Phospholipids (PLs) know-how: exploring and exploiting phospholipase D for its industrial dissemination.
Owing to their numerous nutritional and bioactive functions, phospholipids (PLs), which are major components of biological membranes in all living organisms, have been widely applied as nutraceuticals, food supplements, and cosmetic ingredients. To date, PLs are extracted solely from soybean or egg yolk, despite the diverse market demands and high cost, owing to a tedious and inefficient manufacturing process. A microbial-based manufacturing process, specifically phospholipase D (PLD)-based biocatalysis and biotransformation process for PLs, has the potential to address several challenges associated with the soybean- or egg yolk-based supply chain. However, poor enzyme properties and inefficient microbial expression systems for PLD limit their wide industrial dissemination. Therefore, sourcing new enzyme variants with improved properties and developing advanced PLD expression systems are important. In the present review, we systematically summarize recent achievements and trends in the discovery, their structural properties, catalytic mechanisms, expression strategies for enhancing PLD production, and its multiple applications in the context of PLs. This review is expected to assist researchers to understand current advances in this field and provide insights for further molecular engineering efforts toward PLD-mediated bioprocessing.


Phytase production by solid-state fermentation of groundnut oil cake by Aspergillus niger: A bioprocess optimization study for animal feedstock applications.
This investigation deals with the use of agro-industrial waste, namely groundnut oil cake (GOC), for phytase production by the fungi Aspergillus niger NCIM 563. Plackett-Burman design (PBD) was used to evaluate the effect of 11 process variables and studies here showed that phytase production was significantly influenced by glucose, dextrin, distilled water, and MgSO4 · 7H2O. The use of response surface methodology (RSM) by Box-Behnken design (BBD) of experiments further enhanced the production by a remarkable 36.67-fold from the original finding of 15 IU/gds (grams of dry substrate) to 550 IU/gds. This is the highest solid-state fermentation (SSF) phytase production reported when compared to other microorganisms and in fact betters the best known by a factor of 2. Experiments carried out using dried fermented koji for phosphorus and mineral release and also thermal stability have shown the phytase to be as efficient as the liquid enzyme extract. Also, the enzyme, while exhibiting optimal activity under acidic conditions, was found to have significant activity in a broad range of pH values (1.5-6.5). The studies suggest the suitability of the koji supplemented with phytase produced in an SSF process by the "generally regarded as safe" (GRAS) microorganism A. niger as a cost-effective value-added livestock feed when compared to that obtained by submerged fermentation (SmF).


Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone.
DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.


Paleoparasitological report on the stool from a Medieval child mummy in Yangju, Korea.
Previous studies have successfully shown evidence for parasitic infections in human remains from various archaeological sites. However, in the case of Korea, since there have been very few paleoparasitological reports published, pre-20th century parasitic infection patterns remain obscure. Therefore, in order to partly fill this gap, we are reporting on a case of paleoparasitic infection from the feces of a 15th century child mummy from Yangju, Korea. In the course of the present study, we found the eggs of Clonorchis sinensis, Ascaris lumbricoides, and Trichuris trichiura in the feces of the mummy. Trichuris trichiura eggs were found in far greater numbers than other parasite eggs; in fact, intact bipolar plugs were clearly observed and even the larvae were still visible in some eggs. The eggs of C. sinensis and A. lumbricoides were also well preserved, though not in as great a number. Since we could find a number of well-preserved larvae-containing eggs, we are encouraged that successful extraction, amplification, and sequence determination of ancient DNA from the paleoparasite eggs might be possible in future studies. With additional paleoparasitological investigation using feces from Korean mummies, we hope that a history of parasite infection in Korea will be reconstructed.


Design and synthesis of chiral alpha,alpha-disubstituted amino acids and conformational study of their oligopeptides.
alpha,alpha-Disubstituted amino acids are alpha-amino acids in which the hydrogen atom at the alpha-position of the L-alpha-amino acid is replaced with an alkyl substituent. The introduction of an alpha-alkyl substituent changes the properties of amino acids, with the conformational freedom of the side chain in the amino acids and the secondary structure of their peptides being especially restricted. The author developed a synthetic route of optically active alpha-ethylated alpha,alpha-disubstituted amino acids using chiral cyclic 1,2-diol as a chiral auxiliary. It was found that the preferred secondary structure of peptides composed of chiral alpha-ethylated alpha,alpha-disubstituted amino acids is a fully extended C5-conformation, whereas that of peptides composed of chiral alpha-methylated alpha,alpha-disubstituted amino acids is a 3(10)-helical structure. Also, a new chiral cyclic amino acid; (3S,4S)-1-amino-3,4-di(methoxy)cyclopentanecarboxylic acid {(S,S)-Ac5c(dOM)}, and a bicyclic amino acid; (1R,6R)-8-aminobicyclo[4.3.0]non-3-ene-8-carboxylic acid {(R,R)-Ab5,6= c}, in which the alpha-carbon atom is not the chiral center but chiral centers exist at the side-chain cycloalkane skeleton, were designed and synthesized. The (S,S)-Ac5c(dOM) hexa- and octapeptides preferentially formed left-handed (M) helices, in which the helical-screw direction is exclusively controlled by the side-chain chiral centers. Contrary to the left-handed helices of (S,S)-Ac(5)c(dOM) peptides, the (R,R)-Ab5,6= c hexapeptide formed both diastereomeric right-handed (P) and left-handed (M) helices, and the twelve chiral centers at the side chain showed no preference for helical-screw direction. Thus, the chiral environment at the side chain is important for the control of helical-screw direction. Furthermore, the author designed a new class of chiral cyclic alpha,alpha-disubstituted amino acids that have pendant chiral centers at the substituent of the delta-nitrogen atom. The synthetic route would provide various optically-active cyclic alpha,alpha-disubstituted amino acids bearing a pendant chiral moiety.


Paraoxonase 192 gene polymorphism and serum paraoxonase activity in high grade gliomas and meningiomas.
The purpose of this study was to demonstrate the relationship between serum PON1 activity and PON 192 polymorphism in brain tumours. The distribution of PON 192 polymorphism in 42 high grade gliomas and 42 meningiomas were determined by polymerase chain reaction--based restriction fragment length polymorphism analysis and compared with 50 healthy control subjects. Serum paraoxonase1 activities were also measured and compared in the same population. We found that in both tumour groups serum PON1 activity was significantly lower than the control group (p < 0.001), but did not differ between meningiomas and high grade gliomas. There was no significant difference either in distribution of the AA, AB and BB genotypes or in the allelic frequencies, between the patient group and control subjects (p > 0.05). Our results suggest that serum PON1 as a part of the lipid peroxidation scavenging systems might be involved in the tumourigenesis of brain tumours.


[Enteral feeding. Importance in clinical practice].
The gut is the most important organ for the final digestion, absorption and metabolizing of the nutrients ingested. When the gut is available, it must be used as the ideal way to provide nutrients to the body tissues, either orally or by using a feeding tube to help delivering the nutrients. This type of nutrition has important advantages: One of them is the stimulation of the intestinal cells to preserve its integrity and the guts barrier function; it is economic, safe, efficient and it has been associated to improve the patient's outcome. Nowadays, there are many industrialized formulas available for tube feeding use, as well as a great variety of tubes designed for administrating this formulas, depending on the age, size, and time in which the patient will be using them. The future directions for some cases like its use in critically ill patients or the molecular effects of providing nutrients enterally is still under investigation, and there are still questions to be answered in this broad field.


Interfacial Engineering for Enhanced Light Absorption and Charge Transfer of a Solution-Processed Bulk Heterojunction Based on Heptazole as a Small Molecule Type of Donor.
In the present study, a solution-processed organic semiconductor based on indolocarbazole derivative (heptazole) is introduced as a p-type donor material for a bulk-heterojunction photovoltaic device. The heptazole has an optical band gap of 2.97 eV, and its highest occupied molecular orbital-lowest unoccupied molecular orbital energy levels are compactable with the PC60BM to construct a donor-acceptor heterojuction for energy harvesting and transfer. When the bulk-heterojunction photovoltaic devices consisting of ITO/PEDOT:PSS/heptazole:PC60BM/Al with different blending ratio of heptazole:PC60BM were constructed, the cell with 1:1 blending ratio exhibited the best power conversion efficiency. Further, when an indoline organic dye (D149) was introduced as an interfacial modifier to the above donor/acceptor bulk heterojunction, the device demonstrated an enhanced overall power conversion efficiency from 1.26% to 2.51% hence demonstrating enhancement by the factor of 100%. The device was further characterized using electronic absorption spectroscopy, photoluminescence spectroscopy, electrochemical impedance spectroscopy, and the photovoltage decay kinetics. These studies reveal that the enhanced power conversion efficiency of the device is due to the enhanced charge transfer with the complementary light absorption feature of the interfacial D149 dye molecules.


New Trends in Anterior Cruciate Ligament Reconstruction: A Systematic Review of National Surveys of the Last 5 Years.
The purpose of this study was to analyze national surveys of orthopaedic surgeons on anterior cruciate ligament (ACL) reconstruction to determine their preferences related to the preferred graft, femoral tunnel positioning, fixation and tensioning methods, antibiotic and anti-thromboembolic prophylaxis, and use of tourniquet and drains. A systematic search of PubMed, Web of Science, and Cochrane Library was performed. Inclusion criteria were surveys of ACL reconstruction trends and preferences published in the past 5 years (2011-2016), involving members of national societies of orthopaedics. Information regarding survey modalities, population surveyed, graft choice both in the general or in the athletic population, surgical technique, fixation, use of antibiotic, tourniquet, drains, and anti-thromboembolic prophylaxis was extracted. Eight national surveys were included from Europe (three), North or Latin America (three), and Asia (two). Overall, 7,420 questionnaires were sent, and 1,495 participants completed the survey (response rate ranging from 16 to 76.6%). All surveys reported the hamstring tendon (HT) autograft as the preferred graft, ranging from 45 to 89% of the surveyed population, followed by bone-patellar tendon-bone (BPTB) graft (2-41%) and allograft (2-17%). Only two surveys focusing on graft choice in athletic population underlined how in high-demand sportive population the graft choices changes in favor of BPTB. Single-bundle reconstruction was the preferred surgical technique in the four surveys that investigated this issue. Five surveys were in favor of anteromedial (AM) portal and two in favor of trans-tibial technique. Suspension devices for femoral fixation were the preferred choice in all but one survey, while interference screws were the preferred method for tibial fixation. The two surveys that investigated graft tensioning were in favor of manual tensioning. The use of tourniquet, antibiotics, drains, and anti-thromboembolic prophylaxis were vaguely reported. A trend toward the preference of HT autograft was registered in all the surveys; however, sport participation has been highlighted as an important variable for increased use of BPTB. Single-bundle reconstruction with AM portal technique and suspension femoral fixation and screws fixation for the tibia seem the preferred solution. Other variables such as tensioning, antibiotic, anti-thromboembolic prophylaxis, tourniquet use, and drains were investigated scarcely among the surveys; therefore, no clear trends could be delineated. This is a Level V, systematic review of expert opinion study.


Jamming transitions induced by an attraction in pedestrian flow.
We numerically study jamming transitions in pedestrian flow interacting with an attraction, mostly based on the social force model for pedestrians who can join the attraction. We formulate the joining probability as a function of social influence from others, reflecting that individual choice behavior is likely influenced by others. By controlling pedestrian influx and the social influence parameter, we identify various pedestrian flow patterns. For the bidirectional flow scenario, we observe a transition from the free flow phase to the freezing phase, in which oppositely walking pedestrians reach a complete stop and block each other. On the other hand, a different transition behavior appears in the unidirectional flow scenario, i.e., from the free flow phase to the localized jam phase and then to the extended jam phase. It is also observed that the extended jam phase can end up in freezing phenomena with a certain probability when pedestrian flux is high with strong social influence. This study highlights that attractive interactions between pedestrians and an attraction can trigger jamming transitions by increasing the number of conflicts among pedestrians near the attraction. In order to avoid excessive pedestrian jams, we suggest suppressing the number of conflicts under a certain level by moderating pedestrian influx especially when the social influence is strong.


iRefIndex: a consolidated protein interaction database with provenance.
Interaction data for a given protein may be spread across multiple databases. We set out to create a unifying index that would facilitate searching for these data and that would group together redundant interaction data while recording the methods used to perform this grouping. We present a method to generate a key for a protein interaction record and a key for each participant protein. These keys may be generated by anyone using only the primary sequence of the proteins, their taxonomy identifiers and the Secure Hash Algorithm. Two interaction records will have identical keys if they refer to the same set of identical protein sequences and taxonomy identifiers. We define records with identical keys as a redundant group. Our method required that we map protein database references found in interaction records to current protein sequence records. Operations performed during this mapping are described by a mapping score that may provide valuable feedback to source interaction databases on problematic references that are malformed, deprecated, ambiguous or unfound. Keys for protein participants allow for retrieval of interaction information independent of the protein references used in the original records. We have applied our method to protein interaction records from BIND, BioGrid, DIP, HPRD, IntAct, MINT, MPact, MPPI and OPHID. The resulting interaction reference index is provided in PSI-MITAB 2.5 format at http://irefindex.uio.no. This index may form the basis of alternative redundant groupings based on gene identifiers or near sequence identity groupings.


Priming exercise speeds pulmonary O2 uptake kinetics during supine "work-to-work" high-intensity cycle exercise.
We manipulated the baseline metabolic rate and body position to explore the effect of the interaction between recruitment of discrete sections of the muscle fiber pool and muscle O(2) delivery on pulmonary O(2) uptake (VO(2)) kinetics during cycle exercise. We hypothesized that phase II VO(2) kinetics (tau(p)) in the transition from moderate- to severe-intensity exercise would be significantly slower in the supine than upright position because of a compromise to muscle perfusion and that a priming bout of severe-intensity exercise would return tau(p) during supine exercise to tau(p) during upright exercise. Eight male subjects [35 +/- 13 (SD) yr] completed a series of "step" transitions to severe-intensity cycle exercise from an "unloaded" (20-W) baseline and a baseline of moderate-intensity exercise in the supine and upright body positions. tau(p) was not significantly different between supine and upright exercise during transitions from a 20-W baseline to moderate- or severe-intensity exercise but was significantly greater during moderate- to severe-intensity exercise in the supine position (54 +/- 19 vs. 38 +/- 10 s, P < 0.05). Priming significantly reduced tau(p) during moderate- to severe-intensity supine exercise (34 +/- 9 s), returning it to a value that was not significantly different from tau(p) in the upright position. This effect occurred in the absence of changes in estimated muscle fractional O(2) extraction (from the near-infrared spectroscopy-derived deoxygenated Hb concentration signal), such that the priming-induced facilitation of muscle blood flow matched increased O(2) utilization in the recruited fibers, resulting in a speeding of VO(2) kinetics. These findings suggest that, during supine cycling, priming speeds VO(2) kinetics by providing an increased driving pressure for O(2) diffusion in the higher-order (i.e., type II) fibers, which would be recruited in the transition from moderate- to severe-intensity exercise and are known to be especially sensitive to limitations in O(2) supply.


Comparison of pioglitazone vs glyburide in early heart failure: insights from a randomized controlled study of patients with type 2 diabetes and mild cardiac disease.
Pioglitazone may cause fluid retention, a well-known side effect of thiazolidinediones, and may exacerbate heart failure. Patients with type 2 diabetes and mild cardiac disease (New York Heart Association functional class I) received pioglitazone (n=151) or glyburide (n=149) for 1 year. The primary endpoint was change in distance covered in the 6-minute walk test. Main secondary endpoints included comparison of cardiovascular mortality and morbidity, analysis of changes from baseline in cardiac structure and function by echocardiogram, and lipid panel. There was no significant treatment difference in the mean change from baseline in the 6-minute walk test (-11.7 m [95% confidence interval, -29.79 to 6.42]). Cardiovascular mortality and morbidity were not significantly different between the treatment groups. Echocardiographic data suggested no significant deterioration in cardiac function with pioglitazone, although more heart failure (10 vs 7 patients), edema (21.2% vs 12.8%), and weight gain (2.56+/-4.62 kg vs 0.86+/-3.85 kg) were observed than with glyburide.


Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia.
Previous research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia. A total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015-2016. Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment. In Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.


Natural attenuation of chloroethenes: identification of sequential reductive/oxidative biodegradation by microcosm studies.
A different lines of evidence approach for investigation of biodegradation processes at a chloroethene contaminated site showed well corresponding results of pollutant profiles, redox zonation, characterisation of autochthonic microflora and microcosm studies. In particular microcosm studies allowed identification of the predominating degradation pathways. Perchloroethene and trichloroethene are reductively chlorinated to mainly cis-1,2-dichloroethene (cDCE) under anaerobic conditions. Further reductive degradation to vinyl chloride (VC) is restricted to a distinct strongly anaerobic zone in the plume. Addition of high amounts of sediment material (80 vol%) to groundwater microcosms enabled reductive dechlorination without amendment with further auxiliary substrates. Reductive dechlorination was not irreversibly hindered by initially high nitrate concentrations and initially high oxidation-reduction potential. The products of anaerobic degradation cDCE and VC are subsequently aerobically mineralised, even when only low oxygen concentrations are available. Anaerobic oxidative degradation could not be proven in this study.


Maternal linguistic input to toddlers with slow expressive language development.
Maternal speech styles to children between 20 and 34 months of age who were slow to acquire expressive language were compared to those of mothers with normally speaking toddlers. Aspects of the mothers' speech examined included use of various sentence types (declaratives, negative, questions, etc.); the mother's lexical contingency with regard to the child's utterance; mother's use of pragmatic functions such as requests, comments, and conversational devices; and the mother's use of topic management. Results revealed that mothers of toddlers with slow language development are different from mothers of normal speakers only in their frequency of use of lexical contingency devices, specifically, expansion and extension. However, the proportion of expansions and extensions relative to the number of child utterances is not different, indicating that when late talkers give their mothers something to expand, the mothers do so, but that the late talkers do not give their mothers as much speech to work with as do the normal toddlers. Implications of these findings for parent training are discussed.


Long-term weight control in adults with Prader-Willi syndrome living in residential hostels.
Hyperphagia leading to severe obesity with increased morbidity and mortality is the major manifestation of Prader-Willi syndrome. Caring for these individuals in a home environment is challenging and stressful for caregivers and families. Residential hostels specifically for PWS adults offer programs of diet, exercise, and vocational opportunities, but long-term effects of PWS hostel living have not been reported. We studied long-term changes in body mass index (BMI) for PWS adults living in residential hostels compared with age-matched controls living with families at home. The study included all 34 individuals (18 men) aged >17 years with genetically confirmed PWS living in residential hostels. BMI was recorded at the time of yearly clinic visits and compared to 23 PWS adults (10 men) living at home. BMI on entering the hostel was 36.3 ± 11.0 kg/m2 and decreased to 27.0 ± 5.6 kg/m2 (p < 0.001) after 6.9 ± 3.9 years. For 21 residents, a slight rise of BMI to 28.8 kg/m2 was observed 5.1 ± 2.5 years after the lowest value was achieved. BMI of 23 PWS adults at home was 36.8 ± 12.7 kg/m2 versus 27.9 ± 7.1 kg/m2 for hostel residents in the same age range (p = 0.008). From 2008 to 2019, there were five deaths among PWS individuals aged 18-40 years living at home, compared with one death (a 43-year-old man) among hostel residents. Adults with PWS living in hostels lose weight, maintain BMI values in a normal to mildly overweight range, and have lower mortality in contrast to individuals in a family home environment.


Trends in death associated with pediatric dental sedation and general anesthesia.
Inadequate access to oral health care places children at risk of caries. Disease severity and inability to cooperate often result in treatment with general anesthesia (GA). Sedation is increasingly popular and viewed as lower risk than GA in community settings. Currently, few data are available to quantify pediatric morbidity and mortality related to dental anesthesia. Summarize dental anesthesia-related pediatric deaths described in media reports. Review of media reports in the Lexis-Nexis Academic database and a private foundation website. Dental offices, ambulatory surgery centers, and hospitals. Patients :US-based children (≤21 years old) who died subsequently receiving anesthesia for a dental procedure between 1980-2011. Most deaths occurred among 2-5 year-olds (n = 21/44), in an office setting (n = 21/44), and with a general/pediatric dentist (n = 25/44) as the anesthesia provider. In this latter group, 17 of 25 deaths were linked with a sedation anesthetic. This series of media reports likely represent only a fraction of the overall morbidity and mortality related to dental anesthesia. These data may indicate an association between mortality and pediatric dental procedures under sedation, particularly in office settings. However, these relationships are difficult to test in the absence of a database that could provide an estimate of incidence and prevalence of morbidity and mortality. With growing numbers of children receiving anesthesia for dental procedures from providers with variable training, it is imperative to be able to track anesthesia-related adverse outcomes. Creating a national database of adverse outcomes will enable future research to advance patient safety and quality.


Isolation of herpes simplex virus type 1 from gastric contents of a patient with acute pancreatitis.
Herpes simplex virus type 1 (HSV-1) was isolated from the gastric contents of a young man with acute idiopathic pancreatitis. Although the patient had a marked (eightfold) rise in serum complement fixing antibody titer to HSV-1, there was no evidence of primary infection. The source of the HSV-1 may have been reactivation in the oral or pharyngeal mucous membranes, with swallowing of the virus. HSV-1 is normally quite labile in acid media (less than five minutes at pH less than or equal to 3), but because the patient was receiving cimetidine, lack of gastric acid may have allowed prolonged survival of the virus.


Comparison of combined heart‒liver vs heart-only transplantation in pediatric and young adult Fontan recipients.
Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT. We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT. A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5-52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) (p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes. Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease.


Attentional Sampling between Eye Channels.
Our ability to detect targets in the environment fluctuates in time. When individuals focus attention on a single location, the ongoing temporal structure of performance fluctuates at 8 Hz. When task demands require the distribution of attention over two objects defined by their location, color or motion direction, ongoing performance fluctuates at 4 Hz per object. This suggests that distributing attention entails the division of the sampling process found for focused attention. It is unknown, however, at what stage of the processing hierarchy this sampling occurs, and whether attentional sampling depends on awareness. Here, we show that unaware selection between the two eyes leads to rhythmic sampling. We presented a display with a single central object to both eyes and manipulated the presentation of a reset event (i.e., cue) and a detection target to either both eyes (binocular) or separately to the different eyes (monocular). We assume that presenting a cue to one eye biases the selection process to content presented in that eye. Although participants were unaware of this manipulation, target detection fluctuated at 8 Hz under the binocular condition, and at 4 Hz when the right (and dominant) eye was cued. These results are consistent with recent findings reporting that competition between receptive fields leads to attentional sampling and demonstrate that this competition does not rely on aware processes. Furthermore, attentional sampling occurs at an early site of competition among monocular channels, before they are fused in the primary visual cortex.


Clinical investigations of Toll-like receptor agonists.
Toll-like receptors (TLR) represent a family of surface molecules that function as primary sensors of the innate immune system to recognize microbial pathogens. Ligand binding to TLR results in activation of cellular signaling pathways that regulate expression of genes involved in inflammation and immunity. Use of synthetic TLR ligands (agonists) for treatment and prevention of infectious and neoplastic diseases. Review of literature about clinical investigations of agonists of TLR 4, 7, 8, and 9. Imiquimod was the first TLR agonist approved for treatment of anogenital warts, actinic keratosis and superficial basal cell carcinoma in humans. Several other agonists of TLRs 4, 7, 8 and 9 were also shown to be effective for treatment of infections and cancers and, furthermore, were used as adjuvants for vaccination. Based on safety and efficacy of the TLR agonists used to date, applications are likely to increase in the future.


Chrysin Protects against Memory and Hippocampal Neurogenesis Depletion in D-Galactose-Induced Aging in Rats.
The interruption of hippocampal neurogenesis due to aging impairs memory. The accumulation of D-galactose (D-gal), a monosaccharide, induces brain aging by causing oxidative stress and inflammation, resulting in neuronal cell damage and memory loss. Chrysin, an extracted flavonoid, has neuroprotective effects on memory. The present study aimed to investigate the effect of chrysin on memory and hippocampal neurogenesis in brains aged using D-gal. Male Sprague-Dawley rats received either D-gal (50 mg/kg) by i.p. injection, chrysin (10 or 30 mg/kg) by oral gavage, or D-gal (50 mg/kg) and chrysin (10 or 30 mg/kg) for 8 weeks. Memory was evaluated using novel object location (NOL) and novel object recognition (NOR) tests. Hippocampal neurogenesis was evaluated using Ki-67, 5-bromo-2'-deoxyuridine (BrdU), and doublecortin (DCX) immunofluorescence staining to determine cell proliferation, cell survival, and number of immature neurons, respectively. We found that D-gal administration resulted in memory impairment as measured by NOL and NOR tests and in depletions in cell proliferation, cell survival, and immature neurons. However, co-treatment with chrysin (10 or 30 mg/kg) attenuated these impairments. These results suggest that chrysin could potentially minimize memory and hippocampal neurogenesis depletions brought on by aging.


The REACH protocol: an innovative strategy for home management of infants with complex CHD.
Approximately 32,000 infants are born with CHDs each year in the United States of America. Of every 1000 live births, 2.3 require surgical or transcatheter intervention in the first year of life. There are few more stressful times for parents than when their neonate receives a diagnosis of complex CHD requiring surgery. The stress of caring for these infants is often unrelenting and may last for weeks, months, and often years, placing parents at risk for developing post-traumatic stress disorder, as well as a drastic decrease in quality of life. Anxiety often peaks in the days and weeks after discharge from the hospital as families no longer have immediate access to nursing and medical staff. The purpose of this paper is to describe the methods of a randomised controlled trial that was designed to determine whether REACH would favourably affect parental and infant outcomes by decreasing parental stress, improve parental quality of life, increase infant stability, and decrease resource utilisation in infants with complex CHD.


Influence of spinal cord stimulation on the innervation pattern of muscle fibers in vivo.
In chick embryo, chronic stimulation of the brachial spinal cord at a fast rhythm from days 7 to 18 of development induced an increase in AChE activity sites and ACh receptor (AChR) clusters in slow anterior latissimus dorsi (ALD) muscle. Most AChR clusters and AChE spots were contacted by nerve endings. A previous study showed that such spinal cord stimulation causes changes in ALD muscle properties, especially the appearance of a high proportion of fast type II fibers (Fournier Le Ray et al., 1989). Analysis of the synaptic pattern in different fiber types of experimental ALD muscle indicated a decrease in the distance between successive AChE spots in slow type III fibers compared to controls, whereas the intersynaptic distance in fast type II fibers was very similar to that in the rare fast fibers developing in control ALD. Fast fibers of experimental muscles exhibited less AChR than did slow fibers. The increased number of neuromuscular junctions in ALD muscle after spinal cord stimulation appeared to be preferentially located in slow fibers. Electron microscopy showed no change in the number of axons in ALD nerve after spinal cord stimulation. The activity imposed on brachial motoneurons apparently caused terminal sprouting of ALD nerve in target muscle, thus accounting for the increase in neuromuscular contacts in ALD muscle fibers. Differences in the distribution of nerve contacts indicate that the type of muscle fiber innervated may play a critical role in the synaptic pattern during chick embryogenesis.


Mother-newborn couplet care: Nordic country experiences of organization, models and practice.
Mother-Newborn Couplet Care is a concept and is defined as the provision of care for a sick or preterm newborn in close proximity to and coupled with the care for the mother from the birth of the infant and for as long as the mother needs hospital care. This concept of care requires system change in both obstetrics and pediatrics in terms of the planning and organization of care, equipment and design of units. Accordingly, strong leadership setting clear goals and emphasizing a culture of cohesive care, supported by targeted education and training is crucial to ensure high-quality care of all mother-newborn dyads without separation. We describe various organizational models of Mother-Newborn Couplet Care used in Sweden and Finland and implementation processes. We envision a future where newborns and mothers are always together, irrespective of medical needs, and form an inseparable center around which healthcare services and providers are organized.


Hemodialysis-related headache.
Headache is one of the most frequently encountered neurological symptoms during hemodialysis. According to International Classification of Headache criteria dialysis-related headache was defined as the headache occurring during hemodialysis with no specific characteristic. It resolves spontaneously within 72 hours after the hemodialysis session ends. There are few studies in the literature investigating the clinical features of dialysis headache. The pathophysiology of hemodialysis-related headache is not known, but various triggering factors have been identified, including changes in blood pressure, serum sodium and magnesium levels during hemodialysis sessions, caffeine deprivation and stress. The aim of this article is to evaluate and analyze features of headache in patients undergoing hemodialysis.


Constitutive exposure of phosphatidylserine on viable cells.
Apoptotic cells are quickly recognized and engulfed by phagocytes to prevent the release of noxious materials from dying cells. Phosphatidylserine (PS) exposed on the surface of apoptotic cells is a proposed "eat-me" signal for the phagocytes. Transmembrane protein 16F (TMEM16F), a membrane protein with eight transmembrane segments, has the Ca-dependent phospholipid scramblase activity. Here we show that when lymphoma cells were transformed with a constitutively active form of TMEM16F, they exposed a high level of PS that was comparable to that observed on apoptotic cells. The PS-exposing cells were morphologically normal and grew normally. They efficiently responded to interleukin 3 and underwent apoptosis upon treatment with Fas ligand. The viable PS-exposing cells bound to peritoneal macrophages at 4 °C, but not at 25 °C. Accordingly, these cells were not engulfed by macrophages. When apoptotic cells were injected i.v. into mice, they were phagocytosed by CD11c(+)CD8(+) dendritic cells (DCs) in the spleen, but the PS-exposing living cells were not phagocytosed by these DCs. Furthermore, when PS-exposing lymphoma cells were transplanted s.c. into nude mice, they generated tumors as efficiently as parental lymphoma cells that did not expose PS. These results indicated that PS exposure alone is not sufficient to be recognized by macrophages as an eat-me signal.


Picking up the threads: Comparative osteology and associated cartilaginous elements for members of the genus Trilepida Hedges, 2011 (Serpentes, Leptotyphlopidae) with new insights on the Epictinae systematics.
The threadsnakes of the family Leptotyphlopidae have been historically neglected in terms of their natural history, ecology, systematics, and morphology. Given the relevance of morphological data for resolving systematic, evolutionary, and functional issues, we aimed to provide a detailed comparative description of osteology and associated cartilaginous elements for members of the genus Trilepida. Data were obtained through high-resolution computed tomography images, cleared and stained specimens, and radiography images of a total of 47 specimens and 12 species. Both cranial and axial osteology characters exhibited a relevant degree of intraspecific variation regarding qualitative and quantitative data associated with skull and vertebrae foramina and the shape of bony sutures and processes. The high representativeness of examined species and specimens allows us to provide a comprehensive discussion on the inter- and intraspecific osteological variation, as well as a compelling osteological diagnosis for the entire genus. Trilepida spp. differ from all Epictinae by the presence of the following combination of characters: paired nasals, fused supraoccipitals (distinct from parietal, prootics, and otooccipitals), a single (fused) parietal without a dorsal fontanelle, and the basioccipital participating in the foramen magnum (except in Trilepida nicefori). Our results reinforce the need for integration of detailed anatomical traits to usually conserved external morphological data to provide accurate diagnostic features for Epictinae. In addition, new phylogenetic hypotheses or even taxonomic re-allocations may broadly benefit from these detailed comparative studies.


Autotaxin inhibition: development and application of computational tools to identify site-selective lead compounds.
Autotaxin (ATX) catalyzes the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA). Both ATX and LPA have been linked to pathophysiologies ranging from cancer to neuropathic pain. Inhibition of LPA production by ATX is therefore of therapeutic interest. Here we report the application of previously-developed, subsite-targeted pharmacophore models in a screening workflow that involves either docking or binary QSAR as secondary filters to identify ATX inhibitors from previously unreported structural types, four of which have sub-micromolar inhibition constants. Cell-based assays demonstrate that ATX inhibition and cytotoxicity structure-activity-relationships (SAR) exhibit selectivity cliffs, characterized by structurally similar compounds exhibiting similar biological activities with respect to ATX inhibition but very different biological activities with respect to cytotoxicity. Thus, general cytotoxicity should not be used as an early filter to eliminate candidate ATX inhibitor scaffolds from further SAR studies. Assays using two substrates of vastly different sizes demonstrate that the tools developed to identify compounds binding outside the central core of the active site did identify compounds acting at an allosteric site. In contrast, tools developed to identify active-site directed compounds did not identify active-site directed compounds. The stronger volume overlap imposed when selecting screening candidates expected to bind outside the active site is likely responsible for the stronger match between intended and actual target site.


The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.
The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.


Effects of job strain on fatigue: cross-sectional and prospective views of the job content questionnaire and effort--reward imbalance in the GAZEL cohort.
The objectives this study were (1) to investigate correlations between measures of psychosocial workplace stress as measured in separate years by the Job Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) scales; (2) to establish a valid measure of psychosocial job stress with its components (by identifying the individual and interactive associations of job stress components) and (3) to use the component measures to assess the risk of psychosocial strain at work on fatigue. The JCQ and ERI from the annual survey of the GAZEL cohort established in 1989 initially with 20,624 respondents were used to investigate the associations of workplace stress on mental and physical fatigue in two separate years (1998 and 2006). First, the JCQ measures from separate years (1997 and 1999) were combined to create a measure for the same year as ERI (1998). The new measure was validated for internal and external consistency. Using logistic regression, the subcomponents of stress (upper tertiles of psychological demands, physical demands, decision latitude, social support, effort, reward, ERI and overcommitment) were tested for associations with the highest reporting of mental and physical fatigue. By combining JCQ responses from 1997 to 1999, we were able to increase the amount of information available on psychosocial factors in 1998. Psychometric properties of the workplace stress scales also showed expected factor loadings. Workplace psychosocial factors had greater associations with fatigue among men than women. Although psychosocial factors became less predictive of fatigue at 8 years of follow-up, associations between fatigue and psychosocial components (overcommitment, social support and rewards) remained significant. These analyses continue to validate the various subcomponents scales of workplace stress as measured by the JCQ and effort-reward imbalance model in GAZEL. They also highlight the importance of psychosocial work factors in the experience of overall fatigue even after an 8-year follow-up.


Friedreich's ataxia--yesterday, today and tomorrow.
The present review traces the origin of Friedreich's Ataxia (FA) from the time of Nikolaus Friedreich in the mid-nineteenth century. The early hesitation on the part of the neurological community in accepting FA as a distinct entity, rather than a variant form of tabes dorsalis and multiple sclerosis, has been highlighted. Research within the last 6-7 years, has firmly established FA as a trinucleotide repeat disorder, the location of the offending gene, and the disease-related gene product, frataxin. Frataxin is now thought to interfere with the mitochondrial oxidative process and enhance iron accumulation. However, whether this iron accumulation is a primary causative event for symptom production is not clear and iron chelators are unlikely to be helpful in therapy. Of great promise is the use of free radical scavengers and antioxidants. One such agent idebenone, a short chain analogue of co-enzyme Q10, may have a future.


Care pathways for patients with cancer-associated thrombosis: From diagnosis to long-term follow-up.
Venous thromboembolism (VTE) in patients with cancer is associated with a high risk of bleeding complications and hospitalisation, as well as with increased mortality. Good practice recommendations for diagnosis and treatment of VTE in patients with cancer have been developed by a number of professional bodies. Although these guidelines provide consistent recommendations on what treatment should be offered to patients presenting with cancer-associated thromboembolism (CAT), many questions remain unanswered, in particular about the modalities of management (Who? When? Where?) and, for this reason, we have developed a consensus proposal for an appropriate multidisciplinary care pathway for patients with CAT, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. This proposal is centred on the development of a shared care plan individualised to each patient's needs and expectations, patient information and shared decision-making to promote adherence, involvement of all relevant hospital- and community- based healthcare providers in the development and implementation of the care plan, and regular re-evaluation of the treatment strategy.


GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma.
Glioblastoma is the most common malignant tumor in the central nervous system. The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the malignant biological function of glioma remain ambiguous. CCK-8, colony formation assays, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological functions of GTF2E2 both in vitro and in vivo. GTF2E2 was overexpressed in glioma and was associated with poor prognosis of glioma patients. Biological functions of GTF2E2 were investigated both in vitro and in vi0vo by multiple experiments. Moreover, we explored the possible mechanisms of GTF2E2. In our results, we demonstrated that GTF2E2 could be regulated by miR-340-5p directly or indirectly. CCND1 was transcriptionally affected by GTF2E2 and glioma progression was then regulated. Our data presented the overexpression of GTF2E2 in glioma and indicated the association between GTF2E2 and glioma prognosis. GTF2E2 was found to be regulated by miR-340-5p and thus affect downstream gene expressions and glioma progression. Our results indicate that GTF2E2 might be a potential target in the diagnosis and treatments of glioblastoma.


Health, behavior, and health care disparities: disentangling the effects of income and race in the United States.
The literature on health disparities in the United States typically focuses on race/ethnicity or on socioeconomic status (SES) separately, but not often together. The purpose of the study was to assess the separate effects of race/ethnicity and SES on health status, health behaviors, and health care utilization. Cross-sectional analyses were conducted using the 2008 National Health Interview Survey (n = 17,337 non-elderly adults). SES disparities within specific racial groups were examined, as were race disparities within high and low SES groups. Within each racial/ethnic group, a greater proportion of low versus high SES individuals were in poor health, a lower proportion had healthy behaviors, and a lower proportion had access to care. In both SES groups, blacks and Hispanics had poorer health outcomes than whites. While whites were more likely to exercise than blacks and Hispanics, they are more likely to be smokers and less likely to have no or moderate alcohol consumption. Blacks had similar or better health care use than whites, especially for cancer screening; Hispanics had lower use within each SES group. Race/ethnicity disparities among adults of similar incomes, while important, were dwarfed by the disparities identified between high- and low-income populations within each racial/ethnic group.


A unique pharmacogenetic expression of the N-acetylation polymorphism in the inbred hamster.
Liver N-acetyltransferase (NAT) preparations (105,000 x g cytosol) were obtained from both sexes of 26 strains of inbred hamsters. Liver NAT activity levels were determined for six arylamine substrates; isoniazid, p-aminobenzoic acid (PABA), p-aminosalicylic acid (PAS), sulfamethazine (SMZ), procainamide and 2-aminofluorene. The N-acetylation of isoniazid, SMZ, procainamide and 2-aminofluorene exhibited a monomorphic expression in the hamster as the genetic variation in NAT activity levels between hamster strains was only about 2-fold for each substrate. In contrast, the N-acetylation of PABA and PAS showed a polymorphic expression in the hamster. Two inbred hamster lines (Bio 1.5 and Bio 82.73) had over 400-fold lower PABA NAT and over 20-fold lower PAS NAT activity levels than did the other inbred strains. In addition, the genetically determined N-acetylation differences between the rapid and slow acetylator hamster strains were also demonstrated in vivo for PABA but not for SMZ. Comparison of Michaelis-Menten kinetic constants of PABA NAT activity in a rapid and slow acetylator strain showed a 20-fold lower Km in the rapid acetylator strain suggesting an intrinsic structural difference in rapid and slow acetylator hamster liver NAT. Thus, the pharmacogenetic expression of the N-acetylation polymorphism is quite unique in the inbred hamster, in that PABA and PAS are genetically polymorphic substrates, whereas isoniazid, SMZ, procainamide and 2-aminofluorene are monomorphic, in direct contrast to man and rabbit.


Precise Traits from Sloppy Components: Perception and the Origin of Phenotypic Response.
Organisms perceive their environment and respond. The origin of perception-response traits presents a puzzle. Perception provides no value without response. Response requires perception. Recent advances in machine learning may provide a solution. A randomly connected network creates a reservoir of perceptive information about the recent history of environmental states. In each time step, a relatively small number of inputs drives the dynamics of the relatively large network. Over time, the internal network states retain a memory of past inputs. To achieve a functional response to past states or to predict future states, a system must learn only how to match states of the reservoir to the target response. In the same way, a random biochemical or neural network of an organism can provide an initial perceptive basis. With a solution for one side of the two-step perception-response challenge, evolving an adaptive response may not be so difficult. Two broader themes emerge. First, organisms may often achieve precise traits from sloppy components. Second, evolutionary puzzles often follow the same outlines as the challenges of machine learning. In each case, the basic problem is how to learn, either by artificial computational methods or by natural selection.


Novel Bacteriophages Capable of Disrupting Biofilms From Clinical Strains of Aeromonas hydrophila.
The increase in global warming has favored growth of a range of opportunistic environmental bacteria and allowed some of these to become more pathogenic to humans. Aeromonas hydrophila is one such organism. Surviving in moist conditions in temperate climates, these bacteria have been associated with a range of diseases in humans, and in systemic infections can cause mortality in up to 46% of cases. Their capacity to form biofilms, carry antibiotic resistance mechanisms, and survive disinfection, has meant that they are not easily treated with traditional methods. Bacteriophage offer a possible alternative approach for controlling their growth. This study is the first to report the isolation and characterization of bacteriophages lytic against clinical strains of A. hydrophila which carry intrinsic antibiotic resistance genes. Functionally, these novel bacteriophages were shown to be capable of disrupting biofilms caused by clinical isolates of A. hydrophila. The potential exists for these to be tested in clinical and environmental settings.


Trajectories of caregiver burden in families of adult cystic fibrosis patients.
ABSTRACTObjectives:Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.


LAPAROSCOPIC CHOLECYSTECTOMY: OUTCOME OF FIRST 202 CASES IN A DISTRICT HOSPITAL IN GILGIT.
The incidence of gall stone disease is on the rise in Gilgit Baltistan. The objectives of the study were to assess the outcome of laparoscopic cholecystectomy in terms of conversion rate and postoperative morbidity, in The Aga Khan Medical Centre Gilgit. It was descriptive case series. All patients that underwent laparoscopic cholecystectomy between June 2009 to May 2014 were included. The data was collected prospectively. Demographic features, operative time, and hospital stay were studied. Postoperative complications were documented and evaluated according to outcome measures (bile duct injuries, morbidity, mortality, conversion rates, wound infections). A total of 202 consecutive patients were enrolled with a mean age of 49±15 years. There were 164 (81%) female and 38(19%.) male patients. Twenty nine (15%) patients had hypertension, 51 (25%) patients had diabetes mellitus as comorbid conditions. The mean operative time was 54±21 minutes. The operative time was longer in 52 (26%) patients. Three patients (1.5%) required conversion to open cholecystectomy due to obscured anatomy in the area of Calot's triangle, and empyema gallbladder. The mean hospital stay was 2±0.7 days. No common bile duct injury, solid organ or bowel injury occurred in this study. The mean follow up duration was 30±15 months. Postoperative complications include, port site infection in 8 (2%) patient, chest infection in 5 (2.4%) patients, and one (0.5%) patient had myocardial infarction. There was no mortality reported in this group of patients. Laparoscopic cholecystectomy is a safe procedure with advantages of decreased wound infection, less pain, decreased hospital stay, and early recovery.


Unlocking India's Potential in Managing Endocrine-Disrupting Chemicals (EDCs): Importance, Challenges, and Opportunities.
Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.


Conventional Therapy in Adults With X-Linked Hypophosphatemia: Effects on Enthesopathy and Dental Disease.
Treatment of X-linked hypophosphatemia (XLH) with active vitamin D metabolites and phosphate can partially correct skeletal deformities. It is unclear whether therapy influences the occurrence of two major long-term morbidities in XLH: enthesopathy and dental disease. The objective of the study was to investigate the relationship between treatment and enthesopathy and dental disease in adult XLH patients. The study was designed as observational and cross-sectional. The study was conducted at an academic medical center's hospital research unit. Fifty-two XLH patients aged 18 years or older at the time of the study participated in the study. There were no interventions. The number of enthesopathy sites identified by radiographic skeletal survey and dental disease severity (more than five or five or fewer dental abscesses), identified historically, were measured. Associations between proportion of adult life and total life with treatment and number of enthesopathy sites were assessed using multiple linear regression, whereas associations between these exposure variables and dental disease severity were assessed using multiple logistic regression. All models were adjusted for confounding factors. Neither proportion of adult nor total life with treatment was a significant predictor of extent of enthesopathy. In contrast, both of these treatment variables were significant predictors of dental disease severity (multivariate-adjusted global P = .0080 and P = .0010, respectively). Participants treated 0% of adulthood were more likely to have severe dental disease than those treated 100% of adulthood (adjusted odds ratio 25 [95% confidence interval 1.2-520]). As the proportion of adult life with treatment increased, the odds of having severe dental disease decreased (multivariate-adjusted P for trend = .015). Treatment in adulthood may not promote or prevent enthesopathy; however, it may be associated with a lower risk of experiencing severe dental disease.


Overcoming historical and organizational legacies: AHIMA poises to lead.
Considering leadership as both an individual and an aggregate characteristic, the article examines the leadership potential for members of the American Health Information Management Association (AHIMA) and for AHIMA as a professional organization within the field of health information management. AHIMA and its members are uniquely suited for leadership within this occupational field. The long association with paper records and a hospital maintenance function, however, plus the predominance of women within the field result in organizational features and political factors that could block leadership development.


Interventions for preventing oral mucositis for patients with cancer receiving treatment.
Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. Date of most recent searches June 2002. Trials were selected if they met the following criteria: design - random allocation of participants; participants - anyone with cancer receiving chemotherapy or radiotherapy treatment for cancer; interventions - agents prescribed to prevent oral mucositis; outcomes - prevention of mucositis, pain, amount of analgesia, dysphagia, systemic infection, length of hospitalisation, cost and patient quality of life. Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out. The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models. One hundred and nine studies were eligible. Fifty-seven were excluded for various reasons, usually as there was no useable information on mucositis. Of the 52 useable studies all had data for mucositis comprising 3594 randomised patients. Interventions evaluated were: acyclovir, allopurinol mouthrinse, amifostine, antibiotic pastille or paste, benzydamine, camomile, chlorhexidine, clarithromycin, folinic acid, glutamine, GM-CSF, hydrolytic enzymes, ice chips, oral care, pentoxifyline, povidone, prednisone, propantheline, prostaglandin, sucralfate and traumeel. Of the 21 interventions included in trials, nine showed some evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis. Interventions where there was more than one trial and a significant difference compared with a placebo or no treatment were allopurinal with unreliable evidence for a reduction in the severity of mucositis OR = 0.01 (95% CI: 0 to 0.03), amifostine provided minimal benefit in preventing mucositis RR = 0.95 (95% CI: 0.91 to 0.99), antibiotic paste or pastille demonstrated a moderate benefit in preventing mucositis RR = 0.87 (95% CI: 0.79 to 0.97), GM-CSF prevented mucositis RR = 0.51 (95% CI: 0.29 to 0.91), hydrolytic enzymes reduced the severity of mucositis RR = 0.49 (95% CI: 0.30 to 0.81), and ice chips prevented mucositis OR = 0.42 (95% CI: 0.19 to 0.93). Other interventions showing some benefit with only one study were: benzydamine, oral care protocols and povidone. The NNT to prevent one patient experiencing mucositis over a baseline incidence of 60% for amifostine is 33 (95% CI: 20 to 100), antibiotic paste or pastille 13 (95% CI: 8 to 50), GM-CSF 3 (95% CI: 2 to 20) and ice chips 5 (95% CI: 2 to 31). When the baseline incidence is 40%/90% the NNTs for amifostine are 50/20, for antibiotic paste or pastille 20/8, for GM-CSF 5/2 and for ice chips 6/10. The general reporting of RCTs was poor. However, the quality of the randomisation improved when the authors provided additional information. Several of the interventions were found to have some benefit at preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types hat benefits may be specific for certain cancer types and treatment. There is a need for well designed and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.


Transport of macrophage Fc receptors and Fc receptor-bound ligands to lysosomes.
Mouse macrophage Fc receptors specific for IgG1/IgG2b mediate the binding and pinocytic uptake of soluble IgG-containing antibody-antigen complexes. Internalization of these multivalent IgG complexes is accompanied not only by the intracellular degradation of the ligand, but also by a net decrease in the number of plasma membrane Fc receptors and an accelerated rate of receptor turnover. In contrast, internalized receptors bound to a monovalent ligand, the high affinity Fab fragment of the antireceptor mAb 2.4G2, escape degradation by rapidly recycling to the cell surface. In this paper, we have characterized the intracellular pathway involved in the endocytosis and transport of Fc receptors in the J774 macrophage cell line. The results show that the uptake of multivalent ligands follows the normal pathway of receptor-mediated endocytosis: internalization in clathrin-coated pits and coated vesicles, delivery to endosomes, and finally to acid hydrolase-rich lysosomes. Immunoprecipitation of radiolabeled receptor from Percoll density gradients showed that endocytosis of the IgG complexes also results in the concomitant transport of the receptor to lysosomes. Although uptake of the monovalent Fab fragment had no detectable effect on intracellular receptor distribution, preparations of 2.4G2 Fab rendered multivalent by adsorption to colloidal gold were as effective as the IgG complexes at causing lysosomal accumulation of internalized receptors. Thus, it is likely that the down-regulation and degradation of Fc receptors which occurs during the endocytosis of antibody-antigen complexes is due to the transport of internalized receptors to lysosomes. Moreover, the ability of certain Fc receptor-bound ligands to interfere with receptor recycling and trigger lysosomal transport seems to depend on ligand valency rather than on the presence or absence of Fc domains on intact IgG molecules.


[Surgical treatment of unroofed coronary sinus coexisting with paroxysmal atrial fibrillation; diagnosis by multidetector computed tomography; report of a case].
We experienced a rare case of an unroofed coronary sinus without a persistent left superior vena cava. A 55-year-old man, who was diagnosed with cerebral infarction, presented with suspected atrial septal defect (ASD) coexisting with paroxysmal atrial fibrillation. Before the operation, we diagnosed this case as coronary sinus ASD by contrast-enhanced coronary computed tomography (CT). There was a 20 mm segment of abnormal communication between the base of the left atrium and the roof of the coronary sinus. We repaired the defect by simple direct closure from the left atrium side, so that the coronary veins drained into the right atrium. The postoperative course was uneventful. Imaging played a crucial role in the diagnosis. Coronary CT angiography is well suited to help identify asymptomatic congenital heart disease.


Notoacmeibacter marinus gen. nov., sp. nov., isolated from the gut of a limpet and proposal of Notoacmeibacteraceae fam. nov. in the order Rhizobiales of the class Alphaproteobacteria.
A Gram-stain-negative, short rod-shaped and non-flagellated bacterium, named strain XMTR2A4T, was isolated from the gut of a marine limpet, Notoacmea schrenckii on intertidal rocks. Colonies were small, light grey and circular. Catalase- and oxidase-positive. Growth was observed at 15 to 37 °C (optimum 28-30 °C), with salinity range from 0.5 to 9 % (optimum 1-2 %), and at pH 6 to 9 (optimum pH 7). The almost full-length 16S rRNA gene of strain XMTR2A4T had the highest sequence similarity of 93.7 % with Mycoplana ramosa DSM 7292T, and of 93.5 , 93.5 and 93.4 % with Chelativorans intermedius CC-MHSW-5T, Ensifer fredii ATCC 35423T and Phyllobacterium myrsinacearum IAM 13584T, respectively. Phylogenetic analysis showed that strain XMTR2A4T formed a tight cluster with a cultured but uncharacterized strain, YP382-1-A, which was deeply separated from the species within the order Rhizobiales in the class Alphaproteobacteria. The predominant fatty acid of strain XMTR2A4T was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 83.4 %). Ubiquinone-10 (Q-10) was detected as the sole respiratory quinone. The polar lipids were identified as phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, an unidentified phospholipid and three unknown lipids. The genome size was about 3.6 Mbp and the G+C content was 61.5 mol%. Combining the results above, it was ascertained that strain XMTR2A4Trepresents a novel species of a new genus in the order Rhizobiales, for which the name Notoacmeibacter marinus gen. nov., sp. nov. is proposed. The type strain of the type species is XMTR2A4T (=MCCC 1A01882T=KCTC 52427T). A novel family in the order Rhizobiales, named Notoacmeibacteraceae fam. nov., is also proposed to accommodate the new genus.


An Evaluation of Hybrid Deep Learning Models for Classifying Multiple Lower Limb Actions.
Brain-computer Interfaces (BCIs) interpret electroencephalography (EEG) signals and translate them into control commands for operating external devices. The motor imagery (MI) paradigm is popular in this context. Recent research has demonstrated that deep learning models, such as convolutional neural network (CNN) and long short-term memory (LSTM), are successful in a wide range of classification applications. This is because CNN has the property of spatial invariance, and LSTM can capture temporal associations among features. A combination of CNN and LSTM could enhance the classification performance of EEG signals due to the complementation of their strengths. Such a combination has been applied to MI classification based on EEG. However, most studies focused on either the upper limbs or treated both lower limbs as a single class, with only limited research performed on separate lower limbs. We, therefore, explored hybrid models (different combinations of CNN and LSTM) and evaluated them in the case of individual lower limbs. In addition, we classified multiple actions: MI, real movements and movement observations using four typical hybrid models and aimed to identify which model was the most suitable. The comparison results demonstrated that no model was significantly better than the others in terms of classification accuracy, but all of them were better than the chance level. Our study informs the possibility of the use of multiple actions in BCI systems and provides useful information for further research into the classification of separate lower limb actions.


Physiological roles of nicotinamide nucleotide transhydrogenase.
From the foregoing considerations, the energy-linked transhydrogenase reaction emerges as a powerful and flexible element in the network of redox and energy interrelationships that integrate mitochondrial and cytosolic metabolism. Its thermodynamic features make it possible for the reaction to respond readily to challenges, either on the side of NADPH utilization or on the side of energy depletion. Yet, the kinetic features are designed to prevent a wasteful input of energy when other sources of reducing equivalents to NADP are available, or to deplete the redox potential of NADPH in other than emergency conditions. By virtue of these characteristics, the energy-linked transhydrogenase can act as an effective buffer system, guarding against an excessive depletion of NADPH, preventing uncontrolled changes in key metabolites associated with NADP-dependent enzymes and calling on the supply of reducing equivalents from NAD-linked substrates only under conditions of high demand for NADPH. At the same time, it can provide an emergency protection against a depletion of energy, especially in situations of anoxia where a supply of reducing equivalents through NADP-linked substrates can be maintained. The flexibility of this design makes it possible that the functions of the energy-linked transhydrogenase vary from one tissue to another and are readily adjustable to different metabolic conditions.


Moral distress among Norwegian doctors.
Medicine is full of value conflicts. Limited resources and legal regulations may place doctors in difficult ethical dilemmas and cause moral distress. Research on moral distress has so far been mainly studied in nurses. To describe whether Norwegian doctors experience stress related to ethical dilemmas and lack of resources, and to explore whether the doctors feel that they have good strategies for the resolution of ethical dilemmas. Postal survey of a representative sample of 1497 Norwegian doctors in 2004, presenting statements about different ethical dilemmas, values and goals at their workplace. The response rate was 67%. 57% admitted that it is difficult to criticize a colleague for professional misconduct and 51% for ethical misconduct. 51% described sometimes having to act against own conscience as distressing. 66% of the doctors experienced distress related to long waiting lists for treatment and to impaired patient care due to time constraints. 55% reported that time spent on administration and documentation is distressing. Female doctors experienced more stress that their male colleagues. 44% reported that their workplace lacked strategies for dealing with ethical dilemmas. Lack of resources creates moral dilemmas for physicians. Moral distress varies with specialty and gender. Lack of strategies to solve ethical dilemmas and low tolerance for conflict and critique from colleagues may obstruct important and necessary ethical dialogues and lead to suboptimal solutions of difficult ethical problems.


Ministernotomy aortic valve surgery in patients with prior patent mammary artery grafts after coronary artery bypass grafting.
Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts. From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve. The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively. Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients.


Tuberculosis control in an urban Black community.
A tuberculosis case-finding survey of an urban Black community is described. The programme included health education of the community leaders, tuberculin testing of all scholars at the schools, and of the pre-school and non-schoolgoi ng children in their homes. The insignificant reactors to the tuberculin skin test were BCG-vaccinated. Isoniazid prophylactic therapy of the significant reactors was instituted and their contacts were radiologically investigated. The various results are to be found in the tables in the main body of this review.


Electrical properties of developing rat heart. Effects of dexamethasone.
Action potentials recorded from perinatal rat ventricles exhibited a plateau (phase 2), followed by a rapid repolarization characteristics of all mammalian ventricular cells. Within the second postnatal week, a number of distinct changes occurred in the contour of action potentials. An early slow depolarization, at the foot of the action potential, preceded the beginning of phase zero. The early slow depolarization was observed until day 12 and disappeared by day 13. A second slow depolarization occurred during the terminal phase of the rapid upstroke of the action potential, persisted through day 13 and disappeared by day 14. On day 12, what had been a homogeneous contour of action potentials seen during the first week converted into a heterogeneous contour. Occasionally, action potentials similar to those recorded from Purkinje fibres in adult heart were recorded from hearts as young as 12 days. By day 14, signs of a spike (the hallmark of action potentials from adult heart) were apparent in some fibres. Treatment of newborn rats with dexamethasone on the second day after birth prevented the disappearance of the second slow depolarization. In adult and aged rat hearts, dexamethasone treatment induced a slow depolarization and a plateau in the region of overshoot. In view of the time-dependent change of the second slow depolarization it is suggested that this phase of the action potential is influenced by the levels of circulating glucocorticoid in developing heart and by changes in calcium sensitivity observed in this species. Heterogeneity of action potentials observed on day 12 postnatal may precede structural differentiation of myofilaments.


Effects of positive affect and positive emotions on executive functions: a systematic review and meta-analysis.
Positive emotions (PEs) impact cognitive processes, including executive functions (EFs; i.e. inhibition, working memory, cognitive flexibility). However, previous reviews and meta-analyses report contradicting results. Thus, this review takes a novel approach to overcome conflicting findings by clearly conceptualising PE induction and by providing a detailed description of the tasks used to assess EFs, as well as by exclusively focusing on EFs. A systematic literature review and meta-analysis was performed. Study inclusion criteria required that subjects were healthy individuals over 18 years, PEs were induced in a controlled laboratory setting, a baseline measurement and a control condition was required, and finally, EFs were measured as a dependent variable using valid measurement instruments. The literature search was performed on PRIMUS, including relevant databases such as ERIC, MEDLINE, Psych ARTICLES, Psych INFO or SocINDEX. From a total of 6,661 identified articles, only 13, which featured 20 experimental studies, were included. Results show that the overall induction of PEs successfully caused an increase in valence and/or positive emotions. However, no significant effects of PE on EFs were detected (d = -0.051, p = .405). Reasons and future research will be discussed.


Diving bradycardia and breath-holding time in man.
The hypothesis that the diving response, recorded as diving bradycardia during submersed breath holding in man, would enhance his breath-holding time was tested. Five certified scuba divers served as subjects. They performed breath holds of maximal duration while nonimmersed and during submersion in cool (32 degrees C), cold (20 degrees C), and thermoneutral (35 degrees C) water. The mean breath-holding time and heart rate during the nonimmersed (control) condition were, respectively, 111.2 +/- 14.1 (SE) s and 64.1 +/- 4.7 (SE) beats/min, the relatively long breath-holding times being due primarily to the so-called short-term training effect. Compared to the control values the breath-holding time in 20 degrees C water was 54.9% shorter and heart rate 25.9% lower, in 32 degrees C water the breath-holding time was not different and heart rate was 28.1% lower, and in 35 degrees C water the breath-holding time was longer by 25.6% while there was no difference in heart rate. In all conditions the breath-hold breaking point alveolar PCO2 was the same at about 52 mmHg. The shortening of the breath holds in cold water was ascribed to a 256% increase (over nonimmersed control) in metabolic rate as well as a respiratory drive due to stimulation of skin cold receptors. As for the prolongation of breath holds in thermoneutral water, it was hypothesized that immersion caused a delay in the build-up of chemical stimuli at the chemoreceptors.


A dormant internal ribosome entry site controls translation of feline immunodeficiency virus.
The characterization of internal ribosome entry sites (IRESs) in virtually all lentiviruses prompted us to investigate the mechanism used by the feline immunodeficiency virus (FIV) to produce viral proteins. Various in vitro translation assays with mono- and bicistronic constructs revealed that translation of the FIV genomic RNA occurred both by a cap-dependent mechanism and by weak internal entry of the ribosomes. This weak IRES activity was confirmed in feline cells expressing bicistronic RNAs containing the FIV 5' untranslated region (UTR). Surprisingly, infection of feline cells with FIV, but not human immunodeficiency virus type 1, resulted in a great increase in FIV translation. Moreover, a change in the cellular physiological condition provoked by heat stress resulted in the specific stimulation of expression driven by the FIV 5' UTR while cap-dependent initiation was severely repressed. These results reveal the presence of a "dormant" IRES that becomes activated by viral infection and cellular stress.


Methanoculleus sediminis sp. nov., a methanogen from sediments near a submarine mud volcano.
A mesophilic, hydrogenotrophic methanogen, strain S3Fa(T), was isolated from sediments collected by Ocean Researcher I cruise ORI-934 in 2010 near the submarine mud volcano MV4 located at the upper slope of south-west Taiwan. The methanogenic substrates utilized by strain S3Fa(T) were formate and H2/CO2 but not acetate, secondary alcohols, methylamines, methanol or ethanol. Cells of strain S3Fa(T) were non-motile, irregular cocci, 0.5-1.0 μm in diameter. The surface-layer protein showed an Mr of 128,000.The optimum growth conditions were 37 °C, pH 7.1 and 0.17 M NaCl. The DNA G+C content of the genome of strain S3Fa(T) was 62.3 mol%. Phylogenetic analysis revealed that strain S3Fa(T) was most closely related to Methanoculleus marisnigri JR1(T) (99.3% 16S rRNA gene sequence similarity). Genome relatedness between strain S3Fa(T) and Methanoculleus marisnigri JR1(T) was computed using both genome-to-genome distance analysis (GGDA) and average nucleotide identity (ANI) with values of 46.3-55.5% and 93.08%, respectively. Based on morphological, phenotypic, phylogenetic and genomic relatedness data, it is evident that strain S3Fa(T) represents a novel species of the genus Methanoculleus, for which the name Methanoculleus sediminis sp. nov. is proposed. The type strain is S3Fa(T) ( = BCRC AR10044(T) = DSM 29354(T)).


LncRNA PCAT6 Accelerates the Progression and Chemoresistance of Cervical Cancer Through Up-Regulating ZEB1 by Sponging miR-543.
Cervical cancer (CC) is a common cancer with a poor prognosis due to the chemoresistance of CC cells to cisplatin. This study aimed to investigate the biological significance of lncRNA prostate cancer-associated transcript 6 (PCAT6) in the carcinogenesis of CC. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure the abundance of PCAT6, miR-543 and zinc finger E-box binding protein 1 (ZEB1) in CC tissues and cells. The combination between miR-543 and lncRNA PCAT6 or ZEB1 was predicted by Starbase and was verified by dual-luciferase reporter assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay. Cell proliferation and chemoresistance to cisplatin were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis and metastasis were determined by flow cytometry, Western blot and transwell migration and invasion assays. The abundance of ZEB1 protein was measured by Western blot assay. Murine xenograft model was established to confirm the function of lncRNA PCAT6 in vivo. The abundance of lncRNA PCAT6 was enhanced in CC tissues and cells compared with that in corresponding normal tissues and normal cervical epithelial cells Ect1/E6E7. MiR-543 was a target of PCAT6 and was negatively regulated by PCAT6. PCAT6 accelerated the proliferation, metastasis and the chemoresistance of CC cells to cisplatin while suppressed the apoptosis of CC cells. The overexpression of PCAT6 reversed the inhibitory effects of miR-543 accumulation on the proliferation, metastasis and chemoresistance of CC cells to cisplatin and the promoting impact on the apoptosis of CC cells. ZEB1 was a direct target of miR-543, and it functioned as the downstream gene of PCAT6/miR-543 to exert its oncogenic role in CC. PCAT6 promoted the growth of murine xenograft tumor through miR-543/ZEB1 axis in vivo. LncRNA PCAT6 facilitated the proliferation, metastasis and chemoresistance of CC cells to cisplatin while impeded the apoptosis of CC cells via PCAT6/miR-543/ZEB1 axis. PCAT6/miR-543/ZEB1 axis might be a promising target for CC therapy.


Recent introduction and recombination in Colletotrichum acutatum populations associated with citrus postbloom fruit drop epidemics in São Paulo, Brazil.
Citrus crops in São Paulo State, Brazil, have been severely affected by postbloom fruit drop disease (PFD), which is caused by Colletotrichum acutatum. This disease leads to the drop of up to 100% of young fruits. Previous studies have assumed that this pathogen exhibits a clonal reproductive mode, although no population genetic studies have been conducted so far. Thus, the genetic structure of six C. acutatum populations from sweet orange orchards showing PFD symptoms was determined using nine microsatellite markers, enabling inference on predominant mode of reproduction. C. acutatum populations exhibit a nearly panmictic genetic structure and a high degree of admixture, indicating either ongoing contemporary gene flow at a regional scale or a recent introduction from a common source, since this pathogen was introduced in Brazil only very recently. Sharing haplotypes among orchards separated by 400 km suggests the natural dispersal of fungal propagules, with the possible involvement of pollinators. A significant population expansion was detected, which was consistent with an increase in host density associated with crop expansion toward new areas across the state. Findings of moderate to high levels of haplotypic diversity and gametic equilibrium suggest that recombination might play an important role in these pathogen populations, possibly via parasexual reproduction or a cryptic sexual cycle. This study provides additional tools for epidemiological studies of C. acutatum to improve prevention and management strategies for this disease.


An Epstein-Barr virus-infected lymphoblastoid cell line (D430B) that grows in SCID-mice with the morphologic features of a CD30+ anaplastic large cell lymphoma, and is sensitive to anti-CD30 immunotoxins.
In this study we describe a newly established CD30+ Epstein Barr virus (EBV)-infected B cell line derived from an EBV-infected B cell culture (utilized, once irradiated, as a feeder) which showed a B clonal rearrangement and strong CD30 antigen expression. The cells injected into SCID mice were able to grow giving rise to CD30+ solid tumors with the morphologic features of an anaplastic large cell lymphoma (ALCL). Thus we tried to establish a model to investigate the potency of immunoconjugates containing a CD30 monoclonal antibody (Ber-H2) and ribosome-inactivating proteins (saporin, momordin and ricin A-chain) as toxic moieties. We observed a strong cytotoxic activity of the anti-CD30 immunotoxins on the in vitro growth of D430B cells. High levels of anti-tumor activity were also observed in vivo, in the SCID mouse model. The antitumor immunotoxin therapy was sccessful in our chosen animal model, the effecacy seeming to be associated with strength of CD30 expression. Our data suggest that immunotoxins should be tested (before use) on the tumor cells of the subject to be treated and that immunotoxins should be directed to different tumor-associated antigens to avoid selection of cell populations with different antigenic mosaics.


Unraveling the Genetic Architecture of Two Complex, Stomata-Related Drought-Responsive Traits by High-Throughput Physiological Phenotyping and GWAS in Cowpea (Vigna. Unguiculata L. Walp).
Drought is one of the most devasting and frequent abiotic stresses in agriculture. While many morphological, biochemical and physiological indicators are being used to quantify plant drought responses, stomatal control, and hence the transpiration and photosynthesis regulation through it, is of particular importance in marking the plant capacity of balancing stress response and yield. Due to the difficulties in simultaneous, large-scale measurement of stomatal traits such as sensitivity and speed of stomatal closure under progressive soil drought, forward genetic mapping of these important behaviors has long been unavailable. The recent emerging phenomic technologies offer solutions to identify the water relations of whole plant and assay the stomatal regulation in a dynamic process at the population level. Here, we report high-throughput physiological phenotyping of water relations of 106 cowpea accessions under progressive drought stress, which, in combination of genome-wide association study (GWAS), enables genetic mapping of the complex, stomata-related drought responsive traits "critical soil water content" (θcri) and "slope of transpiration rate declining" (KTr). The 106 accessions showed large variations in θcri and KTr, indicating that they had broad spectrum of stomatal control in response to soil water deficit, which may confer them different levels of drought tolerance. Univariate GWAS identified six and fourteen significant SNPs associated with θcri and KTr, respectively. The detected SNPs distributed in nine chromosomes and accounted for 8.7-21% of the phenotypic variation, suggesting that both stomatal sensitivity to soil drought and the speed of stomatal closure to completion were controlled by multiple genes with moderate effects. Multivariate GWAS detected ten more significant SNPs in addition to confirming eight of the twenty SNPs as detected by univariate GWAS. Integrated, a final set of 30 significant SNPs associated with stomatal closure were reported. Taken together, our work, by combining phenomics and genetics, enables forward genetic mapping of the genetic architecture of stomatal traits related to drought tolerance, which not only provides a basis for molecular breeding of drought resistant cultivars of cowpea, but offers a new methodology to explore the genetic determinants of water budgeting in crops under stressful conditions in the phenomics era.


Genome-Wide Identification and Characterization of the Brassinazole-resistant (BZR) Gene Family and Its Expression in the Various Developmental Stage and Stress Conditions in Wheat (Triticum aestivum L.).
Brassinosteroids (BRs) play crucial roles in various biological processes, including plant developmental processes and response to diverse biotic and abiotic stresses. However, no information is currently available about this gene family in wheat (Triticum aestivum L.). In the present investigation, we identified the BZR gene family in wheat to understand the evolution and their role in diverse developmental processes and under different stress conditions. In this study, we performed the genome-wide analysis of the BZR gene family in the bread wheat and identified 20 TaBZR genes through a homology search and further characterized them to understand their structure, function, and distribution across various tissues. Phylogenetic analyses lead to the classification of TaBZR genes into five different groups or subfamilies, providing evidence of evolutionary relationship with Arabidopsis thaliana, Zea mays, Glycine max, and Oryza sativa. A gene exon/intron structure analysis showed a distinct evolutionary path and predicted the possible gene duplication events. Further, the physical and biochemical properties, conserved motifs, chromosomal, subcellular localization, and cis-acting regulatory elements were also examined using various computational approaches. In addition, an analysis of public RNA-seq data also shows that TaBZR genes may be involved in diverse developmental processes and stress tolerance mechanisms. Moreover, qRT-PCR results also showed similar expression with slight variation. Collectively, these results suggest that TaBZR genes might play an important role in plant developmental processes and various stress conditions. Therefore, this work provides valuable information for further elucidate the precise role of BZR family members in wheat.