text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
A large series of 4-arylcoumarins was synthesized by Suzuki-Miyaura cross-coupling reaction and evaluated for antiprotozoal activity against Plasmodium falciparum and Leishmania donovani. Several compounds were found to strongly inhibit the proliferation of human cell line and/or parasites. The 4-(3,4-dimethoxyphenyl)-6,7-dimethoxycoumarin exhibit a potent activity on L. donovani amastigotes with a selectivity index (SI=265) twice than amphotericin B (SI=140). | Coumarins |
After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV." | Feline Acquired Immunodeficiency Syndrome |
This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures and receptors, and junction proteins. The mechanosignaling pathways presented include the cytoskeleton, integrins, extracellular matrix, and intracellular signaling molecules. These are followed by discussions on mechanical regulation of transcriptome and epigenetics, relevance of mechanotransduction to health and disease, and interactions between VSMCs and ECs. Throughout this review, we offer suggestions for specific topics that require further understanding. In the closing section on conclusions and perspectives, we summarize what is known and point out the need to treat the vasculature as a system, including not only VSMCs and ECs but also the extracellular matrix and other types of cells such as resident macrophages and pericytes, so that we can fully understand the physiology and pathophysiology of the blood vessel as a whole, thus enhancing the comprehension, diagnosis, treatment, and prevention of vascular diseases. | Signal Transduction |
Mortality is very high during the pelagic larval phase of fishes but the factors that determine recruitment success remain unclear and hard to predict. Because of their bipartite life history, larvae of coastal species have to head back to the shore at the end of their pelagic episode, to settle. These settlement-stage larvae are known to display strong sensory and motile abilities, but most work has been focused on tropical, insular environments and on the influence of coast-related cues on orientation. In this study we quantified the in situ orientation behavior of settlement-stage larvae in a temperate region, with a continuous coast and a dominant along-shore current, and inspected both coast-dependent and independent cues. We tested six species: one Pomacentridae, Chromis chromis, and five Sparidae, Boops boops, Diplodus annularis, Oblada melanura, Spicara smaris and Spondyliosoma cantharus. Over 85% of larvae were highly capable of keeping a bearing, which is comparable to the orientation abilities of tropical species. Sun-related cues influenced the precision of bearing-keeping at individual level. Three species, out of the four tested in sufficient numbers, oriented significantly relative to the sun position. These are the first in situ observations demonstrating the use of a sun compass for orientation by wild-caught settlement-stage larvae. This mechanism has potential for large-scale orientation of fish larvae globally. | Life Cycle Stages |
INTRODUCTION: Nocardiosis is an infectious actinomycetic disease with a variable clinical spectrum that makes it difficult to diagnose. It mainly affects immunosuppressed individuals. Advances in molecular genomic technology have helped in identifying new pathogenic Nocardia species. This has made identification of their specific antimicrobial sensitivity possible. AREAS COVERED: It is important to know the taxonomy, clinical features, diagnosis and precise species identification because of the multitude of pathogenic species involved and the different antibiotic susceptibility patterns. The authors review sulfonamides, aminoglycosides, penicillin derivatives, tetracyclines, glycylcyclines, oxazolidinones, carbapenems and the association of other potential drugs, the therapeutic effectiveness of traditional antimicrobials and new monotherapy and combined treatment alternatives. New oxazolidinones and the benzothiazinones are compounds that have been found effective in vitro and in experimental models. EXPERT OPINION: Clinicians should be aware of nocardiosis in patients with different forms of immunosuppression. The identification of organisms, their patterns of antibiotic susceptibility and the adverse effects related to these drugs must be considered. Treatments can vary from traditional schemes with trimethoprim-sulfamethoxazole to other combination therapies and new antibiotics and treatment modalities depending on the organ or site involved, the severity of infection and the presence of comorbidities. | Nocardia Infections |
We studied the histopathological and ultrastructural modifications which the adenocarcinoma type A grafted to C3 H/he-M mice manifested on being treated with vincristine, prospidium chloride and adriamycin. With M/O the tumors treated with prospidium chloride and adriamycin showed a greater proportion of connective stroma and numerous extensive parenchymatous necrosis. Ultrastructurally, in these groups, atypical mitoses were observed with multiple chromosomal fragmentations which can be related to the pharmacological action mechanism. A decrease in the number of viral particles was seen throughout the treatment. | Prospidium |
Bill Didusch was one of the most influential illustrators in American urology. His biography is of great importance not only because of his artistic achievements, but also the work he has accomplished in the service of the American Urological Association. He founded a museum of urological artifacts that bears his name. The article reflects Didusch's biography and emphasizes his impact on American urology and urological illustration as an integral part of visualisation in medicine. | Medical Illustration |
Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that play a central role in host cell recognition and responses to microbial pathogens. TLR-mediated recognition of components derived from a wide range of pathogens and their role in the subsequent initiation of innate immune responses is widely accepted; however, the recent discovery of non-TLR PRRs, such as C-type lectin receptors, NOD-like receptors, and RIG-I-like receptors, suggests that many aspects of innate immunity are more sophisticated and complex. In this review, we will focus on the role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition. | Toll-Like Receptors |
alpha/beta-Hydrolase domain 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes monoacylglycerol (MAG) lipids, particularly the endogenous cannabinoid 2-arachidonoylglycerol (2-AG), in both central and peripheral tissues. ABHD6 and its substrates have been shown to be involved in the modulation of various (patho)physiological processes, including neurotransmission, inflammation, insulin secretion, adipose browning, food intake, autoimmune disorders, as well as neurological and metabolic diseases, making this enzyme a promising therapeutic target to treat several diseases. This review will focus on the molecular mechanism, biological functions and pathological roles of ABHD6, as well as recent efforts to develop ABHD6 inhibitors, providing a strong basis for the development of small molecules by targeting ABHD6 to treat diverse diseases. | Insulin Secretion |
The results of scintigraphy in 29 patients with Cushing's syndrome were evaluated. It was possible to separate bilateral hyperplasia from unilateral abnormality. In cases of unilateral abnormality correct localization of the tumour was accomplished and it was possible to visualize adrenocortical carcinoma. The many advantages of adrenal scintigraphy are listed and it is concluded that adrenal scintigraphy is the best means of investigation to differentiate between ACTH-dependent and ACTH-independent Cushing's syndrome. | 19-Iodocholesterol |
Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6.7 for MHC-I-negative cells and 6.9 for MHC-I-positive cells. That of NK cells was 2.4 for MHC-I-negative cells. Likely due to the higher threshold numbers, killing by CIK cells was delayed in comparison with NK cells: 40% of MHC-negative target cells were killed after 5 h when co-cultured with CIK cells and after 2 h with NK cells. Our data have implications for the rational design of CIK cell-based immunotherapy of cancer patients. | Cytokine-Induced Killer Cells |
Maintenance of genome integrity is of major importance for plus-stranded RNA viruses that are vulnerable to degradation by host ribonucleases or to replicase errors. We demonstrate that short truncations at the 5' end of a model Tomato bushy stunt virus (TBSV) RNA could be repaired during replication in yeast and plant cells. Although the truncations led to the loss of important cis-regulatory elements, the genome repair mechanisms led to the recovery of promoter and enhancer-like sequences in 92% of TBSV progeny. Using in vitro approaches, we demonstrate that the repaired TBSV RNAs are replication-competent. We propose three different mechanisms for genome repair: initiation of RNA synthesis from internal sequences and addition of nonviral nucleotides by the tombusvirus replicase; and via RNA recombination. The ability to repair cis-sequences makes the tombusvirus genome more flexible, which could be beneficial to increase the virus fitness and adaptation to new hosts. | Tombusvirus |
The omasums of 30 healthy cows and 55 cows with various gastrointestinal disorders (10 with left displacement and eight with right displacement of the abomasum, 10 with abomasal volvulus, 10 with traumatic reticuloperitonitis, nine with ileus of the small intestines and eight with reticulo-omasal stenosis) were examined ultrasonographically on the right side of the body with a 3.5 MHz linear transducer. The dorsal and ventral margins of the omasum and its size in the fifth to 11th intercostal spaces were determined. Generally, the ultrasonographic appearance of the omasum did not differ between the healthy and abnormal cows. The omasum appeared as a semicircle, and the omasal wall closest to the transducer was visible as a thick echogenic line. In a few of the abnormal cows, the omasal laminae were visible and the omasum appeared to have motility. In the cows with left and right displacement of the abomasum and abomasal volvulus, the dorsal margin of the omasum was significantly further from the dorsal midline in some intercostal spaces than in the healthy cows. In the cows with left displacement of the abomasum, the ventral margin of the omasum was significantly further from the dorsal midline in the 7th intercostal space than in the healthy cows. In the cows with reticulo-omasal stenosis, traumatic reticuloperitonitis and ileus of the small intestine, the ventral margin of the omasum was significantly closer to the dorsal midline in some intercostal spaces than in the healthy cows. The mean (sd) size of the omasum in the healthy cows varied from 16.3 (1.5) cm to 56.9 (10.0) cm, depending on the intercostal space, and the omasum was significantly smaller in some intercostal spaces in the cows with reticulo-omasal stenosis, right displacement of the omasum, abomasal volvulus and ileus of the small intestine. | Omasum |
A new flavonoid compound isokaempferide 7-O-beta-d-(6''-methylglucuronide) (1) was isolated from flowers of Cirsium rivulare (Jacq.) All. Its structure was elucidated on the basis of spectroscopic studies (UV, (1)H and (13)C NMR, FABMS). Moreover, five known flavonoid compounds: apigenin 7-(6''-methylglucuronide) (2), hispidulin 7-glucoside (3), isokaempferide 7-glucuronide (4), kaempferol 3-galactoside (5), pectolinarin (6) were isolated from this source for the first time. The antimicrobial activity of aqueous, methanolic and 70% ethanolic extracts of Cirsium rivulare flowers and leaves was also evaluated. | Cirsium |
Keratoconus is considered a contraindication for refractive surgery because of the potential corneal instability following surgery. On the other hand, penetrating keratoplasty is the usual surgical modality when the keratoconic patient cannot tolerate a contact lens. In some selected cases, when the central cornea is still transparent, refractive surgical procedures, particularly Intacs implantation, may be used to help the patient to improve visual function. | Keratectomy |
There exist 11 essential elements (iron, copper, iodine, zinc, chromium, cobalt, molybdenum, manganese, nickel, selenium and fluorine) vitally important for human health. The deficiency of these trace elements results in many pathological processes, including such world-wide human diseases, as iron-deficient anemias and other forms of hyposiderosis, endemic hypothyroid goiter, endemic fluorine deficiency states, particularly manifested by dental caries in children and osteoporosis of the advanced age. Selenium deficiency causes endemic cardiopathy in China, is a risk factor for the development and severe course of congestive cardiopathies, as well as myocardial infarction in a number of European countries. Correction of selenium deficiency with sodium selenite reduced to the minimum the mortality rate from endemic cardiopathy in China (Keshan disease) and had a favourable effect on other forms of cardiovascular pathology. Essential trace element deficiency results in many forms of embryonal and fetal pathology and decreases the antitumour resistance in man. New essential trace elements are still being identified and their number reached 19 at present. Development of pathological anatomy of essential trace element deficiency is an important task of modern medicine. | Deficiency Diseases |
Phosphofructokinase-2 is a 66 kD homodimer whose subunits are associated by means of a bimolecular domain, the beta-clasp, which is linked to the larger portion of each subunit by a reentrant chain topology. To investigate how this structural organization determines the folding pathway of Pfk-2, unfolding and folding kinetic experiments were performed. The folding pathway shows an unstructured monomeric intermediate and that most part of the dimer structure is reached as a slow concerted folding/association step with a quite folded transition state in terms of solvent exposure. Unfolding kinetics show a transient intermediate, probably a partially unfolded dimer. We propose that these characteristics arise by a mutual constrain between the large domain and the beta-clasp domain imposed by their interrupted chain connectivity. | Phosphofructokinase-2 |
Global profiling tools are required to fully understand the impact of genetic modifications and toxicological interventions on the network of transcripts, proteins and metabolites found within a cell, tissue or organism. High-resolution 1H NMR spectroscopy in conjunction with statistical pattern recognition is one such technique, referred to as metabonomics or metabolomics, which is increasingly being used to globally profile metabolites. This review examines analytical advances in NMR spectroscopy that have aided this development including high-resolution magic angle spinning NMR spectroscopy, cryogenically cooled probes and high-through put systems. This has allowed the approach to identify genetically modified yeast strains and distinguish both disease presence and severity in coronary heart disease." | Organisms, Genetically Modified |
We have evaluated various aerosol foam types having different compositions and related physico-chemical properties. The foams assessed were hydroethanolic, emulsion, and aqueous based. Composition, appearance, loss on drying, and rheological properties were analysed to characterise the macrostructure of the different aerosol foams. To confirm the validity of the vane rheological technique used, and facilitate intuitive understanding of the data, similar data were collected for a commercial shaving foam. Of the physico-chemical parameters that were evaluated, rheological properties were distinct among hydroethanolic, emulsion, and aqueous aerosol foam types. The results indicate that beyond composition differences, physico-chemical differences do exist between these aerosol foam types. The viscoelastic flow properties provided an insight of the macrostructure of materials that have been foamed. | Aerosol Propellants |
In the central nervous system, a large amount of chelatable Zn(2+) is sequestered in presynaptic vesicles of certain glutamatergic nerve terminals. The exo-endocytotic cycle of synaptic vesicles is strictly linked to the small GTPase Rab3A. Metallothionein-3 (Zn(7)MT-3) has been proposed to be involved in the intracellular trafficking of Zn(2+) in zinc-containing neurons, but its role in this process is not understood. By using affinity precipitation and surface plasmon resonance analysis, we show that Zn(7)MT-3 binds reversibly to Rab3A.GDP (K(D) = 2.6 microM), but not to Rab3A.GTP. The binding of Zn(7)MT-3 to Rab3A.GDP is specific as no binding was observed with the metal-free form of MT-3. Mutational studies of Rab3A mapped the interaction site to the effector binding site of the protein. This location is further supported by the kinetics of GDP exchange, which was found to be unaffected by binding of Zn(7)MT-3 to Rab3A.GDP. The interaction of Zn(7)MT-3 with Rab3A indicates that Zn(7)MT-3 is not merely a cellular Zn(2+) buffer, but actively participates in synaptic vesicle trafficking upstream of vesicle fusion. | rab3A GTP-Binding Protein |
Annotated hemoglobin genes in Chlamydomonas reinhardtii form functional globins, despite unusual architectures. Spectral characteristics show subtle biochemical differences. Multiple globins might help the alga to cope with its versatile environment. The unicellular green alga C. reinhardtii is a photosynthetic, often soil-dwelling organism, subjected to a changeable environment in nature. The alga contains 12 genes encoding so-called truncated hemoglobins that feature a two-on-two helical fold instead of the three-on-three helix arrangement of the long-studied vertebrate globins or plant symbiotic and non-symbiotic hemoglobins. In plants, non-symbiotic hemoglobins often play a role in acclimation to stress, and we could show recently that one of the C. reinhardtii globin genes is vital for anoxic growth. Here, three further globin encoding transcripts (Cre16.g661000.t1.1, Cre16.g661300.t2.1 and Cre16.g662750.t1.2) were heterologously expressed along with the recently studied THB1. UV-Vis and X-ray absorption spectroscopy analyses show that the sequences indeed encode functional hemoglobins, despite their uncommon primary sequences, which include long C-termini without any predictable function, or a split heme-binding domain. The proteins show some variations regarding the coordination of the heme iron or the interaction with diatomic ligands, indicating different functionalities. The respective transcripts are not responsive to the nitrogen source, in contrast to results reported for THB1, but they accumulate in darkness. This work advances experimental data on the very large globin family in general, and, more specifically, on hemoglobins in photosynthetic organisms. | Truncated Hemoglobins |
OBJECTIVE: To evaluate the clinical application of the medial approach for repairing popliteal artery injuries. METHODS: From 2002 to 2008, 11 cases of popliteal artery injuries had been repaired via the medial approach. Of these cases, 8 had limb fractures, 1 had knee dislocation, and 2 had visceral injuries. Ten popliteal arteries were anastomosed directly while one was repaired with a great saphenous vein graft. RESULTS: The operation time ranged from 3 to 4 hours (averaging 3.6 hours). All the injured limbs survived. At the follow up, 8 legs recovered the full function, 2 had minor contracture, and 1 serious Volkmann's contracture without amputation. CONCLUSION: The medial approach for repair of the popliteal artery is effective, applicable, and more advantageous to the management of multi-injures. | Popliteal Artery |
Fermentation kinetics of Penicillium aculeatum ATCC 10409 demonstrated that fungal growth and dextranase release are decoupled. Inoculation by conidia or mycelia resulted in identical kinetics. Two new isoenzymes of the dextranase were characterized regarding their kinetic constants, pI, MW, activation energy and stabilities. The larger enzyme was 3-fold more active (turnover number: 2,230 +/- 97 s(-1)). Pre-treatment of bentonite with H(2)O(2) did not affect adsorption characteristics of dextranase. Enzyme to bentonite ratios above 0.5:1 (w/w) resulted in a high conservation of activity upon adsorption. Furthermore, dextranase could be used in co-immobilizates for the direct conversion of sucrose into isomalto-oligosaccharides (e.g. isomaltose). Yields of co-immobilizates were 2-20 times that of basic immobilizates, which consist of dextransucrase without dextranase. | Dextranase |
Lipoid proteinosis is a rare cause of voice problems. Hoarseness is often the first clinical manifestation of this disorder and can present years before any other symptom. Therefore, it is very important as an otorhinolaryngologist to be familiar with the main characteristics of this disease. We present a case report and a review of current literature to provide a concise overview of this frequently missed diagnosis." | Lipoid Proteinosis of Urbach and Wiethe |
Thrombocytopenia may be caused by abnormal platelet production, accelerated removal owing to immunologic or nonimmunologic reasons, or sequestration of platelets in the spleen. Bleeding associated with thrombocytopenia usually presents as petechial or ecchymotic hemorrhages or epistaxis. Immunologic and nonimmunologic cases of thrombocytopenia may be diagnosed with routine hematology, bone marrow cytology, and platelet specific tests. Thrombocythemia may also be associated with platelet functional abnormalities, contrasting the normal platelet function noted in reactive thrombocytosis. | Thrombocytosis |
PURPOSE: Epidural corticosteroid injections (ESI) are a mainstay of nonoperative treatment for patients with lumbar spine pathology. Recent literature evaluating infection risk following ESI after elective orthopedic surgery has produced conflicting evidence. Our primary objective was to review the literature and provide a larger meta-analysis analyzing the temporal effects of steroid injections on the risk of infection following lumbar spine surgery. METHODS: We conducted a query of the PubMed, Embase, and Scopus databases from inception until April 1, 2022 for studies evaluating the risk of infection in the setting of prior spinal steroid injections in patients undergoing lumbar spine decompression or fusion. Three meta-analyses were conducted, (1) comparing ESI within 30-days of surgery to control, (2) comparing ESI within 30-days to ESI between 1 and 3 months preoperatively, and (3) comparing any history of ESI prior to surgery to control. Tests of proportions were utilized for all comparisons between groups. Study heterogeneity was assessed via forest plots, and publication bias was assessed quantiatively via funnel plots and qualitatively with the Newcastle-Ottawa Scale. RESULTS: Nine total studies were included, five of which demonstrated an association between ESI and postoperative infection, while four found no association. Comparison of weighted means demonstrated no significant difference in infection rates between the 30-days ESI group and control group (2.67% vs. 1.69%, p = 0.144), 30-days ESI group and the > 30-days ESI group (2.34% vs. 1.66%, p = 0.1655), or total ESI group and the control group (1.99% vs. 1.70%, p = 0.544). Heterogeneity was low for all comparisons following sensitivity analyses. CONCLUSION: Current evidence does not implicate preoperative ESI in postoperative infection rates following lumbar fusion or decompression. Operative treatment should not be delayed due to preoperative steroid injections based on current evidence. There remains a paucity of high-quality data in the literature evaluating the impact of preoperative ESI on postoperative infection rates. LEVEL OF EVIDENCE: II. | Injections, Epidural |
BACKGROUND: Early detection of Budd-Chiari syndrome (BCS) to give the appropriate therapy in time is crucial. Angiography remains the golden standard to diagnose BCS. However, to establish the diagnosis of BCS in complicated cirrhotic patients remains a challenge. We used maximum intensity projection (Max IP) and minimum intensity projection (Min IP) from computed tomographic (CT) images to detect this syndrome in such a patient. CASE REPORT: A 55-year-old man with a history of chronic hepatitis B infection and alcoholism had undergone previously a left lateral segmentectomy for hepatic epitheloid angiomyolipoma (4.6 x 3.5 x 3.3 cm) with a concomitant splenectomy. Liver decompensation with intractable ascites and jaundice occurred 4 months later. The reformed images of the venous phase of enhanced CT images with Max IP and Min IP showed middle hepatic vein thrombosis. He then underwent a living-related donor liver transplantation with a right liver graft from his daughter. Intraoperatively, we noted thrombosis of his middle hepatic vein protruding into inferior vena cava. The postoperative course was unevenful. Microscopic findings revealed micronodular cirrhosis with mixed inflammation in the portal areas. Some liver lobules exhibited congestion and sinusoidal dilation compatible with venous occlusion clinically. CONCLUSIONS: We recommend Max IP and Min IP of CT images as simple and effective techniques to establish the diagnosis of BCS, especially in complicated cirrhotic patients, thereby avoiding invasive interventional procedures. | Budd-Chiari Syndrome |
Growth temperature alters temperature dependence of the photosynthetic rate (temperature acclimation). In many species, the optimal temperature that maximizes the photosynthetic rate increases with increasing growth temperature. In this minireview, mechanisms involved in changes in the photosynthesis-temperature curve are discussed. Based on the biochemical model of photosynthesis, change in the photosynthesis-temperature curve is attributable to four factors: intercellular CO2 concentration, activation energy of the maximum rate of RuBP (ribulose-1,5-bisphosphate) carboxylation (Vc max), activation energy of the rate of RuBP regeneration (Jmax), and the ratio of Jmax to Vc max. In the survey, every species increased the activation energy of Vc max with increasing growth temperature. Other factors changed with growth temperature, but their responses were different among species. Among these factors, activation energy of Vc max may be the most important for the shift of optimal temperature of photosynthesis at ambient CO2 concentrations. Physiological and biochemical causes for the change in these parameters are discussed. | Ribulosephosphates |
Interactions of cytochrome c (cyt c) with cardiolipin (CL) play a critical role in early stages of apoptosis. Upon binding to CL, cyt c undergoes changes in secondary and tertiary structure that lead to a dramatic increase in its peroxidase activity. Insertion of the protein into membranes, insertion of CL acyl chains into the protein interior, and extensive unfolding of cyt c after adsorption to the membrane have been proposed as possible modes for interaction of cyt c with CL. Dissociation of Met80 is accompanied by opening of the heme crevice and binding of another heme ligand. Fluorescence studies have revealed conformational heterogeneity of the lipid-bound protein ensemble with distinct polypeptide conformations that vary in the degree of protein unfolding. We correlate these recent findings to other biophysical observations and rationalize the role of experimental conditions in defining conformational properties and peroxidase activity of the cyt c ensemble. Latest time-resolved studies propose the trigger and the sequence of cardiolipin-induced structural transitions of cyt c. | Cardiolipins |
Despite the fact that hemispheric asymmetry of attention has been widely studied, a clear picture of this complex phenomenon is still lacking. The aim of the present study was to provide an efficient and reliable measurement of potential hemispheric asymmetries of three attentional networks, i.e. alerting, orienting and executive attention. Participants (N=125) were tested with the Lateralized Attention Network Test (LANT) that allowed us to investigate the efficiency of the networks in both visual fields (VF). We found a LVF advantage when a target occurred in an unattended location, which seems to reflect right hemisphere superiority in control of the reorienting of attention. Furthermore, a LVF advantage in conflict resolution was observed, which may indicate hemispheric asymmetry of the executive network. No VF effect for alerting was found. The results, consistent with the common notion of general right hemisphere dominance for attention, provide a more detailed account of hemispheric asymmetries of the attentional networks than previous studies using the LANT task. | Arousal |
Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography(1) using an X-ray free-electron laser(2) to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions. | Pheophytins |
Second-derivative absorption spectroscopy was employed to monitor the response of effective symmetry of cytochromes a and a(3) to the redox and ligation states of bovine cytochrome c oxidase (CcO). The Soret band pi --> pi* electronic transitions were used to display the changes in symmetry of these chromophores induced by the reduction of CcO inhibited by the exogenous ligands and during catalytic turnover. The second derivative of the difference absorption spectra revealed only a single Soret band for the oxidized cytochromes a and a(3) and cyanide-ligated oxidized cytochrome a(3). In contrast, two absorption bands were resolved in ferrous cytochrome a and ferrous cytochrome a(3) ligated with cyanide. A transition from one-band spectrum to two-band spectrum indicates the lowering of symmetry of these hemes due to the alteration of their immediate surroundings. It is suggested that the changes in polarity occurring in the vicinity of these cofactors are main reason for the split of the Soret band of both ferrous cytochrome a and cyanide-bound ferrous cytochrome a(3). | Cytochromes a |
In the female macaque monkey acclimated to a primate chair, Collison cannulae were stereotaxically implanted bilaterally in the lateral cerebral ventricle. The voluntary self-selection of ethyl alcohol versus water was determined repeatedly during a series of 12-day test sequences in which the concentration of the alcohol solution offered to the primate was increased systematically over 12 successive days from 3% to 30%. Following control preference sequences, the dopamine-dopaldehyde condensation product, tetrahydropapaveroline (THP), was infused daily in each monkey's cerebral ventricle (ICV) in a volume of 200-400 microliter. THP was dissolved in an artificial CSF, with pH adjusted to 3.8 with 0.1 mg/ml ascorbate, and infused in one of ten doses varying from 0.125-400 microgram. EAch monkey was administered one low and one high dose of the condensation product throughout each of two successive alcohol preference tests. When THP was infused in doses of less than 2.0 microgram, the monkeys' alcohol preference failed to change. However, a marked increase in alcohol intake, in terms of both g/kg/day as well as the proportion of alcohol to water selected, was produced by THP infused ICV in doses of 5.0 to 20.0 microgram. Although average intakes in the latter animals were between 4.0 and 5.0 g/kg/day, the monkeys selected certain concentrations of alcohol in amounts of up to 7.0 g/kg/day. The two highest doses of THP, 40.0 and 400.0 microgram, inhibited the self-selection of alcohol even when presented in low, non-aversive concentrations in the 3% to 6% range. Overall, these results with the primate corroborate earlier findings in the rat of abnormal alcohol intake produced by centrally infused THP. They further support the theory that amine-aldehyde metabolites, if present in certain concentrations in the brain, may constitute a causal neurochemical factor in the addictive or otherwise immoderate drinking of alcohol. | Tetrahydropapaveroline |
INTRODUCTION: We detail the process of developing a workload calculation model (WCM) for a highly integrated curriculum delivered by team-based learning, rationale for workload multipliers, and preliminary results of our effort to implement the WCM. METHODS: Our WCM includes teaching, service, and scholarship, with a time buffer. The WCM utilizes multipliers for most work activities (teaching and service). For other activities, a fixed number of hours per year was used. The WCM was set up using Microsoft Excel. The development of the WCM was an iterative process in collaboration with the school's Faculty Affairs Committee, each department, and then individually with all faculty members. RESULTS: The WCM had three sections. A section each for teaching and service workload calculations and a dashboard section to summarize workload calculations per department that added in time for scholarship and a buffer calculation (to allow flexibility for faculty). Teaching included classroom, experiential, and academic advising, all of which had unique multipliers. Service included committee work at all levels and student organization advising. A fourth section for time spent at individual faculty practice sites. Calculations were kept consistent between departments for most activities. CONCLUSION: We developed a novel WCM to accommodate all of the major areas of workload for faculty at a private institution. The unique approach to building it included representing teaching in a highly integrated curriculum delivered via team-based learning and creating a buffer category to allow for workload individualization. The WCM is actively used in our school to proactively manage workload. | Workload |
In an outbreak of infection due to Corynebacterium diphtheriae in a hospital for mentally subnormal adults sera from 211 members of staff were screened for diphtheria antitoxin titres. Of these, 79 (37%) required immunisation, and a low dose preparation (1 LfU of diphtheria and 10 LfU tetanus toxoids) was offered. Of the 64 subjects who accepted a single immunisation and were subsequently retested, seroconversion to diphtheria toxoid occurred in 45 (70%), the rate being highest in younger adults. Seroconversion to tetanus toxoid occurred in 59% of subjects. Local reactions to the single dose were reported by 29 (43%) subjects, and nine (13%) experienced moderately severe local reactions and systemic symptoms. We conclude that adults should not be vaccinated without previous screening for susceptibility to diphtheria; that neither previous immunisation nor age is reliable in predicting the need for vaccination; and that though a single booster dose of diphtheria toxoid is probably effective in adults under 45, two doses should be given to those in the older age group. | Diphtheria Toxoid |
The ripened seeds of Strychnos nux-vomica L. have been extensively used as herbal medicines in Asian countries. Dihydroindole-type alkaloids are not only the active constituents but also the toxicants in Strychnos. However, the simultaneous determination of these alkaloids in both crude and processed Semen Strychni is still lacking. The present study represents the first quantitation and relative quantitation assay of 12 dihydroindole-type alkaloids in Strychnos nux-vomica unprocessed and sand-processed seeds using high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The relative concentration of ten alkaloids was calculated by semi-quantification using the internal standard and their amounts in unprocessed and detoxified Semen Strychni were compared. We report here for the first time the significant increase of the two alkaloids, 19-N-methyl-strychnine, and 2,3-dimethoxy-19-N-methyl-strychnine, during the processing of Semen Strychni. Our study provides new insight into the true complexity of seed processing procedure and valuable information for assessing the efficacy and safety for clinical applications of Semen Strychni-containing drugs. | Strychnos |
Epidemiologic studies document the overuse of surgical procedures in the United States compared with rates in 11 developed countries. Delay in return to work remains an expensive component in the cost of low back pain for workers' compensation claims. Injury to spinal nerve roots may occur secondary to compression with intraradicular edema or from inflammatory phenomena related to phlogistic properties of the nucleus pulposus, independent of nerve compression. Magnetic resonance imaging findings of intervertebral disk bulging and protrusion occur frequently in asymptomatic individuals. Reviews of adult scoliosis, postpartum back pain, diabetic radiculopathy, insufficiency fractures of the sacrum, diskitis, and facet syndrome have appeared in the literature over the past year. Patient education and minimal limitation of activity are associated with the greatest level of patient satisfaction. Long-term follow-up studies of surgical decompression for intervertebral disk herniation and spinal stenosis have resulted in good outcomes in appropriately selected patients. | Back Pain |
Diethanolamine (DEA) has been extensively utilized as an alkaline buffer in current assays of alkaline phosphatase (ALP) activity in the past decades. While playing the role of a buffer, the chemical reactivity of DEA has been widely ignored in such assays. Herein, we report an interesting chromogenic interaction between DEA and 4-aminophenol (AP) in the presence of H(2)O for the first time, which inspires us to develop a novel DEA-participated ALP activity assay by using 4-aminophenyl phosphate (APP) as a substrate. This APP/DEA-based colorimetric approach has been proved to be comparable and even superior to the conventional p-nitrophenyl phosphate (pNPP)-based one, especially in the low ALP activity region, due to its higher sensitivity. The clear response mechanism and excellent sensing performance ensure that it can be further applied to determining ALP activity in real biological samples, screening potential ALP inhibitors in vitro, establishing ALP-enabled ELISA, and even fluorophore-assisted fluorescent ALP activity assay. It is demonstrated that this strategy not only possesses a good feasibility, but also exhibits a promising outlook for a series of ALP-related and -extended detections. | Aminophenols |
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARalpha, which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARgamma and downregulated the expression of CD36, IL6 and TNFalpha. These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD. | Phycocyanin |
Chromogranin B and secretogranin II are major soluble constituents of large dense core vesicles of presynaptic structures and have been found in neuritic plaques of Alzheimer patients. We examined the distribution and expression of these peptides in both transgenic mice over expressing human amyloid-beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem brain. In transgenic mice, the number of amyloid-beta plaques and chromogranin immunopositive plaques increased from 6 to 12 months. About 60% of amyloid-beta plaques were associated with chromogranin B and about 40% with secretogranin II. Chromogranin immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fibrillary acidic protein- immunoreactivity was expressed in chromogranin immunoreactive structures at any timepoint. Density of chromogranin peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resembled findings in Alzheimer patients. Chromogranin peptides were associated with amyloid-beta plaques, but were not reduced in specific brain areas as previously reported by our group. Therefore specific changes of chromogranin peptides observed in Alzheimer patients can be related to amyloid-beta pathology only. | Chromogranin B |
Three novel alleles, human leukocyte antigen (HLA)-B*0725, B*0728, and B*3808, were discovered during routine genotyping of samples for the Australian Bone Marrow Donor Registry and Australian Cord Blood Bank. The new alleles contain amino acid changes in the antigen-binding site of the expressed HLA protein, which may alter the antigen-binding properties of the functional protein. | HLA-B38 Antigen |
Biotin deficiency was induced in newborn rats by feeding pregnant rats a biotin-deficient, avidin-rich diet. Signs typical of biotin deficiency are seen as soon as the young rat develops its fur. Deficiency of pyruvate carboxylase (PC) activity in the brains of the young animals (70%) is higher than has been reported before. The highest PC activity is found in the brain stem of control and biotin-deficient rats. Normally fed rats show, shortly after birth, a maximum in liver PC activity, which is absent in biotin-deficient animals. The biochemical changes observed in these rats seem to indicate that a specific deficiency of PC activity was induced as exemplified by hyperlactatemia and hypoglycemia and the absence of increased plasma concentrations of propionic acid and beta-methylcrotonic acid. This offers the possibility to use biotin deficiency in the rat as an animal model for patients with lactic acidosis in whom PC deficiency has been postulated." | Pyruvate Carboxylase Deficiency Disease |
BACKGROUND: Cryosurgery is an effective, simple and inexpensive treatment used extensively in general practice and dermatology. It is used most commonly for actinic keratoses and warts; however, a large number of benign, premalignant and malignant skin diseases can also be treated. OBJECTIVE: The objective of this article is to help readers improve their cryosurgery technique. DISCUSSION: Application of the cryogenic agent (most commonly liquid nitrogen) to the skin induces rapid freezing followed by slow thawing. This produces cell injury, vascular stasis and occlusion, and inflammation. The quantity of cryogen delivered onto the skin (dose), technique, duration of thawing and amount of surrounding tissue frozen are dependent on the body region and type of lesion. If clinical diagnosis is not possible, either a skin biopsy or referral to a dermatologist is recommended. We strongly discourage blind treatment of undiagnosed skin lesions. | Cryosurgery |
Counterimmunoelectrophoresis as a test method for making the diagnosis of plasmacytosis in mink demands the specific virus antigen. The method for preparation of the antigen according to Cho & Ingram (1972 a, b) with minor modifications is described in details, and results obtained at 62 antigen preparations are presented. In addition an ultrafiltration method is outlined which may be useful as a replacement for ultracentrifugation procedures used in the technique described by Cho & Ingram (1974). | Amdovirus |
OBJECTIVE: To examine the effects of para-aminobenzoic acid (PABA) on the growth of Actinomyces viscosus. METHODS: Different concentrations of PABA (10(-10)-10(-3) g/L) were each transferred to modified Carlsson medium. Actinomyces viscosus ATCC19246 grew in them. And the cultures were incubated at 37 degrees C anaerobically in the atmosphere of 80%N2, 10%H2, 10%CO2 for 48 h. Actinomyces viscosus OD values (lambda = 540 nm) were obtained with UV-1601. Colony forming unit (CFU) was established by growth of Actinomyces viscosus in culture when different concentrations of PABA (10(-10)-10(-3) g/L) were present. RESULTS: Different concentrations of PABA (10(-10)-10(-4) g/L) had different stimulating effects on the growth of Actinomyces viscosus (P < 0.05). But this kind of stimulating effect declined when PABA concentration was 10(-5) g/L, and as PABA (10(-3) g/L) was present, this kind of effect was missing. CONCLUSION: The phenomena indicated that PABA has stimulating effect on the growth of Actinomyces viscosus, particularly when PABA is at the concentration of 10(-6) g/L. | Actinomyces viscosus |
The high-resolution structure of yeast enolase cocrystallized with its equilibrium mixture of substrate and product reveals the stereochemistry of substrate/product binding and therefore the groups responsible for acid/base catalysis and stabilization of the enolate intermediate. Expression and characterization of site-specific mutant forms of the enzyme have confirmed the roles of amino acid side chains in the catalysis of the first and second steps of the reaction. Coordination of both required magnesium ions to the carboxylate of the substrate/product indicates a role for these cations in stabilization of the intermediate. | Glyceric Acids |
To test the efficacy and safety of creatine (Cr) monohydrate in mitochondrial diseases, 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy were randomized in a crossover design to receive double-blind placebo or 20 g Cr/day for 4 weeks. Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed. | Mitochondrial Myopathies |
A set of PCR primers based on the genome sequence were used to clone a gene encoding a hypothetical nitroreductases (named as Ssap-NtrB) from uropathogenic staphylococcus, Staphylococcus saprophyticus strain ATCC 15305, an oxygen insensitive flavoenzyme. Activity studies of the translation product revealed that the nitroreductase catalyses two electron reduction of a nitroaromatic drug of nitrofurazone (NFZ), cancer prodrugs of CB1954 and SN23862 at optimum temperature of 20 degrees C together with retaining its maximum activity considerably at 3 degrees C. The required electrons for such reduction could be supplied by either NADH or NADPH with a small preference for the latter. The gene was engineered for heterologous expression in Escherichia coli, and conditions were found in which the enzyme was produced in a mostly soluble form. The recombinant enzyme was purified to homogeneity and physical, spectral and catalytical properties were determined. The findings lead us to propose that Ssap-NtrB represents a novel nitro reductase with an unusual cold active property, which has not been described previously for prodrug activating enzymes of nitroreductases. | Aniline Mustard |
BACKGROUND: The importance of the health visitor's role in childhood accident prevention has long been recognized, although previous work suggests that many health visitors are unsure of that role, feel inadequately prepared for it and recognize significant constraints on their accident prevention activity. The Health of the nation suggested that specific accident prevention activities should be undertaken by health visitors. This study aims to assess whether those activities are currently part of routine health visiting practice, as well as the attitudes towards accident prevention and knowledge of childhood accidental injury epidemiology. METHOD: A postal questionnaire survey covering knowledge, attitudes and practices in accident prevention as well as personal characteristics was sent to all health visitors in Nottinghamshire, using the community unit trusts' list of employees as the sampling frame. RESULTS: A response rate of 88.5 per cent was obtained. The majority of health visitors were aware that accidental injuries are the most common cause of death in childhood above the age of one year. The majority of health visitors were also aware of the types of accident most likely to be fatal, and aware of the risk factors for childhood accidental injuries. Many health visitors held positive attitudes towards all accident prevention activities covered in the questionnaire. There was a positive correlation between attitude and knowledge scores (p < 0.01). There were some discrepancies between attitudes and current practices, particularly in the areas of teaching first aid to parents' groups and lobbying or campaigning on local safety issues. CONCLUSIONS: Although many health visitors hold positive attitudes towards, and currently undertake many of the accident prevention activities suggested in the Health of the nation, there are areas where practice could be improved, such as giving advice about stockists of safety equipment including local loan schemes, undertaking first aid sessions in parents' groups and lobbying or campaigning on local safety issues. | Accidents, Home |
6-Chloro-6-deoxy[U-14C]glucose is not metabolised by mature boar spermatozoa nor has it any specific inhibitory action on their metabolic activity in vitro. The compound is metabolised by the male rat and the identification of two urinary metabolites as alpha-chlorohydrin and 3-chlorolactate confirmed that (S)-3-chlorolactaldehyde is produced by this species in vivo. A tissue distribution study revealed that radioactivity from 6-chloro-6-deoxy[U-14C]glucose was more concentrated in rat caudal spermatozoa than in any other of the major tissues. | Deoxyglucose |
Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS and L929 cells were cultured and treated with different concentrations (0-10 mg/ml) of Cornus mass L. extract for 48 and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluated after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p</=0.05). The analysis results of flow cytometry indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers. | Cornus |
Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules. | Ribavirin |
Small prostate stones are often found incidentally during clinical and radiological examination. Large stones, however, also may develop, replacing completely the prostate tissue and causing various symptoms. Such a large stones are commonly formed due to chronic urine reflux. There are 20 publications in the literature devoted to the patients with giant prostate stones. Open as well as endoscopic procedures can be performed. In our clinical case both approaches were done simultaneously. Such tactic was chosen in order to carry out a single-stage intervention, immediately solving two problems, i.e., urethral stricture and a giant prostate stone. | Prostatic Diseases |
Consistent high-quality antibody yield is a key goal for cell culture bioprocessing. This endpoint is typically achieved in commercial settings through product and process engineering of bioreactor parameters during development. When the process is complex and not optimized, small changes in composition and control may yield a finished product of less desirable quality. Therefore, changes proposed to currently validated processes usually require justification and are reported to the US FDA for approval. Recently, design-of-experiments-based approaches have been explored to rapidly and efficiently achieve this goal of optimized yield with a better understanding of product and process variables that affect a product's critical quality attributes. Here, we present a laboratory-scale model culture where we apply a Plackett-Burman screening design to parallel cultures to study the main effects of 11 process variables. This exercise allowed us to determine the relative importance of these variables and identify the most important factors to be further optimized in order to control both desirable and undesirable glycan profiles. We found engineering changes relating to culture temperature and nonessential amino acid supplementation significantly impacted glycan profiles associated with fucosylation, beta-galactosylation, and sialylation. All of these are important for monoclonal antibody product quality. | Hybridomas |
Orexins (also known as hypocretins) are neuropeptides located exclusively in hypothalamic neurons that have extensive projections throughout the central nervous system and bind two different G protein-coupled receptors (OX1R and OX2R). Since its discovery in 1998, the orexin system has gained the interest of the scientific community as a potential therapeutic target for the treatment of different pathological conditions. Considering previous basic science research, a dual orexin receptor antagonist, suvorexant, was the first orexin agent to be approved by the US Food and Drug Administration to treat insomnia. In this review, we discuss and update the main preclinical and human studies involving the orexin system with several psychiatric and neurodegenerative diseases. This system constitutes a nice example of how basic scientific research driven by curiosity can be the best route to the generation of new and powerful pharmacological treatments. | Orexins |
NEW FINDINGS: What is the topic of this review? This review provides a comprehensive overview of Nox5 from basic biology to human disease and highlights unique features of this Nox isoform What advances does it highlight? Major advances in Nox5 biology relate to crystallization of the molecule and new insights into the pathophysiological role of Nox5. Recent discoveries have unravelled the crystal structure of Nox5, the first Nox isoform to be crystalized. This provides new opportunities to develop drugs or small molecules targeted to Nox5 in an isoform-specific manner, possibly for therapeutic use. Moreover genome wide association studies (GWAS) identified Nox5 as a new blood pressure-associated gene and studies in mice expressing human Nox5 in a cell-specific manner have provided new information about the (patho) physiological role of Nox5 in the cardiovascular system and kidneys. Nox5 seems to be important in the regulation of vascular contraction and kidney function. In cardiovascular disease and diabetic nephropathy, Nox5 activity is increased and this is associated with increased production of reactive oxygen species and oxidative stress implicated in tissue damage. ABSTRACT: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), comprise seven family members (Nox1-Nox5 and dual oxidase 1 and 2) and are major producers of reactive oxygen species in mammalian cells. Reactive oxygen species are crucially involved in cell signalling and function. All Noxs share structural homology comprising six transmembrane domains with two haem-binding regions and an NADPH-binding region on the intracellular C-terminus, whereas their regulatory systems, mechanisms of activation and tissue distribution differ. This explains the diverse function of Noxs. Of the Noxs, NOX5 is unique in that rodents lack the gene, it is regulated by Ca(2+) , it does not require NADPH oxidase subunits for its activation, and it is not glycosylated. NOX5 localizes in the perinuclear and endoplasmic reticulum regions of cells and traffics to the cell membrane upon activation. It is tightly regulated through numerous post-translational modifications and is activated by vasoactive agents, growth factors and pro-inflammatory cytokines. The exact pathophysiological significance of NOX5 remains unclear, but it seems to be important in the physiological regulation of sperm motility, vascular contraction and lymphocyte differentiation, and NOX5 hyperactivation has been implicated in cardiovascular disease, kidney injury and cancer. The field of NOX5 biology is still in its infancy, but with new insights into its biochemistry and cellular regulation, discovery of the NOX5 crystal structure and genome-wide association studies implicating NOX5 in disease, the time is now ripe to advance NOX5 research. This review provides a comprehensive overview of our current understanding of NOX5, from basic biology to human disease, and highlights the unique characteristics of this enigmatic Nox isoform. | NADPH Oxidase 5 |
The Don Bloch Award is presented annually by the Collaborative Family Healthcare Association (CFHA) to a person who has made singular contributions to forwarding the cause of collaborative family health care. At the 2012 conference in Austin, Texas, the award was presented to Larry Mauksch of the Department of Family Medicine at the University of Washington. Three nominating talks given at that occasion and Larry's acceptance remarks are provided. | Family Health |
BACKGROUND: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype. METHODS: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21-40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMT C314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate. RESULTS: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMT CT heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p=0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p=0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype. CONCLUSION: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMT C314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms. | Histamine N-Methyltransferase |
We applied social cost-benefit analysis to the economic evaluation of the bovine brucellosis and bovine tuberculosis eradication programmes carried out by the public eradication authority for mountain areas in the Spanish Central Pyrenees. We considered only the effects on animal health and production. We also evaluated several hypotheses corresponding to the different sanitary situations of two valleys studied. The results were different for the two disease programmes. The brucellosis programme was economically efficient over a sufficiently long time frame, but the bovine tuberculosis programme was not. A factor having the greatest influence on the economic efficiency of the programmes was the initial prevalence of the disease in the two valleys studied. The greater this was, the more difficult it was to obtain positive net benefits; this was due the initially high compensation paid for the slaughter of animals testing positive for the disease. The relatively small animal health and production returns derived from the tuberculosis programme explained it's failure to generate positive economic results. The fact that the economic evaluation resulted in unfavourable outcomes is not in itself justification for project termination, because the benefits to the wider community through the prevention of zoonosis were not considered in this analysis. | Brucellosis, Bovine |
An unprecedented Cu(II)-mediated methylthiolation of aryl C-H bonds under oxidative conditions that employs the widely available DMSO as the methylthiolation reagent is described. Various functional groups in the substrates were tolerated, and ethylthiolation was also successfully achieved directly from diethyl sulfoxide under the same reaction conditions. | Sulfoxides |
Natural killer cells play a major role in innate immunity against tumor and virus-infected cells. NK cells express activating and inhibitory receptors to regulate their function. It has been established that modulation in the NK cell receptor profile results in altered function of NK cell against target cells. Here, we study the effect of IL-2 stimulation on NK cell inhibitory receptors Ly49A, Ly49C, and activating receptor Ly49D in C57BL/6 mice. It was observed that there was significant increase in expression of Ly49A but no change in expression of Ly49C and Ly49D on IL-2 stimulation. We further noticed that although IL-2 stimulation increased the NK cell population and expression of activation marker NK1.1 but IL-2 stimulation does not cause hyper-responsiveness in NK cells, as there was no increase in MIP-1alpha and IFN-gamma production in IL-2 stimulated NK cells as compared to unstimulated controls. These findings provide a framework to understand the effect of IL-2 stimulation on cognate and non-cognate receptor ligand interactions and suggest stratagies for immunotherapies in conjunction with IL-2 combinatorial therapies. | Chemokine CCL3 |
BACKGROUND: Metformin is commonly used for the treatment of type 2 diabetes mellitus. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis (MALA), which is associated with a high risk of mortality. Consequently, the early recognition and management of MALA is essential. CASE REPORT: We present the case of a 68-year-old man who had reversible blindness resulting from severe lactic acidosis. On presentation, he was alert, oriented, and had no complaints except mild abdominal discomfort and blindness. He denied any history of trauma or drug abuse. The results of the laboratory studies showed severe metabolic acidosis with a high anion gap and increased levels of serum creatinine. There were no predisposing ocular or neurologic lesions that could have induced the blindness. Although the blood levels of methanol, ethanol, and metformin were not estimated, correction of acidosis and hemodialysis led to a complete recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Rarely, transient blindness may occur in patients with fatal severe metabolic acidosis. Evaluation for the presence of metabolic acidosis and a detailed medical history are essential in the management of acute blindness in such patients. | Acidosis, Lactic |
Adoptive cellular therapies are making major strides in the treatment of cancer, both for hematologic and solid tumors. These cellular products include chimeric antigen receptor T cells and T-cell receptor-modified T cells, tumor-infiltrating lymphocytes, marrow-infiltrating T cells, natural killer cells as well as macrophage-based therapeutics. Advancement in genomics, computational biology, immunology, and cell therapy manufacturing has facilitated advancement of adoptive T cell therapies into the clinic, whereas clinical efficacy has driven Food and Drug Administration approvals. The growth of adoptive cellular therapy has, in turn, led to innovation in the preclinical models available, from ex vivo cell-based models to in vivo xenograft models of treatment. This review focuses on the development and application of in vitro models and in vivo models (cell line xenograft, humanized mice, and patient-derived xenograft models) that directly evaluate these human cellular products. | Receptors, Antigen, T-Cell |
Using beeswax as wrapping matrix, two types of release-controlled TM (thiamethoxam)/BK(beeswax-kaolin) microcapsules were prepared by adsorbing TM on kaolin and then encapsulated with beeswax, or directly wrapping TM with beeswax. The structure and morphology of the TM/BK microcapsules were characterized. The effects of different preparation methods, the particle size, pH conditions and different additives on the release property of the TM/BK microcapsules were investigated in water and soil column to compare the advantages of the two approaches. Finally, the insecticidal effect of the TM/BK microcapsules against sugarcane borer and rice planthopper was tested. The results show that the TM/BK microcapsules have a better sustained-release in both water and soil, and the release rate is different under different pH conditions. In addition, the releasing time of the TM/BK microcapsules can be modified by different preparation methods and combination of different additives. In the field applications, the insecticidal activity of the TM/BK microcapsules was better than that of non-sustained control group. Especially in the rice field test, 45 days after the application, the control group lost the activity against rice planthopper because of drug loss, whereas the TM/BK microcapsule group still retained about 90% of the insecticidal activity. The results suggest that the microcapsules have better agricultural application for insect control. | Thiamethoxam |
INTRODUCTION: Paraffin (kerosene) ingestion is the most common form of childhood poisoning in most developing countries. Despite this, there is a paucity of toxicoepidemiological data which could potentially be used in measures to reduce preventable exposures. This article reports on the patterns of hospital admissions resulting from paraffin exposure in Zimbabwe. METHODS: All cases of paraffin ingestion admitted to eight major referral hospitals in Zimbabwe from January 1998 to December 1999 (inclusive), were identified using ICD-9 codes and ward registers and relevant information recorded on a standard data collection sheet. RESULTS: There were a total of 327 admissions due to oral exposure to paraffin. This represented 11.8% of all the poisoning admissions to the eight study hospitals. Most exposures (300; 91.7%) occurred accidentally, with only 6.7% resulting from deliberate ingestion of the chemical. The median age on admission was 2 years (interquartile range [IQR] 1-2 yrs) with over 85% of cases in the 0-5 year age range and less than 10% above the age of 12 years. The median age on admission was much higher for deliberate self poisoning (23 yrs; IQR 19-26 yrs) compared to that for accidental poisoning (1.5 yrs; IQR 1-2 yrs). Accidental poisoning from paraffin occurred throughout the year. Over three-quarters of patients received an antibiotic either alone, or in combination with another antibiotic or drug. Paracetamol (24.3%) was the next most commonly encountered treatment. The case fatality rate (CFR) was therefore 0.3 deaths per 100 admissions (95% Confidence Interval 0.0-1.7). CONCLUSION: Paraffin ingestion remains an important cause of poisoning morbidity in Zimbabwe throughout the year, particularly in children. Clinical management appears adequate with a low mortality, although there may be overuse of prophylactic antibiotics. Further study specific to this area is warranted to prevent unnecessary antibiotic use and wastage of resources. | Kerosene |
Geriatric trauma patients will continue to increase in prevalence as the population ages, and many specific considerations need to be made to provide appropriate care to these patients. This article outlines common presentations of trauma in geriatric patients, with consideration to baseline physiologic function and patterns of injury that may be more prevalent in geriatric populations. Additionally, the article explores specific evidence-based management practices, the significance of trauma team and geriatrician involvement, and disposition decisions. | Geriatricians |
BACKGROUND: Obesity and pregnancy increase levels of maternal oxidative stress (OS). However, little is known about the maternal, placental, and neonatal OS status. OBJECTIVE: To analyze the relation between prepregnancy obesity and the expression of OS markers and antioxidant capacity in the fetomaternal unit and their association with dietary intake. METHODS: This cross-sectional study included 33 women with singleton, noncomplicated pregnancies. Two groups were formed: women with prepregnancy body mass index (pBMI) within normal range (18.5-24.9 kg/m(2), n = 18) and women with pBMI >/= 30 kg/m(2), suggestive of obesity (n = 15). Dietary and clinical information was obtained by questionnaire and from clinical records. Total antioxidant capacity (TAC) and malondialdehyde (MDA) concentration were measured on maternal and cord serum by colorimetric techniques, and placental expression of glutathione peroxidase 4 (GPx4) was measured by immunohistochemistry. RESULTS: Placental GPx4 expression was lower in the group with pBMI suggestive of obesity than in the normal weight group (ss = -0.08, p = 0.03, adjusted for gestational age and magnesium intake). Concentrations of TAC and MDA in maternal and cord blood were not statistically different between groups (p>0.05). Cord MDA concentration was related to maternal MDA concentration (ss = 0.40, p < 0.01), vitamin A intake (tertile 2: ss = -0.04, p = 0.40, tertile 3: ss = 0.13, p = 0.03, vs tertile 1), and placental GPx4 expression (ss = -0.09, p = 0.02). CONCLUSION: Prepregnancy obesity is associated with a decrease in GPx4 expression in the placenta, which is related to OS in the newborn. The influence of micronutrient intake on OS biomarkers highlights the importance of nutritional assessment during pregnancy and adequate prenatal care. | Obesity, Maternal |
Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs. | Renal Circulation |
Lowe syndrome (LS) is a rare, X-linked disorder characterised by numerous symptoms affecting the brain, the eyes, and the kidneys. It is caused by mutations in the oculocerebrorenal syndrome of Lowe (OCRL) protein, a 5-phosphatase localised in different cellular compartments that dephosphorylates phosphatidylinositol-4,5-bisphosphate into phosphatidylinositol-4-monophosphate. Some patients with LS also have bleeding disorders, with normal to low platelet (PLT) count and impaired PLT function. However, the mechanism of PLT dysfunction in patients with LS is not completely understood. The main function of PLTs is to activate upon vessel wall injury and stop the bleeding by clot formation. PLT activation is accompanied by a shape change that is a result of massive cytoskeletal rearrangements. Here, we show that OCRL-inhibited human PLTs do not fully spread, form mostly filopodia, and accumulate actin nodules. These nodules co-localise with ARP2/3 subunit p34, vinculin, and sorting nexin 9. Furthermore, OCRL-inhibited PLTs have a retained microtubular coil with high levels of acetylated tubulin. Also, myosin light chain phosphorylation is decreased upon OCRL inhibition, without impaired degranulation or integrin activation. Taken together, these results suggest that OCRL contributes to cytoskeletal rearrangements during PLT activation that could explain mild bleeding problems in patients with LS. | Oculocerebrorenal Syndrome |
Lysophosphatidic acid (LPA) is an endogenous bioactive lipid that is produced extracellularly and signals to cells via cognate LPA receptors, which are G-protein coupled receptors (GPCRs). Mature lymphocytes in mice and humans express three LPA receptors, LPA(2) , LPA(5,) and LPA(6) , and work from our group has determined that LPA(5) signaling by T lymphocytes inhibits specific antigen-receptor signaling pathways that ultimately impair lymphocyte activation, proliferation, and function. In this review, we discuss previous and ongoing work characterizing the ability of an LPA-LPA(5) axis to serve as a peripheral immunological tolerance mechanism that restrains adaptive immunity but is subverted during settings of chronic inflammation. Specifically, LPA-LPA(5) signaling is found to regulate effector cytotoxic CD8 T cells by (at least) two mechanisms: (i) regulating the actin-microtubule cytoskeleton in a manner that impairs immunological synapse formation between an effector CD8 T cell and antigen-specific target cell, thus directly impairing cytotoxic activity, and (ii) shifting T-cell metabolism to depend on fatty-acid oxidation for mitochondrial respiration and reducing metabolic efficiency. The in vivo outcome of LPA(5) inhibitory activity impairs CD8 T-cell killing and tumor immunity in mouse models providing impetus to consider LPA(5) antagonism for the treatment of malignancies and chronic infections." | Receptors, Lysophosphatidic Acid |
Following administration of the anticancer agent, procarbazine, or one of its metabolites, monomethylhydrazine, to rats, activities of monoamine oxidases A and B (MAO A and MAO B) and of semicarbazide-sensitive amine oxidase (SSAO) were measured ex-vivo. Both compounds were found to be potent inhibitors of SSAO in tissue homogenates, exhibiting ID50 values in most tissues of approximately 8 mg kg-1 (procarbazine) and 0.08 mg kg-1 (monomethylhydrazine). Concurrent dose-dependent inhibition of MAO activities did not occur. However, in liver, potentiation of MAO B activity, to 140% of that in controls, was apparent following monomethyl-hydrazine and this effect was independent of the drug dose. Both compounds produced a dose-dependent potentiation of MAO A in brown adipose tissue, the elevation being more pronounced following monomethylhydrazine, with activity rising to 350% of that in control homogenates. In a parallel in-vitro study, monomethylhydrazine was without effect on MAO A in brown adipose tissue homogenates. By perfusing the SSAO substrate, benzylamine, through the isolated mesenteric arterial bed of the rat, it was found that pretreatment of animals with procarbazine or monomethylhydrazine reduced metabolism of this amine by a similar degree as had been determined ex-vivo in blood vessel homogenates. The results presented suggest that these compounds would be suitable for use as selective inhibitors in pharmacological examinations of SSAO function in isolated tissues and organs. | Monomethylhydrazine |
The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same. | Yohimbine |
Borna disease virus 1 (BoDV-1) is a neurotropic RNA virus belonging to the family Bornaviridae within the order Mononegavirales. Whereas BoDV-1 causes neurological and behavioral disorders, called Borna disease (BD), in a wide range of mammals, its virulence in humans has been debated for several decades. However, a series of case reports in recent years have established the nature of BoDV-1 as a zoonotic pathogen that causes fatal encephalitis in humans. Although many virological properties of BoDV-1 have been revealed to date, the mechanism by which it causes fatal encephalitis in humans remains unclear. In addition, there are no effective vaccines or antiviral drugs that can be used in clinical practice. A reverse genetics approach to generating replication-competent recombinant viruses from full-length cDNA clones is a powerful tool that can be used to not only understand viral properties but also to develop vaccines and antiviral drugs. The rescue of recombinant BoDV-1 (rBoDV-1) was first reported in 2005. However, due to the slow nature of the replication of this virus, the rescue of high-titer rBoDV-1 required several months, limiting the use of this system. This review summarizes the history of the reverse genetics and artificial replication systems for orthobornaviruses and explores the recent progress in efforts to rescue rBoDV-1. | Borna disease virus |
Twenty-six semisynthetic ent-kaurane derivatives of linearol (1) have been investigated for their anti-HIV effects. Five compounds (4, 7, 11, 25, and 26) showed significant activity against HIV replication in H9 lymphocyte cells with EC(50) values in the range <0.1-3.11 microg/mL. With TI values of 163 and 184, compounds 4 and 25 are especially promising for further development as potential anti-HIV agents. | Sideritis |
There are a number of possible reasons for the lack of effectiveness of attempts at changing dietary behaviors. While lack of information and knowledge about foods and nutrient contents might play a part, motivation to change is likely to be much more important. Food choice, like any complex human behavior, is influenced by many interrelating factors, including various physiological, social and cultural factors, and these need to be taken into account when considering dietary interventions. In many cases people lack motivation to change. This can be related to optimistic bias, where people underestimate the risk to themselves relative to others from a variety of hazards. People feel less at risk personally for many dietary risks and this is related both to the control they feel they have over dietary behaviors and also to their considering themselves to have better diets than the average. The 'stages of change' model is a possible means for trying to address these motivational issues. While this model has been applied to various forms of behavior such as smoking, there are a number of problems transferring such a model from smoking to dietary behaviors, including the lack of clear cut specific behaviors and behavior change targets in the dietary field. | Feeding Behavior |
Cocoa self-compatibility is an important yield factor and has been described as being controlled by a late gameto-sporophytic system expressed only at the level of the embryo sac. It results in gametic non-fusion and involves several loci. In this work, we identified two loci, located on chromosomes 1 and 4 (CH1 and CH4), involved in cocoa self-incompatibility by two different processes. Both loci are responsible for gametic selection, but only one (the CH4 locus) is involved in the main fruit drop. The CH1 locus acts prior to the gamete fusion step and independently of the CH4 locus. Using fine-mapping and genome-wide association studies, we focused analyses on restricted regions and identified candidate genes. Some of them showed a differential expression between incompatible and compatible reactions. Immunolocalization experiments provided evidence of CH1 candidate genes expressed in ovule and style tissues. Highly polymorphic simple sequence repeat (SSR) diagnostic markers were designed in the CH4 region that had been identified by fine-mapping. They are characterized by a strong linkage disequilibrium with incompatibility alleles, thus allowing the development of efficient diagnostic markers predicting self-compatibility and fruit setting according to the presence of specific alleles or genotypes. SSR alleles specific to self-compatible Amelonado and Criollo varieties were also identified, thus allowing screening for self-compatible plants in cocoa populations. | Cacao |
BACKGROUND: Lake Tanganyika (LT) is the oldest of the African Rift Lakes and is one of the richest freshwater ecosystems on Earth, with high levels of faunal diversity and endemism. The endemic species flocks that occur in this lake, such as cichlid fishes, gastropods, catfish and crabs, provide unique comparative systems for the study of patterns and processes of speciation. Mastacembelid eels (Teleostei: Mastacembelidae) are a predominately riverine family of freshwater fish, occurring across Africa and Asia, but which also form a small species flock in LT. METHODS: Including 25 species across Africa, plus Asian representatives as outgroups, we present the first molecular phylogenetic analysis for the group, focusing particularly on the evolutionary history and biodiversity of LT mastacembelid eels. A combined matrix of nuclear and mitochondrial genes based on 3118 bp are analysed implementing different phylogenetic methods, including Bayesian inference and maximum likelihood. RESULTS: LT Mastacembelus are recovered as monophyletic, and analyses reveal the rapid diversification of five main LT lineages. Relaxed molecular clock dates provide age estimates for the LT flock at approximately 7-8 Myr, indicating intralacustrine diversification, with further speciation events coinciding with periods of lower lake level. Our analyses also reveal as yet undescribed diversity of lacustrine and riverine species. A Southern-Eastern African clade, that is younger than the LT flock, is also recovered, while West African taxa are basal members of the African mastacembelid clade. CONCLUSIONS: That the LT species flock of mastacembelid eels appears to have colonised and immediately diversified soon after the formation of the lake, supports the view of LT as an evolutionary hotspot of diversification. We find evidence for biogeographic clades mirroring a similar pattern to other ichthyological faunas. In addition, our analyses also highlight a split of African and Asian mastacembelid eels at approximately 19 Myr that is considerably younger than the split between their associated continents, suggesting a dispersal scenario for their current distribution. | Eels |
Evidence is presented supporting the hypothesis that the positive inotropic effect after an abrupt increase in systolic pressure (Anrep effect) is the recovery from subendocardial ischemia induced by the increase and subsequently corrected by vascular autoregulation of the coronary bed. Major evidence consists of data obtained from an isolated heart preparation showing that the Anrep effect can be abolished with coronary vasodilation, and that with an abrupt increase in systolic pressure there is a significant reduction in the distribution of coronary flow to subendocardial layers of the ventricle. Furthermore, the intracardiac electrocardiogram shows S-T segment and T wave changes after an abrupt increase in ventricular pressure similar to that noted after coronary constriction. Major implications are that normally there may be ischemia of the subendocardial layers tending to reduce myocardial contractility which may account, in part, for the positive inotropic effect of various coronary vasodilators; that with an abrupt increase in ventricular pressure the subendocardium is rendered temporarily ischemic, placing the heart in jeopardy from arrhythmias until this is corrected; and that end-diastolic pressure and the intracardiac electrocardiogram may provide a means of evaluating the adequacy of circulation to subendocardial layers in diseased ventricles when systolic pressure is abruptly increased. | Cerium Isotopes |
IMPORTANCE: Diabetic retinopathy (DR) is a leading cause of blindness in adults worldwide. Early detection and intervention can prevent blindness; however, many patients do not receive their recommended annual diabetic eye examinations, primarily owing to limited access. OBJECTIVE: To evaluate the safety and accuracy of an artificial intelligence (AI) system (the EyeArt Automated DR Detection System, version 2.1.0) in detecting both more-than-mild diabetic retinopathy (mtmDR) and vision-threatening diabetic retinopathy (vtDR). DESIGN, SETTING, AND PARTICIPANTS: A prospective multicenter cross-sectional diagnostic study was preregistered (NCT03112005) and conducted from April 17, 2017, to May 30, 2018. A total of 942 individuals aged 18 years or older who had diabetes gave consent to participate at 15 primary care and eye care facilities. Data analysis was performed from February 14 to July 10, 2019. INTERVENTIONS: Retinal imaging for the autonomous AI system and Early Treatment Diabetic Retinopathy Study (ETDRS) reference standard determination. MAIN OUTCOMES AND MEASURES: Primary outcome measures included the sensitivity and specificity of the AI system in identifying participants' eyes with mtmDR and/or vtDR by 2-field undilated fundus photography vs a rigorous clinical reference standard comprising reading center grading of 4 wide-field dilated images using the ETDRS severity scale. Secondary outcome measures included the evaluation of imageability, dilated-if-needed analysis, enrichment correction analysis, worst-case imputation, and safety outcomes. RESULTS: Of 942 consenting individuals, 893 patients (1786 eyes) met the inclusion criteria and completed the study protocol. The population included 449 men (50.3%). Mean (SD) participant age was 53.9 (15.2) years (median, 56; range, 18-88 years), 655 were White (73.3%), and 206 had type 1 diabetes (23.1%). Sensitivity and specificity of the AI system were high in detecting mtmDR (sensitivity: 95.5%; 95% CI, 92.4%-98.5% and specificity: 85.0%; 95% CI, 82.6%-87.4%) and vtDR (sensitivity: 95.1%; 95% CI, 90.1%-100% and specificity: 89.0%; 95% CI, 87.0%-91.1%) without dilation. Imageability was high without dilation, with the AI system able to grade 87.4% (95% CI, 85.2%-89.6%) of the eyes with reading center grades. When eyes with ungradable results were dilated per the protocol, the imageability improved to 97.4% (95% CI, 96.4%-98.5%), with the sensitivity and specificity being similar. After correcting for enrichment, the mtmDR specificity increased to 87.8% (95% CI, 86.3%-89.5%) and the sensitivity remained similar; for vtDR, both sensitivity (97.0%; 95% CI, 91.2%-100%) and specificity (90.1%; 95% CI, 89.4%-91.5%) improved. CONCLUSIONS AND RELEVANCE: This prospective multicenter cross-sectional diagnostic study noted safety and accuracy with use of the EyeArt Automated DR Detection System in detecting both mtmDR and, for the first time, vtDR, without physician assistance. These findings suggest that improved access to accurate, reliable diabetic eye examinations may increase adherence to recommended annual screenings and allow for accelerated referral of patients identified as having vtDR. | Vision Screening |
Numerous species of marine dinoflagellates synthesize the potent environmental neurotoxic alkaloid, saxitoxin, the agent of the human illness, paralytic shellfish poisoning. In addition, certain freshwater species of cyanobacteria also synthesize the same toxic compound, with the biosynthetic pathway and genes responsible being recently reported. Three theories have been postulated to explain the origin of saxitoxin in dinoflagellates: The production of saxitoxin by co-cultured bacteria rather than the dinoflagellates themselves, convergent evolution within both dinoflagellates and bacteria and horizontal gene transfer between dinoflagellates and bacteria. The discovery of cyanobacterial saxitoxin homologs in dinoflagellates has enabled us for the first time to evaluate these theories. Here, we review the distribution of saxitoxin within the dinoflagellates and our knowledge of its genetic basis to determine the likely evolutionary origins of this potent neurotoxin. | Saxitoxin |
A lipolytic mesophilic fungus which produces lipase extracellularly was isolated from soil. Based on ITS1-5.8S-ITS4 region sequences of ribosomal RNA, it was concluded that the isolate JK-1 belongs to genus Rhizopus and clades with Rhizopus oryzae. The present paper reports the screening, isolation, identification, and optimization of fermentation conditions for the production of lipase (EC 3.1.1.3). Culture conditions were optimized, and the highest lipase production was observed in basal medium with corn steep liquor as nitrogen source and glucose as carbon source. Maximum lipase production was observed at 72 h, which is about 870 U/ml. Optimization of fermentation conditions resulted in 16-fold enhancement in enzyme production. | Rhizopus |
The widespread use of immobilized metal-affinity chromatography (IMAC) for fast and efficient purification of recombinant proteins has brought potentially toxic transition elements into common laboratory usage. However, there are few studies on the leaching of metal from the affinity resin, such as nickel-nitrilotriacetic acid (Ni-NTA), with possible deleterious impact on the biological activity. This is of particular importance when reducing or chelating eluants stronger than imidazole are used. We present a detailed study of hydroxynaphthol blue (HNB) as an indicator of several divalent metal cations, but with emphasis on Ni(2+), clarifying and correcting many errors and ambiguities in the older literature on this dye compound. The assay is simple and sensitive and many metals, notably Ni(2+), Zn(2+), Cu(2+), Pb(2+), Fe(2+), Co(2+), and Al(3+), can be readily detected and quantified at concentrations down to 15-50â¯nM (1-5â¯ppb) at neutral pH and in most commonly used buffers using spectroscopic equipment available in typical biochemistry research labs. Using this method, we show that significant amounts of Ni(2+) (up to 20â¯mM) are co-purified with a target protein (cytochrome bc(1) complex) when histidine is used to elute from Ni-NTA resin. | Nitrilotriacetic Acid |
Lymphangiomas are rare benign congenital tumours, involving both the head and the neck and causing obstructing symptoms in the upper airways as well as aesthetic anomalies. In recent years, sclerosing therapy with OK-432 has become the treatment of choice in the management of these lymphatic malformations. Nonetheless, surgery still seems to be the therapy advocated for resolution of symptoms. Herein, three cases of lymphangiomas involving the head and the neck are described and a review of the English scientific literature is outlined. | Lymphatic Vessel Tumors |
The proposal to produce this final commemorative issue for the Journal of Andrology arose during our regular discussions as current editors soon after it was announced that the Journal would complete its own life course and merge into a new publication (to be named Andrology) with the International Journal of Andrology. We considered the momentous occasion to be one that should be celebrated with an enduring tribute in recognition of the Journal's exceptional 33-year existence. Among the various contributions sought for inclusion in this issue, we envisioned an article assembling collected short essays from all living former editors drawing on notable events and highlights, if not less well-known challenges and successes arising during their editorship eras. We thought that any such production of musings, viewpoints, and most of all words of wisdom from those who have had major roles in the direction and accomplishments of the Journal would offer an illuminating read for the society's members and friends and provide all readers another venue to share in and enjoy the Journal's great history. We are enthralled to have gathered these collections, all personal compositions of the former editors-in-chief, and for their effort that has helped us complete this special endeavor we express to them our tremendous gratitude. Serving as the Journal's last editors, we are also grateful to contribute our essay at the very end as part of this joyous chronicle. | Andrology |
The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24â¯h and 7â¯d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (delta) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7â¯d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. STATEMENT OF SIGNIFICANCE: Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying Ca-nanoparticles. Zn-nanoparticles are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanogels are, therefore, proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanogels is encouraged. | Dentin Sensitivity |
Modified single-loop reconstruction in pancreaticoduodenectomy separates pancreatic secretion from bile. It is performed in cases of high-risk pancreatic remnants to reduce the severity of postoperative pancreatic fistulas and moreover the overall postoperative morbidity. This reconstruction technique is characterized by an extra-long jejunal loop for the construction of the pancreaticojejunostomy and hepaticojejunostomy. The longer distance between these anastomoses and an additional jejuno-jejunostomy between the afferent and efferent limb of the hepaticojejunostomy separate the fluids and prevent backflow of bile towards the pancreaticojejunostomy. Thus, the secretions cannot activate each other and aggravate an existing anastomotic leakage. We observed a reduced rate of severe postoperative pancreatic fistulas after modified single-loop reconstruction compared to conventional single loop reconstruction. The technique is easy to perform, safe, and less time-consuming than a traditional double-loop reconstruction. | Pancreaticojejunostomy |
Many arthropod venom peptides have potential as bioinsecticides, drug leads, and pharmacological tools due to their specific neuromodulatory functions. Assassin flies (Asilidae) are a family of predaceous dipterans that produce a unique and complex peptide-rich venom for killing insect prey and deterring predators. However, very little is known about the structure and function of their venom peptides. We therefore used an E. coli periplasmic expression system to express four disulfide-rich peptides that we previously reported to exist in venom of the giant assassin fly Dolopus genitalis. After purification, each recombinant peptide eluted from a C18 column at a position closely matching its natural counterpart, strongly suggesting adoption of the native tertiary fold. Injection of purified recombinant peptides into blowflies (Lucilia cuprina) and crickets (Acheta domestica) revealed that two of the four recombinant peptides, named rDg3b and rDg12, inhibited escape behaviour in a manner that was rapid in onset (<1 min) and reversible. Homonuclear NMR solution structures revealed that rDg3b and rDg12 adopt cystine-stabilised alpha/ss defensin and inhibitor cystine knot folds, respectively. Although the closest known homologues of rDg3b at the level of primary structure are dipteran antimicrobial peptides such as sapecin and lucifensin, a DALI search showed that the tertiary structure of rDg3b most closely resembles the K(V)11.1-specific alpha-potassium channel toxin CnErg1 from venom of the scorpion Centruroides noxius. This is mainly due to the deletion of a large, unstructured loop between the first and second cysteine residues present in Dg3b homologues from non-asiloid, but not existing in asiloid, species. Patch-clamp electrophysiology experiments revealed that rDg3b shifts the voltage-dependence of K(V)11.1 channel activation to more depolarised potentials, but has no effect on K(V)1.3, K(V)2.1, K(V)10.1, K(Ca)1.1, or the Drosophila Shaker channel. Although rDg12 shares the inhibitor cystine knot structure of many gating modifier toxins, rDg12 did not affect any of these K(V) channel subtypes. Our results demonstrate that multiple disulfide-rich peptide scaffolds have been convergently recruited into asilid and other animal venoms, and they provide insight into the molecular evolution accompanying their weaponisation. | Cystine-Knot Miniproteins |
An efficient route for the formal total synthesis of physostigmine (1) and physovenine (2), alkaloids from 5-methoxyindole-3-acetonitrile, through a Grignard reagent 1,4-addition, is described. 2-Hydroxyindolenine 5, the key advanced intermediate for the synthetic targets, was converted either to esermethole (12) via a high-yielding (28%) seven-step sequence or to the C-ring oxygenated analogue 15 in a five-step sequence and 23% overall yield. (1)H NMR and molecular modeling analyses of esermethole (12) and the furoindolines 13 and 15 were used to deconvolute weighted time-average vicinal coupling constants to provide definite solution-state conformational preferences in CD(2)Cl(2) solvent. | Physostigma |
1. The cell-attached configuration of the patch-clamp technique was used to assess resting membrane potential and firing threshold of CA1 pyramidal cells and interneurones of rat hippocampal slices. 2. Resting potential was inferred from the reversal potential of voltage-gated K+ currents with symmetrical intracellular and pipette K+ concentrations. Its mean value was -74 +/- 9 mV for silent interneurones (mean +/- s.d.; n = 17) and -84 +/- 7 mV for silent pyramidal cells (n = 8). Spontaneous action currents occurred in thirteen out of thirty-two interneurones and two out of ten pyramidal cells. In active cells, membrane potential values fluctuated by up to 20 mV, due in part to the large hyperpolarizations that followed an action current. 3. Membrane potential values determined from K+ current reversal were 13 +/- 6 mV more hyperpolarized than those measured in whole-cell recordings from the same neurones (n = 8), probably due to a Donnan equilibrium potential between pipette and cytoplasm. 4. Firing threshold of silent cells was determined by elevating external K+ until action currents were generated, while membrane potential was monitored from the cell-attached K+ current reversal. Spike threshold was attained at -49 +/- 8 mV for interneurones (n = 17) and at -60 +/- 8 mV for pyramidal cells (n = 8). Increasing external Ca2+ from 2 to 4 mM shifted the neuronal voltage threshold by +5 mV, without affecting resting potential. 5. For comparison with these values, we examined how the rate of membrane polarization influenced firing threshold in whole-cell records. Ramp current injections, of duration 15-1500 ms, revealed that current threshold followed a classical strength-duration relationship. In contrast voltage threshold, determined from current injection or by elevating extracellular K+, varied little with the rate of membrane polarization. 6. The state of activation and inactivation of Na+ and K+ currents might contribute to the stability of the voltage threshold. Cell-attached records showed that 79 +/- 10 % of Na+ channels and 64 +/- 10 % of K+ channels were available for activation at resting potential in silent cells (n = 8). As cells were depolarized to threshold, Na+ current availability was reduced to 23 +/- 10 %, and K+ current availability to 31 +/- 12 %. 7. The speed of transition into the inactivated states also appears to contribute to the invariance of threshold for all but the fastest depolarizations. At potentials close to threshold, the rate of inactivation of Na+ and K+ followed a double exponential time course, such that Na+ currents were 62 % inactivated and K+ currents were 63 % inactivated within 15 ms. | Membrane Potentials |
The direct intrahepatic portacaval shunt (DIPS) is a modification of the TIPS procedure, using intravascular ultrasound-guidance, combined with fluoroscopy. The DIPS procedure was initially conceived to increase the durability of shunt patency and extend the spectrum of patients with portal hypertension for whom endovascular portocaval shunting can be performed. The DIPS procedure involves intravascular ultrasound-guided puncture from the inferior vena cava to the portal vein through the caudate lobe of the liver. The shunt is completed with a polytetrafluoroethylene-covered stent graft. This article describes the indications, technique, and outcomes of the DIPS procedure to enable the interventional radiologist currently experienced with TIPS to incorporate this procedure into their practice. | Portacaval Shunt, Surgical |
PURPOSE: To evaluate the effect of posterior scleral reinforcement in controlling high myopic axial progression in young patients. METHODS: Only one eye of each patient had posterior scleral reinforcement surgery. Before surgery and at each postoperative follow-up, the best corrected visual acuity, intraocular pressure, refractive errors, indirect ophthalmoscopy, B-type ultrasonography, and IOLMASTER reflected light biometry were performed on both eyes. The changes of axial length and the changes of refractive errors from the baseline were compared between the surgery eyes and the contralateral eyes. RESULTS: Thirty patients had a mean age of 7.5 years and a mean spherical equivalent of -9.72 diopters. The mean elongation of axial length was significantly less in the surgery eye group than that in the contralateral eye group (0.75 mm vs. 0.94 mm, p < 0.0001, paired t test) after a mean follow-up of 895 days. The surgical effect was mild but maintained during the follow-up. The eyes with staphyloma gained less surgical effect when compared with the eyes without staphyloma (p = 0.0036). There was also a notable nonstatistically significant trend for younger patients to gain a larger surgical effect (p = 0.0986). CONCLUSIONS: Posterior scleral reinforcement surgery was found effective in slowing down high myopic axial progression in young patients within the study period, but the size of the effect was small. The surgical procedure is well tolerated without vision-threatening complications. | Scleral Diseases |
BACKGROUND: There has been a rise in the prevalence of large newborns over a few decades in many parts of the world. There is ample evidence that fetal macrosomia is associated with increased risk of complications both for the mother and the newborn. In current obstetrics, the macrosomic fetus represents a frequent clinical challenge. Evidence is emerging that being born macrosomic is also associated with future health risks. OBJECTIVE: To provide a review of causes and risks, prevention, prediction and clinical management of suspected large fetus/fetal macrosomia, primarily aimed at clinical obstetricians. METHODS: Medline and EMBASE were searched between 1980 and 2007 by combining either 'fetal macrosomia' or 'large for gestational age' with other relevant terms. The Cochrane Database of Systematic Reviews was searched for the term 'fetal macrosomia'. RESULTS AND CONCLUSIONS: Although the causes of high birthweight include both genetic and environmental factors, the rapid increase in the prevalence of large newborns has environmental causes. The evidence is extensive that maternal overweight and associated metabolic changes, including type 2 and gestational diabetes, play a central role. There is a paucity of studies of the effect of intervention before and/or during pregnancy on the risk of having an 'overweight newborn'. It appears rational, however, that preventive measures should primarily be implemented before pregnancy and should include guidance about nutrition and physical activity in order to reduce the prevalence of overweight. In pregnancy, limited weight gain, especially in obese women, seems to reduce the risk of macrosomia, as do good control of plasma glucose among those with diabetes. Prediction of fetal macrosomia remains an inaccurate task even with modern ultrasound equipment. There is little evidence that routine elective delivery (induction or caesarean section) for the mere reason of suspected macrosomia should be employed in a general population. Vaginal delivery of a macrosomic fetus requires considered attention by an experienced obstetrician and preparedness for operative delivery, shoulder dystocia and newborn asphyxia. | Fetal Macrosomia |
Fotemustine is a cytotoxic alkylating agent, belonging to the group of nitrosourea family. Its mechanism of action is similar to that of other nitrosoureas, characterized by a mono-functional/bi-functional alkylating activity. Worth of consideration is the finding that the presence of high levels of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) in cancer cells confers drug resistance. In different clinical trials Fotemustine showed a remarkable antitumor activity as single agent, and in association with other antineoplastic compounds or treatment modalities. Moreover, its toxicity is generally considered acceptable. The drug has been employed in the treatment of metastatic melanoma, and, on the basis of its pharmacokinetic properties, in brain tumors, either primitive or metastatic. Moreover, Fotemustine shows pharmacodynamic properties similar to those of mono-functional alkylating compounds (e.g. DNA methylating drugs, such as Temozolomide), that have been recently considered for the management of acute refractory leukaemia. Therefore, it is reasonable to assume that this agent could be a good candidate to play a potential role in haematological malignancies. | Nitrosourea Compounds |
The objective of this study was to investigate the temperature sensitivity of labile and relatively recalcitrant forest soil carbon (C) pools amended with biochar during short-term incubation. Biochars were prepared using sugar cane residue under pyrolysis temperatures of 300 and 700 degrees C (i.e., BC300 and BC700), respectively. Coarse particulate organic matter and acid hydrolysis residue were separated from a forest soil and treated as the labile and recalcitrant C pools of the soil, respectively. Temperature sensitivity of the soil C pools was characterized using the Q(10) values (i.e., the proportional increase in respiration per 10 degrees C rise). The increased Q(10) values of treatments in the earlier stage were attributable to instantaneously increased aromatic C content. The following decreased Q(10) values were related to the consumption of labile C. However, the two types of biochars led to similar Q(10) values in the same C pools at the later stage of incubation, which was closely related to the nearly humic-like component content in the dissolved organic matter. The different temporal distributions of Q(10) values were attributable to changes of aromatic C content and continuous consumption of labile components. | Carbon |
Superior mesenteric artery(SMA) syndrome is rare disorder, which is caused by a reduction in the aortomesenteric angle causing a duodenal obstruction. It is usually occurs after a period of weight loss, nausea, and vomiting by a partial obstruction of the third portion of the duodenum. If conservative management fails then a laparotomy with a duodenojejunostomy is indicated. Recently, a minimally invasive or laparoscopic approach to the retroperitoneum or duodenal detachment was introduced. Although the role of a laparoscopy in managing SMA syndrome is not clearly defined, a laparoscopic duodenojejunostomy may be an alternative approach to the surgical treatment of SMA syndrome cases. Two cases of superior mesenteric artery syndrome that were treated laparoscopically after medical therapy failure are described. The 4-port procedure was performed. A dilated bowel on the third portion of the duodenum was observed below the transverse mesocolon and to right of the superior mesenteric artery. A proximal loop of the jejunum was anastomosed to the duodenum using an endoscopic GIA stapler. The surgery time and hospital length of stay were acceptable. No complications were encountered in this study. A laparoscopic duodenojejunostomy is a feasible alternative option for treating SMA syndrome. It provides the benefits of being a definitive and minimally invasive surgical technique in a duodenal obstruction." | Superior Mesenteric Artery Syndrome |
Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising Lactobacillus rhamnosus LOCK 0900, Lactobacillus rhamnosus LOCK 0908, and Lactobacillus casei LOCK 0918 in children under 2 years of age with AD and a cow's milk protein (CMP) allergy. The study enrolled 151 children, who-apart from being treated with a CMP elimination diet-were randomized to receive the probiotic preparation at a daily dose of 10(9) bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant (p < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13-5.8; p = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85-19.67, p = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic LOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565). | Lacticaseibacillus |
Des Thompson was born in Belfast and apart from a four year period of evacuation to the Ballymena area during the war and five years studying in Dublin he's never lived anywhere else. His sister qualified as a doctor and his Mother, who unfortunately died when he was at College, was a science graduate. His Father, Uncle and Grandfather were all veterinary surgeons. Des qualified with honours from Trinity College Dublin University in 1961 and immediately joined his father's practice in the centre of Belfast. He has been President of BSAVA, UEVP, SPVS, NIVA, RCVS and CABTSG | Veterinary Medicine |
In a previous work, a Cicer arietinum cDNA clone (CaXTH1) encoding a xyloglucan endotransglucosylase/hydrolase (XTH1) protein was isolated and characterized. CaXTH1 showed an expression pattern specific to growing tissue: mostly epicotyls and the upper growing internodes of adult stems. CaXTH1 mRNA was not detected in any other organs of either seedlings or adult plants, suggesting an involvement of the putative XTH encoded by CaXTH1 in the chickpea cell expansion process. After the generation of polyclonal antibodies by using the XTH1 recombinant protein and the analysis of the specificity of the antibodies for XTH proteins, here the specific location of the chickpea XTH1-cross-reacting protein in cell walls of epicotyls, radicles, and stems is reported, evaluated by western blot and immunocytochemical studies. The results indicate a function for this protein in the elongation of parenchyma cells of epicotyls and also in developing vascular tissue, suggesting a role in the elongation of vascular cells. | Cicer |
CONTEXT: Poverty is a well-established risk factor for the development of behavior problems, yet little is known about how timing of exposure to childhood poverty relates to behavior problems in early adolescence. OBJECTIVE: To examine the differential effects of the timing of poverty between birth and late childhood on behavior problems in early adolescence by modeling lifecourse models, corresponding to sensitive periods, accumulation of risk and social mobility models. METHODS: We used the Quebec Longitudinal Study of Child Development (N = 2120). Poverty was defined as living below the low-income thresholds defined by Statistics Canada and grouped into three time periods: between ages 0-3 years, 5-7 years, and 8-12 years. Main outcomes were teacher's report of hyperactivity, opposition and physical aggression at age 13 years. Structured linear regression analyses were conducted to estimate the contribution of poverty during the three selected time periods to behavior problems. Partial F-tests were used to compare nested lifecourse models to a full saturated model (all poverty main effects and possible interactions). RESULTS: Families who experienced poverty at all time periods were 9.3% of the original sample. Those who were poor at least one time period were 39.2%. The accumulation of risk model was the best fitting model for hyperactivity and opposition. The risk for physical aggression problems was associated only to poverty between 0 and 3 years supporting the sensitive period. CONCLUSION: Early and prolonged exposure to childhood poverty predicted higher levels of behavior problems in early adolescence. Antipoverty policies targeting the first years of life and long term support to pregnant women living in poverty are likely to reduce behavior problems in early adolescence. | Poverty |
Row crop and livestock production contaminate soils and groundwater of the karst aquifers within south-central Kentucky's Pennyroyal Plateau. Transport of atrazine from field application to the epikarstic drainage system beneath a field with active row-crop farming was investigated. The Crumps Cave study site is a shallow autogenic drainage system with a recharge area of approximately 1 ha that contains two epikarst drains (WF-1 and WF-2) which were monitored for atrazine, deethylatrazine (DEA), and deisopropylatrazine (DIA) concentrations from January 2011 to May 2012. Atrazine concentrations in both drains did not increase above winter background levels for nearly 2 mo after application when levels suddenly spiked and reached peak concentrations for the study during an event in May 2011. Atrazine, DEA, and DIA were detected in 100% of samples, and metabolites accounted for 54 to 94% of the monthly total loads, except in May 2011. Median dealkylated metabolite/atrazine ratios (DMAR) were approximately 5:1 at both sites, and seasonal DMAR patterns corresponded with changes in soil temperature. These data support the hypothesis that a combination of sorption and degradation in the soil column above the epikarst controlled the transport of atrazine and its metabolites. This resulted in delayed atrazine transport after application and prolonged transport of atrazine and its weakly sorbed metabolites to the epikarst aquifer. Management practices that reduce herbicide inputs, such as diverse crop rotations, cover crops, and use of low-rate and strong-sorbing herbicides, would improve groundwater quality in areas of the Corn Belt with intensive row cropping on karst topography. | Atrazine |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.