Intraocular injection of tetrodotoxin in goldfish decreases fast axonal transport of [3H]glucosamine-labeled materials in optic axons.
When physiological activity in goldfish visual system was abolished by repeated intraocular injection of tetrodotoxin (TTX), the fast axonal transport of radioactive amino acid-labeled protein in the optic axons was unaltered. However, the TTX treatment reduced the amount of [3H]glucosamine-labeled glycolipids that were axonally transported to the optic tectum, and may have decreased their rate of turnover in the tectum. A similar though smaller effect was observed for glucosamine-containing glycoproteins. These alterations in axonal transport may be the basis for at least some of the deleterious effects of TTX on axonal regeneration in this system.


Chronic myeloid leukemia with a rare fusion transcript, e19a2 BCR-ABL1: A report of three cases from India.
The μ-bcr breakpoint connects exon 19 of BCR with ABL giving rise to the e19a2 transcript corresponding to the p230 fusion protein (micro-BCR breakpoint) which is rarely seen in chronic myeloid leukemia (CML) patients. Here we report three patients with p230 fusion protein presenting with different clinical presentations and diagnosed as CML-CP. These patients received Imatinib (tyrosine kinase inhibitor-TKI) and are still in remission.


Role of the PI3-kinase/mTor pathway in the regulation of the stearoyl CoA desaturase (SCD1) gene expression by insulin in liver.
The stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids. This enzyme is a critical control point regulating hepatic lipogenesis and lipid oxidation. Therefore SCD1 may be a potential therapeutic target in the treatment of obesity and metabolic syndrome. Regulation of SCD1 expression occurs primarily at the level of transcription. In the present study, we characterized the insulin response elements (IREs) and the insulin signaling pathway mediating the regulation of SCD1 gene transcription in liver. In chicken embryo hepatocytes (CEH) and HepG2 cells, insulin stimulates SCD1 promoter activity by 2.5 folds. This activation is mediated by two different IREs on the chicken promoter, one localized between -1,975 and -1,610 bp and one between -372 and -297 bp. The latter binds both NF-Y and SREBP-1 transcription factors in response to insulin. We also demonstrated that insulin induction of SCD1 gene expression and promoter activity is abolished by pre-incubation of cells with specific inhibitors of both PI3-kinase (LY294002) and mTor (Rapamycin) or by over-expression of a dominant negative mutant of PI3-kinase. The PI3-kinase and mTor pathway mediates the insulin response on both IREs. In summary, insulin activates SCD1 gene expression in liver via a signaling pathway that involves PI3-kinase and mTor and the downstream transcription factors NF-Y and SREBP-1. Sentence summary: Insulin regulates SCD1 gene expression via two different IREs. The most 3' IRE is localized between -372 and -297 bp and binds the NF-Y and SREBP-1 transcription factors in response to insulin. PI3-kinase and mTor mediate the action of insulin on both IREs.


A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals.
Nerve growth factor (NGF) is a neurotrophin that induces neuritogenic and trophic signals by binding to TrkA and/or p75 receptors. We report a comparative study of the binding, internalization, and biological activity of NGF versus that of NGF in association with an anti-NGF monoclonal antibody (mAb NGF30), directed against the C termini of NGF. NGF.mAb complexes do not bind p75 effectively but bind TrkA with high affinity. After binding, NGF. mAb complexes stimulate internalization faster and to a larger degree than NGF. NGF.mAb-induced activation of TrkA, Shc, and MAPK is transient compared with NGF-induced activation; yet NGF and NGF. mAb afford identical trophic responses. In contrast, NGF induces Suc-1-associated neurotrophic activating protein phosphorylation and neuritogenic differentiation, but NGF.mAb does not. Thus, an absolute separation of trophic and neuritogenic function is seen for NGF.mAb, suggesting that biological response modifiers of neurotrophins can afford ligands with selected activities.


Differential diagnosis of dementia: a prospective evaluation of the DAT Inventory.
To compare prospectively the concordance between the diagnosis of dementia based on clinical criteria and using the DAT Inventory. A prospective study of 81 consecutive patients referred to a Memory Clinic. Only patients for whom a definitive diagnosis of dementia was established after 8 to 20 months follow-up were retained in the study (n = 76). The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of the DAT Inventory were calculated. Kappa values were also computed. Based on all patients (n = 76), sensitivity and specificity were 71% and 95%, respectively, with 98% positive prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of 21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi-infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases, were classified as non-DAT on the DAT Inventory. When mixed, very mild, and borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity increased to 94%, and specificity remained unchanged at 95%, with 97% positive and 91% negative prediction, 94% overall accuracy, and kappa of 0.88. In general, scores above the designated cutoff point (> 14/20) on the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA criteria). Concordance is best in cases of mild to moderate dementia (Clinical Dementia Rating 1-2). The Inventory is less discriminating as a differential diagnostic instrument in cases of very mild dementia, atypical presentations of DAT, or in cases of mixed pathology.


Ultrasound-guided endoscopic transgastric drainage of a post-traumatic pancreatic pseudocyst in a child.
Despite of a number of techniques in the armentarium of the paediatric surgeon, the management of pancreatic pseudocysts remains a challenge. We report on a case of a 5-year-old child with a post-traumatic pancreatic pseudocyst who was successfully treated with endoscopic ultrasound-guided transgastric approach. Endoscopic ultrasound-guided transgastric drainage of a pancreatic pseudocyst is effective and safe in children.


Laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl.
We describe the successful laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl. A 47-year-old man with hypertension and diabetes mellitus was found to have an abdominal mass beside the aorta. The tumor was diagnosed as a functional paraganglioma by diagnostic imaging and biochemical tests. We then performed a transperitoneal laparoscopic resection for removal. After freeing the left ureter, resecting the inferior mesenteric artery, and dividing the small blood vessels, the tumor was isolated and found to be preserved in its capsule. It was retrieved in a bag through an enlarged incision. The operation time was 450 min and blood loss was 410 ml. The postoperative course was uneventful and there has been no local recurrence or distant metastasis during the 18-month follow-up period. Laparoscopic resection of functional extraadrenal paragangliomas is technically feasible and safe if adequate pre- and intraoperative medical management and a careful, steady surgical technique are used.


Mutations in TRPV4 cause an inherited arthropathy of hands and feet.
Familial digital arthropathy-brachydactyly (FDAB) is a dominantly inherited condition that is characterized by aggressive osteoarthropathy of the fingers and toes and consequent shortening of the middle and distal phalanges. Here we show in three unrelated families that FDAB is caused by mutations encoding p.Gly270Val, p.Arg271Pro and p.Phe273Leu substitutions in the intracellular ankyrin-repeat domain of the cation channel TRPV4. Functional testing of mutant TRPV4 in HEK-293 cells showed that the mutant proteins have poor cell-surface localization. Calcium influx in response to the synthetic TRPV4 agonists GSK1016790A and 4αPDD was significantly reduced, and mutant channels did not respond to hypotonic stress. Others have shown that gain-of-function TRPV4 mutations cause skeletal dysplasias and peripheral neuropathies. Our data indicate that TRPV4 mutations that reduce channel activity cause a third phenotype, inherited osteoarthropathy, and show the importance of TRPV4 activity in articular cartilage homeostasis. Our data raise the possibility that TRPV4 may also have a role in age- or injury-related osteoarthritis.


Arc in synaptic plasticity: from gene to behavior.
The activity-regulated cytoskeletal (Arc) gene encodes a protein that is critical for memory consolidation. Arc is one of the most tightly regulated molecules known: neuronal activity controls Arc mRNA induction, trafficking and accumulation, and Arc protein production, localization and stability. Arc regulates synaptic strength through multiple mechanisms and is involved in essentially every known form of synaptic plasticity. It also mediates memory formation and is implicated in multiple neurological diseases. In this review, we will discuss how Arc is regulated and used as a tool to study neuronal activity. We will also attempt to clarify how its molecular functions correspond to its requirement in various forms of plasticity, discuss Arc's role in behavior and disease, and highlight critical unresolved questions.


Homocysteine and post-angioplasty restenosis.
To review the effect of moderate hyperhomocysteinemia on restenosis after coronary angioplasty. Hyperhomocysteinemia is associated with arterial neointimal proliferation in subjects with homocystinuria, atherosclerosis and coronary graft disease. In the rat model, it exacerbates neointimal proliferation after carotid injury. In humans, restenosis after coronary angioplasty is inconsistently associated with hyperhomocysteinemia. A large clinical trial has shown that the administration of folic acid lowers homocysteinemia and the risk of restenosis after coronary angioplasty. Hyperhomocysteinemia is probably a weak risk factor for coronary restenosis after angioplasty, although it is still difficult to ascertain whether homocysteine plays a causative role in restenosis. Further studies of restenosis prevention after coronary stenting are necessary before the routine post-angioplasty administration of folic acid can be recommended.


Proteomic analysis of human articular cartilage: identification of differentially expressed proteins in knee osteoarthritis.
The mechanisms underlying the development of age related osteoarthritis (OA) remain unclear. To better understand the pathogenesis of OA and the molecular basis of progressive destruction of articular cartilage in OA, we compared the proteome of OA cartilage with that of normal cartilage. After removal of proteoglycans and collagens, proteins extracted from either normal or OA knee joint cartilage were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins in OA cartilage were chosen to be further identified by linear ion trap-Fourier transform ion cyclotron resonance mass spectrometry (LTQ-FT/MS). A total of 1436+/-49 or 1472+/-7 protein spots were resolved by 2-DE of normal or OA cartilage extractions, respectively. Sixteen spots from OA cartilage samples were found to have statistically significant changes in the amount of protein compared with normal samples. Of 16 spots, the identities of 14 proteins were unambiguously determined by LTQ-FT/MS. These OA associated proteins fell into five groups, including glycolysis and energy production (ADH, ADK, ENOA, KPYM and FR), signaling (ANNX-I, PEBP and TUB), Redox (PRDX3 and SODM), and cartilage matrix (COLL-I and COLL-VI). Interestingly, two novel RING (Really Interesting New Gene) domain-containing proteins, RF, Zn-RF, were identified, suggesting novel pathways of cartilage protein regulation. This study shows that 2-DE followed by LTQ-FT/MS can be successfully used to characterize the proteome of cartilage without in vitro culturing which could obfuscate physiological differences. The definition of unique OA-associated proteins described here provides significant mechanistic insights into OA by corroborating previously suggested mechanisms and by defining unique players with roles yet to be defined in disease pathogenesis.


Association of the G-protein β3 subunit gene polymorphism with the incidence of cardiovascular disease independent of hypertension: the Funagata study.
Association of the C825T G-protein β3 subunit (GNB3) gene polymorphism with cardiovascular disease (CVD) incidence was examined in a population-based longitudinal study of the Japanese individuals. The incidence of CVD (stroke and coronary heart disease (CHD)) was assessed in a cohort population (n=1524) consisting of participants of the 2001-2005 Funagata study through March 2008. Cumulative incidences according to genotype were compared with the Kaplan-Meier product-limit method. During the follow-up, 78 subjects experienced a CVD event (stroke: n=54; CHD: n=30; both consecutively: n=6). At the end of the follow-up (longest and median follow-up periods: 81 and 68 months, respectively), the cumulative incidence of CVD for the TT genotype was significantly higher than that of the C-carriers (0.077 vs 0.042, P=0.004). Blood pressures and the prevalence of hypertension were not different between the genotypes. Cox's proportional hazard analysis showed that the TT genotype is a significant risk factor for CVD (hazard ratio (HR)=1.82 (95% confidence interval (CI) 1.14-2.89); P=0.012) and stroke (HR=1.76 (95% CI: 1.01-3.07); P=0.048) incidences after adjustment for age, sex, hypertension, hyperlipidemia, diabetes, alcohol drinking and smoking at baseline. The TT genotype of the C825T GNB3 gene polymorphism was found to be a significant risk factor for the incidence of CVD and stroke independent of hypertension and other established CVD risk factors in a Japanese population.


[Bacterial flora of the eyelids following preoperative disinfection].
After careful preoperative disinfection of the periorbita, the eye, and the lids, cultures were taken from the upper and lower lash bases of 100 patients waiting for intraocular operations. Despite the careful disinfection 36% of the cultures from the upper and 48% of those from the lower lash bases were positive. A method of covering the lids adequately with adhesive material is recommended as a means of avoiding this potential source of infection.


Occurrence of Cellulose-Producing Gluconacetobacter spp. in Fruit Samples and Kombucha Tea, and Production of the Biopolymer.
Cellulose producing bacteria were isolated from fruit samples and kombucha tea (a fermented beverage) using CuSO4 solution in modified Watanabe and Yamanaka medium to inhibit yeasts and molds. Six bacterial strains showing cellulose production were isolated and identified by 16S rRNA gene sequencing as Gluconacetobacter xylinus strain DFBT, Ga. xylinus strain dfr-1, Gluconobacter oxydans strain dfr-2, G. oxydans strain dfr-3, Acetobacter orientalis strain dfr-4, and Gluconacetobacter intermedius strain dfr-5. All the cellulose-producing bacteria were checked for the cellulose yield. A potent cellulose-producing bacterium, i.e., Ga. xylinus strain DFBT based on yield (cellulose yield 5.6 g/L) was selected for further studies. Cellulose was also produced in non- conventional media such as pineapple juice medium and hydrolysed corn starch medium. A very high yield of 9.1 g/L cellulose was obtained in pineapple juice medium. Fourier transform infrared spectrometer (FT-IR) analysis of the bacterial cellulose showed the characteristic peaks. Soft cellulose with a very high water holding capacity was produced using limited aeration. Scanning electron microscopy (SEM) was used to analyze the surface characteristics of normal bacterial cellulose and soft cellulose. The structural analysis of the polymer was performed using (13)C solid-state nuclear magnetic resonance (NMR). More interfibrillar space was observed in the case of soft cellulose as compared to normal cellulose. This soft cellulose can find potential applications in the food industry as it can be swallowed easily without chewing.


Preclinical validation of a new hybrid molecule loaded in liposomes for melanoma management.
The aggressiveness of melanoma and lack of effective therapies incite the discovery of novel strategies. Recently, a new dual acting hybrid molecule (HM), combining a triazene and a ʟ-tyrosine analogue, was synthesized. HM was designed to specifically be activated by tyrosinase, the enzyme involved in melanin biosynthesis and overexpressed in melanoma. HM displayed remarkable superior antiproliferative activity towards various cancer cell lines compared with temozolomide (TMZ), a triazene drug in clinical use, that acts through DNA alkylation. In B16-F10 cells, HM induced a cell cycle arrest at phase G0/G1 with a 2.8-fold decrease in cell proliferation index. Also, compared to control cells, HM led to a concentration-dependent reduction in tyrosinase activity and increase in caspase 3/7 activity. To maximize the therapeutic performance of HM in vivo, its incorporation in long blood circulating liposomes, containing poly(ethylene glycol) (PEG) at their surface, was performed for passively targeting tumour sites. HM liposomes (LIP HM) exhibited high stability in biological fluids. Preclinical studies demonstrated its safety for systemic administration and in a subcutaneous murine melanoma model, significantly reduced tumour progression. In a metastatic murine melanoma model, a superior antitumour effect was also observed for mice receiving LIP HM, with markedly reduction of lung metastases compared to positive control group (TMZ). Biodistribution studies using 111In-labelled LIP HM demonstrated its ability for passively targeting tumour sites, thus correlating with the high therapeutic effect observed in the two experimental murine melanoma models. Overall, our proposed nanotherapeutic strategy was validated as an effective and safe alternative against melanoma.


Simultaneous bilateral rupture of patellar tendons in diabetic hemodialysis patient: A case report.
Bilateral rupture of the patellar tendon is a very rare injury, which takes place in relation to chronic systemic diseases. These injuries are known causes. Some of these causes are particular in patellar tendon rupture and another are in quadriceps tendon rupture. 70-year-old diabetic man with simultaneous bilateral patellar tendon disruption of proximal insertion without trauma, receiving long-term hemodialysis. In the present study, we report a case of patellar tendon rupture that has two differences with literature: first, renal failure is a known risk factor for quadriceps tendon rupture, and secondly, the prevalent age of patellar tendon rupture is less than 40 years. Clinical picture, diagnosis, pathogenesis and treatment are discussed. Finally, the literature is reviewed based on previous studies.


Rearrangements of Aromatic Nitrile Oxides and Nitrile Ylides: Potential Ring Expansion to Cycloheptatetraene Derivatives Mimicking Arylcarbenes.
Nitrile imines, nitrile oxides and nitrile ylides are widely used in 1,3-dipolar cycloaddition reactions. They also undergo thermal and photochemical rearrangements to carbodiimides, isocyanates, and ketenimines, respectively. Calculations at DFT and CASPT2 levels of theory reveal novel, potential rearrangements, in which the aromatic 1,3-dipoles mimic phenylcarbene and undergo ring expansion to cycloheptatetraene derivatives. These rearrangements can potentially take place in both the singlet ground states and the triplet excited states, and they are accelerated by m,m'-bis(dimethylamino) substitution on the phenyl moieties. The new rearrangement becomes the energetically preferred path for m,m'-bis(dimethylamino)benzonitrile oxide in the triplet state. In the m,m'-bis(dimethylamino)benzo nitrile ylide, the cyclization to the 2-phenyl-1-azirine is favored over the ring expansion to a cycloheptatetraene by ca. 5 kcal mol-1 in the singlet state. In the bent triplet states, 1,3-hydrogen shifts interconverting nitrile ylides are potentially possible.


Ramp descent performance with the C-Leg and interrater reliability of the Hill Assessment Index.
Transfemoral amputees have decreased ability to descend ramps and hills. The Hill Assessment Index quantifies transfemoral amputee ramp performance, but interrater reliability has not been assessed. To determine whether C-Leg use improves hill descent gait and evaluate the Hill Assessment Index's interrater reliability. Twenty-one transfemoral amputees descended a ramp while timed and video recorded, using their nonmicroprocessor prosthetic knee. Subjects were fitted and accommodated with a C-Leg and retested. Test times were compared, and ramp performances were independently reviewed using the Hill Assessment Index by two raters. Hill Assessment Index scores were compared between knee conditions within raters for performance and between raters to assess the Hill Assessment Index's interrater reliability. Mean Hill Assessment Index scores were greater for C-Leg compared to nonmicroprocessor prosthetic knee for both raters. C-Leg resulted in faster ramp descent. Strong correlations resulted between raters on Hill Assessment Index scores for nonmicroprocessor prosthetic knee (intraclass correlation coefficient = 0.97) and C-Leg (intraclass correlation coefficient = 0.99). C-Leg improves Hill Assessment Index ramp descent performance and time. In descent quality, C-Leg offers the possibility of eliminating assistive device use and/or improving step length in the absence of an assistive device. C-Leg resulted in 23% gait speed increase during ramp descent. The Hill Assessment Index had very good interrater reliability but should be assessed for intrarater reliability, minimal detectable change, and validity.


Loss of POC and DOC on seagrass sediments by hydrodynamics.
Coastal development and climate change are sparking growing concern about the vulnerability of the organic carbon (OC) stocks in marine sediments to remineralization, especially in high threaten coastal ecosystems like seagrass meadows. Uncertainties still exist regarding the role played by hydrodynamics, seagrass canopies and sediment properties in OC resuspension and remineralization. A set of laboratory experiments were conducted to assess, for the first time, the mechanisms by which the particulate and dissolved organic carbon (POC and DOC) may be released and remineralized under hydrodynamic conditions (i.e., unidirectional and oscillatory flows) in two eelgrass densities and sediments properties (i.e., grain size and OC content). After a gradually increase in hydrodynamic forces, our results demonstrated that the presence of eelgrass reduced sediment erosion and OC loss in high-density canopies, while low-density canopies promote OC resuspension (on average, 1.8-fold higher than high-density canopies). We also demonstrated that unidirectional and oscillatory flows released similar DOC from surface sediments (on average, 15.5 ± 1.4 and 18.4 ± 1.8 g m-2, respectively), whereas oscillatory flow released significantly more POC than unidirectional flows (from 10.8 ± 1.1 to 32.1 ± 5.6 g m-2 for unidirectional and oscillatory flows, respectively). POC and DOC released was strongly influenced by both seagrass meadow structure (i.e., lower eelgrass density and shoot area) and sediment properties (i.e., lower mud and higher sediment water content). We found that, although >74 % of OC in upper sediments was remineralized within 30 days, a relatively high amount of OC in high-density canopies is recalcitrant, highlighting its potential for the formation of blue carbon deposits. This study highlights the vulnerability of OC deposits in seagrass sediments to resuspension if the meadow is degraded and/or the climate change yield stronger storms, which could potentially weaken the seagrass meadows' service as blue carbon ecosystem in the future.


Molecular analysis of Rickettsia spp. and related tick-borne pathogens detected in dogs in Korea.
Ticks are widespread in nature and serve as primary vectors for several tick-borne pathogens (TBPs). Ticks and TBPs cause considerable harm to humans and animals and have emerged as a major global public health concern. Domestic dogs are the major reservoirs of zoonotic agents owing to their constant interaction with humans. This study aimed to assess the prevalence and risk factors of canine TBPs, such as Rickettsiales, Coxiella burnetii, hepatozoa, and Borrelia spp., using molecular analyses. A total of 906 dogs were examined and 4 TBPs were identified: Anaplasma phagocytophilum (5; 0.6%), Hepatozoon canis (9; 1.0%), Candidatus Rickettsia longicornii (2; 0.2%), and Rickettsia tamurae (1; 0.1%). Ehrlichia spp., C. burnetii, and Borrelia spp. were not detected. To the best of our knowledge, this is the first study to perform a phylogenetic analysis of Candidatus R. longicornii and R. tamurae in dogs. These findings can help determine the potential public health risks by enhancing our understanding of the geographical and vector distributions of TBPs in Korea.


Multi-objective optimization and parametric study of a hybrid waste gasification system integrated with reverse osmosis desalination.
The increasing population has created two fundamental issues on the islands (in this case, Kish Island): an expansion in waste production and handling and a rise in the need for freshwater for daily consumption. Waste gasification can be used to reduce waste and generate energy. Sea salt water can be converted into drinkable freshwater using energy. This article describes a computational code using a combination of EES (Engineering Equation Solver) and MATLAB software for a hybrid cycle that includes waste gasification and reverse osmosis to generate freshwater and power. Kish Island waste data was carefully collected onsite. An exergy evaluation has been conducted to verify the cycle's irreversibility. Lastly, optimization has been performed to identify the best operation mode. In terms of irreversibility, a gasifier is far more irreversible than any other type of plant equipment. Based on the parametric analysis, salt water and waste flow significantly impact freshwater production. Approximately 20,000 m3/day are consumed on Kish Island each day, so if the entire production power of the steam turbine is used in the reverse osmosis high-pressure pump, 2860 m3/day can be obtained each day (14% of the required amount).


In vitro activity of DNA gyrase inhibitors, singly and in combination, against Mycobacterium avium complex.
The in vitro activities of the DNA gyrase inhibitors ciprofloxacin, coumermycin, and novobiocin against 31 clinical isolates of Mycobacterium avium complex were studied using a microdilution technique. Minimal inhibitory concentrations (MICs) were determined in 4 days using Middlebrook 7H9 broth, and minimal bactericidal concentrations (MBCs) were determined by subculturing to Middlebrook 7H10 agar. MICs were: ciprofloxacin, 0.5-greater than 16 (mean, 4.1) micrograms/ml; novobiocin, 4-greater than 128 (mean, 54.7) micrograms/ml; and coumermycin, 2-greater than 16 (mean, 17.5) micrograms/ml. MBCs were usually more than two dilution steps higher than MICs. Checkerboard studies failed to reveal synergistic or antagonistic inhibitory activity of DNA gyrase-A and DNA gyrase-B inhibitors in vitro.


The juxtaphrenic peak (Katten's sign) is produced by rotation of an inferior accessory fissure.
Tenting of the diaphragm (Katten's sign) is a common finding in upper lobe collapse or where there is loss of volume. Twenty-nine patients have been studied, 12 of these prospectively following upper lobectomy. Division of the inferior pulmonary ligament was carried out in these 12 patients. The computed tomography findings confirm that this sign is due to an accessory oblique fissure.


Bioremediation potential of select bacterial species for the neonicotinoid insecticides, thiamethoxam and imidacloprid.
Thiamethoxam (THM) and imidacloprid (IMI), are environmentally persistent neonicotinoid insecticides which have become increasingly favored in the past decade due to their specificity as insect neurotoxicants. However, neonicotinoids have been implicated as a potential contributing factor in Colony Collapse Disorder (CCD) which affects produce production on a global scale. The present study characterizes the bioremediation potential of six bacterial species: Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas aeruginosa, Alcaligenes faecalis, Escherichia coli, and Streptococcus lactis. In Phase I, we evaluated the utilization of IMI or THM as the sole carbon or nitrogen source by P. fluorescens, P. putida, and P. aeruginosa. All three species were better able to utilize THM over IMI as their sole carbon or nitrogen source. Thus, further studies proceeded with THM only. In Phase II, we assessed the kinetics of THM removal from aqueous media by the six species. Significant (p < 0.0001) reductions in 70 mg/L THM concentration were observed for P. fluorescens (67%), P. putida (65%), P. aeruginosa (52%), and A. faecalis (39%) over the 24-day study period, and for E. coli (60%) and S. lactis (12%) over the 14-day study period. The THM removal by all species followed a first-order kinetic reaction. HPLC chromatograms of P. fluorescens, P. putida, and E. coli cultures revealed that as the area of the THM peak decreased over time, the area of an unidentified metabolite peak increased. In Phase III, we examined the effect of temperature on the transformation capacity of the bacterial species which was observed at 2 ℃, 22 ℃, and 30 ℃. Maximal THM removal occurred at 30 °C for all bacterial species assessed. Identification of the metabolite is currently underway. If the metabolite is found to be less hazardous than THM, further testing will follow to evaluate the use of this bioremediation technique in the field.


Xenon enhancement in tumours and infarcts.
Computed topography (CT) before and during xenon enhancement and computer subtraction has been performed in 11 patients with intracerebral tumours and 7 with ischaemic lesions. The amount of xenon uptake was expressed where possible as a percentage of that in the corresponding region of the contralateral apparently normal hemisphere. The amount of xenon uptake did not appear to be specific for any particular tumour histology. The margins of tumours were better defined during enhancement, but not to a degree which affected management; large cysts did not enhance and were well demonstrated. Cavities due to mature infarcts did not enhance and the central parts of most large recent infarcts showed markedly diminished enhancement. In recent infarcts delayed xenon uptake at the periphery and sometimes throughout the lesion reflects diminished perfusion of potentially viable tissue. One patient with an ischaemic parietal lesion in which xenon uptake was normal made a complete clinical recovery.


Human Papillomavirus Antibody Levels Following Vaccination or Natural Infection Among Young Men Who Have Sex With Men.
Australia introduced a school-based gender-neutral human papillomavirus (HPV) vaccination program for girls and boys aged 12-13 years in 2013. We examined HPV type-specific antibody levels in unvaccinated young men who have sex with men (MSM) with natural infection and compared these with levels in those vaccinated against HPV. Serum specimens at baseline were collected from MSM aged 16-20 years in the HYPER1 (Human Papillomavirus in Young People Epidemiological Research) and HYPER2 studies, conducted in 2010-2013 and 2017-2019, respectively. Merck's 4-plex HPV competitive Luminex Immunoassay was used to quantify HPV6-, HPV11-, HPV16-, and HPV18-specific antibodies. We compared antibody levels for each HPV genotype between unvaccinated men (HYPER1) and vaccinated men (HYPER2) using the Mann-Whitney U test. There were 200 unvaccinated men and 127 vaccinated men included in the analysis. Median antibody levels among vaccinated men were significantly higher than levels among unvaccinated men for HPV6 (223 milli-Merck units per milliliter [mMU/mL] vs 48 mMU/mL, P < .0001), HPV11 (163 mMU/mL vs 21 mMU/mL, P < .0001), HPV16 (888 mMU/mL vs 72 mMU/mL, P < .0001), and HPV18 (161 mMU/mL vs 20 mMU/mL, P < .0001). Antibody levels did not change over time for up to 66 months for all 4 genotypes among vaccinated men. Among young MSM vaccinated with the quadrivalent HPV vaccine, antibody levels for HPV6, HPV11, HPV16, and HPV18 were significantly higher than those in unvaccinated MSM following natural infection. Antibody levels following vaccination appeared to remain stable over time. NCT01422356 for HYPER1 and NCT03000933 for HYPER2.


Myelomastocytic leukemia: evidence for the origin of mast cells from the leukemic clone and eradication by allogeneic stem cell transplantation.
Myelomastocytic leukemia is a term used for patients with advanced myeloid neoplasms, in whom elevated numbers of immature atypical mast cells are found, but criteria for a primary mast cell disease are not met. The origin of mast cells in these patients is presently unknown. We have analyzed clonality of mast cells in an 18-year-old patient suffering from acute myeloid leukemia with a complex karyotype including a t(8;21) and mastocytic transformation with a huge increase in immature mast cells and elevated serum tryptase level, but no evidence for a primary mast cell disease/mastocytosis. As assessed by in situ fluorescence hybridization combined with tryptase staining, both the tryptase-negative blast cells and the tryptase-positive mast cells were found to contain the t(8;21)-specific AML1/ETO fusion gene. Myeloablative stem cell transplantation resulted in complete remission with consecutive disappearance of AML1/ETO transcripts, decrease of serum tryptase to normal range, and disappearance of neoplastic mast cells. These data suggest that mast cells directly derive from the leukemic clone in patients with myelomastocytic leukemia.


Increased UV sensitivity of Escherichia coli cells after introduction of foreign photolyase genes.
High-expression plasmids for photolyase (phr) genes from the bacteria Escherichia coli, Anacystis nidulans, Streptomyces griseus and Halobacterium halobium and the yeast Saccharomyces cerevisiae were constructed and introduced into E. coli phr recA cells. As previously reported, al introduced phr genes provided the host cells with photoreactivation-repair activity and the introduced E. coli phr gene rendered the host cells more UV-resistant in the dark. E. coli cells harboring foreign phr genes, however, were found to be more sensitive to UV light in the dark than cells containing the vector plasmid only. These differences in UV sensitivity in the dark disappeared when the host cells had an additional mutation, uvrA, suggesting that the foreign photolyases inhibited the E. coli excision-repair system.


Facing dementia: integrating palliation into all aspects of care.
Dementia is fast becoming a serious public health concern. The lack of understanding of the terminal nature of dementia frequently results in overly aggressive treatment during the end stage of the disease. Nurses need to recognize and encourage a paradigm shift in the way dementia is perceived and treated, including promoting early initiation of palliative care services.


A thermodynamic model of the cooperative interaction between the archaeal transcription factor Ss-LrpB and its tripartite operator DNA.
Ss-LrpB is a transcription factor of the archaeon Sulfolobus solfataricus that belongs to the leucine-responsive regulatory protein family. This protein binds to three distinct binding sites in the control region of its own gene, suggestive of autoregulation. Here, we present a detailed study of the thermodynamic and conformational rules that govern the interaction between Ss-LrpB and its tripartite operator DNA. Lane-per-lane partition analysis of macroscopic binding state populations in electrophoretic mobility shift assays, probing binding to full-length, truncated and mutated forms of the operator, allowed determination of equilibrium association constants and cooperativity parameters. The resulting thermodynamic model demonstrates that the Ss-LrpB-operator regulatory complex is formed with a significant positive cooperativity, which is mostly arising from dimer-dimer interactions between pairs of adjacent binding sites. There is a constraint on the spacing between these binding sites, with a preference for a cis-alignment on the DNA helix and with a 16-bp linker yielding maximal pairwise cooperativity. DNase I footprinting assays demonstrated that the extent of Ss-LrpB-induced DNA deformations depends on linker length. The knowledge of the thermodynamic principles underlying the Ss-LrpB-operator interaction, presented here, will contribute to unraveling of the cis-regulatory code of Ss-LrpB autoregulation.


Does lack of diapause result in less insect seasonality?
Unlike their temperate zone and tropical African relatives, flesh flies from the Neotropics lack the capacity for diapause. Yet, our trapping data reveal marked seasonality in flies from Panama, demonstrating that diapause is not essential for generating their seasonal patterns of abundance.


Canada's health human resource challenges: what is the fate of our healthcare heroes?
Each year, the Canadian health education system graduates thousands of health professionals who have the best intentions of practising to their full scope of knowledge and skills to help improve the patient care experience in this country. However, a recent research study points to the fact that members of the healthcare team may be practising in a challenging environment in which only a limited number of their skills are actually being used. The Michener Institute for Applied Health Sciences believes that these issues, which include increased role specialization, limited scopes of practice, rapidly advancing technology, and challenges transitioning from hospital to community settings, have broader health education and health system implications that need to be addressed by policy makers, educators, and healthcare system leaders in order to enhance health professional education as well as patient care.


Linoleic acid amplifies polychlorinated biphenyl-mediated dysfunction of endothelial cells.
Selected dietary lipids may increase the atherogenicity of environmental chemicals, such as polychlorinated biphenyls (PCBs), by cross-amplifying mechanisms leading to dysfunction of the vascular endothelium. To investigate this hypothesis, cultured endothelial cells were treated with 90 microM linoleic acid (18:2n-6), followed by either one of two PCBs, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) or 2,2'4,4',5,5'-hexachlorobiphenyl (PCB 153). These PCBs were selected for their varying binding activities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 disrupted endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. Prior cellular enrichment with 18:2 before PCB treatment further diminished endothelial barrier function, as compared to cells treated only with the PCB. This phenomenon appears to be mediated by increased oxidative stress, which is supported by enhanced 2,7-dichlorofluorescein fluorescence, activation data of the oxidative stress-sensitive nuclear transcription factor-kappaB (NF-kappaB), as well as an observed decrease in vitamin E content in the culture media. Similar to the endothelial permeability data, pre-enrichment of cells with 18:2 further increased the PCB-mediated induction of cytochrome P450 1A. In contrast to PCB 77, PCB 153 (or 18:2 plus PCB 153) had little or no effect on endothelial barrier function. Our results suggest that certain unsaturated fatty acids can potentiate PCB-mediated endothelial cell dysfunction and that oxidative stress and activation of the cytochrome P450 1A subfamily may be, in part, responsible for these metabolic events. These findings have implications for understanding the involvement of certain environmental contaminants in diseases that involve dysfunction of the vascular endothelium.


Pulmonary veno-occlusive disease after chemotherapy.
A case of pulmonary veno-occlusive disease (PVOD) in a 41-year-old woman who had received chemotherapy (bleomycin, mitomycin-C, and cis-platinum) for metastatic cervical carcinoma is reported. Before her death, pulmonary hypertension and right ventricular heart failure had been attributed to lung toxicity induced by chemotherapy, but the postmortem findings were characteristic of PVOD. The authors support the view that PVOD is a syndrome, not a distinct entity, and present the case as a further example of the many situations in which PVOD can arise. Whether the lesions of the pulmonary veins developed as a result of the chemotherapy or whether the two conditions were associated by chance must remain, for now, a subject of speculation. Pathologists are urged to devote special attention to the examination of the pulmonary vessels in patients who have received chemotherapy.


Erosion of the principal investigator role in a climate of industry dominance.
The academic investigator who was central to the development of anticancer therapeutics during the first several decades of that ushered in oncotherapeutics must now contend with working side-by-side with the pharmaceutical and biotechnology industries who are dominating the scene. However, the relationships between industry and academic investigator are often strained, largely because of their incongruent and competing interests. Although the pharmaceutical and biotechnology industries are now developing some of the most exciting therapeutics to come along in many years, the academic investigator is facing a loss of autonomy and creativity, which may have been responsible for the successful development of many anticancer agents that would have not been developed in the present environment. This commentary discusses the impact of the pharmaceutical and biotechnology industries on the academic investigator, new challenges, and potential threats to optimal therapeutic development.


Oral sucrose and non-nutritive sucking goes some way to reducing pain during retinopathy of prematurity eye examinations.
To evaluate the efficacy of oral sucrose combined with non-nutritive sucking for reducing pain associated with retinopathy of prematurity screening. This was a randomised controlled study of 64 infants undergoing eye examination for retinopathy of prematurity screening. Topical anaesthetic (Proparacaine; Alcaine(®) drop 0.5%: ALCON CANADA Inc., Mississauga, Canada) was applied 30 sec before the eye examination in all infants. The infants in intervention group (Group 1, n = 32) received 0.5 mL/kg of 24% sucrose with a pacifier. The control group (Group 2, n = 32) received 0.5 mL/kg of sterile water with a pacifier. The groups had similar gestational ages (28.5 ± 2.8 weeks), mean birthweight (1304 ± 466 g) or corrected gestational age (35.4 ± 3.7 weeks) at examination. The intervention group had a significantly lower mean Premature Infant Pain Profile score during examination of the first eye, following insertion of the speculum (Group 1:13.7 ± 2.1 vs. Group 2:16.4 ± 1.8, p = 0.001). Although sucrose combined with non-nutritive sucking modestly reduces pain scores during eye examinations, there is need to further studies to explore significant pain relief for infants undergoing retinopathy of prematurity screening.


Novel pharmacotherapies in diabetic retinopathy: Current status and what's in the horizon?
The blood-retinal barrier (BRB) alteration is the hallmark feature of diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a potent vasopermeability factor that has been implicated in the pathogenesis of BRB alteration. Inflammation also plays a crucial role in this process with involvement of several chemokines and cytokines. Multiple anti-VEGF drugs are widely used as in the treatment of diabetic macular edema (DME) as well as proliferative diabetic retinopathy. Several clinical trials have proved the beneficial effects of these drugs in improvement of vision and prevention of vision loss. However, the response to anti-VEGF drugs in DME is not complete in a significant number of patients. The effect seems transient in this latter group, and many patients do not show complete resolution of fluid. Potential novel therapies targeting molecules beyond VEGF are being developed and examined in clinical trials.


Modulation of tubulin synthesis by tri-iodothyronine in the embryonic chick brain.
In organ cultures of embryonic chick brain, tri-iodothyronine is shown to elicit an age-dependent stimulation of the synthesis of tubulin. In cultures of brains from 8-day embryos where the response is maximal, a 70-100% increase in the rate of synthesis of tubulin is elicited by T3 within 2 h. The stimulatory response is dose-dependent, requires transcription, and is temporally coincident with the early phase of the normal ontogenic rise in level of tubulin and of intense neuronal differentiation in the embryonic chick brain. The overall results indicate the involvement of T3 in regulating the biogenesis of tubulin in the developing brain.


Case report: Wide-complex tachycardia one week post-CRT-D implantation in a patient with pre-existing left bundle branch block.
A 37-year-old female with dilated cardiomyopathy, whose baseline ECG showed sinus rhythm with left bundle branch block pattern, received a cardiac resynchronization therapy defibrillator (CRTD). One week post-implantation, she presented to the emergency department with palpitations, diaphoresis and chest discomfort. ECG showed a wide-complex tachycardia (WCT) episode, which spontaneously converted to sinus rhythm, and was later diagnosed as typical slow-fast atrioventricular nodal re-entrant tachycardia. This report outlines the differential diagnoses for WCT and the reasoning behind the eventual diagnosis, taking into consideration the device interrogation findings and results of the electrophysiology study.


Founder genetic variants of ABCC4 and ABCC11 in the Japanese population are not associated with the development of subacute myelo-optico-neuropathy (SMON).
Subacute myelo-optico-neuropathy (SMON) is a severe neurological disorder associated with clioquinol administration, which frequently occurred in Japan during the 1950s and 1960s. The unique genetic background of the Japanese population is considered to be strongly involved in the development of this neurological disease. Recently, genetic variants of ABCC4 (OMIM: 605250) and ABCC11 (OMIM: 607040), which are particularly common in the Japanese population, were suggested as possible genetic susceptibility factors for the development of SMON. We analyzed 125 Japanese SMON patients who provided consent for this study. Patient DNA was collected from peripheral blood, and genetic analysis was performed for ABCC4 rs3765534 (c.2268G>A, p.Glu857Lys) and ABCC11 rs17822931 (c.538G>A, p.Gly180Arg) polymorphisms using the Sanger sequencing method and/or TaqMan PCR method. The frequency distribution of each polymorphism was compared with that in healthy Japanese people recorded in two genomic databases (Human Genomic Variation Database and Integrative Japanese Genome Variation Database), and each genotype was compared with the clinical features of patients. The frequencies of ABCC4 rs3765334 and ABCC11 rs17822931 polymorphisms in SMON patients and healthy Japanese people were not significantly different in the multifaceted analysis. We conclude that the ABCC4 rs3765334 and ABCC11 rs17822931 polymorphisms are not associated with the development of SMON.


Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer.
Krüppel-like factors (KLFs) are key transcriptional regulators of cell differentiation and proliferation. Among the KLF family, the expression of KLF4 (GKLF) and KLF5 (IKLF) is highly restricted in the epithelial cells of several organs such as the gut and skin, and it has been reported that these epithelial-type KLF genes may be involved in colon carcinogenesis. Recently we found that Klf4 and Klf5 genes were significantly expressed in the developmental bladder epithelium of mice as well. Therefore, in this report we studied the involvement of the KLF4 and KLF5 genes in bladder carcinogenesis. First, we analyzed the expression of KLF4 and KLF5 in a variety of human bladder cancer cell lines and surgical specimens by RNA blot and in situ hybridization analyses. Both genes were highly expressed in the normal bladder epithelium, whereas KLF4, but not KLF5, was frequently downregulated in bladder cancer cell lines and cancer tissues. We then transduced the KLF4 and KLF5 genes into the bladder cancer cell lines using adenoviral vectors to examine the biological activities of the genes on those cells. The transduction of KLF4, but not KLF5, suppressed cell growth and induced apoptosis. Our study suggests that inactivation of KLF4 is one of the frequent steps towards bladder carcinogenesis.


Chronic hepatitis ameliorates anaemia in haemodialysis patients.
Study for influence of chronic hepatitis (CH) on anaemia in haemodialysis (HD) patients remains inconclusive. We aim to characterize the red cell status between CH and hepatitis-free groups among the HD population. We retrospectively analysed 80 chronic HD patients from Taipei Medical University Hospital with monthly sampled biochemical study between December 2004 and December 2005. Data classified according to the hepatitis-free, chronic hepatitis B and C groups were expressed as mean +/- standard deviation. Student's t-test and anova were used to determine the mean difference for continuous variables. Age, Kt/V, systolic or diastolic blood pressure, body mass index, total cholesterol and triglyceride were not different between CH and hepatitis-free groups. HD duration (P = 0.0002), aspartate (P < 0.0001), alanine aminotransferase (P < 0.0001), alkaline phosphatase (P = 0.04), haemoglobin (P = 0.0066) and haematocrit (P = 0.002) were significantly more elevated in the CH group demanding less erythropoietin dose than in the hepatitis-free group. Our study demonstrated that lessened anaemia was observed in CH, which demanded less erythropoietin dose.


Modeling of the migration of the European glass eel.
The characteristics of glass eel migration at the mouth of river Bojana have been investigated by seasonal field studies from February to April 1998. Samples were collected by two fyke nets, one on each riverside, for 12 hours each night. A total of about 3,300 individuals were caught. In this work we present the results obtained from three successive migration waves in 1998. The data obtained on the number of eels caught during one migration wave, as a function of time, had two components: a bell-shaped curve, lasting 7-14 days, over which an impulse (sudden burst in the number of caught eels, during 1-2 days) was observed. We propose a mathematical model for total number of captured eels within one migration wave. Impulse components were observed during the first and second migration waves. After their removal, the remaining experimental data of the three migration waves were fitted with normal distribution functions. A decrease in the values of fitting parameters as a function of time (migration wave number) was obtained. Our data indicate multiple causes for the observed migration waves.


Hypothalamic-pituitary-adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology.
Stress and depression have each been associated with relapse risk. In clinical practice, chronic alcohol use is often accompanied by poor emotional and self-regulatory processes. Tonic and phasic changes in stress responsivity impact an individual's relapse risk to alcohol. A further complicating factor is the pervasive coexistence of depressive symptoms in those with Alcohol Use Disorder (AUD), where the contribution of depressive symptomatology to these processes is not well understood. Individuals with AUD (AD) (21 with and 12 without sub-clinical depressive symptoms) and 37 social drinking controls (16 with and 21 without sub-clinical depressive symptoms) as part of a more extensive study (Fox et al., 2019). All participants were exposed to two 5-min personalized guided imagery conditions (stress and neutral) in a randomized and counterbalanced order across consecutive days. Alcohol craving, negative mood, Stroop performance, and plasma measures (cortisol, adrenocorticotrophic hormone, and salivary alpha-amylase) were collected before and after imagery exposure. Elevations in autonomic response (heart rate) to imagery (stress and neutral) were observed as a function of drinking (in both depressed and non-depressed individuals with alcohol use disorder compared with depressed and non-depressed social drinkers). Conversely, suppressed cortisol following stress was observed as a function of depressive symptomatology across both drinking groups. Individuals with comorbid AD and depressive symptoms demonstrated attenuated Adrenocorticotropic Hormone and poor Stroop performance compared with the other groups, indicating an interactive effect between drinking and depression on pituitary and inhibitory systems. Sub-clinical depressive pathophysiology may be distinct from drinking severity and may alter relapse-related stress adaptations during protracted abstinence from alcohol.


The gut microbiome is associated with bone turnover markers in postmenopausal women.
The association of the gut microbiome with bone turnover markers (BTMs) in postmenopausal women is poorly understood. Fecal samples were collected from 97 Chinese postmenopausal women, and the serum CTX and P1NP were determined. Individuals with serum CTX lower or higher than the median value were divided into LCTX and P1NP groups; and individuals with serum P1NP lower or higher than the median value were grouped into LP1NP and HP1NP groups. Microbiota profiles were determined by high-throughput 16S rRNA gene sequencing. In postmenopausal women, only Faecalibacterium showed significant alteration in the HCTX group compared with the LCTX group (P=0.004, q=0.143). Linear discriminant analysis effect size (LEfSe) analysis revealed that Clostridiaceae (P=0.015, LDA=2.89), Faecalibacterium (P=0.017, LDA=4.60), Prevotella (P=0.040, LDA=3.61) and Clostridium (P=0.007, LDA=2.79) were abundant in the LCTX group, and Facklamia (P=0.044, LDA=3.10) was enriched in the HCTX group. Peptostreptococcaceae (P=0.048, LDA=2.83) and the SMB53 (P=0.028, LDA=2.05) genus were enriched in the LPINP group, and Veillonellaceae (P=0.025, LDA=4.43) and the S24_7 (P=0.023, LDA=3.08) family were enriched in the HPINP group. Six taxa correlated with BTMs in all subjects, including Clostridium (Clostridiaceae) that was negatively correlated with serum CTX amounts significantly (r=-0.34, P<0.001). This study identified taxa-specific differences in the intestinal microflora associated with BTMs, notably CTX. These findings may help in uncovering the roles of gut microbiota on bone metabolism.


[Dermal and systemic side effects of fluocortin butylester. Comparative skin tearing experiments with active principles from commercial preparations].
Different concentrations of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester FCB, Vaspit) and of clobetasone-17-butyrate, clobetasole-17-propionate and hydrocortisone-17-butyrate have been administered topically in order to investigate dermal and systemic side effects. It could be shown that FCB exhibits by far the least side effects. A specially devised apparatus covering the site of substance application, guaranteed an exclusive dermal absorption. Side effects, therefore, cannot be ascribed to oral ingestion of the drugs.


Oxidative stress responses of golden and brown noble scallops Chlamys nobilis to acute cold stress.
The noble scallop Chlamys nobilis is an important edible marine bivalve that is widely cultivated in the sea of southern China. Unfortunately, the mass mortality of noble scallops frequently occurs during the winter months. The present study investigated the effects of acute cold stress (8 °C) to the physiological responses of polymorphic noble scallops, by assessing the HSP70 gene expression, total carotenoid content (TCC), total antioxidant capacity (TAC), malondialdehyde (MDA) content, catalase (CAT) activity and superoxide dismutase (SOD) enzymatic activity in different tissues of golden and brown scallops. The results of the present study revealed that MDA, TCC and CAT increased drastically in most tissues in the early stage of acute cold stress (0-3 h), but TCC, SOD and CAT generally showed a downward trend. Within 3-6 h of acute cold stress, MDA content decreased in most tissues and the SOD content increased significantly in most tissues, while TCC and CAT remained at peak. After 6 h of acute cold stress, MDA content continued to increase in most tissues, while TCC, CAT, SOD and TAC decreased or remained at a lower level. For HSP70 expression, up-regulation of the HSP70 gene was observed only in mantle of brown scallops and hemolymph of golden scallops at 3 h and 24 h, respectively. The findings of the present study can better understand the physiological response of noble scallops to acute cold stress.


Demographic, socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt.
Egypt has been plagued by many neglected tropical diseases since Pharaonic time. These diseases are Schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis, leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases. Indeed, theses diseases still persist as public health problem in the country by the influence of demographic, socioeconomic and environmental obstacles. This study seeks for understanding the contribution of each factor in each obstacle in neglected tropical diseases perpetuation which in turn could help the governorate in planning integrated control strategies. It was found that poverty, unregulated urbanization and inadequate sanitation are important socioeconomic factors that have great effect on the transmission dynamics of the diseases. The environmental factors which affect the epidemiology of these diseases in the country are scarcity of water, construction of dams, land reclamation for agriculture beside the climate factors. Unfortunately, the panic increase in the population growth rate minimizes the efforts done by the governorate to elevate the public health services. These conditions also affect the transmission of epidermal parasitic skin diseases including scabies, head lice and hookworm-related cutaneous larva migrans. The control programs and the recommendations to combat the diseases were discussed. The present study showed that the ecological factors affecting each neglected tropical disease in Egypt are somewhat similar which makes it worthy to develop an integrated control approaches aiming at improving the leading factors of neglected tropical diseases circulation in the country.


Persistent vaginal estrus and serum hormones after chlordecone (kepone) treatment of adult female rats.
The effects of chlordecone on vaginal estrus and neuroendocrine responses were examined in adult ovariectomized and intact females. Persistent vaginal estrus was seen in females given 50 mg/kg or more of chlordecone. The development of vaginal estrus was similar to that seen in ovariectomized females after treatment with estrogen. Since chlordecone is known to have estrogen-like effects on the reproductive system, the persistent vaginal estrus probably results from this estrogen-like action and chlordecone's long half-life in the organism. Neuroendocrine effects of chlordecone also resembled, to some degree, estrogen's effects on pituitary secretions. Chlordecone increased serum prolactin and decreased serum luteinizing hormone (LH) in ovariectomized females 30 to 36 hr after a single exposure to 50 mg/kg of the pesticide. Basal LH levels were not altered in intact females, but the proestrous LH surge was suppressed by 36 hr after treatment. Both basal and proestrous levels of prolactin were suppressed. Unlike the effects of estrogen, serum follicle stimulating hormone was not altered by chlordecone. These results indicate an effect on the hypothalamic pituitary axis by chlordecone treatment and offer a possible explanation for the reduced fertility seen in adult females after chlordecone exposure. However, blockage of the proestrous LH surge was not obligatory for the appearance of vaginal estrus. Although chlordecone produced peripheral changes in the vaginal smear pattern as well as neuroendocrine alterations, the peripheral changes were not always indicative of the neuroendocrine events.


Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia.
The identification of immunophenotypic aberrancies through multiparametric flow cytometry makes the differentiation between normal and leukemic cells relatively simple and quick, and is therefore an attractive method for the investigation of minimal residual disease (MRD). In this report, we have analyzed the impact on relapse and relapse-free survival (RFS) of detecting immunophenotypical aberrant cells in acute lymphoblastic leukemia (ALL) patients in cytomorphologic complete remission (CR). Two hundred eleven bone marrow (BM) samples from 53 consecutive ALL (37 precursor B-ALL and 16 T-ALL) patients were analyzed. The only selection criteria were to have at least one aberrant immunophenotypic feature at diagosis and to have achieved cytomorphologic CR after induction therapy. For MRD detection, all follow-up samples were analyzed with triple labelings using a two-step acquisition procedure, in which 106 cells were screened for the possible persistence of residual leukemic cells with the same phenotypic aberrancy as that identified diagnosis. Patients who displayed a gradual increase in MRD levels showed a higher relapse rate (90% v22%; P < .00001) and shorter median RFS (12 months v not reached; P < .0001) than those with stable or decreasing MRD levels. This adverse prognostic influence also was observed when children and adults, as well as B-ALL and T-ALL patients, were analyzed separately. An MRD level > or = or greater than 10(-3) discriminated two risk groups of ALL patients with significantly different relapse rates and RFS at all treatment phases (end of induction, consolidation, maintenance, and out of treatment). Multiparametric flow cytometry of MRD in ALL patients is a valuable tool for relapse prediction and for the identification of a cohort of patients with very poor prognosis.


The validation of synthetic spectra used in the performance evaluation of radionuclide identifiers.
This work has evaluated synthetic gamma-ray spectra created by the RASE sampler using experimental data. The RASE sampler resamples experimental data to create large data libraries which are subsequently available for use in evaluation of radionuclide identification algorithms. A statistical evaluation of the synthetic energy bins has shown the variation to follow a Poisson distribution identical to experimental data. The minimum amount of statistics required in each base spectrum to ensure the subsequent use of the base spectrum in the generation of statistically robust synthetic data was determined. A requirement that the simulated acquisition time of the synthetic spectra was not more than 4% of the acquisition time of the base spectrum was also determined. Further validation of RASE was undertaken using two different radionuclide identification algorithms.


Oxidation of the meso-methylmesoheme regioisomers by heme oxygenase. Electronic control of the reaction regiospecificity.
The oxidation of heme by heme oxygenase (HO-1) results in highly regiospecific extrusion of the alpha-meso-carbon as CO and the formation of biliverdin IXalpha. The first step in the accepted mechanism for this process is alpha-meso-hydroxylation of the heme. To define further the reaction mechanism, the oxidations of the four isomers of meso-methylmesoheme by human truncated HO-1 supported by NADPH-cytochrome P450 reductase, H2O2, or ascorbate have been examined. Surprisingly, the results establish that (a) HO-1 can oxidize an alpha-meso-methyl-substituted heme to biliverdin IXalpha without proceeding via the alpha-meso-hydroxy intermediate; (b) the normal HO-1 alpha-regiospecificity is inverted in favor of the substituted gamma-position by introduction of a gamma-meso methyl group; and (c) the beta- and delta-meso-methylmesohemes are oxidized less regiospecifically to mixtures of methyl-substituted and -unsubstituted mesobiliverdins. The results indicate that electronic rather than steric effects primarily control the regiospecificity of heme cleavage by HO-1.


Evaluation of different factors on metal leaching from nickel tailings using generalized additive model (GAM).
Compared with sulfide tailings, the oxidation and transformation of certain substances in oxidized tailings into more soluble forms may affect the bioaccumulation and biomagnification properties and enhance the risk of toxic effects in the ecosystem. This study aimed to apply the generalized additive model (GAM) to evaluate factors affecting heavy metal leaching from nickel (Ni) tailings. We created an orthogonal experiment table (L18(37)) to evenly distribute the different combinations of factor values. The Ni tailings were immersed in solutions with different combinations of factor values for 16 d, and samples were taken on days 1, 2, 4, 7, 11, and 16 to measure the pH and heavy metal concentration of the leachate. The GAM was used to fit the concentration of heavy metals of the leachate and the initial factors of the leaching solution. The results showed that the pH and Cr concentration of the leachate increased with time and stabilized after 1 d (pH of approximately 7), while the Mn, Ni, and Tl concentrations gradually decreased and stabilized after peaking on the first day. An analysis of the GAM results showed that the Cr concentration was highly sensitive to the solid-liquid ratio (F = 127.8) and tailing particle size (F = 10.7). The Cr concentration of the leachate was significantly higher when exposed to a high solid-liquid ratio or a fine particle size, whereas the Mn, Ni, and Tl concentrations were highly sensitive to the KCl concentration and solid-liquid ratio (F = 77.4, 146.9, and 315.9 respectively). The GAM identified interactions between key factors, which have complex and strong effects on the leaching of tailings and the migration of heavy metals, either promotional or antagonistic. The prediction of the minimum Cr leaching concentration shows that GAM can be used to determine the conditions associated with minimum leaching concentrations of heavy metals and to effectively predict the metal concentrations of leachate. As such, the results of this study can be applied to the management of nickel tailings.


Salt or co-crystal? Determination of protonation state by X-ray photoelectron spectroscopy (XPS).
Combined (15)N ssNMR and X-ray photoelectron spectroscopy (XPS) investigations for theophylline, a theophylline co-crystal, and a theophyllinium salt demonstrate that XPS allows direct observation of the degree of proton transfer, and thus identification of whether a salt or a co-crystal has been formed. The presence of a strongly binding-energy-shifted N 1s XPS peak with protonation indicates a salt (C==NH(+)), while this peak is unmistakably absent in the co-crystal. XPS should be considered as an alternative and complementary technique to single crystal X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy (ssNMR).


Plasma fibrinogen level: an independent risk factor for long-term survival in Chinese patients with peripheral artery disease?
Fibrinogen, an inflammatory marker as well as a fundamental part of the coagulation cascade, is suggested to play a significant role in the pathogenesis of atherosclerosis and complications of atherothrombotic diseases. The aim of this study was to determine if plasma fibrinogen is an independent risk factor for long-term survival in patients with peripheral artery disease (PAD). Altogether, 139 Chinese patients (88 men, 51 women) with PAD were consecutively recruited for the study. Atherothrombotic risk factors and fibrinogen levels were determined at presentation, and all patients were followed up for mortality prospectively. The mean follow-up was 6 years. All variables were first correlated with survival rates using Kaplan-Meier analysis and compared by means of the log-rank test. Significant risk factors were identified, and multivariate Cox regression analysis was used to evaluate the independent contribution of the fibrinogen level to the risk of mortality. During follow-up, 95 patients (68.3%) died. The overall survival rate was 77.7% at 3 years, 56.8% at 5 years, and 31.2% at 10 years (standard errors 0.05, 0.06, and 0.07, respectively). All-cause mortality rate increased with an elevated fibrinogen level. Eighty percent of patients with a fibrinogen level > 3.4 g/L had a survival time of less than 3 years (p = 0.002). This relation was also demonstrated within patients with critical ischemia. The plasma fibrinogen level was thus identified as an independent risk factor for mortality in PAD patients after adjusting for confounding factors.


Sensitive determination of alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) in whole blood and urine using gas chromatography-mass spectrometry.
We devised a sensitive and simple method to determine alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) in whole blood and urine, using gas chromatography-mass spectrometry (GC-MS). AMT and 5MeO-DIPT were extracted using an Extrelut column with an internal standard, bupivacaine, followed by derivatization with acetic anhydride. The derivatized extract was used for GC-MS analysis of EI-SIM mode. The calibration curves of AMT and 5MeO-DIPT were linear in the concentration range from 10 to 750 ng/ml in both blood and urine samples. The method detection limit (MDL) of AMT and 5MeO-DIPT were 1 ng/ml each in whole blood and 5 ng/ml each in urine. This method should be most useful to accurately determine the presence of these drugs in blood and urine in clinical and forensic cases.


Selection of the appropriate avibactam concentration for use with ceftibuten in broth microdilution susceptibility testing.
Ceftibuten is an oral cephalosporin approved by the US Food and Drug Administration in 1995 that is in early clinical development to be combined with an oral prodrug of avibactam. We evaluated the activity of ceftibuten-avibactam against molecularly characterized Enterobacterales that produced clinically relevant β-lactamases and assessed the best avibactam concentration to be combined with ceftibuten for susceptibility testing. Resistance mechanisms were evaluated by whole genome sequencing. MIC values were determined by broth microdilution of ceftibuten, avibactam, and ceftibuten combined with fixed concentrations (2, 4, and 8 mg/L) and ratios (1:1 and 2:1) of avibactam. The organism collection (n = 71) included Enterobacterales producing ESBLs, KPC, metallo-β-lactamases, AmpC, K-1, OXA-48, and SME, as well as isolates with porin alterations. The ceftibuten-avibactam combination that best separated isolates with β-lactamases inhibited by avibactam from isolates with resistance mechanisms that are not affected by avibactam was the combination with avibactam at a fixed concentration of 4 mg/L.


[Transcutaneous electrostimulation--method leading to a permeation system of electroanalgesia in oncological practice].
Analgetic transcutaneous electrostimulation with the newly-designed Soviet-made ELIMAN-101 installation was used for treatment of tumor-induced pain in 84 cases (as a component of general intraoperative anesthesia--in 29, for postoperative pain--54, for analgesia in cases of advanced tumor--in 11 patients). Intraoperative application of the said procedure resulted in a 2.4-fold decrease in phentanyl consumption. In early postoperative period, pain was relieved in 65.6% and alleviated in 34.5% of patients, the latter requiring non-narcotic drugs as an adjunct to electroanalgetic treatment. Transcutaneous electrostimulation offered an adequate means for management of chronic cancer pain. The procedure did not involve resistance development and ensured a nearly 6-fold decrease in opiates consumption.


Characterization of the beta-adrenergic receptors of cultured human epidermal keratinocytes.
The presence of beta-adrenergic receptors has been demonstrated in membrane preparations from passaged human epidermal keratinocytes. The receptors were characterized in terms of density and binding properties. Using the titrated beta-adrenergic antagonists dihydroalprenolol and propranolol, the equilibrium dissociation constant (Kd) was found to be about 1.4 nM for the two antagonists with a receptor density of approximately 280 fmol/mg membrane protein. Stereospecificity of the binding sites was shown by the much lowered affinity to D-isoproterenol as compared to that of L-isoproterenol. By the use of subtype specific antagonists, the receptors were classified as beta 2 adrenoceptors. This finding is supported by the relative order of affinities of the agonists isoproterenol greater than epinephrine greater than norepinephrine. The Kd value for dihydroalprenolol was approximately the same when determined from equilibrium binding studies or from association and dissociation kinetics, suggesting that the ligand binding is a single step bi-molecular reaction.


Scoping review of head and neck neoplasms presenting with obstructive sleep apnoea: the importance of flexible nasendoscopy.
Obstructive sleep apnoea (OSA) can be caused by neoplasms involving the upper aerodigestive tract. Currently, many of these patients have this diagnosis missed, as most adults diagnosed with OSA do not undergo adequate head and neck examination including flexible nasendoscopy. We performed a review of the literature to shed light on this phenomenon and outline the pathologies and issues surrounding this sub-population of patients diagnosed with OSA. A scoping review of the literature was conducted on head and neck neoplasms presenting with OSA. Data were extracted on demographics, clinical presentation, histopathology, treatment and patient outcomes. Sixty-seven articles were included, describing 79 patients. Mean age was 45.8 years, and 77.2% were male. Symptoms of OSA were present for an average of 29.2 months before a diagnosis of causative neoplasm was made. Forty-two different benign and malignant histopathological entities were reported. At diagnosis, the causative pathology of 100% of patients was visible on head and neck examination including flexible nasendoscopy, while only 53.2% were visible on trans-oral examination. One-third of patients had commenced inappropriate treatment for OSA, including three who had undergone sleep surgical procedures. The majority of patients were treated with surgery alone (72.2%). Although rare, neoplasms of the upper aerodigestive tract should be considered as a cause of OSA, especially in patients experiencing other symptoms in addition to the typical symptoms of OSA. They should particularly be considered in patients with comparatively lower body mass index or those with worsening OSA without an apparent cause identified.


Quantitative PCR assay for the simultaneous identification and enumeration of multiple Karenia species.
Quantitative PCR (qPCR) is the method of choice for specific detection and quantification of harmful algal bloom (HAB) species. Development of qPCR assay for simultaneous enumeration of species that frequently co-exist in HABs is required. A high sensitivity TaqMan qPCR assay, using probe and primers, located at ITS1-5.8S-ITS2 rDNA region, detecting, specifically, Karenia selliformis, K. bidigitata, and K. mikimotoi, was designed. ITS1-5.8S-ITS2 rDNA region copy numbers per Karenia cell genome were estimated to 217.697 ± 67.904, allowing cell quantification. An application of the designed methodology in field samples has been conducted, and it showed high sensitivity (detection of around 10-1 cell/100 mg of bivalve mollusk tissue, equivalent to about 20 copies of the target sequence). We suggest that the optimized method could contribute to early detection of three closely related Karenia species in seafood cultivating areas to promote control quality, guarantee a fast and effective intervention, and improve public health prevention.


Purification and characterization of poly(ADP-ribose) synthetase from calf thymus.
Poly(ADP-ribose) synthetase from calf thymus has been purified to apparent homogeneity by a simple and rapid method with a recovery of 10 to 20%. The enzyme activity absolutely requires the presence of DNA. Histone further stimulates the reaction. The Km for NAD and the maximal velocity at 25 degrees C and pH 8.0 in the presence of both compounds are 55 micron and 1,400 nmol/min/mg, respectively. The sedimentation coefficient (s020,w) of the enzyme is 5.80 S. The molecular weight is calculated to be 108,000 by sedimentation equilibrium method using a partial specific volume of 0.736 ml/g. This value is in good agreement with the molecular weight values of 115,000 and 120,000 determined by gel filtration on Sephadex G-200 and gel electrophoresis in the presence of sodium dodecyl sulfate, respectively. The enzyme is colorless and its absorption spectrum shows a maximum at 280 nm. From a CD spectrum, alpha helical content is estimated to be approximately 30%. The enzyme is a basic protein having a pI value of 9.8 and is rich in lysine rather than arginine. Neutral sugar, phospholipid, and DNA are not detected in the final preparation. These data indicate that the purified enzyme is a simple globular protein composed of a single polypeptide having an approximate molecular weight of 110,000.


Eye-tracking to assess anxiety-related attentional biases among a large sample of preadolescent children.
A considerable body of research in adults has demonstrated that anxiety disorders are characterised by attentional biases to threat. Findings in children have been inconsistent. The present study examined anxiety-related attention biases using eye tracking methodology in 463 preadolescents between 10 and 12 years of age, of whom 92 met criteria for a DSM-5 anxiety disorder and 371 did not. Preadolescent's gaze was recorded while they viewed adolescent face pairs depicting angry-neutral and happy-neutral expressions with each face pair presented for 5000 ms. No group differences were observed across any eye tracking indices including probability of first fixation direction, latency to first fixation, first fixation duration and dwell time. The sample overall showed faster initial attention towards threat cues, followed by a later broadening of attention away from threat. There is a need to identify the types of threats and the developmental period during which visual attention patterns of anxious and non-anxious youth diverge to inform more developmentally sensitive treatments.


Facile synthesis of an all-in-one graphene nanosheets@nickel electrode for high-power performance supercapacitor application.
We report a facile and novel approach for the fabrication of all-in-one supercapacitor electrodes by in situ electrochemical exfoliation of flexible graphite paper (FGP) on a nickel collector. The binder-free three dimensional (3D) graphene nanosheets@Ni (GNSs@Ni) supercapacitor electrodes exhibit a high specific capacitance of 196.4 F g-1 and 36.2 mF cm-2, respectively, at a scan rate of 50 mV s-1. Even at the high scan rate of 2500 mV s-1 the specific capacitance of the capacitor still shows a retention of 85.6% (168 F g-1, 31 mF cm-2). Meanwhile, the as-prepared electrode offers excellent cycling performance with 91.5% capacitance retention after 100 000 charging-discharging cycles even at the high current density of 11 A g-1. Such high rate capability, specific capacitance and exceptional cycling ability of the GNSs@Ni electrode are attributed to the all-in-one architecture which provides unique properties including high electrical conductivity, large specific surface area and excellent electrochemical stability. We anticipate that these results will shed light on new strategies to synthesize high-performance hybrid nanoarchitectures electrodes using the prepared graphene nanosheets as the support, which offers great potential in energy storage devices and electrochemical catalysis applications.


Retracted: Big Data Enabled the Development of Public Sports Health Emergency Corpus: Taking MACPHE as an Example.
[This retracts the article DOI: 10.1155/2022/8717072.].


A mediating model of mindfulness, sense of purpose in life and mental health among Chinese graduate students.
The purpose of the present study is to examine the relationship between mindfulness and mental health of graduate students and the mediating effects of sense of purpose in life on mindfulness and mental health. The participants include 419 graduate students from 6 universities in China, and there are 190 males and 229 females. The Hayes Process is adopted to analyze the effects of the sense of purpose in life on mindfulness and mental health of graduate students. The results reveal that mindfulness can effect the mental health of graduate students positively and significantly. The sense of purpose in life is found to mediate the relationship between mindfulness and mental health. In further moderated mediation analyses, the effect of mindfulness on mental health can be adjusted by family economic condition. The type of degree can adjust the effect of mindfulness on sense of purpose, and academic Interest can adjust the mediating effect of sense of purpose. Finally, this study discusses several empirical and methodological implications of the findings.


Toxicity patterns of cytotoxic drugs.
Toxicity is a major concern for anticancer drugs. These compounds present a narrow therapeutic index, with a small difference between the dose required for an antitumor effect and that responsible for unacceptable toxicity. Their recommended doses are determined according to the toxicity endpoint. Moreover, toxicity is observed earlier than the therapeutic effect, so, toxic effects represent a major endpoint for pharmacodynamic studies of cytotoxic drugs. Knowledge of toxicity patterns and main factors of toxicity of anticancer drugs is required before modeling data of these studies. Hematological toxicities represent the main toxicity of the cytotoxic. However, non-hematological toxicities have become more important than hematological toxicities as pharmacodynamic endpoints in some circumstances such as high-dose chemotherapy associated with bone marrow transplantation. This paper will describe the main toxicity of the cytotoxic drugs, and its factors of both inter- and intra-patient variability. The toxicity pattern of topotecan will be examined as an example. Knowledge of the toxicity pattern of a drug constitutes a prerequirement before modeling its pharmacodynamics.


Assessment of recurrence rate and risk factors of relapse in stage in IA vulvar carcinoma.
To evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. Population-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011-2017. A central pathology review was performed on tumors from women with recurrent disease. 62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6). Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. Pathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC. Resection margins <8 mm and tumor size were associated with relapse of the disease.


The projection from striate and extrastriate cortical areas to the superior colliculus in the rat.
Following single injections of horseradish peroxidase (HRP) in the superior colliculus (SC) and [3H]proline in the striate cortex of rats, a close correspondence was observed in the topographical arrangements of extrastriate cortical fields of HRP retrograde label and of isotope anterograde label. These results support the notion that extrastriate cortex is divided into multiple physiologically and anatomically defined areas, and they suggest that these areas project separately to SC.


Where do pharmaceuticals on the market originate? An analysis of the informal drug supply in Cotonou, Benin.
This anthropological study, conducted in Cotonou, Benin between 2005 and 2007, investigates the informal pharmaceuticals market. It was carried out through a long-term participant observation of informal vendors and semi-directive and unstructured interviews. A classification of products sold in the informal market was developed. The fact that a high percentage of them come from Anglophone countries near Benin (Nigeria and Ghana) led to a comparison of the sources of pharmaceutical supply in these three countries as well as their current legislation regarding pharmaceutical distribution. Our study results highlight a new understanding of the phenomenon of the informal market. Nigeria and Ghana rely on a liberal pharmaceutical distribution system with little intervention from public authorities. Conversely, the government maintains considerable influence over pharmaceutical distribution in Benin. Hence, the differences between these three countries in terms of variety of supply sources and flexibility of access to drugs are understood through an investigation of Benin's informal market. Therefore, it appears that beyond issues concerning the quality of the pharmaceuticals, this phenomenon illustrates a kind of liberalization of pharmaceutical distribution and the ensuing public health issues.


Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants.
Pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are associated with an increased lifetime risk of pancreatic ductal adenocarcinoma (PDAC), and more recently have been associated with increased risk of biliary tract cancers (BTC). This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry a BRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed. The BOADICEA algorithm was used to estimate the probability that an untested relative of a known BRCA1/2 PV carrier with PDAC was a carrier. We reviewed 3252 family pedigrees, 1193 contained a proband who underwent testing for BRCA1/2 based on Manchester score ≥ 15. Among 128 BRCA2 PV-positive families, 27 (21%) contained a 1st/2nd/3rd-degree relative with PDAC, while of 116 BRCA1 PV-positive families, 11 (9%) contained a 1st/2nd/3rd-degree relative with PDAC. Within these 38 families, 25 patients with PDAC had ≥ 50% likelihood of being a BRCA1/2 PV carrier. This cohort had a median age at diagnosis of 55 years (range 33-75), with a mean (55 years) lower than 8364 patients with PDAC identified through the National Cancer Registry of Ireland (71 years, p < 0.0001). Six BRCA2 positive (5%) and 2 BRCA1 positive pedigrees (2%) included an individual with BTC; median age at diagnosis was 65 years (range 33-99). PDAC and BTC are prevalent in Irish families harbouring a BRCA2 PV and are associated with early-onset malignancy. This supports current guidelines recommending universal germline testing for PDAC patients.


DC potential and K+ activity in experimental endolymphatic hydrops.
No alteration in K+ activity of endolymph and perilymph was seen during development of endolymphatic hydrops in guinea pigs. The DC-potential was not changed during enlargement of endolymphatic space.


Students achieve comparable performance scores for clinical placements in public and private sectors: a longitudinal observational study.
Does student clinical performance differ according to healthcare sector? Does student clinical performance at Macquarie University differ from other Australian graduate entry-level programs? A longitudinal observational study with comparison to national data. A total of 284 physiotherapy students from Macquarie University. Each student's clinical performance was evaluated by a clinical educator using the Assessment of Physiotherapy Practice (APP) tool at the end of four 5-week clinical placements. Four measures of clinical performance were analysed: Total APP score, Employability Skills, Clinical Skills and a global rating of performance. A between-group difference in the APP results of 5% was nominated a priori as large enough to be considered important. Of the 1,136 placements, 533 (47%) were undertaken in the private sector. Among their four placements, 99% of students had at least one private sector placement and 70% had two or more private sector placements. There were negligible differences between private and public sector placements in Total APP scores (MD 0%, 95% CI -1 to 1), Employability Skills scores (MD 2% higher in the public sector, 95% CI 1 to 3) and Clinical Skills scores (MD 1% higher in the private sector, 95% CI -1 to 3). On the global rating of performance, 88% of placements in each sector were rated as being either good or excellent. Students in the private sector were 9% (95% CI 3 to 14) more likely to be rated as excellent compared with the public sector. There were negligible differences in clinical performance between the Macquarie University and other Australian graduate-entry students. Macquarie University's practice of increasing private sector participation in clinical education had no adverse effects on student clinical performance, and it is likely to be beneficial in better preparing students for work in the private sector.


Biodecolorization of biogas plant effluent derived from anaerobically digested distillery wastewater by naturally selected Pseudomonas putida.
Effluent from biogas plants can contribute to serious environmental issues due to its high organic compound content and its dark color. This study utilizes Pseudomonas putida strains isolated from activated sludge in a wastewater treatment plant to reduce the organic compound content and dark color of biogas plant effluent. The treatment of effluent from the anaerobic digestion of distillery wastewater with P. putida in the best evaluated conditions (sample concentration of 50% v/v, agitation and aeration rates of 250 rpm and 1.0 vvm for 6 days) produced significant decolorization and organic removal efficacies of 34.29 ± 0.87% and 38.94 ± 0.63%, respectively. Bioremediation efficiency was dependent on bacterial growth, and the organic content and dissolved oxygen in the sample during cultivation were key factors in bacterial growth. The naturally selected bacterium could tolerate relatively high levels of organic content and work synergistically with other indigenous microorganisms found in the biogas plant effluent. Therefore, the bioremediation of biogas plant effluent using naturally selected P. putida can feasibly be applied in biogas power plants where sterilization is not necessary.


Measuring working alliance and technical alliance from the perspective of healthcare professionals working with people with mild intellectual disabilities: adaptation, factor structure and reliability.
The establishment of a valuable and meaningful working alliance between people with mild intellectual disabilities (IDs) and healthcare professionals is critically important for improving both the quality of life and impact of therapy for people with mild IDs. Measuring the working alliance as a treatment or support component is therefore of utmost relevance. In light of the increased use of eHealth tools, it is also essential to measure the alliance using these tools, which is referred to as technical alliance. There was a lack of validation of these two measurements for healthcare professionals working with people with mild IDs, which this study sought to address. Both the validated Working Alliance Inventory - Short Form - MID (WAI-SF-MID) and Technical Alliance Inventory - Short Form - MID (TAI-SF-MID) for general patient populations were adapted for healthcare professionals working with people with mild IDs. A two-step approach was conducted to systematically adapt both measurements with an expert group of healthcare professionals. Confirmatory factor analysis was conducted to test a three-factor structure for both the WAI-SF-MID (N = 199) and the TAI-SF-MID (N = 139), and internal consistency was determined for both scales. An acceptable-to-good model fit was found for both the WAI-SF-MID and the TAI-SF-MID; confirmatory factor analysis confirmed a three-factor model for both measurements. Cronbach's alpha and McDonald's omega were excellent for both total scales (≥0.90) and acceptable to good for sub-scales of both versions. Both the WAI-SF-MID and the TAI-SF-MID are promising measurements for determining healthcare professionals' perspective on the (digital) working alliance with people with mild IDs.


Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren's syndrome.
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative costimulatory molecule that displays a wide range of anti-inflammatory properties and is currently approved to treat rheumatoid arthritis as a recombinant fusion protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary Sjögren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS. A recombinant adeno-associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta galactosidase (LacZ) were administered by retrograde cannulation of the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was measured by ELISA and salivary glands were assessed for inflammation and activity. Recombinant CTLA4IgG blocked B7 expression on macrophages in vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and decreased T and B cell infiltration as well as dendritic cells and macrophages in the glands compared with control mice. In addition a decrease in several proinflammatory cytokines and an increase in transforming growth factor beta-1 (TGF-β1) expression were also observed. These data suggest expression of CTLA4IgG in the salivary gland can decrease the inflammation and improve the xerostomia reported in these mice.


High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.
Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.


Fenton-like degradation of Methylene Blue using paper mill sludge-derived magnetically separable heterogeneous catalyst: Characterization and mechanism.
For the paper industry, the disposal and management of the yielded sludge are a considerable challenge. In our work, the paper mill sludge-derived magnetically separable heterogeneous catalyst (PMS-Fe-380) was prepared easily through a facile synthesis method. The morphology and structure of PMS-Fe-380 were fully characterized by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and Brunauer-Emmet-Teller analysis. The catalytic activity of PMS-Fe-380 was evaluated by degradation of Methylene Blue (MB). The reusability and stability of PMS-Fe-380 were evaluated in five repeated runs, which suggested that PMS-Fe-380 manifested excellent stability of catalytic activity. Moreover, leaching tests indicated that the leached iron is negligible (<0.5mg/L). This study provides an alternative environmentally friendly reuse method for paper mill sludge and a novel catalyst PMS-Fe-380 that can be considered as a promising heterogeneous Fenton-like catalyst.