Soluble mediators released from PI-IBS patients' colon induced alteration of mast cell: involvement of reactive oxygen species.
Growing evidence suggests that patients with post-infectious irritable bowel syndrome (PI-IBS) have increased mast cell activation, and that mucosal soluble mediators are involved in the pathophysiology of visceral hyperalgesia. In addition, previous findings show that reactive oxygen species (ROS) and protease-activated receptors (PARs) are mediators of persistent hyperalgesia. This article aims to investigate: (1) the ability of soluble factors from colonic biopsies to active peritoneal mast cells (PMCs) in vitro; (2) whether the effects of PMCs degranulation induced by soluble mediators are related to PARs activation; and (3) the ability of phenyl N-tert-butylnitrone (PBN), a ROS scavenger, to modify these alterations. Supernatant (SUP) from colonic biopsies was collected and applied to PMCs for 12 h. Activation of PMCs was evaluated. The expression of PAR(2) in PMCs was examined by RT-PCR and double-immunofluorescence staining. PBN (10 mM) treatment was administered, then previous alterations were observed again. Stimulation with SUP of PI-IBS led to an increase in activation of PMCs. PAR(2)mRNA expression was significantly increased in PMCs induced by SUP of PI-IBS compared to healthy subjects. After being treated by PBN, the SUP-induced enhancement of PMCs activities could be weakened, and PAR(2)mRNA expression was significantly decreased. A similar result of immunoreactivity for PAR(2) was observed in PMCs. The study shows that ROS scavenger reverses the SUP of PI-IBS-induced enhancement of PMCs activities, and that these effects may be related to activation of PAR(2). These findings might pave the way to new therapeutic targets in PI-IBS.


Structure-mutagenicity relationships of 5-nitro-2-furylethylenes in Salmonella typhimurium TA98.
Mutagenicity of three selected series of 2-furylethylene was determined by the Ames test. These included: nine alkylesters and eleven N-alkylamides of 5-nitro-2-furylacrylic acid (NFAA) and ten derivatives differing not only at exocyclic double bond, but also in the position 5 of the furan ring. Mutagenicity of the derivatives depends on the presence of the 5-nitro-furan centre in the molecule; side chains in the position 2 modify the degree of mutagenicity. Among the derivatives of NFAA tested as changing the substituents virtually does not affect chemical properties of the 5-nitrofuran ring. Mutagenicity of the n-alkyl congeners decreases linearly with increasing lipophilicity. Mutagenicity of the derivatives with branched alkyl substituents is lower than expected from the behaviour of the n-alkyl homologues.


Activation of macrophages by substance P: induction of oxidative burst and thromboxane release.
Substance P (SP), a putative neuropeptide transmitter, was examined for its effects on macrophages. Guinea-pig peritoneal macrophages were purified by adherence, challenged with SP and incubated for up to 18 h. Culture supernatants were collected to determine the release of O-2, H2O2 and TXB2. SP dose-dependently evoked O-2 and H2O2 production by C. parvum-activated macrophages and liberation of TXB2 from albumin-elicited macrophages. Generation of these proinflammatory macrophage products by SP may be relevant in the context of neuroinflammatory disease.


Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT.
The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.


Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL): a familial cause of depression and headache.
A 31 year-old man with a history of a depressive episode presented with acute severe 'thunderclap' headache. Magnetic resonance imaging (MRI) revealed abnormalities typical of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), which was subsequently confirmed by genetic analysis. The psychiatric features of this genetic cause of depression and headache are discussed.


The effect of intraoperative immersion solutions on acellular dermal matrix: Biofilm formation and mechanical property.
Acellular dermal matrix (ADM) is generally used on implant-based breast operations; However, it can increase surgical site infection. Many immersion solutions are applied to ADM, however, the most effective solution is unknown. The purpose of this study is to determine the effect of different solutions on the biofilm formation and mechanical properties of ADM. Aseptic porcine-derived ADMs were immersed in 5 different solutions for 30 min; sterile normal saline, 10% povidone-iodine, 0.5% chlorhexidine, antibiotics (cefazolin, gentamicin, and vancomycin), and taurolidine. They are transferred to 10 ml suspension of methicillin-sensitive/resistant Staphylococcus aureus (MSSA/MRSA) or Staphylococcus epidermidis and an overnight culture was performed. After rinsing and sonication to obtain the biofilm on ADM, colony forming unit (CFU) was measured. In addition, the maximum load before ADM deformation and the elongation length of ADM at the start of the maximum load was determined. Regardless of strains, povidone-iodine, chlorhexidine, and taurolidine group had lower CFUs than the saline group with statistical significance. Meanwhile, the antibiotics group did not show statistical difference from the saline group. Moreover, only taurolidine group showed higher tensile strength (MRSA, p = 0.0003; S. epidermidis, p = 0.0023) and elongation length (MSSA, p = 0.0015) than the saline group. The antibiotics and chlorhexidine group yielded lower tensile strength and elongation length than the povidone-iodine and taurolidine groups. It was suggested that the 10% povidone-iodine or taurolidine solution is effective. In contrast, the antibiotics solution could be considered as an effective intraoperative solution.


USP6 gene rearrangement in nodular fasciitis and histological mimics.
Nodular fasciitis is known to be a benign mimic of sarcoma, both clinically and histologically. Accurate diagnosis, particularly on small biopsies, remains a challenge, as the morphology can be varied and the immunophenotype is essentially non-specific. Recently, rearrangement of the ubiquitin-specific protease 6 (USP6) gene has been reported as a recurrent and specific finding in nodular fasciitis. The aim of this this study was to evaluate the diagnostic utility of USP6 fluorescence in-situ hybridization (FISH) analysis in a subset of spindle-cell proliferations in which nodular fasciitis enters into the differential diagnosis. A database search was performed at the Middlemore Hospital Histopathology Department. All in-house cases diagnosed between 2002 and March 2014 in which nodular fasciitis was considered as a differential diagnosis were retrospectively identified. Twenty cases were retrieved, reviewed and categorized as 'definite', 'possible' or 'definitely not' nodular fasciitis by consensus morphological opinion of three experienced pathologists. FISH analysis for USP6 rearrangement was performed in each case, with a commercially available break-apart probe. Of seven cases that were morphologically categorized as 'definite' nodular fasciitis, six were FISH-positive and one was FISH-negative. Of four cases categorized as 'possible' nodular fasciitis, one was FISH-positive and three were FISH-negative. Nine cases categorized as 'definitely not' nodular fasciitis were all FISH-negative. In the morphologically definitive cases, FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of nodular fasciitis. The positive predictive value was 100%, and the negative predictive value 90%. USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration.


Improved method of fire hazard assessment taking into account the effect of the primary temperature of a coal seam on the desorption ratio of gas indicators.
The methods of fire risk assessment in its early phase employed so far used to take into account only the temperature of the heating of coal. The research works reported so far in this field have been conducted at ambient temperatures, without considering the rock mass primary temperature occurring in a particular coal seam and neglecting the depth of coal seams. The method for the determination of the composition of gases emitted from coal samples, employed in the study presented here, takes into account the effect of rock mass pressure, and therefore the depth of the coal seam, as well as the temperature typical for the rock mass in a particular coal mine. In the paper the results of the experimental research on the effects of the primary temperature of a coal seam on the content of gases emitted from coal, performed with the use of a specially designed experimental stand are presented. The method may be useful in developing fire hazard predictions for longwalls with residual coal in goafs. The relations between the self-ignition characteristics as well as selected physical properties of coal samples and carbon monoxide emission were also given. The research results proved that the accurate fire hazard assessment requires considering other than just self-heating of coal causes of carbon monoxide emission, including the rock mass primary temperature, which is expected to improve the existing methods of fire risk assessment in coal mines and post-mining areas.


Esophageal sclerotherapy: an effective modality in children.
During the past five years, sclerotherapy has been used at our institution in 13 children for the management of recurrent major variceal bleeding. The varices were secondary to extrahepatic portal hypertension in seven patients and to intrahepatic portal hypertension in the remaining six. Sclerotherapy was performed under direct vision using either rigid or flexible endoscopic equipment, and the sclerosing agents were injected directly into the varices. The average age at initiation of sclerotherapy was 9 years (range: 1 to 19 years). The follow-up has ranged from 2 to 4 1/2 years with a mean of 3 1/2 years. Complete obliteration of all varices was obtained in eight of these patients. Two children have minimal residual varices, in one of whom 17 sclerotherapy procedures have been performed to date. One additional patient had a severe episode of bleeding during esophagoscopy, and transesophageal ligation of varices was required for control. Two patients have died following initiation of sclerotherapy. In neither case was the death the result of bleeding esophageal varices or a complication of endosclerosis. Bleeding from varices was the major clinical problem in all of these children, and this problem has been largely corrected by the sclerotherapy program. With one exception, there have been no episodes of variceal bleeding requiring transfusion in these patients following initiation of this therapy. One child developed an esophageal ulcer postinjection, but none have developed esophageal strictures. One patient developed an allergic reaction to the sclerosant that was treated during subsequent injections with prior administration of an antihistamine (diaphenhydramine chloride) and steroids.(ABSTRACT TRUNCATED AT 250 WORDS)


Gaze following among toddlers.
Children's cooperative activities with their peers become markedly coordinated during the 3rd year of life. During these activities, the child needs to follow his/her peers' gaze to objects, and look at the same objects to initiate coordinated action. Since 3-year-olds' ability to follow their peers' gaze has not been studied, we experimentally investigated this in our study. In the experimental trials, an experimenter induced a child (looker) to look at a doll on display, and observed the reaction of another child (follower) who was in front of the looker (and not looking at the doll). In the control trials, the experimenter displayed the doll in an identical manner when the follower was alone. The followers followed the gaze of the lookers, looking at the doll in approximately 90% of the experimental trials, compared with 20% of the control trials. These results indicate that 3-year-olds can follow their peers' gaze.


Role of arachidonic acid metabolism in Stat5 activation induced by oleic acid in MDA-MB-231 breast cancer cells.
Epidemiological studies and animal models suggest an association between high levels of dietary fat intake and an increased risk of breast cancer. In breast cancer cells, the free fatty acid oleic acid (OLA) induces proliferation, migration, invasion and an increase of MMP-9 secretion. However, the role of OLA on Stat5 activation and the participation of COX-2 and LOXs activity in Stat5 activation induced by OLA remain to be investigated. We demonstrate here that stimulation of MDA-MB-231 breast cancer cells with 100 μM OLA induces Stat5 phosphorylation at Tyr-694 and an increase of Stat5-DNA complex formation. The Stat5 DNA-binding activity requires COX-2, LOXs, metalloproteinases and Src activities. In addition, OLA induces cell migration through a Stat5-dependent pathway. In summary, our findings establish that OLA induces cell migration through a Stat5-dependent pathway and that Stat5 activation requires AA metabolites in MDA-MB-231 breast cancer cells.


Prehension synergies: trial-to-trial variability and hierarchical organization of stable performance.
We studied multi-digit synergies as relations among digit forces and points of their application across multiple repetitions of a static prehensile task. The task required holding a grasped object (14.9 N) against different external torques. Subjects (n=6) performed 25 trials for each torque condition: -1.0, -0.5, 0, +0.5 and +1.0 Nm. In spite of the variability of individual forces and points of their application, stable performance was achieved. Individual performance variables were organized into two subsets. Variables within each subset highly correlated with each other (the coefficients of correlation were close to +/- 1.0) while there was no correlation among variables from different subsets. The two subsets were associated with two components of the prehension task: grasp control (preventing an object from slipping out of the hand) and torque control (maintaining a desired object orientation).


Plasmacytoma of the large bowel: a review of the literature and a case report of multiple myeloma involving the rectosigmoid.
Large bowel involvement is a rare manifestation of plasma cell tumors, especially in association with multiple myeloma. A review of the world literature reveals only 21 reported cases, the majority of which are classified as the solitary form of the disease. A case of multiple myeloma with rectosigmoid involvement is herein presented, and the radiological findings of reported cases are summarized.


Preparation, Characterization and Evaluation of the Anti-Inflammatory Activity of Epichlorohydrin-β-Cyclodextrin/Curcumin Binary Systems Embedded in a Pluronic®/Hyaluronate Hydrogel.
Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpiβCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpiβCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpiβCD complex is a great alternative to treat topical inflammatory diseases.


Rapid PCR of STR markers: Applications to human identification.
Multiplex PCR with fluorescently labeled primers has been an essential method for the amplification of short tandem repeats used in human identify testing. Within the STR workflow of extraction, quantitation, amplification, separation, and detection, multiplex PCR is commonly identified as the bottleneck in the process. The time requirement of up to three hours to complete 28-30 cycles of multiplex PCR for STR genotyping is the greatest amount of time required for a single step within the process. The historical use of commercially available thermal cyclers and heat stable polymerases may have given the impression that large multiplex will always require long PCR cycling times to ensure that all of the varying sized targets (typically 100-400bp) can be amplified in a balanced manner throughout the multiplex. However, with the advent of improved polymerases and faster thermal cyclers the time required for the amplification of large STR multiplexes is no longer on the order of three hours, but as little as 14min. Faster amplification times can be performed while retaining the balance and integrity of large multiplex PCRs by implementation of alternate polymerases and thermal cyclers. With the reduction in PCR cycling times there has also been an impact on the development of integrated and microfluidics devices which employ the use of reduced or rapid thermal cycling protocols as part of their integration. Similarly, PCR inhibitor resistant polymerases can also reduce overall STR processing times for reference samples by eliminating the need for DNA extraction and purification that is additionally implemented within the development of integrated DNA typing devices.


Visual noise consisting of X-junctions has only a minimal adverse effect on object recognition.
In 1968, Guzman showed that the myriad of surfaces composing a highly complex and novel assemblage of volumes can readily be assigned to their appropriate volumes in terms of the constraints offered by the vertices of coterminating edges. Of particular importance was the L-vertex, produced by the cotermination of two contours, which provides strong evidence for the termination of a 2-D surface. An X-junction, formed by the crossing of two contours without a change of direction at the crossing, played no role in the segmentation of a scene. If the potency of noise elements to affect recognition performance reflects their relevancy to the segmentation of scenes, as was suggested by Guzman, gaps in an object's contours bounded by irrelevant X-junctions would be expected to have little or no adverse effect on shape-based object recognition, whereas gaps bounded by L-junctions would be expected to have a strong deleterious effect when they disrupt the smooth continuation of contours. Guzman's roles for the various vertices and junctions have never been put to systematic test with respect to human object recognition. By adding identical noise contours to line drawings of objects that produced either L-vertices or X-junctions, these shape features could be compared with respect to their disruption of object recognition. Guzman's insights that irrelevant L-vertices should be highly disruptive and irrelevant X-vertices would have only a minimal deleterious effect were confirmed.


Complications of Tenckhoff catheter implantation in patients with multiple previous intraabdominal procedures for ovarian carcinoma.
In patients with minimal residual ovarian carcinoma after aggressive surgical and chemotherapeutic treatment, nephrotoxicity and/or peripheral neuropathy often prohibit continued treatment with intravenous combination cisplatin-based chemotherapy. It is attractive to continue treatment of these patients with intraperitoneal (ip) delivered chemotherapy. From 1981 through 1984 a Tenckhoff catheter was implanted in 59 women for ip chemotherapy after a staging laparoscopy or laparotomy. Minor complications occurred in 8 patients and could be treated conservatively. Ten patients suffered major complications, leading to three (re)laparotomies and catheter extraction in 7 of 10 patients. No patient died of complications, but mean hospitalization time of patients with major complications was 25 days as compared to 11 days for patients without complications. An analysis of nine factors that could lead to postoperative complications failed to reveal a statistically significant risk factor. From this study no profile of a typical high-risk patient emerges.


Fluorometric enzyme-linked immunosorbent assay for the measurement of IgE antibody to mite Dermatophagoides farinae.
We have developed a fluorometric enzyme-linked immunosorbent assay for measuring IgE antibody to Dermatophagoides farinae. Polystyrene microplates were coated with proteins extracted from the mites. The IgE antibody which attached to the solid-phase antigen was detected by anti-IgE antibody conjugated with beta-galactosidase. Four-methylumbelliferyl-beta-D-galactoside was used as the enzyme substrate and the fluorescence intensity of the reaction product was measured. The antibody levels determined by this method well correlated with those determined by the radioallergosorbent test (RAST). This method is simpler and less expensive to carry out than the RAST when dealing with a large number of serum specimens for seroepidemiological studies of asthma and nasal allergy.


Zinc and fluorine ions dual-modulated NiCoP nanoprism array electrocatalysts for efficient water splitting.
Designing efficient, stable, and low-cost bifunctional catalysts for overall water splitting is significant but challenging. In this work, Zn and F ions co-doped NiCoP nanoprism arrays grown directly on nickel foam (Zn/F-NiCoP/NF) was synthesized via hydrothermal method followed by phosphorization treatment. The resultant Zn/F-NiCoP/NF exhibits high electrocatalytic activity towards hydrogen evolution reaction (HER, η10 = 59 mV) and oxygen evolution reaction (OER, η50 = 285 mV). An alkaline electrolyzer using Zn/F-NiCoP/NF as both cathode and anode requires a low cell voltage of 1.568 V at a current density of 10 mA cm-2 with a high long-term stability of up to 40 h, which outperforms many reported Ni,Co-based catalysts. Density functional theory (DFT) calculations proof that simultaneous doping of NiCoP with Zn and F ions provides flexibility to regulate the electronic configuration and downshifts the transition metal d-band center, thereby optimizing adsorption energy between reactants and intermediates, which enhances the HER and OER catalytic activities. This work highlights that cation-anion co-doping strategy is an effective way to develop highly active transition metal phosphides electrocatalyst for water splitting.


Digital rat brain: a computerized atlas.
Digital brain mapping provides the techniques required for 3 dimensional (3D) reconstruction and display. This paper describes work which extends the data published in the Paxinos and Watson (1982) atlas of the rat brain to a computerized form. The product of these experiments is a 3D digital neuroanatomic atlas. The data were transformed from 2D outlines to 3D volumes each associated with a specific neuroanatomic structure. The system which manages this transformation also provides tools to manipulate the composition, orientation and appearance of the displays interactively.


Pb speciation in rare earth minerals and use of entropy and fuzzy clustering methods to assess the migration capacity of Pb during mining activities.
Ionic rare earth mining is of strategic importance in China; however, the heavy metal pollution it causes is of great concern, both at home and abroad. Data on Pb speciation at a rare earth mine were used to analyse the migration capacity of Pb during the process of ore leaching. The major factors thought to influence the migration capacity of Pb, including the clay mineral content, soil pH, oxidation-reduction potential, organic matter content, and cation exchange capacity (CEC), were quantified. Entropy and fuzzy clustering methods were used to identify the most predictive factors. The results showed that the clay mineral content of the soil exerts the strongest influence on the migration capacity of Pb in rare earth mines; the other factors demonstrated relatively weak influences on the transport processes. The results obtained from the classification of Pb per the potential migration index (PMI) approximated those obtained from fuzzy clustering, and the results of entropy analyses were consistent with those of fuzzy clustering. Thus, the methods upon which the proposed model is based are suitable for predicting the migration capacity of Pb in ore during the mining of ionic rare earth minerals.


[Smith-Magenis syndrome is an association of behavioral and sleep/wake circadian rhythm disorders].
Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features.


A general method for the isolation of haptoglobin 1-1, 2-1, and 2-2 from human plasma.
A general method for the isolation of haptoglobin 1-1, 2-1, and 2-2 human plasma is described. Plasma is fractionated by affinity chromatography on chicken hemoglobin-Sepharose using the full capacity of the column; then after washing the column thoroughly, haptoglobin is eluted with 8 M urea and the eluate is collected in fractions to separate active and denatured haptoglobin. The urea-free, active fractions of haptoglobin are fractionated by affinity chromatography on Affi-Gel Con A to remove nonglycoproteins, principally apolipoprotein A-I, and the haptoglobin is eluted with 0.5 M glucose. Then the haptoglobin-containing fractions are fractionated by negative immunoadsorption chromatography on anti-chicken hemoglobin-protein A-Sepharose to remove chicken hemoglobin-human haptoglobin complexes. Haptoglobin prepared by this three-step procedure is biologically active and nearly homogeneous. The recovery is approximately 70%, irrespective of phenotype. The procedure can be completed in 3 days. A partial purification of apolipoprotein A-I is obtained simultaneously by this method.


Impact of fatigue on quality of life in patients with Parkinson's disease.
Fatigue is frequent and important in the lives of Parkinson's disease (PD) patients. It is multidimensional, with physical and mental aspects. The aim of our study was to explore the impact of fatigue on quality of life (QoL) for PD patients. The sample consisted of 175 PD patients from Eastern Slovakia (52% males, mean age 68.2 +/- 9.2, mean disease duration 7.4 +/- 6.7). The Multidimensional Fatigue Inventory (five dimensions), the Parkinson's Disease Quality of Life Questionnaire (eight dimensions) and the Unified Parkinson's Disease Rating Scale were used. Demographic data were obtained in a structured interview. Fisher's exact test, t-test, and multiple linear regression analysis were used. Different aspects of fatigue selectively explained different domains of QoL - physical dimensions of fatigue were connected with Mobility and Activities of daily living; mental fatigue dimensions affected Cognition, Emotional well-being, Communication and Activities of daily living; general fatigue was related to Bodily discomfort. The explained variances varied from 5% (Social support) to 65% (Activities of daily living). Fatigue combined with worse functional status appears to be a significant contributor to poor quality of life. Its multidimensional construct can be used to develop strategies for improving specific aspects of fatigue to improve QoL for PD patients.


[Health inequalities in old age : Theoretical perspectives and methodological challenges].
While it has been long known that health inequalities persist until higher ages, less is known about the underlying mechanisms and health trajectories over the life course. This article gives an overview on recent developments regarding theoretical concepts and methodological considerations in this field of research. It can be concluded that studies on the explanation of the social gradient in health are scarce and even less is known about societal contexts that enable healthy aging irrespective of the socioeconomic position. The existing evidence on causal mechanisms and developments over the life course warrants cautious interpretation due to selective study samples and cross-sectional study designs.


Laparoscopic Left Renal Vein Transposition for Nutcracker Syndrome.
The left renal vein (LRV) reimplantation into the distal inferior vena cava is considered to be the gold standard of care for symptomatic nutcracker syndrome (NCS). The vast majority of these surgical procedures are performed by open surgery. Experiences with minimally invasive laparoscopic surgery in this field are very limited. We present a case of a 17-year-old boy with NCS in whom the transposition of the LRV was done laparoscopically. The patient suffered from left flank pain, painful left-sided varicocele, microscopic hematuria, proteinuria, and oligoasthenospermia. There were no intraoperative complications, and the postoperative course was uneventful. At 12-month follow-up, hematuria, left flank pain, and left testicular pain resolved. Duplex ultrasonography revealed patent LRV. Laparoscopic LRV transposition appears to be safe, feasible, and has favorable postoperative course.


Oral disease in adults treated with hemodialysis: prevalence, predictors, and association with mortality and adverse cardiovascular events: the rationale and design of the ORAL Diseases in hemodialysis (ORAL-D) study, a prospective, multinational, longitudinal, observational, cohort study.
People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated. Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required. The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022. This large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease.


Prenatal administration of betamethasone for prevention of respiratory distress syndrome.
The outcome of 114 infants of birth weight 750 to 1,750 gm who received prenatal betamethasone therapy was compared retrospectively to that of 138 infants delivered to untreated women. The incidence of respiratory distress syndrome in all treated infants was 37.7% compared with 50.7% (P = 0.05) in untreated infants. There was no apparent benefit of therapy among infants delivering less than 48 hours after the first dose and among infants less than 750 gm birth weight. Among infants delivering two to ten days after therapy, RDS 25.0 vs 50.7%) and mortality (8.9 vs 22.5%) were significantly reduced. Among surviving infants with RDS, fewer infants in the two to ten-day treated group required oxygen at FIO2 greater than 0.5 for more than 24 hours. Our findings confirm previous reports that prenatal glucocorticoid treatment reduces the incidence of RDS and mortality in premature infants. In addition, they indicate that therapy is more effective when delivery is delayed at least two days, that very small premature infants do not benefit from treatment, and that RDS may be less severe after prenatal exposure to betamethasone.


The effect of Gal expression on pig cells on the human T-cell xenoresponse.
Lack of Gal expression on pig cells is associated with a reduced primate humoral immune response as well as a reduction in cytokine production by human cells in vitro. We investigated whether lack of Gal expression is associated with reduced human T-cell response in vitro. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy humans and naïve baboons. Human CD4+ and CD8+ T cells were isolated. Porcine aortic endothelial cells (pAECs) were isolated from wild-type (WT) and α1,3-galactosyltransferase gene-knockout (GTKO) pigs. WT pAECs were treated with α-galactosidase, reducing Gal expression. Swine leukocyte antigen (SLA) class I and II expression on pAECs was measured, as was T-cell proliferation and cytokine production in response to pAECs. Reduced Gal expression on WT pAECs after α-galactosidase treatment was associated with reduced human PBMC proliferation (P<0.005). SLA class I and II expression on WT and GTKO pAECs was comparable. Human CD4+ and CD8+ T-cell proliferation was less against GTKO pAECs before (P<0.001) and after (P<0.01 and P<0.05, respectively) activation. Human and baboon PBMC proliferation was less against GTKO pAECs before (P<0.05) and after (P<0.01 and P<0.05, respectively) activation. Human PBMCs produced a comparable cytokine/chemokine response to WT and GTKO pAECs. However, there was less production of IFN-γ/TNF-α by CD4+ and IFN-γ/granzyme B/IP-10 by CD8+ T cells in response to GTKO pAECs. The absence of Gal on pig cells is associated with reduced human T-cell proliferation (and possibly selected cytokine production). Adaptive primate T-cell responses are likely to be reduced in GTKO xenograft recipients.


Affinity purification of proteins binding to kinase inhibitors immobilized on self-assembling monolayers.
Kinase inhibitors represent a relatively new class of drugs that offer novel therapies targeting specific -malfunctioning kinase-mediated signaling pathways in oncology and potentially inflammation. As the ATP binding sites of the ∼500 human kinases are structurally conserved and because most current drugs target the ATP binding site, there is a need to profile all the kinases that a drug may bind and/or inhibit. We have developed a chemical proteomics method that affinity purifies kinases from cell or tissue lysates using kinase inhibitors immobilized on self-assembling monolayers. The method can be applied to assess the selectivity of a given kinase inhibitor and thus to guide its preclinical or clinical development.


Appropriate hinge position for prevention of unstable lateral hinge fracture in open wedge high tibial osteotomy.
Open wedge high tibial osteotomy (OWHTO) for medial-compartment osteoarthritis of the knee can be complicated by intra-operative lateral hinge fracture (LHF). We aimed to establish the relationship between hinge position and fracture types, and suggest an appropriate hinge position to reduce the risk of this complication. Consecutive patients undergoing OWHTO were evaluated on coronal multiplanar reconstruction CT images. Hinge positions were divided into five zones in our new classification, by their relationship to the proximal tibiofibular joint (PTFJ). Fractures were classified into types I, II, and III according to the Takeuchi classification. Among 111 patients undergoing OWHTOs, 22 sustained lateral hinge fractures. Of the 89 patients without fractures, 70 had hinges in the zone within the PTFJ and lateral to the medial margin of the PTFJ (zone WL), just above the PTFJ. Among the five zones, the relative risk of unstable fracture was significantly lower in zone WL (relative risk 0.24, confidence interval 0.17 to 0.34). Zone WL appears to offer the safest position for the placement of the osteotomy hinge when trying to avoid a fracture at the osteotomy site. Cite this article: Bone Joint J 2017;99B10:1313-18.


Clinical and genetic backgrounds of hypertrophic cardiomyopathy with mid-ventricular obstruction.
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. This study aimed to reveal the clinical and genetic backgrounds of the unique HCM with mid-ventricular obstruction (HCM-MVO) subtype. We identified 34 patients with HCM-MVO in our cohort, and about half (47%) of these patients experienced adverse events. We analyzed 67 cardiomyopathy-associated genes in the patients. In total, 44% of patients with HCM-MVO carried the cardiomyopathy-associated genetic variant (CAGV) in 14 genes. Only 21% of patients carried HCM-associated CAGVs in major sarcomere-encoding genes, while 18% of patients carried CAGVs in dilated cardiomyopathy/arrhythmogenic right ventricular cardiomyopathy-associated genes. CAGVs were more frequent in patients with asymmetric septal hypertrophy (ASH) than in those without ASH. These findings suggest that HCM-MVO is a high-risk group and may have different etiologies from typical HCM.


Sympathetic Innervation and Adrenergic Receptors in Equine Deep Digital Flexor Tendinopathy: Preliminary Results.
The aim of this study was to delineate the pattern of sympathetic innervation in the suprasesamoidean region of the deep digital flexor tendon (DDFT) in horses with tendinopathy by immunohistochemical labelling for tyrosine hydroxylase (TH) and α-1 adrenergic receptor (α1-AR). Twelve forelimbs were obtained from 10 horses with DDFT tendinopathy and six feet obtained from six horses were used as healthy controls. Post-mortem radiographic, ultrasonographic and gross examinations were performed on the suprasesamoidean area of the DDFT to assess the presence of tendinopathy. Longitudinal sections were collected and processed. Lesions were classified as core lesions, dorsal border lesions and parasagittal oblique splits. Immunohistochemistry was performed and the degree of immunoreaction was classified as absent, mild or marked. Seven core lesions, four dorsal border lesions and one parasagittal oblique split were identified. There was no increased expression of sympathetic innervation in samples with a dorsal border lesion of the DDFT compared with healthy samples. In contrast, core lesions showed increased expression of α1-AR and reduced expression of TH, which supports the hypothesis of a compensatory imbalance between the sympathetic mediator and the sympathetic receptors as a cause or effect of structural damage. In addition, adrenergic activation could stimulate cell proliferation and differentiation within these lesions.


Bilateral multicystic dysplastic kidneys.
High-resolution ultrasound examination of the fetus enables early detection of congenital malformations of the urinary tract. This information is of value in determining fetal prognosis, in deciding the method of delivery, and in alerting the pediatricians to supportive and corrective measures which may need to be taken in the postnatal period. Prenatal diagnosis of bilateral multicystic kidneys was made in a 33-34 week old fetus. A short discussion of this anomaly follows.


Analysis of the degree of pulmonary thallium washout after exercise in patients with coronary artery disease.
An abnormal increase in pulmonary thallium activity may be visualized on post-stress thallium images in patients with coronary artery disease. Because this increased pulmonary thallium activity usually disappears by the time of redistribution imaging, this study was designed to assess whether measurement of the degree of pulmonary thallium washout between stress and redistribution might improve the detection of increased pulmonary thallium activity in patients with coronary artery disease. Quantitative analysis revealed abnormal (that is, greater than 2 standard deviations of normal values) pulmonary thallium washouts in 59 (64%) of 92 patients with coronary artery disease, but in only 2 (25%) of 8 subjects with angiographically normal arteries (p less than 0.06). By comparison, the visual analysis of pulmonary thallium washout and use of initial pulmonary to myocardial thallium ratio were significantly (p less than 0.05) less sensitive in detecting abnormality in patients with coronary artery disease. Abnormal pulmonary thallium washout was related to both the anatomic extent and functional severity of disease: it occurred with greatest frequency in patients with multivessel disease and in those with exercise-induced left ventricular dysfunction (p less than 0.005). When added to the quantitative analysis of myocardial scintigraphy, the analysis of pulmonary thallium washout increased the detection of coronary artery disease from 84 to 93% (p less than 0.05), but the sample size was too small to assess specificity. Thus, the analysis of pulmonary thallium washout is a useful diagnostic variable because it: 1) provides an objective measurement of abnormal pulmonary thallium activity and is more sensitive than other methods; 2) correlates with both the extent of coronary artery disease and the degree of exercise-induced left ventricular dysfunction, and 3) improves the sensitivity of quantitative myocardial thallium scintigraphy to detect the presence of coronary artery disease.


Effect of first order chemical reactions on the dispersion coefficient associated with laminar flow through fibrosis affected lung.
In this paper, we worked on the effective area average concentration and dispersion coefficient associated with the unsteady flow, to understand the dispersion in the fibrosis-affected lung. We assumed that the tube wall (i.e. alveolar or pulmonary capillary wall) is thicker than its normal size due to fibrosis and chemical species may go through linear first-order kinetic reactions, one is reversible phase exchange with the wall material and other is irreversible absorption into the tube wall. By considering diffusivity as a function of thickness, the dispersion can be calculated by the distribution of concentration of gas along a tube. Mathematical modeling is done by using diffusion equation; and effects of various dimensionless parameters e.g., the Damkohler number (DA), phase partitioning number (α), dimensionless absorption number (Γ), thickness and permeability of wall are observed. Numerical simulation shows that the diffusion rate through the respiratory wall is decreased significantly as the thickness of wall increases, while it increased with the increment in the porosity of wall, the concentration of species increased when the tube wall thickness increases; which cause reduction in the spread of the species; additionally, the dispersion coefficient achieves the steady-state values in a very short time when 0 < DA ⩽1 and absorption rate < 1, while for 1 < DA ⩽20 and absorption rate = 1 long time dispersion is achieved.


T cell immune awakening in response to immunotherapy is age-dependent.
Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8+ immune-effector memory T cells (TIE cells) whose expansion was associated with response to ICB and increased overall survival. To improve our understanding of peripheral T cell dynamics, we examined the clinical correlates associated with these immune signatures. Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral TIE cell dynamics by age before treatment (T0) and after the first cycle of treatment at week 3 (W3). We observed a correlation between TIE abundance and age at T0 (r = 0.40), which reduced following treatment at W3 (r = 0.07). However, at W3, we observed two significantly opposing patterns (p = 0.03) of TCR repertoire rearrangement in patients who responded to treatment, with patients ≥70 years of age showing an increase in TCR clonality and patients <70 years of age showing an increase in TCR diversity. We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies.


Estimating the human immunodeficiency virus infection curve of intravenous drug users in Lombardia, Italy.
We present a model to estimate the infection curve of the human immunodeficiency virus in intravenous drug users in Lombardia. We based estimates on AIDS incidence data, according to a backcalculation model accounting for 'therapy' and changes in the surveillance definition of AIDS.


A blacksmith's tale: use of a rare earth magnet to facilitate safe removal of a metallic fragment from the face.
A 48-year-old blacksmith presented to A&E after sustaining facial injuries while operating a metal punch press. Radiographs revealed the presence of a metallic foreign body within the cheek, but this was clinically impalpable. By using a neodymium rare earth magnet extraorally, it was possible to identify the position of the fragment several centimetres lateral to the entry wound. Triangulation of the fragment's position allowed retrieval under local anaesthetic through the original penetration wound, without need for cross sectional imaging or extensive exploration under general anaesthetic. This case highlights an application for magnets in detection and removal of impalpable metallic foreign bodies embedded in superficial soft tissues.


Medical profile of the language-delayed child: otitis-prone versus otitis-free.
Delay in language development may be associated with an underlying anatomical, neurosensory, or psychological disorder such as: deafness, cerebral palsy, cleft palate, autism, or mental retardation. A condition called specific developmental language delay may occur in children devoid of any other identifiable disorder or developmental delay. Language delay associated with early onset, severe-to-profound hearing impairment has been well documented. Controversial studies have also appeared in the communicative disorders' literature suggesting that fluctuating conductive hearing loss in early childhood can significantly affect the development of language and related academic skills. Some authors have claimed that these deleterious effects can be irreversible. This study focuses on 3 groups of preschool children, in whom hearing acuity has been documented: One group with recurrent otitis and language delay; a second group with an equally well documented otitis history but without language delay; and a third group with documented language delay in the absence of any known predisposing conditions, including early-onset, recurrent otitis media. Prenatal, birth and developmental histories of the children in each group were compared in detail to identify any factors which may enhance or ameliorate the effects of fluctuating conductive hearing loss on language development. In a population of 1864 children (ages 9-59 months) referred for otolaryngologic and/or communicative evaluation, 480 otherwise normal children (67.6% males; 32.4% females) were found to have a history of early-onset, recurrent otitis media and/or delayed speech and language development on the basis of an extensive evaluation battery. This population was further subdivided into 3 groups (I = otitis-positive/normal language; II = otitis-positive/language delay; and III = otitis-free/language delay). Among the 329 children with positive histories for early otitis media (Groups I & II), a significantly higher percentage of those demonstrating language delay were from homes in the lower socio-economic category. Race and sex showed no significant relationship to language delay among the otitis-positive groups, although males were twice as numerous as females in the over-all study population. Articulation errors on speech measures and borderline delays in other developmental milestones (standing, walking, and toilet training) were also significantly greater in the language-delayed group when compared with otitis-positive children whose language was age-appropriate.(ABSTRACT TRUNCATED AT 400 WORDS)


MAP-2 expression in the human adenohypophysis and in pituitary adenomas. An immunohistochemical study.
MAP-2, a well characterized member of the microtubule associated protein (MAP) family, binds to and stabilizes microtubules and is involved in cell proliferation as well as neuronal differentiation. The aim of the present work was to study MAP-2 expression in human adenohypophyses and pituitary adenomas. To our knowledge, data regarding MAP-2 expression in human pituitaries has not been reported to date. For immunohistochemistry, the streptavidin-biotin-peroxidase complex method was used. Nine non-tumorous adenohypophyses and 77 adenomas (GH-, PRL-, ACTH-, TSH-, FSH/LH- and/or alpha subunit- producing or immunonegative tumors) were investigated. The results show that MAP-2 is expressed in the cytoplasm of non-tumorous adenohypophysial cells as well as of various pituitary adenoma types. No significant correlation was found between MAP-2 expression and gender, patient age, mitotic activity, MIB-1 labelling indices, hormone immunoprofile, and endocrine status, ie. hormonal activity or lack thereof. Thus MAP-2 expression cannot be used to estimate cell proliferation rate, growth potential, endocrine activity or biologic behaviour of an adenoma. Immunopositivity appeared to be stronger in the cytoplasm of adenoma cells than in that of non-tumorous adenohypophysial cells, implying that the adenoma cells contain larger quantities of MAP-2. It can be concluded that the functional activity of MAP-2 is not associated with the manufacture of any specific adenohypophysial hormone(s) and is not limited to one specific cell type.


Iced saline perfusion of Simon Nitinol Filters: improved control during transfemoral delivery: technical note.
Simon Nitinol inferior vena cava filters were placed via a transfemoral venous route in 14 patients. The initial seven caval filters were placed using refrigerated saline infused at a slow rate. In these cases, Simon Nitinol filter expansion was explosive and difficult to control. In the next seven caval filters, the saline infusate was partially frozen and delivered at a higher infusion rate. In this group, the Simon Nitinol filter expansion was noticeably slower with improved ability to control filter placement in the inferior vena cava.


Clinical trial data and emerging strategies: HER2-positive breast cancer.
A deeper insight into tumor biology and HER2 signaling has led to the development of novel anti-HER2 drugs that have significantly improved the prognosis of patients with HER2-positive breast cancer. The breast cancer immune microenvironment has emerged as a potential prognostic factor. Moreover, the host immune system not only seems to play a critical role in the prognosis of HER2-positive breast cancer, but also seems to modulate treatment response to some HER2-targeted agents. Here, we review the latest evidence of the role of immunotherapy in HER2-positive breast cancer and present emerging strategies.


The Application of Thromboelastography in Understanding and Management of Ecchymosis After Total Knee Arthroplasty.
Ecchymosis is a common complication after total knee arthroplasty (TKA). However, only a few studies have been conducted to determine the coagulation status of these patients. Using thromboelastography (TEG), a new technique recording the viscoelastic changes of a whole-blood sample, this study was performed to understand the ecchymosis-related coagulation status and its risk factors. Seventy-five patients receiving unilateral TKA were recruited in this observational study. Oral rivaroxaban was applied as prophylaxis treatment after surgery. TEG was performed 1 day before surgery and 4 days after surgery. Total blood loss and hidden blood loss were recorded and calculated. Univariate and multivariate analyses were conducted to determine risk factors. Twenty-five patients (33.3%) developed ecchymosis within 2-3 days after TKA. Compared with the baseline before TKA, the α-angle (P = .032) and calculated coagulation index (CI; P = .012) were increased in non-ecchymosis group, whereas in the ecchymosis group, there was no significant difference regarding any variable of postoperative TEG evaluation. The ecchymosis group exhibited more hidden blood loss (P = .007) and total blood loss (P = .011). Value change of CI (OR = 0.666, 95% confidence interval = [0.496, 0.895], P = .007) and hidden blood loss (OR = 1.008, 95% confidence interval = [1.002, 1.013], P = .004) were recognized as the independent risk factors for postoperative ecchymosis. In TEG evaluation, the value change of CI and hidden blood loss are independent risk factors of ecchymosis. In view of the relative hypocoagulation status, it is reasonable to stop anticoagulation therapy in patients with excessive ecchymosis. Personalized anticoagulation therapy may be helpful for managing ecchymosis after TKA.


Rapid separation of gram quantities of phospholipids from biological membranes by preparative high performance liquid chromatography.
We present a detailed description of a rapid preparative high performance liquid chromatography (HPLC) procedure for isolation of large scale quantities (a minimum of 200 mg) of rat liver microsomal and mitochondrial phospholipid classes in 40 min on a 25 X 2.5 cm preparative HPLC column of 7-mu silica gel particles using a linear gradient of hexane-isopropanol-water mixtures. A minimum of 1.5 g of phospholipids can be quantitatively separated per day into diphosphatidylglycerol (cardiolipin), phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, sphingomyelin, and a phosphatidylcholine-sphingomyelin fraction. The procedure uses no salts, buffers, acids, or bases, and the isolated phospholipids are suitable for preparing model membranes.


Transplantation of a reverse facial artery pedicled submandibular gland in a dog.
This study was performed to evaluate the possibility of using reverse facial artery pedicled submandibular gland transfer for treating keratoconjunctivitis sicca. A reverse facial artery pedicled submandibular gland, including the duct, from a beagle dog was transplanted into the temporal region in the same animal. 99mTc pertechnetate scintigraphy was used to monitor graft viability, and the grafted glands were examined histologically 12 weeks after transplantation. Postoperative 99mTc pertechnetate scintigraphy demonstrated viable salivary gland tissue in the transplanted region. Histologically, some of the acinar cells in the graft had atrophied. The transplantation of a reverse facial artery pedicled submandibular gland was successful and may be a simple, reliable treatment for patients with keratoconjunctivitis sicca.


Induction of central T cell tolerance: recombinant antibodies deliver peptides for deletion of antigen-specific (CD4+)8+ thymocytes.
In order to prevent or ameliorate autoimmune disease, it would be desirable to induce central tolerance to peripheral self-antigens. We have investigated whether recombinant antibodies (Ab) that deliver T cell epitopes to antigen-presenting cells (APC) in the thymus can be used to induce thymocyte deletion. Troybodies are recombinant Ab with V regions specific for APC surface molecules that have T cell epitopes genetically introduced in their C domains. When MHC class II-specific Troybodies with the lambda2(315)T cell epitope were injected into lambda2(315)-specific TCR transgenic mice, a profound deletion of (CD4+)8+ thymocytes was observed. MHC class II-specific Troybodies were 10-100-fold more efficient than non-targeting peptide Ab, and 500-fold more efficient than synthetic peptide at inducing deletion. Similar findings were observed when MHC class II-specific Troybodies with the OVA(323-339) T cell epitope were injected into OVA-specific TCR transgenic mice. Although deletion was transient after a single injection, newborn mice repeatedly injected with MHC class II-specific Troybodies for 4 weeks, had reduced antigen-specific T cells in peripheral lymphoid tissues and reduced T cell responses. These experiments suggest that Troybodies constructed to target specifically thymic APC could be useful tools for induction and maintenance of central T cell tolerance in autoimmune diseases.


PRC2 insufficiency causes p53-dependent dyserythropoiesis in myelodysplastic syndrome.
EZH1 and EZH2 are enzymatic components of polycomb repressive complex (PRC) 2, which catalyzes histone H3K27 tri-methylation (H3K27me3) to repress the transcription of PRC2 target genes. We previously reported that the hematopoietic cell-specific Ezh2 deletion (Ezh2Δ/Δ) induced a myelodysplastic syndrome (MDS)-like disease in mice. We herein demonstrated that severe PRC2 insufficiency induced by the deletion of one allele Ezh1 in Ezh2-deficient mice (Ezh1+/-Ezh2Δ/Δ) caused advanced dyserythropoiesis accompanied by a differentiation block and enhanced apoptosis in erythroblasts. p53, which is activated by impaired ribosome biogenesis in del(5q) MDS, was specifically activated in erythroblasts, but not in hematopoietic stem or progenitor cells in Ezh1+/-Ezh2Δ/Δ mice. Cdkn2a, a major PRC2 target encoding p19Arf, which activates p53 by inhibiting MDM2 E3 ubiquitin ligase, was de-repressed in Ezh1+/-Ezh2Δ/Δ erythroblasts. The deletion of Cdkn2a as well as p53 rescued dyserythropoiesis in Ezh1+/-Ezh2Δ/Δ mice, indicating that PRC2 insufficiency caused p53-dependent dyserythropoiesis via the de-repression of Cdkn2a. Since PRC2 insufficiency is often involved in the pathogenesis of MDS, the present results suggest that p53-dependent dyserythropoiesis manifests in MDS in the setting of PRC2 insufficiency.


Two-dimensional 1H nuclear magnetic resonance studies on the gene V-encoded single-stranded DNA-binding protein of the filamentous bacteriophage IKe. II. Characterization of the DNA-binding wing with the aid of spin-labelled oligonucleotides.
The DNA-binding domain of the single-stranded DNA-binding protein IKe GVP was studied by means of 1H nuclear magnetic resonance, through use of oligonucleotides of two and three adenyl residues in length, that were spin-labelled at their 3' and/or 5' termini. These spin-labelled ligands were found to cause line broadening of specific protein resonances when bound to the protein, although they were present in small quantities, i.e. of the order of 0.04 molar equivalent and less. The line broadening of protein resonances was made manifest by means of difference one and two-dimensional spectroscopy. Difference one-dimensional experiments revealed line broadening of the same protein resonances upon binding of either 3' or 5' spin-labelled oligonucleotides. Evidence in favour of the existence of a fixed 5' to 3' orientation in the binding of oligonucleotides to the protein surface was therefore not obtained from the spin-labelled oligonucleotide binding studies. Residue-specific assignments of broadened resonances could not, or could only sparsely, be derived from the difference one-dimensional spectra, because of the tremendous overlap in the aliphatic region of the spectrum. In contrast, such assignments were easily obtained from the difference two-dimensional spectra, which were recorded by means of both total correlated spectroscopy and nuclear Overhauser effect spectroscopy. Difference signals were detected for 15 spin systems; ten out of these were assigned to the residues I29, Y27, S20, G18, R16, T28, K22, Q21, V19 and S17 in the amino acid sequence of IKe GVP; the other five spin systems could be assigned to a phenylalanyl residue, an arginyl or lysyl residue, an aspartic acid or asparagyl residue, a glycyl residue and a glutamic acid or glutamyl residue. From the evaluation of the relative difference signals, it was concluded that the direct surroundings of the spin-label group of the labelled oligonucleotide in the bound state is composed of the first five residues in the former group of residues and the five residues in the latter group.(ABSTRACT TRUNCATED AT 400 WORDS)


Facile Amide Bond Formation with TCFH-NMI in an Organic Laboratory Course.
A new undergraduate organic laboratory experiment has been developed for amide bond formation between biorenewable 2-furoic acid and either of two substituted piperazines to prepare medicinally relevant amide products using a procedure with industrial significance. The reactions proceeded smoothly under ambient conditions using the combination of N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and N-methylimidazole (NMI) in a minimal volume of acetonitrile with a direct crystallization upon addition of water. Students successfully collected their product by filtration and then characterized it by NMR (1H, 13C, COSY, DEPT-135, HSQC), IR, MS, and melting point. Students also explored the reaction mechanism and compared green chemistry aspects of their procedure with literature routes. A virtual version of the experiment was adapted for remote instruction.


Manifestation and management of intravenous leiomyomatosis: A systematic review of the literature.
Intravenous leiomyomatosis (IVL) is characterized by the presence of vascular extension and invasion of benign smooth muscle lesions in a worm-like manner from uterine fibroids into the systemic vasculature system. Surgery with complete tumour resection remains the main treatment approach, however both treated and untreated of this disease is associated with high morbidity and mortality. The aim of this systematic review is to highlight the systemic manifestations and surgical management of IVL.


Human herpesvirus 6 (HHV-6) infection in the central nervous system.
Human herpesvirus 6 (HHV 6) was isolated from patients with exanthema subitum (ES) with a high frequency, and it is now believed that this virus causes ES as a primary infection in childhood. HHV 6 infection is highly prevalent in early childhood and this virus may infect infants through the saliva mainly from mother to child. HHV 6 has a tropism to CD4+ cells and destroys cells in vitro. Although children recover from ES without any sequelae, neurological symptoms associated with exanthema subitum are often observed, and we could detect HHV 6 in the cerebrospinal fluid of ES patients. This result suggests that HHV 6 may invade the central nervous system and cause neurological symptoms.


Effects of guanfacine monotherapy on blood pressure, heart rate, plasma renin activity, aldosterone, and catecholamines in hypertensive patients with chronic glomerulonephritis.
Effects of guanfacine, a centrally acting antihypertensive, on blood pressure, heart rate, plasma renin activity, serum aldosterone, plasma norepinephrine, and renal function were evaluated in 16 patients with hypertension with biopsy-proved chronic glomerulonephritis. Guanfacine monotherapy with a daily dose of 1 to 2.5 mg at bedtime for 6 months brought about a significant reduction in blood pressure (171 +/- 2/110 +/- 2 to 144 +/- 2/89 +/- 1 mm Hg; P less than 0.01), with concurrent decreases in heart rate (78 +/- 2 to 70 +/- 2 bpm; P less than 0.01), plasma renin activity (1.96 +/- 0.12 to 1.21 +/- 0.19 ng/ml/hr; P less than 0.05), aldosterone (14.6 +/- 1.5 to 9.7 +/- 0.9 ng/dl; P less than 0.05), plasma norepinephrine (220.5 +/- 24.2 to 132.8 +/- 27.7 pg/ml; P less than 0.05). There was no change in serum creatinine, beta 2-microglobulin, or endogenous creatinine clearance during guanfacine monotherapy. Our data suggest that guanfacine exerts its antihypertensive effect via the inhibition of sympathetic outflow and in part the suppression of the reninangiotensin-aldosterone system and that guanfacine is suitable for the effective treatment of hypertension associated with chronic glomerulonephritis.


Which factors predict parametrial involvement in early stage cervical cancer? A Turkish multicenter study.
To evaluate the clinical and pathological factors for predicting the parametrial involvement (PI) in early stage cervical cancer. This study included 406 patients with type III radical hysterectomy + pelvic ± para-aortic lymphadenectomy and FIGO stage I and II cervical adenocarcinoma, squamous type, and adenosquamous type cervical cancer. The entire cohort of patients had lymphadenectomy performed. Early stage cervical cancer patients were evaluated. FIGO 2014 stage, uterine invasion, LVSI, surgical border involvement, vaginal metastasis, stromal invasion and lymph node metastasis were found to be effective for PI on univariate analyses. However; age, tumor type and tumor size did not determine the parametrial invasion. LVSI (HR: 4.438, 95%CI: 1.771-11.121; p = 0.001), lymph node metastases (HR: 2.418, 95%CI: 1.207-4.847; p = 0.013) and vaginal involvement (HR: 4.109, 95%CI: 1.674-10.087; p = 0.02) are independent prognostic factors on multivariate analysis. Lymph node metastases, LVSI and surgical border involvement are independent prognostic factors for PI in early stage cervical cancer patients. Therefore, less radical surgical approaches for early stage tumors with no nodal spread, negative LVSI and no surgical border involvement are applicable.


The relationship between disease incidences of fatteners registered at slaughter and environmental factors in herds.
The incidences of penumonia, pleurisy and white spots in liver were registered on slaughtered fattening pigs and herd identity. Disease incidences were found to be close related to herd environmental factors, e.g. hygiene and husbandry, recruitment forms and raising methods, and ventilation efficiency.


Co-Addition of Mg2Si and Graphene for Synergistically Improving the Hydrogen Storage Properties of Mg-Li Alloy.
Mg-Li alloy possesses a high hydrogen capacity. However, the hydrogenation and dehydrogenation performances are still far from practical application. In this work, Mg2Si (MS) and graphene (G) were employed together to synergistically improve the hydrogen storage properties of Mg-Li alloy. The structures of the samples were studied by XRD and SEM methods. The hydrogen storage performances of the samples were studied by nonisothermal and isothermal hydrogenation and dehydrogenation, thermal analysis, respectively. It is shown that the onset dehydrogenation temperature of Mg-Li alloy was synergistically reduced from 360°C to 310°C after co-addition of Mg2Si and graphene. At a constant temperature of 325°C, the Mg-Li-MS-G composite can release 2.7 wt.% of hydrogen within 2 h, while only 0.2 wt.% of hydrogen is released for the undoped Mg-Li alloy. The hydrogenation activation energy of the Mg-Li-MS-G composite was calculated to be 86.5 kJ mol-1. Microstructure and hydrogen storage properties studies show that graphene can act as a grinding aid during the ball milling process, which leads to a smaller particle size for the composites. This work demonstrates that coaddition of Mg2Si and graphene can synergistically improve the hydrogen storage properties of Mg-Si alloy and offers an insight into the role of graphene in the Mg-Li-MS-G composite.


The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications.
CRLs (Cullin-RING E3 ubiquitin ligases) are the largest E3 ligase family in eukaryotes, which ubiquitinate a wide range of substrates involved in cell cycle regulation, signal transduction, transcriptional regulation, DNA damage response, genomic integrity, tumor suppression and embryonic development. CRL4 E3 ubiquitin ligase, as one member of CRLs family, consists of a RING finger domain protein, cullin4 (CUL4) scaffold protein and DDB1-CUL4 associated substrate receptors. The CUL4 subfamily includes two members, CUL4A and CUL4B, which share extensively sequence identity and functional redundancy. Aberrant expression of CUL4 has been found in a majority of tumors. Given the significance of CUL4 in cancer, understanding its detailed aspects of pathogenesis of human malignancy would have significant value for the treatment of cancer. Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor. Finally, we discuss its potential value in cancer therapy.


Intravaginal metronidazole/miconazole for the treatment of vaginal trichomoniasis.
Trichomonas vaginalis is the causative agent of the most common curable sexually transmitted disease in the world. The infection is treated with a single oral dose of metronidazole or tinidazole, currently the only licensed class of drugs available for this indication; however, both of these antimicrobials are associated with significant gastrointestinal adverse effects, and some individuals are unable to tolerate them because of these adverse effects. Randomized, dose-ranging pilot study conducted in 2 phases consisting of 20 participants in each phase. In the first phase, participants were randomized to the vaginal suppository (metronidazole 750 mg/miconazole nitrate 200 mg) twice a day for 7 days versus oral metronidazole 2 g single dose. In the second phase, participants randomized to suppository used it once a day for 7 days. Women were reevaluated on days 12 to 15 and 30 to 35. Treatment failures were defined as persistence of trichomonas by wet prep and/or culture. There were no significant differences in cure rates between the vaginal suppositories and oral metronidazole in either phase. The overall efficacy across both follow-up visits was 80% versus 90% for the suppository (2×/d) versus oral medication arms in phase 1 (P = 1.00) and 78% versus 70% for the suppository (1×/d) versus oral medication arms in phase 2 (P = 1.00). The results were also nonsignificant when combining results across arm (P = 1.00). High-dose intravaginal metronidazole combined with miconazole offers the possibility of a well-tolerated treatment that avoids the systemic adverse effects of nitroimidazoles for the treatment of trichomoniasis.


Estimation of genetic parameters for longevity considering the cow's age at last calving.
The aim of this study was to estimate heritability and predict breeding values for longevity among cows in herds of Nellore breed, considering the trait cow's age at last calving (ALC), by means of survival analysis methodology. The records of 11,791 animals from 22 farms were used. The variable ALC has been used by a criterion that made it possible to include cows not only at their first calving but also at their ninth calving. The criterion used was the difference between the date of each cow's last calving and the date of the last calving on each farm. If this difference was greater than 36 months, the cow was considered to have failed and uncensored. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The survival model used for the analyses was the proportional hazards model, and the base risk was given by a Weibull distribution. The heritability estimate obtained was equal to 0.25. It was found that the ALC variable had the capacity to respond to selection for the purpose of increasing the longevity of the cows in the herds.


Calibration of an in vitro assay system using a non-adherent cell line to evaluate the effect of a drug on Toxoplasma gondii.
A TG 180 non-adherent cell culture with Toxoplasma gondii and spiramycin was performed in order to calibrate TG 180 cells used in a therapeutic assay system. TG 180 cells were infected with the RH strain of T. gondii, and spiramycin was added at final concentrations of 1, 2, 4, 8, 12, 16, 20 and 25 micrograms/ml. A least-squares linear regression with confidence interval was calculated from the experimental curve and allowed the determination of the 50% inhibitory concentration of spiramycin. The IC50 of 13.7 micrograms/ml obtained is comparable with the results of the literature. The system including TG 180 cells (recently cultured in vitro) provides a rapid, accurate and economical determination of the effects of a drug on Toxoplasma gondii.


Inherited deficiencies of complement components in man.
Isolated inherited deficiency states of almost every complement protein have been recognized. Almost all are autosomal recessive traits. Deficiency of the early-acting components C1, C4 and C2 is associated with increased risk of immune complex disease, particularly systemic lupus erythematosus. Patients with deficiency of C3, factor I or factor H have increased susceptibility to infection by pyogenic bacteria, whereas those with deficiencies of properdin, C5, C6, C7 or C8 are prone to systemic neisserial infection. Inherited deficiency of C1 inhibitor is transmitted as an autosomal dominant trait, is genetically heterogeneous, and is associated with attacks of angioedema and consumption of C4 and C2. There is evidence that a plasmin-modified fragment of C2 is responsible for the angioedema in this disorder. Administration of androgens tends to correct the biochemical abnormalities of hereditary angioedema and to prevent attacks.


Autoantibodies to brain endothelial cells in the sera of patients with human T-lymphotropic virus type I associated myelopathy and other demyelinating disorders.
We examined the sera of 21 cases of human T-lymphotropic virus type I (HTLV-1)-associated myelopathy (HAM), 30 cases of neuro-Behçet (N-B) syndrome, and 36 cases of multiple sclerosis (MS) for the presence of autoantibodies to brain endothelial cells by enzyme-linked immunosorbent assay (ELISA) using cultured brain endothelial cells. The concentrations of immunoglobulin G (IgG) which bound to brain endothelial cells were significantly increased in the sera of patients with HAM before (P less than 0.001) and after (P less than 0.01) blocking Fc receptors compared to those of controls. The levels of IgG binding to brain endothelial cells were also significantly increased in the sera of patients with N-B syndrome (P less than 0.01), and MS (P less than 0.001) especially those in an exacerbation compared to those of controls regardless of blocking Fc receptors. These results suggest that IgG binding to brain endothelial cells may be mediated via an immunologically specific antigen-antibody interaction as a result of the blood-brain barrier (BBB) damage in cases of HAM, N-B syndrome and MS.


A computer program in BASIC for estimation of ED50 and LD50.
A BASIC computer program for calculating ED50 and LD50 values and their confidence limits by probit analysis and weighted linear regression is presented. It also includes the Chi square procedure for testing the mathematical model and allows on-screen high resolution graphic display. The portable program can easily be modified for use in different models of microcomputers.


Massive human ingestion of orpiment (arsenic trisulfide).
Because the toxicity of arsenic is well known, arsenic-containing compounds have frequently been ingested for suicidal purposes. We report a case of attempted suicide by massive ingestion of arsenic trisulfide, an arsenic mineral of low solubility, which resulted in minimal symptoms. An asymptomatic 57-year-old man presented to an Emergency Department 13h after his reported ingestion of approximately 84g of arsenic contained in a mineral specimen of orpiment (arsenic trisulfide) that had been crushed and mixed with an alcoholic beverage and food. His only symptom before presentation was nausea. Physical examination was unremarkable, and diagnostic tests included a normal electrolyte panel, a normal serum lactate, and a normal electrocardiogram. An abdominal radiograph revealed hyper-dense material scattered throughout the large intestine. As per the recommendations of the regional poison center, the patient was managed with whole bowel irrigation with a polyethylene glycol solution, maintenance intravenous hydration, and observation on a telemetry unit. Chelation was not performed. A spot urine specimen collected 12h after admission contained 1490μg of total arsenic per liter (background range<50μg per liter). The patient remained asymptomatic throughout his hospital course. Follow-up studies revealed a diminution in both intra-abdominal radiopacities and urine arsenic concentration. X-ray diffraction analysis of the specimen confirmed its identity as arsenic trisulfide. Our experience demonstrates that massive ingestion of a poorly soluble inorganic arsenic compound can be successfully managed with gastrointestinal decontamination alone without chelation, provided that the patient remains asymptomatic during close clinical monitoring.


Protective effect of dexpanthenol against nephrotoxic effect of amikacin: An experimental study.
Amikacin has the largest spectrum among aminoglycosides, its nephrotoxic effect limits its utilization. Our purpose in this study is to review the protective effect of dexpanthenol against the nephrotoxic effect of amikacin, accompanied with histopathological and biochemical parameters. 32 rats were randomly separated into four groups with eight in each (amikacin (1.2mg/kg/day), amikacin (1.2mg/kg/day)+dexpanthenol (500mg/kg/day), dexpanthenol (500mg/kg/day) and control). In order to assess the oxidative balance and renal damage between groups, biochemical parameters (total antioxidant capacity (TAS), total oxidant stress (TOS), catalase (CAT), paraoxonase (PON), arylesterase (ARES), urea, and creatinin) were studied from the blood samples. At the end of the 14th day, renal tissues were reviewed blindly by a pathologist. TOS and oxidative stress index (OSI) values were significantly lower in the group which was administered with dexpanthenol+amikacin compared to the group which only received amikacin (respectively, p=0.001, p=0.002). Antioxidant biochemical parameters (TAS, CAT, PON, and ARES) were significantly higher in the group which was administered with dexpanthenol+amikacin compared to the group administered only with amikacin (respectively, p=0.007, p=0.001, p=0.003, p=0.003). Urea and creatitin values were found to be significantly lower in the group which was administered with dexpanthenol+amikacin compared to the group administered only with amikacin (respectively, p=0.002, p=0.001). Histopathologic changes such as glomerular and tubular epithelium changes and interstitial edema were clearly observed in the group administered only with amikacin, such findings were insignificant in the group administered with dexpanthenol+amikacin. It was revealed with biochemical and histopathologic data that nephrotoxic effects created by amikacin administration can be limited with dexpanthenol by using them together, and further advanced clinical studies are required.


The value of two combined chemoradiotherapy approaches in the treatment of inoperable esophageal cancer.
The antitumor activity of 5-fluorouracil (5-FU), combined either with bleomycin or adriamycin plus radiation, was studied in a controlled randomized clinical trial. Sixty-one previously untreated inoperable esophageal cancer patients entered the study and 56 have been evaluated: 58 male and 3 female patients with a mean age of 57 years (range 37-74). Concerning localization of the tumors in the esophagus, 2 were in the upper third, 36 in the middle third and 18 in the lower third. The length of the filling defects in the esophagogram (X-ray) was in 9 patients less than 5 cm, in 31 5-8 cm, and in 16 patients greater than 8 cm. Squamous cell carcinoma was found in 51 patients, adenocarcinoma in 3, and anaplastic (squamous cell) carcinoma in 2 patients. Modality A consisted of a combination of 5-FU (10 mg/kg i.v. 2 X weekly, 4 weeks) and bleomycin (10 mg/m2 i.v., 2 X 4 weeks) which was given concurrently with radiation (3600-4000 rad - 1000 rad weekly). In modality B the combination of 5-FU (same dose) and adriamycin (30 mg/m2 i.v. day 1, 2, 23 and 24) was applied with the same schedule and dosage of radiation. Seventy-five percent of the patients (21/28) have responded to treatment (CR + PR) in modality A, with 11 complete and 10 partial responses. In arm B, response was recorded in 64% of patients (18/28), with 2 complete and 16 partial responses. The difference in complete responses (39% vs 8%) was statistically significant (P less than 0.05). The median remission duration in complete responders was 12 months in modality A (range 6-18 months), and 6.8 months in modality B (range 3-10 months). All the responses occurred in patients with squamous cell carcinoma, except one partial response in a case of adenocarcinoma. As far as the age is concerned (less than 55 vs greater than 55 years), no significant difference in response rate was found (67% vs 71%). More favorable results were observed in the group of patients with less than 10% weight loss (79% vs 63%). Toxicity was moderate (myelosuppression, cardiotoxicity), but one treatment-related death (pulmonary fibrosis, cardiac failure) was recorded in arm A, as well as one death (rupture of aorta) in group B. Approximately 60% of patients in both modalities suffered from severe mucositis and retrosternal pain. The results of the study showed that the combination of 5-FU with adriamycin and particularly with bleomycin, given concurrently with lower radiation dosage, is an effective palliative treatment for inoperable esophageal cancer.


Low-dose Dexamethasone Increases Autophagy in Cerebral Cortical Neurons of Juvenile Rats with Sepsis Associated Encephalopathy.
Studies have shown that a certain dose of dexamethasone can improve the survival rate of patients with sepsis, and in sepsis associated encephalopathy (SAE), autophagy plays a regulatory role in brain function. Here, we proved for the first time that small-dose dexamethasone (SdDex) can regulate the autophagy of cerebral cortex neurons in SAE rats and plays a protective role. Cortical neurons were cultured in vitro in a septic microenvironment and a sepsis rat model was established. The small-dose dexamethasone (SdDex) or high-dose dexamethasone (HdDex) was used to intervene in neurons or SAE rats. Through fluorescence microscopy and western blot analysis, the expressions of microtubule-associated protein 1 light chain 3 (LC3), p62/sequestosome1 (p62/SQSTM1), mammalian target of rapamycin (mTOR) signaling pathway related proteins, and apoptosis-related proteins were detected. Theresultsshowthat compared with those in SAE rats, the cortical pathological changes in SAE rats treated with SdDex were improved, and damaged substances were encapsulated and degraded by autophagosomes in neurons. Additionally, similar to neurons in vitro, cortical autophagy was further activated and the mTOR signaling pathway was inhibited. After HdDex treatment, the mTOR signaling pathway in cortex is inhibited, but further activation of autophagy is not obvious, the cortical pathological changes were further worsened and the ultrastructure of neurons was disturbed. Furthermore, the HdDex group exhibited the most obvious apoptosis. SdDex can regulate autophagy of cortical neurons by inhibiting the mTOR signaling pathway and plays a protective role. Brain damage induced by HdDex may be related to the activation of apoptosis.


Transmission of beneficial yeasts accompanies offspring production in Drosophila-An initial evolutionary stage of insect maternal care through manipulation of microbial load?
Parent-to-offspring transmission of beneficial microorganisms is intimately interwoven with the evolution of social behaviors. Ancestral stages of complex sociality-microbe vectoring interrelationships may be characterized by high costs of intensive parental care and hence only a weak link between the transmission of microbial symbionts and offspring production. We investigate the relationship between yeast symbiont transmission and egg-laying, as well as some general factors thought to drive the "farming" of microscopic fungi by the fruit fly Drosophila melanogaster, an insect with no obvious parental care but which is highly dependent on dietary microbes during offspring development. The process of transmitting microbes involves flies ingesting microbes from their previous environment, storing and vectoring them, and finally depositing them to a new environment. This study revealed that fecal materials of adult flies play a significant role in this process, as they contain viable yeast cells that support larval development. During single patch visits, egg-laying female flies transmitted more yeast cells than non-egg-laying females, suggesting that dietary symbiont transmission is not random, but linked to offspring production. The crop, an extension of the foregut, was identified as an organ capable of storing viable yeast cells during travel between egg-laying sites. However, the amount of yeast in the crop reduced rapidly during periods of starvation. Although females starved for 24 h deposited a smaller amount of yeast than those starved for 6 h, the yeast inoculum produced still promoted the development of larval offspring. The results of these experiments suggest that female Drosophila fruit flies have the ability to store and regulate the transfer of microorganisms beneficial to their offspring via the shedding of fecal material. We argue that our observation may represent an initial evolutionary stage of maternal care through the manipulation of microbial load, from which more specialized feedbacks of sociality and microbe management may evolve.


Nitrogen fixation as evidence for the reducing nature of the early biosphere.
Probably the first nitrogen fixers were anaerobic, non-photosynthetic, bacteria, i.e. fermenters. During the evolution of N2 fixation they still needed nitrogen on the oxidation level of ammonia. Because of the complexities in structure and function of nitrogenase this evolution must have required a long time. The photosynthetic and later the respiring bacteria inherited the capacity for N2 fixation from the fermenters, but the process did not change a great deal when it was taken over. Because of the long need for NH3, which is unstable in a redoxneutral atmosphere, a long-persisting reducing atmosphere was needed. The transition to a redoxneutral atmosphere, dominated by CO2, H2O and N2, cannot have been rapid, and the NH3 in it was recycled. Probably the atmosphere contained for a long time, as was suggested by Urey but is often denied now, a great deal of methane as a reductant. The recycling occurred with participation of intermediates like cyanide, through energy input as UV radiation or as electric discharges. A stationary state was set up. The hypothesis is recalled that coloured, photosynthetic, NH3 bacteria, analogous to coloured sulphur bacteria, may have existed, or may still exist, in reducing conditions. A few remarks are made about the origin of nitrification in the later, oxidizing atmosphere.


The feasibility of closed mitral valvotomy in pregnancy.
Rheumatic mitral valve stenosis is an important nonobstetric complication of pregnancy in an African country. Between January 1965 and September 1985 41 closed mitral valvotomies with a Tubbs dilator were performed in 39 pregnant women (two first trimester, 22 second trimester, and 17 third trimester). All patients experienced symptomatic improvement from New York Heart Association Class 3.01 (average) preoperatively to 1.22 postoperatively. There were no deaths related to the operation and delivery. Fetal deaths were due to postoperative spontaneous abortion in two cases (4.9%) or premature labour in three cases (7.3%), for an overall survival of 36 babies (87.8%). Fetal morbidity was due to prematurity or dismaturity in three infants, all of whom survived. Thirty-three normal infants were delivered at term. Nine patients needed subsequent surgical procedures for mitral valve restenosis 5 to 17 years (mean 10.2 years) after the initial closed valvotomy: Repeat closed valvotomy was performed in three patients after 5, 8, and 10 years (the first two during subsequent pregnancies), an open procedure was performed in one after 6 years, and five patients underwent subsequent mitral valve replacement after 11 (two), 12 (two), and 17 (one) years. Two late deaths occurred; one after 10 years, as a result of pneumonia and meningitis, and the other after 12 years, before a mitral valve replacement for restenosis could be performed. None of the remaining patients has required further surgical procedures, but two have moderate symptoms. Closed mitral valvotomy gives satisfactory results in pregnant patients with severe mitral stenosis. When indicated during pregnancy, it should be performed at any stage of the pregnancy.


Plant thiol peroxidases as redox sensors and signal transducers in abiotic stress acclimation.
The temporal and spatial patterns of reactive oxygen species (ROS) in cells and tissues decisively determine the plant acclimation response to diverse abiotic and biotic stresses. Recent progress in developing dynamic cell imaging probes provides kinetic information on changes in parameters like H2O2, glutathione (GSH/GSSG) and NAD(P)H/NAD(P)+, that play a crucial role in tuning the cellular redox state. Central to redox-based regulation is the thiol-redox regulatory network of the cell that integrates reductive information from metabolism and oxidative ROS signals. Sensitive proteomics allow for monitoring changes in redox-related posttranslational modifications. Thiol peroxidases act as sensitive peroxide and redox sensors and play a central role in this signal transduction process. Peroxiredoxins (PRX) and glutathione peroxidases (GPX) are the two main thiol peroxidases and their function in ROS sensing and redox signaling in plants is emerging at present and summarized in this review. Depending on their redox state, PRXs and GPXs act as redox-dependent binding partners, direct oxidants of target proteins and oxidants of thiol redox transmitters that in turn oxidize target proteins. With their versatile functions, the multiple isoforms of plant thiol peroxidases play a central role in plant stress acclimation, e.g. to high light or osmotic stress, but also in ROS-mediated immunity and development.


Child obesity and anaesthetic morbidity.
To knock down the following myths: obesity in paediatric patients is rare and mainly a North-American problem; obesity in childhood has no long-term harmful effects. To sensitize the anaesthesiologists to a problem seldom addressed in the anaesthetic literature. Recent medical information concerning the incidence and pathophysiology of obesity in paediatric patients is summarized. The early manifestations of the comorbidities associated with obesity in adults are already present in overweight and obese children and should be addressed for their safe anaesthetic management. Perioperative respiratory events seem more frequent in overweight and obese patients.


Scottish validation study of Cancer Registration data childhood leukaemia 1968-1981--I.
This study attempted to validate central registration data on all childhood leukaemia cases in Scotland between 1968 and 1981 in line with the Black Enquiry concerning West Cumbria. Missing files precluded a complete verification, but minor errors of registration were found in 44% of cases. A small number of important mistakes of omission (eight cases), wrong diagnosis (six cases) and postal code errors (nine cases) were found which might affect epidemiological studies of these relatively rare diseases. Precise and verified prospective data collection at the time of diagnosis is essential if the spatial distribution of childhood cancers is being studied.


Patient selection of anatomical double bundle or traditional single bundle ACL reconstruction.
This study was designed as a questionnaire survey to reveal the preference in technique of patients faced with anterior cruciate ligament (ACL) reconstruction. One hundred and ten subjects (35 patients and 75 medical students) were included in this study. A questionnaire survey was conducted, and the following questions were asked: (1) How old are you? (2) Prior to this survey, did you know what the ACL was? (3) Prior to this survey, did you have any knowledge about ACL reconstruction technique? (4) Prior to this survey, did you know the difference between anatomical double bundle (DB) technique and traditional single bundle (SB) technique? (5) If you had to have an ACL reconstruction, which technique would you prefer? In the same questionnaire, between questions (3) and (4), a description of SB and DB was provided. Sixty-nine percent of patients and 100% of medical students knew what the ACL was. Forty-three percent of patients and 85% of medical students had previous knowledge about ACL reconstruction. None of the patients and only 29% of the medical students had prior knowledge about the difference between DB and SB. Six percent of patients selected SB, and 40% selected DB. Nine percent of medical students selected SB, and 67% selected DB. In this study, 46% of patients and 76% of medical students selected one of the operation techniques. The trend in selection of the operation technique was significantly influenced by the subjects' prior medical knowledge. It might be possible to apply the principle of "informed patient choice" to the selection of DB or SB for ACL reconstruction. Decision analysis, Level III.