indicates that young and stabilised patients show normal functional brain asymmetry and normal ability to modulate attention. It is suggested that impairments in functional asymmetry and attentional modulation may follow a continuum related to symptomatology and age/duration of illness.


Drug transport from thin applications of topical dosage forms: development of methodology.
There are presently no standards for in vitro research dealing with the release and delivery of drugs from semisolid dosage forms, largely because of inherent experimental difficulties. Among the problems, it has proven difficult to apply dosage forms to membranes mounted in in vitro diffusion cells in facsimile to the manner in which the dosage forms are applied clinically. In the present studies, methodology has been developed which allows films with thicknesses approaching clinical dimensions to be spread evenly over silicone rubber membranes. Using methyl p-aminobenzoate as a test permeant and gelled water and water/propylene glycol solvent systems as test vehicles, it has proven possible to spread films as thin as 75 microns, yielding highly reproducible delivery profiles. Using this application technique, it has been shown how the diffusive clearance of drug from films of fixed composition placed over a resistant membrane is dependent on the thickness of application. For a given medium and thickness of application, when the vehicle composition is enriched in propylene glycol, partitioning into the membrane is suppressed, resulting in a lessening of the absolute rate of delivery and, consequently, a prolongation of the period over which drug is released. Increasing the membrane's resistance, i.e., increasing the membrane's thickness, likewise slows down the absolute delivery rate, extending the effective period of total clearance of drug from the applied film.


Impaired natural killer cell activity in Bloom's syndrome could be restored by human recombinant IL-2 in vitro.
Natural killer (NK) activity against K562 tumor cells was evaluated in peripheral blood nonadherent mononuclear cells (PBMNC) obtained from four patients with Bloom's syndrome. NK activity of PBMNC from all patients was found to be depressed to less than half of age-matched control values. However, all patients showed the normal percentages of large granular lymphocytes and of cells expressing the NK-cell-associated determinants (OKM1, Leu-7, and Leu-11). Although recombinant interferon-beta or -gamma augmented NK activity of patients' PBMNC in a manner similar to their effects on NK activity of normal individuals, impaired NK activity of PBMNC from Bloom's patients could be restored to normal ranges only by recombinant interleukin 2 (IL-2). These results suggested that IL-2 and interferons might participate in boosting NK activity of Bloom's syndrome in different ways.


Pregnancy associated with both insulin-dependent diabetes mellitus and sickle cell disease. A report of two cases.
Two pregnant women were treated for both insulin-dependent diabetes and sickle cell disease. Careful application of treatments developed for each of these conditions allowed both pregnancies to be successfully carried to term.


Neuroprotective Effect of 2-Aminoethoxydiphenyl Borate (2-APB) in Amyloid β-Induced Memory Dysfunction: A Mechanistic Study.
β-Amyloid (Aβ) peptide is a characteristic feature of Alzheimer's disease (AD) and accumulation of Aβ is associated with loss of synaptic plasticity and neuronal cell death. Aggregation of Aβ initiates numerous molecular signalling pathways leading to oxidative stress, mitochondrial dysfunction as well as an imbalance of calcium ion influx homeostasis. Recently, it has been shown that transient receptor potential melastatin 2 (TRPM2), a non-selective calcium-permeable cation channel has been postulated to play a vital role in the neuronal death, indicating the potential of TRPM2 inhibition in CNS disease. In this study, neuroprotective potential of 2-aminoethoxydiphenyl borate (2-APB), a broad-spectrum calcium channels blocker was investigated in Aβ-induced memory deficits in rats. In addition, effect of 2-APB on TRPM2 channels gene and protein expressions and also on calcium and memory related proteins was investigated in the hippocampus. Intracerebroventricular (I.C.V.) administration of Aβ (Aβ25-35, 10 μg) markedly induced cognitive impairment and upregulation of mRNA and protein expression of TRPM2 in the hippocampus. In addition, AChE activity was also increased in the cortex of the Aβ administered animals. Three-week treatment with 2-APB led to the down-regulation of TRPM2 mRNA and protein expression in the hippocampus and also improved the cognitive functions which was evident from the behavioral parameters. Moreover, 2-APB treatment also increased the calcium and memory associated proteins namely p-CaMKII, p-GSK-3β, p-CREB and PSD-95 in the hippocampus and reduced the mRNA level of calcium buffering proteins and calcineurin A (PPP3CA) in the hippocampus. Furthermore, 2-APB treatment significantly reduced the AChE activity in the cortex. Thus, our findings suggest the neuroprotective effect of 2-APB in Aβ-induced cognitive impairment.


Hyperlexia in Spanish-speaking children: report of 2 cases from Colombia, South America.
Hyperlexia is a condition rarely reported in Spanish-speaking children, characterized by the ability to recognize written words without formal training. We present two unrelated autistic children with hyperlexia from Colombia (South America) who were followed for 8 years with formal neuropsychological evaluations of language, motor skills, visual perception, attention and behavior. Both children taught themselves to read before 5 years of age but showed minimal comprehension; both displayed obsessional reading and difficulties in social skills and attention. Brain CT scans were normal. Hyperlexia has been associated with hyperactivation of the left superior temporal cortex; we conclude that the orthographic route is a probable mechanism for the development of hyperlexia.


SEB genotyping: SmartAmp-Eprimer binary code genotyping for complex, highly variable targets applied to HBV.
SmartAmp-Eprimer Binary code (SEB) Genotyping is a novel isothermal amplification method for rapid genotyping of any variable target of interest. After in silico alignment of a large number of sequences and computational analysis to determine the smallest number of regions to be targeted by SEB Genotyping, SmartAmp primer sets were designed to obtain a binary code of On/Off fluorescence signals, each code corresponding to a unique genotype. Applied to HBV, we selected 4 targets for which fluorescence amplification signals produce a specific binary code unique to each of the 8 main genotypes (A-H) found in patients worldwide. We present here the proof of concept of a new genotyping method specifically designed for complex and highly variable targets. Applied here to HBV, SEB Genotyping can be adapted to any other pathogen or disease carrying multiple known mutations. Using simple preparation steps, SEB Genotyping provides accurate results quickly and will enable physicians to choose the best adapted treatment for each of their patients.


The contribution of intracortical connections to horizontal spread of activity in the neocortex as revealed by voltage sensitive dyes and a fast optical recording method.
Coronal slices from guinea-pig visual neocortex were stained with voltage-sensitive fluorescence dyes RH414 or RH795. Activity was evoked by electrical stimulation of either the white matter or layer I. Emitted light intensity changes representing summated changes of membrane potential were recorded by a 10 x 10 photodiode array with a temporal resolution of 0.4 ms and a spatial resolution of 94 microns. The distribution and spread of activity in the horizontal direction was analysed. Following stimulation of the white matter or layer I, two regions of activity were differentiated in the medio-lateral direction: a central region (approximately 1 mm wide) of high-amplitude activity close to the stimulation electrode and, distant from the stimulation electrode, peripheral regions of low-amplitude activity. Central and peripheral regions differed in their rates of decline, their relative extent with stimulation of different sites and within different layers. The total extent of non-synaptic evoked activity did not exceed that of the central region of high-amplitude activity. Along the extent of non-synaptic activity, onset latencies of potentials were almost constant. Thus, activity of high amplitude in the central region was likely mediated by simultaneous activation of distributed afferent fibres. In contrast, no non-synaptic activity was found in peripheral regions. Therefore it is suggested that this low-amplitude activity was mediated without direct afferent activation but via long-distance intracortical horizontal pathways. These pathways are known to terminate in layer III, and accordingly latencies of responses in the periphery were shortest in upper cortical layers, whereas in the central region, latencies increased from lower to upper cortical layers.


Evaluation of a proposed method for phenytoin maintenance dose prediction following an intravenous loading dose.
A large clinical study, designed to investigate the induction of theophylline metabolism by phenytoin, provided the opportunity to test a previously proposed method for estimating dose requirements of phenytoin. This method involves prediction of the oral maintenance dosage from data obtained following the administration of an intravenous loading dose. In 30 subjects, trough plasma concentration at steady-state were 12.0 +/- 4.9 micrograms X ml-1 (mean +/- SD) and differed by -2.7 +/- 39.3% from a mean target plasma concentration of 12.5 +/- 1.5 micrograms X ml-1. A Bayesian regression programme was used to forecast an estimate of each subject's individual pharmacokinetics. These were then used to predict the steady-state plasma concentrations which would be expected from a standard dosing regimen (4 mg per kg per day). When compared to the results expected from the use of this standard dosage, the proposed method gave acceptable steady-state plasma phenytoin concentrations with significant reductions in deviations from target concentrations. This method for the rapid individualization of phenytoin dosage requirements provides an improvement over more traditional methods of choosing an arbitrary dose adjusted for body weight followed by dosage adjustments based on achieved plasma concentration.


Bacterial sinusitis as a cause of beak deformity in an Antipodes Island parakeet (Cyanoramphus unicolor).
From 26 days of age, an Antipodes Island parakeet (Cyanoramphus unicolor) was noted to have a severe beak deformity and reduced bodyweight gain compared to its nest mate. The bird was euthanised at 43 days of age. The beak abnormality consisted of distortion of the right nares and severe shortening resulting in deviation of the upper maxilla to the right and cranially. On sectioning the head, copious mucoid material was found in the infraorbital sinus and the bony sinus architecture was disrupted. Histopathological examination of the infraorbital sinuses revealed a large focus of chronic but active inflammation, bony lysis on the right side and pockets of a mixed population of bacteria. Severe beak deformity, likely secondary to bacterial sinusitis. The case illustrates the need to look for underlying aetiologies to beak malformation, particularly in young parrots. Sinusitis, beak malformation, Antipodes Island parakeet, parrot, beak growth.


A second update to the checklist of Finnish long-legged flies (Diptera: Dolichopodidae), with a re-evaluation of the status of Hydrophoruscallosoma Frey, 1915.
Eighteen species of long-legged flies (Dolichopodidae) are reported as new to Finland. A further species, Microphorellapraecox (Loew), is confirmed as a Finnish species. The status of Hydrophoruscallosoma Frey, 1915 is re-evaluated and a lectotype is designated for the species. Hydrophorusalbosignatus Ringdahl, 1919 is found to be a junior synonym of Hydrophoruscallosoma (syn. n.). Characters for identifying both sexes of Hydrophoruscallosoma and Hydrophorusaltivagus Aldrich are presented and illustrated with high-quality photographs.


Role of miR-24-3p and miR-146a-5p in dendritic cells' maturation process induced by contact sensitizers.
MiRNAs are non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Although allergic contact dermatitis has been studied extensively, few studies addressed miRNA expression and their role in dendritic cell activation. The main aim of this work was to investigate the role of miRNAs in the underlying mechanism of dendritic cell maturation induced by contact sensitizers of different potency. Experiments were conducted using THP-1-derived immature DCs (iDCs). Contact allergens of different potency were used: p-benzoquinone, Bandrowski's base, and 2,4-dinitrochlorobenzene as extreme; nickel sulfate hexahydrate, diethyl maleate and 2-mercaptobenzothiazole as moderate; and α-hexyl cinnamaldehyde, eugenol, and imidazolidinyl urea as weak. Selective inhibitor and mimic miRNAs were then used and several cell surface markers was evaluated as targets. Also, patients patch tested with nickel were analyzed to determine miRNAs expression. Results indicate an important role of miR-24-3p and miR-146a-5p in DCs activation. miR-24-3p was up-regulated by extreme and weak contact allergens, while miR-146a-5p was up-regulated by weak and moderate contact allergens and down-regulated only by the extreme ones. Also, the involvement of PKCβ in contact allergen-induced miR-24-3p and miR-146a-5p expression was demonstrated. Furthermore, the expression of the two miRNAs maintains the same trend of expression in both in vitro and in human conditions after nickel exposure. Results obtained suggest the involvement of miR-24 and miR-146a in DCs maturation process in the proposed in vitro model, supported also by human evidences.


Molecular cloning of a molluscan gonadotropin-releasing hormone receptor orthologue specifically expressed in the gonad.
Despite their economic importance, only very little information is available regarding (neuro)endocrine mechanisms of reproduction in bivalve molluscs. To gain insights into the molecular control of gonadic development of these animals, G protein-coupled receptors (GPCR) expressed in the gonad of the pacific oyster Crassostrea gigas were investigated. One such receptor was cloned by RT-PCR using oligonucleotide primers derived from consensus sequences of various vertebrate (neuro)peptide receptors. This receptor named Cg-GnRH-related receptor (Cg GnRH-R) exhibits a high degree of amino acid sequence identity with both vertebrate GnRH receptors and insect AKH receptors. Quantitative RT-PCR shows a specific expression of Cg-GnRH-R in both male and female gonads during the reproductive cycle. This demonstrates for the first time the plausible involvement of a GnRH receptor orthologue in the control of reproduction in a protostomian invertebrate.


Ruptured renal artery aneurysm: coil packing with GDCs.
Renal artery aneurysm (RAA) is a relatively uncommon occurrence, but it can be life-threatening when rupture (although rare) occurs. We present the successful endovascular treatment of a ruptured RAA, which was achieved by packing the aneurysm using Guglielmi and interlocking detachable coils.


Histidine decarboxylase in human basophilic leukemia (KU-812-F) cells. Characterization and induction by phorbol myristate acetate.
The human leukemic cell line KU-812-F is known to differentiate into mature basophil-like cells under serum-free culture conditions. In the present study, the activity of histidine decarboxylase (HDC), a histamine-forming enzyme, in KU-812-F cells was found to be high, ranging from 10 to 57 pmol/min/mg protein. The great variation in HDC activity appeared to be due to different percentages and degrees of maturity of basophil-like cells during differentiation of this cell line. The enzyme was inhibited by alpha-fluoromethylhistidine but not by carbidopa, was unable to form dopamine from L-3,4-dihydroxyphenylalanine, and had a Km value for histidine of 0.27 mM, indicating that it was HDC and not aromatic amino acid decarboxylase. The HDC activity increased 1.8-fold when the cells were stimulated by phorbol myristate acetate, which is known to activate protein kinase C, and this increase was blocked by staurosporine, a potent inhibitor of protein kinase C.


[Early results of first-line chemotherapy with paclitaxel and carboplatin in patients with epithelial ovarian carcinoma].
Paclitaxel-carboplatin combination chemotherapy has been administered worldwide in the first-line adjuvant treatment of epithelial ovarian cancers since the mid 1990's. Goal was to evaluate the early results of the first-line paclitaxel-carboplatin treatment practiced at the Gynecological Department of National Institute of Oncology, Budapest between November 2000 and August 2002. Paclitaxel and carboplatin were administered in the doses of 175 mg/m2/3 h and AUC 5, respectively. Average age of patients was 54 +/- 9.8 years. The patients were considered into stage I in 18.4% and in stage II-III and IV in 4.6%, 52.9% and 8%. The surgeon did not reported the stage in 16.1% of patients. Statistical analysis was performed by the product limit method of Kaplan and Meier. The progression free interval was found to be 100%, 50%, 71.7% and 71.4% in stages I, II, III and IV, at the end of the 6th chemotherapy course and decreased to 100%, 50%, 52.2% and 42.9% in the same stages at the time of evaluation (16 December 2002). Authors found a 77% CR in the patients at the end of chemotherapy. Only progression free interval till the end of treatment could be evaluated because of the short follow up period. The observed 77% CR is similar to the data of the literature. The final conclusions will be made by later follow up.


Universities and the clinical monitoring industry: feckless independents or fruitful partners?
Since 1955 clinical monitoring in anesthesia care and critical care has improved markedly. However, both industry and academia find temptation to congratulate themselves on this achievement. Reflection, however, might suggest that, in comparison with analogous unrelated fields, the process of progress has been tardy, wasteful, expensive, and inefficient. 'State of the art' clinical monitoring may actually be viewed as woefully inadequate when measured by the yardstick of the possible. Analysis suggests that industry sometimes fails to grasp opportunities for progress by shared effort while academia, sometimes guilty of aloofness and isolation, may occasionally fail to cooperate actively to promote progress by sharing its experience with industry. To hasten the more efficient development of clinical monitoring by a new alliance of the clinical monitoring and computing industry and those universities, professors, and physicians with interests in clinical monitoring and computing is here proposed. A Foundation for Research, Development, and Advancement of Clinical Monitoring and Computing Devices should be established, to promote basic and practical research and development (R&D), sponsor shared specialized clinical testing facilities, special scholarships for physicians training as specialists in development of clinical monitoring devices, and promote and expand continuing medical education programs. By this multidisciplinary, cooperative activity, it is asserted that progress in the introduction of useful new clinical monitoring devices can be accelerated.


Flow cytometric evidence for minimal residual disease and cytological heterogeneities in acute lymphoblastic leukemia with severe hypodiploidy.
Two subpopulations of small and large leukemia cells and binucleated cells were present in the bone marrow of a 10-year-old girl with acute lymphoblastic leukemia (ALL). Cytogenetic studies showed some cells with a karyotype of 34,X,-X,-2,-3,-4,-5,-7,-9,-13,-15,-16,-17,-20, and others with a karyotype that was exactly double the chromosome set in the cells with 34 chromosomes. Flow cytometric (FCM) examination of surface common ALL antigen (CALLA) and DNA content of the lymphoblasts led to the identification of the primary hypodiploid DNA stemline (DI = 0.72), which corresponds to the small-sized blasts, and the secondary hyperdiploid DNA stemline (DI = 1.44), which corresponds to the large-sized blasts. Sequential bone marrow examinations with FCM and cytogenetics revealed the persistence of the primary hypodiploid clone during remission and their proliferation with chromosomal evolution at full relapse. These results suggest that more rational inductive therapy should be designed to achieve the favorable outcome of ALL with severe hypodiploidy and that FCM is a useful tool to monitor the minimal residual disease of this subgroup in ALL.


The zinc-finger protein ZCCHC2 suppresses retinoblastoma tumorigenesis by inhibiting HectH9-mediated K63-linked polyubiquitination and activation of c-Myc.
Retinoblastoma (RB) is the most common intraocular malignancy. The tumor propagation of RB is maintained by several core transcriptional regulators, including c-Myc. Strictly regulated posttranslational modifications control the c-Myc protein. However, the posttranslational regulatory mechanisms for c-Myc in retinoblastoma remain largely unclear. Here, we identified the zinc-finger protein ZCCHC2 as a critical negative regulator of c-Myc-associated tumorigenesis. Knockout of ZCCHC2 promoted retinoblastoma cell proliferation, whereas ZCCHC2 overexpression had the opposite effect. Meanwhile, the level of ZCCHC2 was positively correlated with retinoblastoma tumorigenesis and animal survival in vivo. Mechanistically, ZCCHC2 was associated with c-Myc and negatively regulated the K63-linked polyubiquitination of c-Myc. We demonstrated that ZCCHC2 inhibits the interaction of the E3 ubiquitin ligase HectH9 with c-Myc and that ZCCHC2 inhibits HectH9-mediated K63-linked polyubiquitination and activation of c-Myc. Altogether, these data suggest that ZCCHC2 plays a role in the regulation of RB tumorigenesis through the inhibition activity of c-Myc.


A High-Energy Diet and Spirulina Supplementation during Pre-Gestation, Gestation, and Lactation do Not Affect the Reproductive and Lactational Performance of Primiparous Sows.
Feeding high-energy (HED) or high-fat diets during gestation and lactation to pigs may help cover the energy requirements of high-prolific sows but may also adversely affect their reproductive performance. The microalga Arthrospira plantensis (Sp), rich in bioactive compounds, has been described to exert beneficial health effects. The present study investigated the effects of HED and Sp intake during gestation and lactation in pigs. Twenty-four primiparous crossbred sows were fed either a HED or a control diet. Half of the sows per group were supplemented with 20 g/day of Sp. Despite a higher gross energy intake, consuming the HED did not affect the sows' reproductive and lactational performance but significantly modified the colostrum fatty acid (FA) composition and tended to decrease the number of weaned piglets. The Sp supplementation did not affect the reproduction and lactation traits, but slightly affected the colostrum FA composition. A trend was observed for an interaction of diet and Sp in terms of offspring sex ratio with a 50% lower male-to-female ratio in the HED group compared to all other animals. These findings suggest that an HED and Sp intake hardly influence reproduction in sows. However, the HED modified the colostrum FA composition, whereas the Sp had only fewer effects, which may potentially affect offspring performance.


Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.
The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. Retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-hour proteinuria from SGLT2i initiation to 3,6,9,12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate(eGFR), proteinuria reduction by type of disease, and reduction of proteinuria ≥ 30% from SGLT2i initiation. Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8%, -10.5% at 3,6,9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as predictor of ≥ 30% proteinuria reduction (odds ratio for albumin < 3.5 g/dl: 0.53; 95%CI 0.30-0.91; p = 0.02). A slower eGFR decline was observed in patients achieving a ≥ 30% proteinuria reduction: -3.7 versus -5.3 ml/min/1.73m2/year (p = 0.001). The overall tolerance to SGLT2i was good. The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥ 30% proteinuria reduction.


Design of naturally inspired jellyfish-shaped cyclopolylactides to manage osteosarcoma cancer stem cells fate.
We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c-PLA, c-PLA-FA, c-PLA-Rhod) obtained by an optimized combination of ROP and click chemistry reactions. Cyclo-PLA having a number average molecular weight of 6000 g mol-1 and a polydispersity index of 1.52 was synthetized by click ring-closure of well-defined α,ω-heterodifunctional linear precursors, followed by quaternarization of N3-triazole nodes, and subsequent CuAAC with azido-folate and azido-rhodamine yielding jellyfish-shaped c-PLA-FA and c-PLA-Rhod. Salinomycin (Sal) was loaded into jellyfish-shaped c-PLA-FA and c-PLA-Rhod nanoparticles (NPs) by nanoprecipitation, with a good encapsulation efficiency (79% and 84%, respectively) and loading content (7.1% and 7.6%, respectively). The biological studies focused on their antiproliferative effects on osteosarcoma bulk MG63 and cancer stem cells (CSCs). The cycloPLA-based NPs, with a size ranging between 125 and 385 nm, killed CSCs and MG63, with a higher efficacy on CSCs; they (unloaded or Sal-loaded) evoked on CSCs a cellular response similar to the payload, with a higher effect than the free Sal. Internalization studies indicated a fast cellular uptake (within 2 h) and sarcospheres remained fluorescent till 72 h. To the best of our knowledge, this is the first study reporting anti-CSCs properties of cycloPLA with jellyfish architecture and we believe could contribute to the development of effective strategies for osteosarcoma targeting.


Sleep learning during stage 2 and REM sleep.
Pairs of subjects were presented with a 20-item picture series at bedtime. In the latter part of the night, a tape-recorded series of 10 words, the verbal equivalent of half the original series of pictures, was repeated 10 times during either Stage 2 or REM sleep. Morning recall and recognition for repeated words was found to be facilitated following repetition during Stage 2 sleep, but relatively unaffected following repetition during REM sleep. However, adjusting for recall, the number of additional words elicited through recognition was found to be significantly greater for REM repeated words than for Stage 2 repeated words. It was suggested that retrieval limitations, perhaps as a result of REM state dependency, rather than storage inhibition may be the main locus of the initial recall failure. By comparison, Stage 2 sleep would seem to present both a lower barrier to memory storage and retrieval compatibility with wakefulness.


Regulation of PCNA and CAF-1 expression by the two tuberous sclerosis gene products.
Tuberous sclerosis is an autosomal dominant tumor suppressor gene syndrome affecting about 1 in 6000 individuals. Two genes have been shown to be responsible for this disease: TSC1, encoding hamartin and TSC, encoding tuberin. A variety of tumors characteristically occur in different organs of tuberous sclerosis patients and are believed to result from defects in cell cycle/cell size control. In this study, we performed two-dimensional gel electrophoresis with subsequent mass spectrometrical identification of protein spots after overexpression of TSC1 or TSC2. We found expression of PCNA and the p48 subunit of CAF-1 to be regulated by two tuberous sclerosis gene products. CAF-1 and PCNA interact as major regulators of chromatin assembly during DNA repair. We suggest that deregulation of the control of chromatin assembly might contribute to development of tumors in tuberous sclerosis patients and provide important new insights into the molecular development, especially since deregulation of chromatin assembly and DNA repair results in genomic instability, a hallmark of tumor development.


Trophic versus structural effects of a marine foundation species, giant kelp (Macrocystis pyrifera).
Foundation species create milieus in which ecosystems evolve, altering species abundances and distribution often to a dramatic degree. Although much descriptive work supports their importance, there remains little definitive information on the mechanisms by which foundation species alter their environment. These mechanisms fall into two basic categories: provision of food or other materials, and modification of the physical environment. Here, we manipulated the abundance of a marine foundation species, the giant kelp Macrocystis pyrifera, in 40 × 40-m plots at Mohawk Reef off Santa Barbara, California and found that its biomass had a strong positive effect on the abundance of bottom-dwelling sessile invertebrates. We examined the carbon (C) stable isotope values of seven species of sessile invertebrates in the treatment plots to test the hypothesis that this positive effect resulted from a nutritional supplement of small suspended particles of kelp detritus, as many studies have posited. We found no evidence from stable isotope analyses to support the hypothesis that kelp detritus is an important food source for sessile suspension-feeding invertebrates. The isotope composition of invertebrates varied with species and season, but was not affected by kelp biomass, with the exception of two species: the tunicate Styela montereyensis, which exhibited a slight enrichment in C stable isotope composition with increasing kelp biomass, and the hydroid Aglaophenia sp., which showed the opposite effect. These results suggest that modification of the physical habitat, rather than nutritional subsidy by kelp detritus, likely accounts for increased abundance of sessile invertebrates within giant kelp forests.


Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions.
To explore the role of nitric oxide (NO) in controlling microvascular O2 pressure (P(O2)mv) at rest and during contractions (1 Hz). We hypothesized that at the onset of contractions sodium nitroprusside (SNP) would raise P(O2)mv and slow the kinetics of P(O2)mv change whereas l-nitro arginine methyl ester (L-NAME) would decrease P(O2)mv and speed its kinetics. We superfused the spinotrapezius muscle of female Sprague-Dawley rats (n = 7, body mass = 298 +/- 10 g) with SNP (300 microM) and L-NAME (1.5 mm) and measured P(O2)mv (phosphorescence quenching) during contractions. SNP decreased mean arterial pressure (92 +/- 5 mmHg) below that of control (CON, 124 +/- 4 mmHg) and L-NAME (120 +/- 4 mmHg) conditions. SNP did not raise P(O2)mv at rest but it did elevate the P(O2)mv-to-MAP ratio (50% increase, P < 0.05) and slow the kinetics by lengthening the time-delay (TD, 14.0 +/- 5.0 s) and time constant (tau, 24.0 +/- 10.0 s) of the response compared with CON (TD, 8.4 +/- 3.3 s; tau, 16.0 +/- 4.5 s, P < 0.05 vs. SNP). L-NAME decreased P(O2)mv at rest and tended to speed tau (10.1 +/- 3.8 s, P = 0.1), while TD (8.1 +/- 1.0 s) was not significantly different. L-NAME also caused P(O2)mv to fall transiently below steady-state contracting values. These results indicate that NO availability can significantly affect P(O2)mv at rest and during contractions and suggests that P(O2)mv derangements in ageing and chronic disease conditions may potentially result from impairments in NO availability.


Comparative virulence of some English strains of Haemophilus pleuropneumoniae serotypes 2 and 3 in the pig.
Between 10(7.5) and 10(8.1) viable organisms of four English and one Danish strain of Haemophilus pleuropneumoniae serotype 2 and five English strains of serotype 3 were inoculated intranasally into groups of conventional pigs. Among the English isolates of both serotypes there were virulent and non-virulent strains. Four of the serotype 2 strains, including the Danish strain, and two of the serotype 3 strains produced varying degrees of pulmonary consolidation with abscess formation and pleurisy in at least three of the five pigs in the individual groups. H pleuropneumoniae was isolated from the pulmonary lesions in all save one instance, frequently from the tonsil but less frequently from other parts of the respiratory tract. Purulent arthritis and tenosynovitis developed in one animal infected with serotype 3. Apart from the latter pig no clinical signs of illness were detected except for febrile reactions which reflected the prevalence of the thoracic lesions in the various groups. A humoral antibody response was detected by indirect immunofluorescence in two-thirds of the pigs which developed lesions but in fewer by complement fixation.


Pathogenesis of chronic obstructive pulmonary disease.
The pathogenesis of chronic obstructive pulmonary disease (COPD) encompasses a number of injurious processes, including an abnormal inflammatory response in the lungs to inhaled particles and gases. Other processes, such as failure to resolve inflammation, abnormal cell repair, apoptosis, abnormal cellular maintenance programs, extracellular matrix destruction (protease/antiprotease imbalance), and oxidative stress (oxidant/antioxidant imbalance) also have a role. The inflammatory responses to the inhalation of active and passive tobacco smoke and urban and rural air pollution are modified by genetic and epigenetic factors. The subsequent chronic inflammatory responses lead to mucus hypersecretion, airway remodeling, and alveolar destruction. This article provides an update on the cellular and molecular mechanisms of these processes in the pathogenesis of COPD.


Advantage of the use of human liver S9 in the Ames test.
The mutagenicity of 13 chemicals was compared using human liver S9 or liver S9 prepared from male Sprague-Dawley rats either non-treated (R-n) or pretreated with phenobarbital/5,6-benzoflavone (R-i). The test compounds used in this study were well recognized procarcinogens requiring cytochrome P450 for metabolic activation. These included polycyclic aromatic hydrocarbons, aromatic amines, heterocyclic aromatic amines, nitrosoamines, and nitropyrene. We used four human liver S9 fractions, one of which was prepared from the liver sample having higher levels of the P450-catalyzed drug metabolizing enzyme activities, a possible explanation for which was enzyme induction by anti-asthma agents for 10 years. The results of the present study are as follows: (1) there were individual differences in the magnitude of the mutagenic activity of the procarcinogens by each S9 fraction used, (2) equivalent mutagenicity of chemicals was seen with three human S9 fractions (H3, H8, and H12), while a human H14 S9 fraction showed higher P450 enzyme activity, leading to much higher mutagenicity than the other three human S9 specimens, (3) the order of magnitude of the mutagenicity of the procarcinogens using human and rat liver S9 fractions was R-i>/=H14>/=R-n>/=H3, H8, and H12, while with 2-aminoanthrathene, N-nitrosodimethylamine, and 1-nitropyrene, this relationship was H3, H8, H12, and H14>/=R-n>/=R-i. The experimental data in the present study strongly suggest that the complementary use of human liver S9 fraction in the Ames test is a much more useful tool than rat S9 for evaluation of genotoxicity to humans.


Atypical repair on Pap smears: clinicopathologic correlates in 647 cases.
The Bethesda system separates atypical reparative changes (ARC) from "typical" repair and places it into the atypical squamous cells of undetermined significance (ASC-US) category. The cytologic diagnosis of ARC represents both diagnostic and management challenges because its clinical significance is controversial and has not been fully investigated. On the basis of scant literature on follow-up of women with ARC on Papanicolaou (Pap) test, we reviewed data from our patient population, which consists of a mixture of low- and high-risk women. Six hundred forty-seven patients with ARC on their Pap tests were identified in a 7-yr period. Of this, 189 (29%) women were lost to follow-up. Of the 458 women with follow-up, 31% had cervical biopsies and 69% were followed by repeated Pap tests. The age ranged from 16 to 86 (mean 47 yr). The incidence of squamous intraepithelial lesion was 5.2% (5% low-grade and 0.2% high-grade). Most women (62%) with ARC on Pap test had a benign condition on follow-up. For some women, the immediate cause was not known and the Pap abnormality resolved spontaneously. Our study questions the validity of reporting ARC within the ASC-US category.


Clinical-radiomics-based treatment decision support for KIT Exon 11 deletion in gastrointestinal stromal tumors: a multi-institutional retrospective study.
gastrointestinal stromal tumors (GISTs) with KIT exon 11 deletions have more malignant clinical outcomes. A radiomics model was constructed for the preoperative prediction of KIT exon 11 deletion in GISTs. Overall, 126 patients with GISTs who underwent preoperative enhanced CT were included. GISTs were manually segmented using ITK-SNAP in the arterial phase (AP) and portal venous phase (PVP) images of enhanced CT. Features were extracted using Anaconda (version 4.2.0) with PyRadiomics. Radiomics models were constructed by LASSO. The clinical-radiomics model (combined model) was constructed by combining the clinical model with the best diagnostic effective radiomics model. ROC curves were used to compare the diagnostic effectiveness of radiomics model, clinical model, and combined model. Diagnostic effectiveness among radiomics model, clinical model and combine model were analyzed in external cohort (n=57). Statistics were carried out using R 3.6.1. The Radscore showed favorable diagnostic efficacy. Among all radiomics models, the AP-PVP radiomics model exhibited excellent performance in the training cohort, with an AUC of 0.787 (95% CI: 0.687-0.866), which was verified in the test cohort (AUC=0.775, 95% CI: 0.608-0.895). Clinical features were also analyzed. Among the radiomics, clinical and combined models, the combined model showed favorable diagnostic efficacy in the training (AUC=0.863) and test cohorts (AUC=0.851). The combined model yielded the largest AUC of 0.829 (95% CI, 0.621-0.950) for the external validation of the combined model. GIST patients could be divided into high or low risk subgroups of recurrence and mortality by the Radscore. The radiomics models based on enhanced CT for predicting KIT exon 11 deletion mutations have good diagnostic performance.


[Intravenous regional anesthesia (author's transl)].
Experiences, with about 1500 cases of intravenous regional anesthesia in outpatient surgery of the limbs over 10 years are reported. In 1975, 158 operations out of 5960 were done using this technique. Intravenous regional anesthesia is suitable for surgery of the limbs, but time of operation should not exceed 90 min, nor should hemostasis be a major problem to consider and the course of surgery should be predictable. Contraindications for this type of anesthesia are hypertonia, lack of accessible veins, heart failure, children, as well as surgery of undefinite extent or for local sepsis. When these rules were followed, no serious complications were seen.


Marital adjustment among patients with chronic obstructive pulmonary disease who are participating in pulmonary rehabilitation.
Marital adjustment has been associated with morbidity and mortality across various chronic diseases but has been largely ignored among patients with chronic obstructive pulmonary disease (COPD). This study was designed to evaluate the relationship among marital adjustment, quality of life, psychologic functioning, and functional capacity among married patients with COPD who are participating in a 5-week exercise rehabilitation program and their spouses. A convenience sample of 31 patients with COPD and their partners was included. A prospective 1-group pretest-posttest study was conducted. Marital adjustment scores indicated that patients and partners were, on average, satisfied with their marriages. Patient marital adjustment was associated with patient psychologic well-being, whereas partner marital adjustment was associated with patient physical functioning. In addition, patient and partner perceptions of marital adjustment predicted change in patient functioning after exercise rehabilitation. Patients who entered the program with poor marital adjustment experienced a greater magnitude of improvement in mental health after rehabilitation than did well-adjusted patients. These findings suggest that marital adjustment is associated with both psychologic well-being and physical functioning among patients with COPD, and that it may predict change among patients with COPD participating in exercise rehabilitation.


A quantitative and qualitative analysis of ultrasonic versus sonic endodontic systems on canal cleanliness and obturation.
The purpose of this study was to compare 2 irrigation techniques by evaluating canal cleanliness and obturation of lateral/accessory canals. Seventy-five extracted canines were instrumented to a size #40/0.06 taper. The EndoActivator (EA) was compared with an ultrasonic unit for final irrigation. Each unit was used for 1 minute each with 6.15% NaOCl and 17% EDTA. A control group received syringe irrigation. Thirty teeth were sectioned and evaluated for debris removal and open dentinal tubules at 3/5 mm from the apical foramen with a scanning electron microscope. Forty-five teeth were examined for obturation of lateral canals. The EA was significantly better in removing debris at all levels when compared with other treatment groups (P < .05) and resulted in obturation of significantly more numbers of lateral canals (P < .01.) The EA provided better obturation of lateral and accessory canals and resulted in less remaining debris.


Toxic trace metals in food. II. A comparative study of the levels of toxic trace metals in wine by differential pulse anodic stripping voltammetry and electrothermal atomic absorption spectrometry.
A new high-performance analytical procedure for the determination of the toxic trace metals cadmium, lead and copper in wines by differential pulse anodic-stripping voltammetry (DPASV) subsequent to UV irradiation of the sample is compared with the hitherto more common application of electrothermal atomic absorption spectrometry (AAS). In this manner also mutually the accuracy attainable with both alternatives has been established. The particularly favourable potentialities of the new voltammetric approach for toxic metal control of wines are demonstrated by the investigation of a typical selection of 36 wines from recent vintages and common vine types of the German and some European wine cultivating regions.


Evaluating economic and ecological management to determine the economic size of pastoral units for different climatic zones in the northeast of Iran.
Stocking rate and rangeland area are key variables to provide the livelihood of herders in different climatic zones. To evaluate the economic and ecological management of pastoral units, this study aims to determine the optimal economic size of pastoral units for livestock grazing use considering the ecological capacity of semi-arid rangelands in different climatic scenarios. Therefore, 12 pastoral units (an area of 47,355 ha) were selected in two climatic zones (summer and winter rangelands) in the Kalat region of Razavi Khorasan Province, Iran. By measuring forage production, carrying capacity was calculated. Based on the results, the costs of traditional livestock management in winter rangelands are higher than those of summer rangelands. Moreover, the current size of the assigned rangeland, especially the summer rangeland, is lower than that of the economic justification. The results emphasize that rangeland-based livestock husbandry cannot create a good livelihood for herders in the region, and it is necessary to pay special attention to other services and aspects, despite the existing ecological and socio-economic complexities. In this regard, providing multi-purpose rangeland use and useable technologies to better manage these areas is necessary to increase per capita household income and reduce the stocking rate in the region's rangelands. Ultimately, both increasing the level of available rangelands and reducing costs by applying new technology are required, as is the economic consideration of pastoral units by using rangelands for multiple purposes.


Job satisfaction of primary healthcare professionals: a cross-sectional survey in Greece.
The role of job satisfaction is essential for the operation of public Primary Healthcare Centers in Greece. The dimensions of job satisfaction can be used to gauge employees' engagement and performance. Job Satisfaction Survey was employed among healthcare professionals in 32 Primary Healthcare Centers, between June 2019 and October 2020. The 36 items of the questionnaire are expressed on a six-point Likert scale divided into 9 aspects: salary, promotion, supervision, fringe benefits, contingent rewards, operating procedures, co-workers, nature of work, and communication. Additional questions were added covering sociodemographic characteristics. A total of 1,007 professionals completed the questionnaire (83.92% response rate), of which 51.04% were nurses, 27.61% physicians, and 21.35% other healthcare employees. The average overall job satisfaction score indicates ambivalence (3.63 out of 6). Participants were dissatisfied with salaries (2.38) and promotion (2.84) aspects and ambivalent regarding fringe benefits (3.04), operating procedures (3.23), and contingent rewards (3.30). Moderate satisfaction was reported for the nature of work (4.53), supervision (4.52), co-workers (4.37), and communication (4.22). Nurses by far reported the lower levels of satisfaction in all dimension except communication compared to the other groups. The findings suggest that decreasing administrative workload and the improvement of working conditions, procedures, payment, and provision of better opportunities for the promotion of PHC professionals might be the most effective ways to subsequently improve their subjective well-being and their job satisfaction which in turn will improve their performance.


Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy.
Topical corticosteroids are frequently used drugs, but little is known of the exposure during pregnancy and birth outcome. In a population-based follow-up study restricted to primigravida women, we examined the risk of low birth weight, malformations and other birth outcomes following pregnancy upon exposure to topical corticosteroids. We compared the offspring of 363 women exposed to topical corticosteroids during pregnancy with 9263 controls, who received no prescriptions at all. The prevalence of malformations was 2.9% among 170 infants exposed during the first trimester and 3.6% among the controls. Adjusted odds ratios for low birth weight, malformations and preterm delivery among women receiving weak/medium strong corticosteroids were 0.7 (95% CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively, and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI 0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively. The study showed no increased risk of low birth weight, malformations or preterm delivery in the offspring of women exposed to topical corticosteroid during pregnancy.


Patterning with Diffusion Barriers.
Notch signaling instructs equivalent cells to form precise differentiation patterns. In this issue of Developmental Cell, Cinquin et al. (2015) characterize diffusion barriers that enhance Notch patterning within the Caenorhabditis elegans gonad.


Study the prevalence of rifampicin resistance among pulmonary tuberculosis patients by genexpert assay from a tertiary care hospital of North India.
Rifampicin (RIF) resistance (RR) tuberculosis (TB) has posed a great challenge to TB control programs globally. Evidence of RIF-RR can help as a surrogate marker to find out multidrug-resistance cases. The study aimed to determine the prevalence of RIF-RR in pulmonary TB (PTB) patients over the 4 years at Dr. RPGMC, Tanda, from the year 2018 to 2021. This was a retrospective study conducted at Dr. RPGMC, Tanda at Kangra, where we checked (from January 2018 to December 2021) clinically suspected PTB patients, whose samples were sent to the laboratory for GeneXpert assay to identify Mycobacterium TB/RIF (MTB/RIF) testing. Of the total 11,774 clinically suspected PTB specimens were collected, and identified by GeneXpert MTB/RIF assay, in which 2358 samples were MTB positive and 9416 were MTB negative. Among 2358 MTB-positive samples, 2240 (95%) samples were RIF sensitive, in which 1553 (65.9%) were males and 687 (29.1%) were females, 76 (3.2%) samples were RIF-RR, in which 51 (2.2%) were males and 25 (1%) were females, and 42 (1.8%) samples were RIF indeterminate, in which 25 (1%) were males and 17 (0.8%) were females. The rate of RIF-RR was found 3.2% of total samples which was more in males. The overall positivity rate was 20%, and the rate of positivity decreased from 32% to 14% over the 4 years in sputum samples. Hence, the GeneXpert assay was found to be very important tool to detect RIF-RR among suspected PTB patients.


Making the implicit explicit: A visual model for lowering the risk of implicit bias of mental/behavioural disorders on safety and quality of care.
Persons with mental illness and/or addictions have poorer health outcomes than the general population. Lower quality of healthcare has been identified as an important factor. A main contributor to lower quality of care for people with mental illnesses and/or addictions may be the cognitive implicit bias of mental versus physical care when assessing and categorizing a patient's clinical presentation. The objective of this article is to highlight how this implicit cognitive bias of mental versus physical care can result in human factor risks to quality of care. We provide three specific case examples of where these quality concerns arise. We also propose the use of a new visual tool to help educate and create awareness of this implicit-bias-based risk and quality care problem.


Localization of the noncovalent binding site between amyloid-beta-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry.
Abnormal accumulation and aggregation of amyloid-beta-peptide (Abeta) eventually lead to the formation and cerebral deposition of amyloid plaques, the major pathological hallmark in Alzheimer's disease (AD). Oleuropein (OE), an Olea europaea L. derived polyphenol, exhibits a broad range of pharmacological properties, such as antioxidant, anti-inflammatory, and antiatherogenic, which could serve as combative mechanisms against several reported pathways involved in the pathophysiology of AD. The reported noncovalent interaction between Abeta and OE could imply a potential antiamyloidogenic role of the latter on the former via stabilization of its structure and prevention of the adaptation of a toxic beta-sheet conformation. The established beta-sheet conformation of the Abeta hydrophobic carboxy-terminal region and the dependence of its toxicity and aggregational propensity on its secondary structure make the determination of the binding site between Abeta and OE highly important for assessing the role of the interaction. In this study, two different proteolytic digestion protocols, in conjunction with high-sensitivity electrospray ionization mass spectrometric analysis of the resulting peptide fragments, were used to determine the noncovalent binding site of OE on Abeta and revealed the critical regions for the interaction.


Quantification of brain atrophy in patients with myotonic dystrophy and proximal myotonic myopathy: a controlled 3-dimensional magnetic resonance imaging study.
Myotonic dystrophy (DM1) and proximal myotonic myopathy (PROMM or DM2) are two distinct muscular disorders with multisystemic involvement. Both have previously been reported to be associated with cognitive impairment and white matter lesions detected by cerebral magnetic resonance imaging (MRI). In this study, the extent of brain atrophy was investigated in vivo in ten DM1 and nine PROMM patients in comparison to age-matched healthy controls for each group. The diagnosis was confirmed by DNA analysis of all patients. As a quantitative marker, the ratio of brain parenchymal to intracranial volume, called brain parenchymal fraction (BPF), was calculated from 3-dimensional MRI data using an automated analysis technique. Compared to age-matched healthy controls (mean BPF 0.852 +/- 0.032), the BPF in DM1 patients (0.713 +/- 0.031) was highly significantly decreased (P < 0.001). In contrast, the PROMM patients (mean BPF 0.792 +/- 0.029) showed only slightly decreased BPF values (P < 0.05). BPF was not significantly correlated to any of the clinical or genetic parameters in both diseases (disease duration, motor score, educational level, and number of CTG repeats in the expanded allele). In summary, global brain atrophy was demonstrated to occur in both diseases, but was more severely manifestated in DM1 patients.


A pregnancy complicated by mature abdominal burn scarring and its surgical solution: a case report.
Complications of pregnancy secondary to old abdominal burn scars are uncommon but have been reported. Common problems include failure of the scar to stretch (resulting in uterine displacement), maternal discomfort, and occasionally scar breakdown. We report the case of a 23-year-old patient who had a tight circumferential scar involving the majority of the abdomen. The uninvolved skin of the lower abdomen stretched remarkably, but the uterus was displaced inferiorly and anteriorly by the scar. The pregnancy progressed to term under careful supervision. After delivery, a flap created by the naturally expanded skin of the lower abdomen was used to replace a portion of the abdominal burn scar to prevent similar problems in future pregnancies. We know of no other reported case where the naturally expanded skin of pregnancy was used to reconstruct a mature burn scar.


A Swin Transformer-based model for mosquito species identification.
Mosquito transmit numbers of parasites and pathogens resulting in fatal diseases. Species identification is a prerequisite for effective mosquito control. Existing morphological and molecular classification methods have evitable disadvantages. Here we introduced Deep learning techniques for mosquito species identification. A balanced, high-definition mosquito dataset with 9900 original images covering 17 species was constructed. After three rounds of screening and adjustment-testing (first round among 3 convolutional neural networks and 3 Transformer models, second round among 3 Swin Transformer variants, and third round between 2 images sizes), we proposed the first Swin Transformer-based mosquito species identification model (Swin MSI) with 99.04% accuracy and 99.16% F1-score. By visualizing the identification process, the morphological keys used in Swin MSI were similar but not the same as those used by humans. Swin MSI realized 100% subspecies-level identification in Culex pipiens Complex and 96.26% accuracy for novel species categorization. It presents a promising approach for mosquito identification and mosquito borne diseases control.


Biochemical biorefinery: A low-cost and non-waste concept for promoting sustainable circular bioeconomy.
The transition from a fossil-based linear economy to a circular bioeconomy is no longer an option but rather imperative, given worldwide concerns about the depletion of fossil resources and the demand for innovative products that are ecocompatible. As a critical component of sustainable development, this discourse has attracted wide attention at the regional and international levels. Biorefinery is an indispensable technology to implement the blueprint of the circular bioeconomy. As a low-cost, non-waste innovative concept, the biorefinery concept will spur a myriad of new economic opportunities across a wide range of sectors. Consequently, scaling up biorefinery processes is of the essence. Despite several decades of research and development channeled into upscaling biorefinery processes, the commercialization of biorefinery technology appears unrealizable. In this review, challenges limiting the commercialization of biorefinery technologies are discussed, with a particular focus on biofuels, biochemicals, and biomaterials. To counteract these challenges, various process intensification strategies such as consolidated bioprocessing, integrated biorefinery configurations, the use of highly efficient bioreactors, simultaneous saccharification and fermentation, have been explored. This study also includes an overview of biomass pretreatment-generated inhibitory compounds as platform chemicals to produce other essential biocommodities. There is a detailed examination of the technological, economic, and environmental considerations of a sustainable biorefinery. Finally, the prospects for establishing a viable circular bioeconomy in Nigeria are briefly discussed.


Influence of inoculum size on aflatoxin production in home-made yoghurt.
In previous works we have studied the influence of different factors on the aflatoxin production in yoghurt. In the present paper we complete our investigations with the study of the influence of the inoculum size.The inoculum sizes used by us were from 4 × 10(1) to 4 × 10(6). As can be expected, the fungal growth, expressed as dry mycelium weight, was lower in 4 × 10(1) and higher in 4 × 10(6).The amount of aflatoxin in the mycelium was stable, or increased slightly with the inoculum size. In the substrate, the amount of aflatoxin was stable with little fluctuations, with a higher level of toxin in 4 × 10(3) and lower one in 4 × 10(6). We detected a higher aflatoxin level in the mycelium than in the substrate.


Information entropy tradeoffs for efficient uncertainty reduction in estimates of air pollution mortality.
Implementing effective policy to protect human health from the adverse effects of air pollution, such as premature mortality, requires reducing the uncertainty in health outcomes models. Here we present a novel method to reduce mortality uncertainty by increasing the amount of input data of air pollution and health outcomes, and then quantifying tradeoffs associated with the different data gained. We first present a study of long-term mortality from fine particulate matter (PM2.5) based on simulated data, followed by a real-world application of short-term PM2.5-related mortality in an urban area. We employ information yield curves to identify which variables more effectively reduce mortality uncertainty when increasing information. Our methodology can be used to explore how specific pollution scenarios will impact mortality and thus improve decision-making. The proposed framework is general and can be applied to any real case-scenario where knowledge in pollution, demographics, or health outcomes can be augmented through data acquisition or model improvements to generate more robust risk assessments.


Determination of 17-oxosteroid glucuronides and sulphates in urine by liquid chromatography using 2,4-dinitrophenylhydrazine as a prelabelling reagent for spectrophotometric detection.
A direct, convenient method using high-performance liquid chromatography with spectrophotometric detection has been developed for the determination of conjugated 17-oxosteroids in urine without hydrolysis. Conjugated 17-oxosteroids are extracted with a Sep-Pak C18 cartridge, prelabelled with 2,4-dinitrophenylhydrazine in trichloroacetic acid-benzene solution and then separated by high-performance liquid chromatography on a reversed-phase C18 column using a mobile phase of 70% methanol in a buffer consisting of 50 mM sodium acetate in 2% (v/v) acetic acid. The eluate is monitored by a spectrophotometer at 380 nm and a linear response was found for absorbance readings (peak heights) from amounts of various conjugated oxosteroids between 25 and 250 ng. The method provides a sensitive, reliable technique for the analysis of urinary 17-oxosteroid conjugates.


Prevalence and prognostic impact of inhalation injury among burn patients: A systematic review and meta-analysis.
The objective of our study was to perform a systematic review and meta-analysis aimed at assessing the prevalence of inhalation injury in burn patients and its prognostic value in relation to in-hospital mortality. We searched the PubMed and EMBASE databases for noninterventional studies published between 1990 and 2018 investigating in-hospital mortality predictors among burn patients.The primary meta-analysis evaluated the association between inhalation injury and mortality. A secondary meta-analysis determined the global estimate of the prevalence of inhalation injury and the rate of mortality. Random effects models were used, and univariate meta-regressions were used to assess sources of heterogeneity. This study is registered in the PROSPERO database with code CRD42019127356. Fifty-four studies including a total of 408,157 patients were selected for the analysis. A pooled inhalation prevalence of 15.7% (95% confidence interval, 13.4%-18.3%) was calculated.The summarized odds ratio of in-hospital mortality secondary to an inhalation injury was 3.2 (95% confidence interval, 2.5-4.3). A significantly higher odd of mortality was found among the studies that included all hospitalized burn patients, those that included a lower proportion of male patients, those with a lower mean total body surface area, and those with a lower prevalence of inhalation injury. Despite our study's limitations due to the high risk of bias and the interstudy heterogeneity of some of our analyses, our results revealed a wide range of prevalence rates of inhalation injury and a significant association between this entity and in-hospital mortality in burn patients. However, this association is not significant if adjusted for disease severity. Systematic review/meta-analysis, level III.


Cellular response to tissue hypoxia and its involvement in disease progression.
Multicellular organisms show adaptive reactions for their survival when they are exposed to an atmosphere with reduced oxygen concentration. These reactions include increase in respiratory volume, switch from aerobic to anaerobic metabolism, erythropoiesis and angiogenesis. For these reactions, cells must change the expression of several hypoxia-responsive molecules such as erythropoietin and vascular endothelial growth factor. Hypoxia-responsible element (HRE) was delineated in the genes of hypoxia-responsive molecules as the sequence indispensable for their hypoxia-induced transcriptional activation, and hypoxia-inducible factor 1 (HIF-1) was identified as a transcriptional factor that binds to HRE and regulates the expression of various hypoxia-responsive molecules. Increasing evidence has revealed that HIF-1 is a key molecule regulating the cellular response to tissue hypoxia. HIF-1 is composed of two subunits, HIF-1alpha and HIF-1beta, and HIF-1 activity depends mainly on the intracellular level of HIF-1alpha protein, which is regulated to be in inverse relation to the oxygen concentration by an oxygen-dependent enzyme, prolyl hydroxylase 2 (PHD2). Thus, cells respond to tissue hypoxia by sensing the oxygen concentration as the enzyme activity of PHD2, regulating the HIF-1 activity and consequently changing the expression of various hypoxia-responsive molecules. Cellular response controlled by hypoxia-HIF-1 cascade is also involved in pathological situations such as solid tumor growth, diabetic retinopathy and rheumatoid arthritis. Under these pathological situations, the activation of hypoxia-HIF-1 cascade often leads to the acceleration of disease progression. Understanding an aspect of disease progression triggered by tissue hypoxia might provide a clue to new therapeutic strategies for intractable diseases.


The conchal butterfly graft in secondary reconstruction of the bilateral cleft lip nasal deformity.
The bilateral cleft nasal deformity is characterized by a short columella and a broad, flattened nasal tip. Secondary correction is challenging and often complicated by skin envelope scarring and hypoplastic alar cartilages. Adequate and durable tip projection requires a procedure that adequately augments the nasal tip and maximizes tip support. We describe a novel technique for secondary correction of this deformity in the immature pediatric population. The conchal butterfly graft technique utilizes a folded cartilage construct to simultaneously increase tip projection and provide tip support. A retrospective review of 19 consecutive patients with bilateral cleft lip who underwent secondary tip rhinoplasty utilizing our technique over a 7-year period was conducted. Charts were reviewed for age at operation, length of follow-up and secondary revision procedures. Pre- and post-operative photographs were compared using two different methods to assess the degree of change and overall aesthetic result. Three plastic surgeons who previously were unfamiliar with the technique independently rated seven nasal tip characteristics. Nasal tip projection (NTP) was then measured objectively by two widely utilized methods: the Goode method and the Baum method-modified by Powell. Long lasting correction of the bilateral cleft nasal deformity was achieved utilizing this technique in 19 patients over a 7-year period with a mean length of follow-up of 5.4 years. We demonstrate augmented nasal tip projection that approaches ideal relationships from both relative measurement and survey data. The conchal butterfly graft technique is effective for reconstruction of the bilateral cleft nasal deformity, and in our experience, has resulted in long lasting nasal projection and overall improved facial balance.


Changes in white matter integrity follow excitatory rTMS treatment of post-stroke aphasia.
In this study, we examine whether an excitatory repetitive transcranial magnetic stimulation (rTMS) protocol called intermittent theta burst stimulation (iTBS) applied to the affected left hemisphere leads to changes in white matter fractional anisotropy (FA). Diffusion tensor imaging (DTI) data were collected in 8 aphasic stroke patients before and after 10 daily iTBS treatments. Alignment of structural and DTI data and derivation of diffusion index maps were performed using Analysis of Functional NeuroImages software followed by Tract-Based Spatial Statistics using FMRIB Software Library. Paired t-tests were performed to compare pre- to post-rTMS changes in FA. There were significant (p < 0.001) left-hemispheric FA increases near the inferior and superior frontal gyri and anterior corpus callosum. FA also increased in the right midbrain and bilaterally near temporal, parietal and posterior cingulate regions. FA decreased bilaterally near the fusiform gyrus and in left cerebellum. Overall, left-hemispheric regions that showed increased FA corresponded to areas previously shown to have increases in fMRI language activation after iTBS. The increased white matter integrity near the stimulation sites may reflect improvements in cortical function mediated by excitatory rTMS through its ability to facilitate synaptic connections.


Discrepancy of synaptic and microtubular protein phosphorylation in the hippocampus of APP/PS1 and MAPT×P301S transgenic mice at the early stage of Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, and is caused by multiple pathological factors, such as the overproduction of β-amyloid (Aβ) and the hyperphosphorylation of tau. However, there is limited knowledge of the mechanisms underlying AD pathogenesis and no effective biomarker for the early diagnosis of this disorder. Thus in this study, a quantitative phosphoproteomics analysis was performed to evaluate global protein phosphorylation in the hippocampus of Aβ overexpressing APP/PS1 transgenic mice and tau overexpressing MAPT×P301S transgenic mice, two in vivo AD model systems. These animals, up to ten weeks old, do not exhibit cognitive dysfunctions and are widely used to simulate early-stage AD patients. The number of differentially phosphorylated proteins (DPPs) was greater for APP/PS1 transgenic mice than for MAPT×P301S transgenic mice. The function of the DPPs in APP/PS1 transgenic mice was mainly related to synapses, while the function of the DPPs in MAPT×P301S transgenic mice was mainly related to microtubules. In addition, an AD core network was established including seven phosphoproteins differentially expressed in both animal models, and the function of this core network was related to synapses and oxidative stress. The results of this study suggest that Aβ and tau induce different protein phosphorylation profiles in the early stage of AD, leading to the dysfunctions in synapses and microtubule, respectively. And the detection of same DPPs in these animal models might be used for early AD diagnosis.


Annual intakes of (226)Ra, (228)Ra and (40)K in staple foodstuffs from a high background radiation area in the southwest region of Cameroon.
Concentrations of naturally occurring radionuclides (226)Ra, (228)Ra and (40)K were determined in five most consumed vegetables in a high-level background radiation area (HLBRA) in the southwest region of Cameroon. A total of 25 foodstuff samples collected from Akongo, Ngombas, Awanda, Bikoué and Lolodorf rural districts were analyzed by gamma spectrometry. The average activity concentration values of (226)Ra, (228)Ra and (40)K were respectively 2.30, 1.50 and 140.40 Bq kg(-1) fresh-weights. The effective dose for individual consumption of the investigated foodstuff types was calculated on an estimated annual intake of such diets in the study area. The estimated total daily effective doses from the ingestion of the investigated foodstuffs for each studied long-life natural radionuclide were respectively 0.41 μSv for (226)Ra, 0.84 μSv for (228)Ra and 0.71 μSv for (40)K. The total annual effective dose was estimated at 0.70 mSv y(-1). (228)Ra (44%) and (40)K (36%) were found to be the main sources for internal irradiation which is very likely due to the specific uptake of these radionuclides by the studied plants.


Treatment of imported severe malaria with artesunate instead of quinine--more evidence needed?
Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions remain regarding safety profiles and drug resistance. For imported severe malaria, additional unanswered questions are related to generalizability of the findings from endemic countries and to legal aspects, as there is no Good Manufacturing Practice-conform drug available yet. Here, the implications of existing evidence for the treatment of imported severe malaria are discussed.


Contemplating the necessity of surgical treatment for posterior lenticonus: a case report.
Posterior lenticonus is an uncommon congenital abnormality that causes a progressive, localized spherical or conical bulging of the posterior capsular membrane, resulting in an abnormal shape of the lens. A 13-year-old girl presented with ametropia in both eyes. After mydriasis, examination revealed an oval bubble-shaped alteration with a distinct boundary above the temporal region on the center of the posterior capsule of her left lens. The subcortical region surrounding the alteration appeared feathery and turbid. The patient had no history of trauma or family history of visual impairment. Systemic investigations were normal. A thorough eye examination was performed, which included optometry, ultrasound biomicroscopy, ocular B-Scan, and anterior segment optical coherence, to assess the disease. The patient was diagnosed with posterior lenticonus in the left eye, as well as ametropia and anisometropia in both eyes. Conservative treatment was initiated since the patient's current best corrected visual acuity was good, and regular monitoring of the condition's progression was scheduled. This case report presents a rare instance of posterior lenticonus. The findings of this report raise new considerations regarding the necessity of surgical intervention for this condition.


Spatially Homogeneous QM/MM for Systems of Interacting Molecules with on-the-Fly ab Initio Force-Field Parametrization.
Quantum and classical mechanics are combined in a hybrid many-body interaction model to enable the computationally affordable study of systems containing many interacting molecules. This model treats intramolecular and pairwise intermolecular interactions quantum mechanically, while many-body electrostatic induction effects are approximated using a polarizable force field. In this paper, we demonstrate that parametrizing the force field with distributed multipoles and atom-centered polarizabilities obtained on-the-fly from ab initio quantum mechanical monomer calculations makes the model very accurate and eliminates nearly all empiricism. Test calculations on water, formamide, hydrogen fluoride, and glycine-water clusters, all of which exhibit strong many-body interactions, are presented. The performance of the hybrid model is competitive with related point-charge embedding models.


A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species.
Acute myeloid leukemia (AML) is a heterogeneous and fatal disease with an urgent need for improved therapeutic regimens given that most patients die from relapsed disease. Irrespective of mutation status, the development of aggressive leukemias is enabled by increasing dependence on signaling networks. We demonstrate that a hyperactive signalosome drives addiction of AML cells to a tumor-specific Hsp90 species (teHsp90). Through genetic, environmental, and pharmacologic perturbations, we demonstrate a direct and quantitative link between hyperactivated signaling pathways and apoptotic sensitivity of AML to teHsp90 inhibition. Specifically, we find that hyperactive JAK-STAT and PI3K-AKT signaling networks are maintained by teHsp90 and, in fact, gradual activation of these networks drives tumors increasingly dependent on teHsp90. Thus, although clinically aggressive AML survives via signalosome activation, this addiction creates a vulnerability that can be exploited with Hsp90-directed therapy.


Neocurromycin A, a new GRP78 downregulator from Streptomyces sp. RAI364.
A new curromycin-related compound, neocurromycin A (2), was isolated from the fermented broth of Streptomyces sp. RAI364. The molecular formula of 2 was established as C35H44N4O7 by ESI-MS and the structure was elucidated by NMR spectroscopic analyses. Neocurromycin A showed selective cytotoxicity against MKN45 human gastric cancer cells in a nutrient-deprived medium with an IC50 of 380 nM and inhibited the expression of the molecular chaperone GRP78 in HT1080 G-L cells in the presence of 10 mM of 2-deoxyglucose with an IC50 of 1.7 µM.


Fetal vascular responses to maternal glucose administration in streptozocin-induced ovine diabetes mellitus.
To assess the impact of administration of a glucose load to the pregnant diabetic ewe on fetal biochemistry and umbilical-placental perfusion. Six pregnant ewes were rendered glucose intolerant by the administration of streptozocin at 85-90 days gestation. An intravenous glucose load was administered to the 6 diabetic ewes and 4 control animals at 125-130 days gestation. Assessment of the fetal responses to this glucose load was made by cardiovascular monitoring, biochemical evaluation and measurement of fetal blood flows by the radioactive microsphere technique. In the fetus of the diabetic ewe the arterial pH progressively decreased from 7.36 +/- 0.04 to 7.10 +/- 0.09 (p < 0.05) 180 minutes after the maternal glucose load. These fetuses displayed a consistent and significant reduction in arterial oxygen tension compared to controls, with a decrease in pO2 from 14.9 +/- 3.3 mmHg at baseline to 11.3 + 3.7 mmHg after 180 minutes. Umbilical-placental blood flow did not alter significantly in the fetus of the diabetic ewe following glucose administration, although in the control fetuses there was a significant reduction from baseline after 60 minutes. Blood flow to the fetal brain and kidney were significantly elevated in the fetus of the diabetic ewe compared to control at all times, suggesting a metabolic adaptation to preserve oxygen delivery may be present. Maternal hyperglycemia produces profound metabolic alterations in the ovine fetus which are unaccompanied by significant alterations in umbilical-placental blood flow. In the chronically hyperglycemic pregnant ewe, a glucose load produces a major disturbance of fetal homeostasis.


Corrigendum: Acute Exercise-Induced Oxidative Stress Does Not Affect Immediate or Delayed Precursor Cell Mobilization in Healthy Young Males.
[This corrects the article DOI: 10.3389/fphys.2020.577540.].


Stress-dependent inhibition of polarized cell growth through unbalancing the GEF/GAP regulation of Cdc42.
Cdc42 GTPase rules cell polarity and growth in fission yeast. It is negatively and positively regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), respectively. Active Cdc42-GTP localizes to the poles, where it associates with numerous proteins constituting the polarity module. However, little is known about its downregulation. We describe here that oxidative stress causes Sty1-kinase-dependent Cdc42 inactivation at cell poles. Both the amount of active Cdc42 at tips and cell length inversely correlate with Sty1 activity, explaining the elongated morphology of Δsty1 cells. We have created stress-blinded cell poles either by eliminating two Cdc42 GAPs or through the constitutive tethering of Gef1 to cell tips, and we biochemically demonstrate that the GAPs Rga3/6 and the GEF Gef1 are direct substrates of Sty1. We propose that phosphorylation of Rga3/6 and Gef1 mediates the Sty1-dependent inhibition of Cdc42 at cell tips, halting polarized growth during stress adaptation.


Report of the 2nd International Conference on Envenomations in Africa (Deuxième Colloque International sur les Envenomations en Afrique).
An international meeting on envenomations in Africa was held in Cotonou, Republic of Benin, the 19th and 20th of September, 2004, to gather clinical practitioners, epidemiologists, health authorities and antivenom producers to present and discuss the most recent available data on the prevalence of snake envenomations in Africa. The meeting concluded with a round table which had the objective of evaluating the problems facing the epidemiology and therapy of envenomations by African snakes and making some general recommendations at the level of national health authorities, researchers, medical practitioners, and international antivenom producers.


[Association of early diarrhea after the low anterior resection of rectal cancer and anastomotic leakage].
To evaluate the association of early diarrhea(postoperative day 1 to 7) and anastomotic leakage after low anterior resection for rectal cancer. Clinical data of 192 cases (group A, tumor from the anal verge 4-7 cm) from May 2004 to May 2007 and 236 cases(group B) from July 2007 to May 2010 in our hospital who received low anterior resection of rectal cancer were analyzed retrospectively. In group A, the incidence of early postoperative diarrhea was 19.3%(37/192), of which 9 cases were treated with anti-diarrhea drugs. The morbidity of anastomotic leakage in patients with diarrhea was significantly higher than those without early diarrhea(16.2% vs. 5.2%, P<0.05). In group B, the incidence of early postoperative diarrhea was 16.5%(39/236). All the patients were treated with anti-diarrhea drugs. There was no difference in the morbidity of anastomotic leakage between patients with diarrhea and those without early diarrhea(16.2% vs. 5.2%, P<0.05). There was no difference in early diarrhea between groups A and B(P>0.05). However, the incidence of anastomotic leakage in patients with early diarrhea was lower in group B(P<0.05). Early diarrhea after the low anterior resection of rectal cancer may indicate anastomotic leakage. Treatment of early postoperative diarrhea may reduce the risk of anastomotic leakage.


Autophagy-deficiency in hepatic progenitor cells leads to the defects of stemness and enhances susceptibility to neoplastic transformation.
Autophagy is a highly conserved and lysosome-dependent degradation process which assists in cell survival and tissue homeostasis. Although previous reports have shown that deletion of the essential autophagy gene disturbs stem cell maintenance in some cell types such as hematopoietic and neural cells, it remains unclear how autophagy-deficiency influences hepatic progenitor cells (HPCs). Here we report that Atg5-deficiency in HPCs delays HPC-mediated rat liver regeneration in vivo. In vitro researches further demonstrate that loss of autophagy decreases the abilities of colony and spheroid formations, and disrupts the induction of hepatic differentiation in HPCs. Meanwhile, autophagy-deficiency increases the accumulations of damaged mitochondria and mitochondrial reactive oxygen species (mtROS) and suppresses homologous recombination (HR) pathway of DNA damage repair in HPCs. Moreover, in both diethylnitrosamine (DEN) and CCl4 models, autophagy-deficiency accelerates neoplastic transformation of HPCs. In conclusion, these findings demonstrate that autophagy contributes to stemness maintenance and reduces susceptibility to neoplastic transformation in HPCs.


Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain.
The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI. This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed. Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040. Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain. clinicalTrials.gov Identifier: NCT04928170.


Arsenic adsorption enhancement performances of Mn-modified γ-Al2O3 with flue gas constituents involved.
Some flue gas constituents have negative effects on As2O3 adsorption of γ-Al2O3 so promoting arsenic adsorption performances under complicated flue gas conditions is necessary based on previous studies. In this study, γ-Al2O3 is modified with manganous nitrate and then Mn-modified γ-Al2O3 is used as the adsorbents in experiments. Besides, molecular dynamics (MD) simulations and density functional theory (DFT) calculations are performed to explore mechanisms of how loadings of Mn enhance arsenic adsorption features of γ-Al2O3 when being affected by flue gas constituents in microscale and mesoscale, respectively. As for DFT calculations, it is uncovered that electron transfer/interaction among As2O3, flue gas constituents and Mn-modified γ-Al2O3 mostly influences arsenic adsorption. For MD simulations, it is expounded that the collision and aggregation of As2O3 and flue gas constituent molecules have most impact on arsenic adsorption. As far as experiments are concerned, they are conducted to show the macroscopic characterizations of arsenic adsorption performances, corresponding to results of DFT calculations and MD simulations. The understanding of these three different aspects could supply significant references for utilization of Mn-modified γ-Al2O3 in real industries to remove arsenic under complex flue gas conditions.


Molecular mobility in raffinose in the crystalline pentahydrate form and in the amorphous anhydrous form.
The aims of the study are to characterize the slow molecular mobility in solid raffinose in the crystalline pentahydrate form, as well as in the anhydrous amorphous form (Tg = 109 degrees C at 5 degrees C/min), and to analyze the differences and the similarities of the molecular motions in both forms. Thermally stimulated depolarization current (TSDC) is used to isolate the individual modes of motion present in raffinose, in the temperature range between -165 and +60 degrees C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in raffinose. The features of the glass transition relaxation in raffinose were characterized by differential scanning calorimetry (DSC). A complex mobility was found in the crystalline form of raffinose. From the analysis of the TSDC data, we conclude that these molecular motions are local and noncooperative. A sub-Tg relaxation, or secondary process, was also detected and analyzed by TSDC in the amorphous phase. It has low activation energy and low degree of cooperativity. The glass transition was studied by DSC. The fragility index (Angell's scale) of raffinose obtained from DSC data is m = 148. TSDC proved to be an adequate technique to study the molecular mobility in the crystalline pentahydrate form of raffinose. In the amorphous form, on the other hand, the secondary relaxation was analyzed by TSDC, but the study of the glass transition relaxation was not possible by this experimental technique as a consequence of conductivity problems. The DSC study of the glass transition indicates that raffinose is an extremely fragile glass former.


Synergic role of ferrate and nitrite for triggering waste activated sludge solubilisation and acidogenic fermentation: Effectiveness evaluation and mechanism elucidation.
Enhancing anaerobic treatment efficiency of waste activated sludge (WAS) toward preferable resource recovery would be an important requirement for achieving carbon-emission reduction, biosolids minimization, stabilization and security concurrently. This study demonstrated the synergic effect of potassium ferrate (PF) and nitrite on prompting WAS solubilisation and acidogenic fermentation toward harvesting volatile fatty acids (VFAs). The results indicated the PF+NaNO2 co-pretreatment boosted 7.44 times and 1.32 times higher WAS solubilisation [peak soluble chemical oxygen demand (SCOD) of 2680 ± 52 mg/L] than that by the single nitrite- and PF-pretreatment, respectively, while about 2.77 times and 2.11 times higher VFAs production were achieved (maximum VFAs accumulation of 3536.25 ± 115.24 mg COD/L) as compared with the single pretreatment (nitrite and PF)-fermentations. Afterwards the WAS dewaterability was improved simultaneously after acidogenic fermentation. Moreover, a schematic diagram was established for illustrating mechanisms of the co-pretreatment of PF and nitrite for enhancing the VFAs generation via increasing key hydrolytic enzymes, metabolic functional genes expression, shifting microbial biotransformation pathways and elevating abundances of key microbes in acidogenic fermentation. Furthermore, the mechanistic investigations suggested that the PF addition was conducive to form a relatively conductive fermentation environment for enhancing electron transfer (ET) efficiency, which contributed to the VFAs biotransformation positively. This study provided an effective strategy for enhancing the biodegradation/bioconversion efficiency of WAS organic matters with potential profitable economic returns.


Oxygenation of fluorinated tyrosines by mushroom tyrosinase releases fluoride ion.
The reactions of 2-fluoro- and 3-fluoro-L-tyrosine with mushroom tyrosinase have been investigated. Both fluorinated tyrosines are good substrates for tyrosinase, with Vmax and Vmax/Km values similar to those for L-tyrosine. Oxygenation of 2-fluorotyrosine is regioselective, and only 6-fluorodopa was detected by HPLC in reaction mixtures. Oxygenation of both isomers of monofluorotyrosine results in fluoride ion production in the absence of ascorbic acid; however, 2-fluorotyrosine also produces fluoride in the presence of ascorbic acid. These results are consistent with previous studies demonstrating rapid intramolecular cyclization of nascent 6-fluorodopaquinone (M.E. Rice, B. Moghaddan, C.R. Creveling, and K.L. Kirk, 1987, Anal. Chem. 59, 1534-1538), which is competitive with reduction by ascorbate, resulting in elimination of the aromatic fluorine as fluoride ion.