Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial natriuretic peptide binding involves inflammation.
A peripheral 5-HT(2A) receptor-mediated hemodynamic change prompted formation of indole-2,3-dione, an endogenous inhibitor of atrial natriuretic peptide (ANP) receptor binding and G protein-mediated intracellular signaling (IC(50): 0.4 microM). This effect was significantly suppressed by dexamethasone, indomethacin and the 5-HT(2) receptor antagonists, ketanserin or ritanserin. 5-HT(2A) receptor-mediated acute hemodynamic change was not modified significantly by indomethacin, prazosin or propranolol pretreatment. A tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, but not a dopamine beta hydroxylase inhibitor, diethyldithiocarbamate, abolished the 5-HT(2A) receptor-mediated increase in indole-2,3-dione. Exogenous indole-2,3-dione induced a significant increase in plasma catecholamine levels and decrease in urine volume. A 5-HT(2A) receptor-mediated decrease in capillary flow may have caused an inflammatory process and peripheral sympathetic activation via ANP signaling inhibition. 3,4-dihydroxyphenylalanine (DOPA)/dopamine may contribute to the progression of inflammation or the generation of a precursor of indole-2,3-dione. The observation that indole-2,3-dione abolished angiotensin AT(1) receptor-mediated NADPH activation in both human umbilical vein endothelial cells and smooth muscle cells at 20 microM may suggest that sulfhydryl-reactive indole-2,3-dione could influence mitochondrial function and cellular redox states via flavoenzyme inhibition and/or regulation of dehydrogenase-oxidase conversion.


One-pot synthesis of benzolactones and lactams via a cobalt-catalyzed regioselective [2 + 2 + 2] cocyclotrimerization of alkynyl alcohols and amines with propiolates.
An efficient method for the synthesis of benzolactones and benzolactams via a cobalt-catalyzed [2 + 2 + 2] cocyclotrimerization of alkynyl alcohols and alkynyl amines with propiolates is described.


Overt expression of AP-1 reduces alpha myosin heavy chain expression and contributes to heart failure from chronic volume overload.
Reduced expression of alpha-MHC plays a significant role in cardiac contractile dysfunction from hemodynamic overload. Previously, Pur proteins and YY1 have been shown to play a role in alpha-MHC repression during heart failure induced by pressure overload and by spontaneous hypertension, respectively. This was not observed in volume-overload-induced heart failure, suggesting additional regulatory mechanisms for alpha-MHC repression. The present study was performed to identify volume overload responsive transcription factors involved in alpha-MHC gene regulation. DNA binding activity of several transcription factors was evaluated in a functionally characterized rat model of heart failure induced by aorto-caval shunt. After 10 weeks of shunt, severe LV dilatation and reduced LV function were accompanied by increased expression of ANF and beta-MHC, and decreased expression of alpha-MHC. This was associated with dramatic (10-fold) activation of AP-1 together with increased expression of c-fos and c-jun. AP-1 activation was not observed following 4 weeks of shunt when cardiac function was preserved. In cultured cardiomyocytes, induction of AP-1 by PMA attenuated alpha-MHC mRNA by 60%. Transient transfection assays mapped PMA responsive sequence to -582 to -588 bp of alpha-MHC promoter. Deletion or mutation of these nucleotides had minimal effect on basal promoter activity but played a dominant role in PMA-mediated repression of alpha-MHC promoter activity. Over-expression of c-fos and c-jun in cardiomyocytes inhibited alpha-MHC promoter activity in a concentration dependent manner. Data suggest a repressive role of AP-1 in alpha-MHC expression and its possible involvement in the transition from compensatory hypertrophy to heart failure in chronic volume overload.


Validation of a Rapid Microbiological Method for the Detection and Quantification of the Burkholderia cepacia Complex in an Antacid Oral Suspension.
Despite the broad adoption of Soleris® technology in the food industry as semiquantitative method, it is almost completely unexplored in the pharmaceutical industry as a quantitative method for quantification of Burkholderia cepacia complex (Bcc). The efficacy of an automated growth-based system for a quantitative determination of the Bcc in an antacid oral suspension was studied. The main purpose of this validation study was to prove that the alternative method's entire performance is not inferior to the conventional method for a quantitative determination of Bcc. The antacid oral suspension's preservatives were neutralized, leading to the Burkholderia complex's recovery by means of the alternative method and the reference method. A calibration curve was generated for each strain by plotting DTs relative to the corresponding log CFU values. An equivalence of results was done through the construction of calibration curves that allowed the establishment of numerically equivalent results between the enumeration data from the reference method and the alternative method. Thus following the guidelines of USP, essential validation parameters were shown, such as equivalence of results (CC >0.95), linearity (R2 >0.9025), accuracy (% recovery >70%), operating range, precision and ruggedness (DS <5 and CV <35%), specificity (inclusivity and exclusivity), limit of detection (LOD), and limit of quantification (LOQ). It was shown that all the test results obtained from the alternative method were in statistical agreement with the standard method. Thus this new technology was found to meet all the validation criteria needed to be considered as an alternative method for the quantification of the Burkholderia complex in the antacid oral suspension tested. As outlined in USP chapter <1223> and demonstrated in this research the implementation of alternative methods can offer benefits in execution and automation while improving accuracy, sensitivity, and precision and can reduce the microbiological process time compared to the traditional ones.


External mass transfer analysis for simultaneous removal of carbohydrate and protein by immobilized activated sludge culture in a packed bed batch bioreactor.
External mass transfer effects were analyzed for removal of carbohydrate and protein by immobilized activated sludge culture in a packed bed bioreactor. The bioreactor was made from 52 cm glass tubing with 5.0 cm inner diameter (with a total volume of 1020 cm(3)). The microbial culture was immobilized on microporus polyurethane cut into cubic pieces of approximately 1.5 cm in length. The effect of flow rate on mass transfer and removal of carbohydrate and protein were analyzed theoretically and compared with experimental data. The rate constants were estimated using external film diffusion models at different flow rates (900, 1200, 1800 cm(3)h(-1)). Based on the experimental data, correlations between the Colburn factor (J(D)) and Reynolds number (Re) as J(D)=5.7 × Re(-0.90) and J(D)=5.7 × Re(-0.18) were found to be adequate to predict the removal of carbohydrate and protein, respectively.


Square cervical laminoplasty incorporating spinous process: surgical technique.
We have used a laminoplasty technique in multilevel cervical canal stenosis that incorporates spinous process in the neural arch and does not require free graft or foreign material. In this technique, laminae and spinous processes were used to enlarge stenotic cervical spinal canal. Three patients (mean age 34.6 years) formed the study group with a mean follow-up period of 24.6 months. Postoperative computed tomography (CT) and lateral radiographs were used to assess results in terms of bony union, canal diameter, and alignment of cervical spine. All patients noted some improvement in both sensory and motor functions. The average increase in sagittal diameter of cervical spinal canal was 4.2 mm, and decrease in range of motion (ROM) was 13.2 degrees. Bony fusions at the gutters were seen after 6 months. This new technique of cervical laminoplasty is safe, effective, relatively easy, and avoids complications related to free grafts or metallic or nonmetallic foreign materials used in other techniques


Recurrent intragenic exon rearrangements of SOBP and AUTS2 in non-Hodgkin B-cell lymphoma.
Expression of intragenic exon rearrangements (IERs) has reportedly been detected in both normal and cancer cells. However, there have been few reports of occurrence of these rearrangements specific to neoplasms including malignant lymphoma. In this study, we detected IERs of ten genes (NBPF8, SOBP, AUTS2, RAB21, SPATA13, ABCC4, WDR7, PHLPP1, NFATC1 and MAGED1) in non-Hodgkin B cell lymphoma (B-NHL) cell line KPUM-UH1 using a high-resolution single nucleotide polymorphism array and reverse transcription polymerase chain reaction using reversely directed divergent primers within exons involved in genomic intragenic gains followed by sequencing analysis. Among them, the IERs involved in SOBP (6q21) exon 2 and 3 and AUTS2 (7q11.22) exon 2-4 were the molecular lesions specific to tumors and were frequently detected in B-NHL samples. These IERs constitute novel genetic alterations of B-NHL, which might be associated with tumorigenesis and be useful as genetic biological markers.


ARHGAP44 expression is associated with the metastasis of osteosarcoma and is a promising prognostic biomarker.
Osteosarcoma (OS) is the most domain primary malignant bone tumor. Treatment resistances and metastases result in a decreasing 5-year overall survival rate of OS. However, Rho GTPase-activating protein 44 (ARHGAP44) has not been well studied in OS. The OS patient data were obtained from Therapeutically Applicable Research to Generate Effective Treatments and Gene Expression Omnibus databases. We utilized Survival and Survminer package for survival analysis based on Kaplan-Meier method. The association between ARHGAP44 expression with the prognosis of OS was determined by Wilcoxon rank-sum test and multivariate Cox regression analysis. The real-time polymerase chain reaction and western blotting were conducted to validate the results. Gene set enrichment analysis was done to find significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The OS sample ARHGAP44 expression level was significantly higher than that in normal samples, which was validated in cell lines. High ARHGAP44 expression was associated with metastasis of OS. The OS patients with high ARHGAP44 expression had worse prognosis compared with low ARHGAP44 expression OS patients. In total, 10 KEGG pathways significantly activated in high ARHGAP44 expression OS patients, such as Hedgehog signaling pathway, Steroid biosynthesis, and so on. In summary, high ARHGAP44 expression was closely correlated with the metastasis and poor prognosis of OS. ARHGAP44 was a potential prognostic biomarker for OS.


Small bowel adenocarcinoma in Crohn's disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes.
Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn's disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31-2.33) per 1000 CD patients. Only 11% (CI: 0.04-0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18-0.41), and 33% (CI: 0.26-0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.


Synthesis and antimicrobial activity of some imidazo-[1,2-a]pyridine-2- carboxylic acid arylidenehydrazide derivatives.
Imidazo[1,2-a]pyridine-2-carboxylic acid, ethyl esters were reacted with hydrazine hydrate to furnish imidazo[1,2-a]pyridine-2-carboxylic acid hydrazide. The hydrazides formed were treated with various aldehydes to obtain 28 imidazo[1,2-a]pyridine-2-carboxylic acid arylidenehydrazides. Antimicrobial activity of the compounds were examined.


Traditional Medicare Episode-Related Spending on Postacute Care for Dual-Eligible and Medicare-Only Beneficiaries, 2009-2017.
Dual-eligible beneficiaries with Medicare and Medicaid coverage generally have greater utilization and spending levels than Medicare-only beneficiaries on postacute services, raising questions about how strategies to curb postacute spending will affect dual-eligible beneficiaries. We compared trends in postacute spending and use related to inpatient episodes at a population and episode level for dual-eligible and Medicare-only beneficiaries over the years 2009-2017. Although dual-eligible beneficiaries had consistently higher inpatient and postacute service use and spending than Medicare-only populations, both populations experienced similar declines in inpatient and postacute measures over time. Conditional on having an inpatient stay, most types of postacute service use increased regardless of dual-eligible status. These consistent patterns in episode-related postacute spending for Medicare-only and dual-eligible beneficiaries-decreased episode-related spending and use on a per beneficiary basis and increased use and spending on a per episode basis-suggest that changing patterns of care affect both populations.


Effect of exercise, DDAVP, and epinephrine on the factor VIII:C/von Willebrand factor complex in normal dogs and von Willebrand factor deficient Doberman pinscher dogs.
Endothelial cells in biopsied blood vessels from von Willebrand factor (vWf)-deficient Doberman pinscher dogs contain immunologically detectable vWf. These dogs and normal dogs were treated with DDAVP (0.6 microgram/kg) and epinephrine (0.5 microgram/kg/min for 30 minutes) and were exercised, using 5 different exercise protocols, (3-4 m/s for 5-40 minutes at 0-5% grade) to determine if treatments reported to increase plasma factor VIII:C/vWf complex in humans would elevate canine plasma vWf. Following the two most strenuous exercise conditions--30 and 40 minutes--plasma von Willebrand factor antigen (vWf:Ag) increased in normal dogs by 30% and 70%, respectively. Factor VIII:C was increased 47% by the most strenuous exercise conditions. The vWf-deficient dogs would not exercise beyond 30 minutes and neither vWf:Ag nor factor VIII:C activity increased. Following DDAVP, plasma vWf:Ag increased in the normal dogs by 47% and factor VIII:C activity was increased by 48%. Factor VIII:C activity increased by 30% in the vWf-deficient dogs, but there was only a slight change in vWf:Ag. Bleeding time decreased in 5 of 6 vWf-deficient dogs. In the normal dogs vWf:Ag increased by 14% after epinephrine infusion, but factor VIII:C activity did not change; neither parameter was altered in the vWf-deficient dogs. While the factor VIII:C/vWf:Ag complex was increased in the normal dog by exercise and DDAVP, the increase is not as pronounced as has been reported for humans. It is not known whether the poor response of the vWf-deficient dog is due to low levels of vWf in their endothelium or to a release defect.


ICPMS analysis of proteins separated by Native-PAGE: Evaluation of metaloprotein profiles in human synovial fluid with acute and chronic arthritis.
The role of trace elements bound to proteins in the etiology and pathogenesis of rheumatoid arthritis (RA) remains unclear. In this sense, the identification and detection of metalloproteins has a strong and growing interest. Metalloprotein studies are currently carried out by polyacrylamide gel electrophoresis (PAGE) associated to inductively coupled plasma mass spectrometry (ICPMS), and despite that complete information can be obtained for metals such as Fe, Cu and Zn, difficulties due to poor sensitivity for other trace elements such as Sn, As, etc, are currently faced. In the present work, a simple and fast method for the determination of trace metals bound to synovial fluid (SF) proteins was optimized. Proteins from SF (long and short-term RA) were separated in ten fractions by native PAGE, then dissolved in nitric acid and peroxide hydrogen, and analyzed by ICPMS. Fifteen metals were determined in each separated protein fraction (band). Adequate calibration of proteins molecular weight allowed stablishing which protein type were bound to different metals.


Kinetic subpopulations detected by single-molecule spectroscopy: fundamental property of functional nucleic acids or experimental artefact?
Single-molecule spectroscopy allows the direct observation of conformational dynamics in individual biomolecules. Here, we describe how single-molecule Förster resonance energy transfer (smFRET) reveals heterogeneous kinetics in the EBS1*/IBS1* interaction, two RNA sequences that play an important role in group II intron mediated self-cleavage. Further examples of dynamic heterogeneity in functional nucleic acids are provided and the possible origins of this phenomenon are discussed.


In vitro susceptibility of Mycobacterium tuberculosis clinical isolates to garenoxacin and DA-7867.
The in vitro activities of DA-7867, a novel oxazolidinone, and garenoxacin (BMS-284756) were compared to those of linezolid in 67 susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis. DA-7867 was the most active drug with an MIC(90) of 0.125 microg/ml, compared to the MIC(90)s of 4 microg/ml of garenoxacin and 2 microg/ml of linezolid.


Sky-Blue Organic Light Emitting Diode with 37% External Quantum Efficiency Using Thermally Activated Delayed Fluorescence from Spiroacridine-Triazine Hybrid.
Extremely efficient sky-blue organic electroluminescence with external quantum efficiency of ≈37% is achieved in a conventional planar device structure, using a highly efficient thermally activated delayed fluorescence emitter based on the spiroacridine-triazine hybrid and simultaneously possessing nearly unitary (100%) photoluminescence quantum yield, excellent thermal stability, and strongly horizontally oriented emitting dipoles (with a horizontal dipole ratio of 83%).


Three year results of photoastigmatic refractive keratectomy for mild and atypical keratoconus.
To evaluate the long-term effect of photoastigmatic refractive keratectomy (PARK) on mild keratoconus. Laser Unit, Ein Tal Eye Center, Tel Aviv, Israel. Eight eyes of 6 patients with stable compound myopic astigmatism and topography features of keratoconus were treated with a VISX Twenty-Twenty excimer laser. The laser beam slit width ranged between 4.8 and 5.0 mm according to the degree of cylinder. Preoperative slitlamp examination did not reveal significant thinning, ectasia, or scarring. Astigmatism ranged between -2.00 and -7.50 diopters and follow-up, between 36 and 48 months. In 7 of 8 eyes, uncorrected visual acuity (UCVA) before PARK ranged between 6/30 and finger counting. After PARK, it ranged between 6/9(-) and 6/15, and patients could manage in most of their daily activities without using spectacles. In 2 eyes, the final UCVA was 6/15(-) and 6/15. In 1 eye, treatment failed to improve UCVA and corneal topography revealed progression of the keratoconus. Photoastigmatic keratectomy was partially effective in eyes with mild stable keratoconus. However, the long-term results may be altered by progression of corneal thinning and ecstatic disease. In addition to the mild nature of the keratoconus, this is a small series and further studies are needed to confirm these results.


A text-mining tool generated title-abstract screening workload savings: performance evaluation versus single-human screening.
Text-mining tool, Abstrackr, may potentially reduce the workload burden of title and abstract screening (Stage 1), using screening prioritization and truncation. This study aimed to evaluate the performance of Abstrackr's text-mining functions ('Abstrackr-assisted screening'; screening undertaken by a single-human screener and Abstrackr) vs. Single-human screening. A systematic review of treatments for relapsed/refractory diffuse large B cell lymphoma (n = 7,723) was used. Citations, uploaded to Abstrackr, were screened by a human screener until a pre-specified maximum prediction score of 0.39540 was reached. Abstrackr's predictions were compared with the judgments of a second, human screener (who screened all citations in Covidence). The performance metrics were sensitivity, specificity, precision, false negative rate, proportion of relevant citations missed, workload savings, and time savings. Abstrackr reduced Stage 1 workload by 67% (5.4 days), when compared with Single-human screening. Sensitivity was high (91%). The false negative rate at Stage 1 was 9%; however, none of those citations were included following full-text screening. The high proportion of false positives (n = 2,001) resulted in low specificity (72%) and precision (15.5%). Abstrackr-assisted screening provided Stage 1 workload savings that did not come at the expense of omitting relevant citations. However, Abstrackr overestimated citation relevance, which may have negative workload implications at full-text screening.


Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.
Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.


Excimer laser programming of refractive astigmatism vs. anterior corneal astigmatism in the case of ocular residual astigmatism (ORA).
To determine whether manifest refractive astigmatism (RA) or anterior corneal astigmatism (CA) is the best value for excimer laser programming in cases of ocular residual astigmatism (ORA). Patients who had undergone LASIK surgery with a disagreement between manifest refractive and corneal cylinder (ocular residual astigmatism ORA)>0.75 D were included retrospectively in this study. We calculated target induced astigmatism vector (TIA), surgically induced astigmatism vector (SIA), difference vector between the astigmatism correction programmed in the excimer laser and refractive astigmatism (DVRA), difference vector between the astigmatism correction programmed in the excimer laser and corneal astigmatism (DVCA) and difference vector between TIA and SIA (DV), by the Alpins method. Vectorial differences between DV and DVRA, and between DV and DVCA, were then calculated to determine whether RA or CA was closest to the ideal cylinder for laser programming. Of a total of 104 eyes undergoing LASIK, 22 eyes of 12 patients (21.1%) had an ORA>0.75 D and were included. Mean ORA was 0.9±0.2 D and mean postoperative subjective cylinder was 0.45 D. The DV-DVRA difference vector was 0.57±0.2 D, and the DV-DVCA difference vector was 0.86±0.4 D (P=0.02). RA was closer than CA to the ideal astigmatism correction. In cases of discrepancy between manifest astigmatism and corneal astigmatism, correction of manifest refractive astigmatism seems to give a better refractive result.


Side effects of opioids during short-term administration: effect of age, gender, and race.
Little is known about risk factors that increase the risk of development of opioid side effects. Our objective was to evaluate the effect of the type of opioid, age, gender, and race on the incidence of side effects from short-term opioid use. A secondary analysis of a retrospective cohort study in 35 community-based and tertiary hospitals was done. There were 8855 black or white subjects aged 16 years and older. Patients received meperidine (INN, pethidine), morphine, or fentanyl as part of their treatment. Measurements were made to assess the presence of nausea and vomiting and respiratory depression. Of the patients, 26% had nausea and vomiting and 1.5% had respiratory depression after opioid administration. After adjustment for opioid dose, route of administration, age, gender, and race, meperidine produced less nausea and vomiting (odds ratio [OR] = 0.7; 95% confidence interval [CI], 0.5-0.8) and less respiratory depression (OR = 0.6; 95% CI, 0.2-0.9) than morphine. The risk of respiratory depression increased with age. Compared with patients aged between 16 and 45 years, those aged between 61 and 70 years had 2.8 times the risk of development of respiratory depression (95% CI, 1.2-6.6); those aged between 71 and 80 years had 5.4 times the risk (95% CI, 2.4-11.8); and those aged older than 80 years had 8.7 times the risk (95% CI, 3.8-20.0). Men had less nausea and vomiting than women (OR = 0.5; 95% CI, 0.4-0.6). White subjects had more nausea and vomiting than black subjects (OR = 1.4; 95% CI, 1.1-1.7). Meperidine produced fewer side effects than morphine during short-term use. The risk of respiratory depression increases substantially after 60 years of age. Women have nausea and vomiting more often than men. The effect of race deserves further investigation.


First isolation of a calicivirus from the Steller sea lion (Eumetopias jubatus).
A calicivirus was isolated from the rectum of a Steller sea lion (Eumetopias jubatus) pup on Rogue Reef, off the southern Oregon coast. Based on the results of neutralization tests with specific typing antisera, the isolate was identified as San Miguel sea lion virus serotype 6 (SMSV-6). Blood obtained from nine of 37 pups (24%) during virus sample collection procedures had specific neutralizing antibodies to SMSV-6. The isolation of SMSV-6 from a Steller sea lion represents, to our knowledge, the first isolation of any virus from this widely distributed marine mammal species, and serves to reconfirm the host-nonspecificity of yet another calicivirus of marine origin.


Gardner's syndrome: a case report and review of the literature.
Gardner's syndrome is an autosomal dominant disease characterized by the presence of colonic polyposis, osteomas and a multitude of soft tissue tumors. The syndrome may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 11-year-old female patient with Gardner's syndrome who presented with a lumbar area desmoid tumor and treated with resection of the desmoid, restorative proctocolectomy and ileal pouch anal anastomosis, A review of the current literature has been performed.


Wilms' tumour with persistent intravascular extension: a review of the surgical aspects of management.
To review the surgical management of Wilms' tumour with persistent intravascular (vena caval +/- atrial) tumour extension. Data were collected regarding operative details, tumour and 'thrombus' histology, and long-term outcome for patients with Wilms' tumour with cavo-artial extension. From 1988 to 2004, 13 patients underwent treatment for Wilms' tumour with persistent intravascular extension. Preoperative chemotherapy was administered in 11/13 patients and postoperative radiotherapy in eight patients. Intravascular involvement was upto IVC (5), and right atrium (8) patients. Techniques employed for excision of intra-vascular component were: local cavotomy (3), extensive infra-diaphragmatic cavotomy without cardiopulmonary bypass (CPB) (1), and excision of cavo-atrial tumour with CPB (+/- hypothermia and cardiac arrest) (9). Mean time on CPB was 90 min. Caval repair was accomplished by primary repair (6) and pericardial graft in (7) patients. There were no intraoperative deaths and few major complications. Tumour thrombus contained malignant cells in 10/13 cases. Mean follow up has been for 55.4 months. To date, seven patients remain disease-free (one lost to follow up), disease recurred in five patients, three of whom have died. There were no symptoms related to the graft. Surgery for Wilms' tumour with persistent intravascular extension despite chemotherapy is technically challenging. CPB +/- hypothermia and cardiac arrest and extensive caval repair with a graft is safe and reliable in the long term.


Analogs of Eu3+ DOTAM-Gly-Phe-OH and Tm3+ DOTAM-Gly-Lys-OH: synthesis and magnetic properties of potential PARACEST MRI contrast agents.
Chelated lanthanide ions, especially gadolinium, have found wide use as contrast agents in magnetic resonance imaging. A new paradigm for generating contrast, termed PARACEST, was recently described that requires the slow exchange of water or other exchangeable protons present in the ligand framework. In previous work, we have described a synthetic method for the preparation of dipeptide conjugates of DOTAM for use as PARACEST agents. Two compounds possessed interesting magnetic properties: the Eu(3+) complex of DOTAM-Gly-Phe-OH and the Tm(3+) complex of DOTAM-Gly-Lys-OH. To understand the relationship between the structure of these complexes and their magnetic properties, we have expanded our synthetic methodology and prepared several new complexes. Ligands have been prepared in which the terminal phenylalanine moieties have been replaced with tryptophan or tyrosine, the distance to the amino acid residue possessing an alpha-substituent has been changed, or phenylalanine and lysine have been combined in the peptide sequence. The preparation of lanthanide(III) complexes of these ligands has been achieved and their PARACEST properties have been determined.


Musculoskeletal Problems Among Greek Perioperative Nurses in Regional Hospitals in Southern Peloponnese : Musculoskeletal Problems in Perioperative Nurses.
The surgery unit is a particularly labor-intensive environment in the hospital. Studies reflect the correlation of labor risk factors for musculoskeletal injuries among nurses but few have investigated the relationship to perioperative nurses. The purpose of this study is the identification and definition of ergonomic risk factors in the operating room and their connection with musculoskeletal disorders in perioperative nurses in regional hospitals in Greece. Forty four Greek perioperative nurses working in regional hospitals in southern Peloponnese participated. Anonymous self-administered questionnaire was used to collect the data, which consisted of three parts (investigating musculoskeletal symptoms, description of work, psychometric evaluation). The analysis was done with the statistical program SPSS.19. Symptoms of musculoskeletal problems emerged. Specifically, 54.4% in the lumbar, 47.7% in the neck, 45.5% in the shoulder, followed by smaller percentages of the hip, knee, elbow and ankle. 6.8% of participants indicated no musculoskeletal symptoms in the last year while 74.9% of those who had symptoms presented them in two or more areas. Activities rated as a major problem among others were the manual handling, tools with weight and vibration etc. 100% of respondents agreed that the work in the surgery unit is demanding and has anxiety. The lack of support from the government (81.8%), combined with the low perioperative nurses (6.8%) having the opportunity to participate in administrative decisions concerning them were related to problems in the organization and management of work. Apart from engineers target factors, a main aim should be the organization of work within the framework of a national policy based on European directives on the protection and promotion of the health and safety of workers.


Identification of dihydroetorphine in biological fluids by gas chromatography-mass spectrometry.
A method for the monitoring of dihydroetorphine hydrochloride, a powerful anaesthetic and analgesic drug, in biological fluids was developed, involving GC-MS with multiple selected-ion monitoring. Dihydroetorphine was extracted from human blood and urine with dichloromethane and then derivatized with N-heptafluorobutyrylimidazole after having been concentrated to dryness. A dihydroetorphine monoheptafluorobutyl derivative was formed, which showed good behaviour in GC-MS with electron impact ionization. Its molecular ion, m/z 609, and its main fragments, m/z 576, 534, 522 and 508, were selected as the ions for identification owing to their relative peak intensities and characteristics. The target drug was identified based on its retention time, its selected multiple ions and their relative intensities. This method was successfully used for the detection of dihydroetorphine in blood and urine from a dihydroetorphine addict and a poisoned patient, respectively.


Monitoring and analysis of surface deformation in alpine valley areas based on multidimensional InSAR technology.
Joshimath has received much attention for its massive ground subsidence at the beginning of the year. Rapid urbanization and its unique geographical location may have been one of the factors contributing to the occurrence of this geological disaster. In high mountain valley areas, the complex occurrence mechanism and diverse disaster patterns of geological hazards highlight the inadequacy of manual monitoring. To address this problem, the inversion of deformation of the Joshimath surface in multiple directions can be achieved by multidimensional InSAR techniques. Therefore, in this paper, the multidimensional SBAS-InSAR technique was used to process the lift-track Sentinel-1 data from 2020 to 2023 to obtain the two-dimensional vertical and horizontal deformation rates and time series characteristics of the Joshimath ground surface. To discover the causes of deformation and its correlation with anthropogenic activities and natural disasters by analyzing the spatial and temporal evolution of surface deformation. The results show that the area with the largest cumulative deformation is located in the northeastern part of the town, with a maximum cumulative subsidence of 271.2 mm and a cumulative horizontal movement of 336.5 mm. The spatial distribution of surface deformation is based on the lower part of the hill and develops towards the upper part of the hill, showing a trend of expansion from the bottom to the top. The temporal evolution is divided into two phases: gentle to rapid, and it is tentatively concluded that the decisive factor that caused the significant change in the rate of surface deformation and the early onset of the geological subsidence hazard was triggered by the 4.7 magnitude earthquake that struck near the town on 11 September 2021.


An oncofetal 60-kilodalton protein in the plasma of tumor-bearing and carcinogen-treated rats.
A Mr 60,000 protein, detected by its ability to induce the release of RNA from isolated nuclei, is present in the plasma of tumor-bearing and carcinogen-treated rats, together with low amounts of 2 messenger RNA transport proteins identified earlier in normal cells. The Mr 60,000 protein has been identified in tumor cell cytoplasm and in amniotic fluid, but does not appear to cross the placental barrier. Significant amounts of the Mr 60,000 oncofetal protein appear in the plasma of carcinogen-treated rats within a few weeks of treatment. It may be the fetal form of the adult messenger RNA transport proteins.


Kinetic Analysis of the Hydrolysis of Pentose-1-phosphates through Apparent Nucleoside Phosphorolysis Equilibrium Shifts*.
Herein, we report an addition to the toolbox for the monitoring and quantification of the hydrolytic decay of pentose-1-phosphates, which are known to be elusive and difficult to quantify. This communication describes how apparent equilibrium shifts of a nucleoside phosphorolysis reaction can be employed to calculate hydrolytic loss of pentose-1-phosphates based on the measurement of post-hydrolysis equilibrium concentrations of a nucleoside and a nucleobase. To demonstrate this approach, we assessed the stability of the relatively stable ribose-1-phosphate at 98 °C and found half-lives of 1.8-11.7 h depending on the medium pH. This approach can be extended to other sugar phosphates and related reaction systems to quantify the stability of UV-inactive and hard-to-detect reaction products and intermediates.


Cytoskeletal organelles and myelin structure of beaded nerve fibers.
Freshly removed cat peripheral nerves and lumbar spinal cord roots were prepared by freeze-substitution to study the form changes, cytoskeletal alterations and myelin structure in beaded nerve fibers. Fibers of unstretched nerves so prepared were close to cylindrical. When lightly stretched with tensions of 2-10 g before being rapidly frozen, beading appeared as a series of constrictions between the more normally expanded regions of the internodes with the paranodal regions spared. Beading also was seen in the fibers of sciatic and radial nerves fast-frozen in situ with the limbs placed in full extension to cause stretching. The cross-sectional area of the axon in the constrictions of beaded fibers was reduced by as much as 95%. The compaction of the microtubules and neurofilaments in the constructions was accounted for by the movement of axoplasmic fluid from the constrictions axially into the nearby regions where the axon and fiber diameters are close to normal. The electron-lucid area approximately 5 nm thick around the microtubules appeared to hinder their close approach in the constrictions although some microtubules touch. The neurofilaments are generally separated at a mean distance of 8-10 nm and approach to a mean distance of 4 nm in the constrictions. Neither the beading nor the reversal of beading, which occurs on relaxation from stretch, was blocked by periods of anoxia lasting several hours. Deletion of calcium from the incubating medium initiated some small amount of beading and additionally greatly augmented the beading on stretch. Beading also was present in some of the myelinated fibers of the dorsal columns of the spinal cord where stretch would not be present. These findings suggest that beading is due to a contractile process in the axon initiated by stretch and by other changed states of the fiber. Concomitantly with the contraction of the axon in the beading constrictions, the myelin sheath in that region was greatly reduced in circumference, to as much as 1/3 to 1/5 of normal. The decrease of the sheath diameter was not accompanied by a change in its thickness or in its lamellar fine structure. A repeat distance of the dense lines of 14 nm was measured in both the constricted and nonconstricted regions. To account for these findings lipid, and most likely other components of the myelin lamellar membranes, must move longitudinally from the constrictions in the plane of the lamellar membranes, and do this within 5-10 s.(ABSTRACT TRUNCATED AT 400 WORDS)


Comparison of calcium scores from thick- and thin image slice-computed tomography scanning in predicting future coronary events.
Computed tomographic image slices between 2.5 and 3.0 mm are commonly used for coronary calcium scanning. To evaluate the comparative accuracy of thicker image slices (5 to 6 mm) for predicting coronary events, we acquired both types of scans in 280 research participants and clinically followed them up for 7 years. We found that thick-slice image scanning and image assessment ranked calcium scores similarly and that measurements from both scanning methods predicted coronary heart disease events equally.


Chronic hypoxia alters cardiac mitochondrial complex protein expression and activity in fetal guinea pigs in a sex-selective manner.
We hypothesize that intrauterine hypoxia (HPX) alters the mitochondrial phenotype in fetal hearts contributing to developmental programming. Pregnant guinea pigs were exposed to normoxia (NMX) or hypoxia (HPX, 10.5% O2), starting at early [25 days (25d), 39d duration] or late gestation (50d, 14d duration). Near-term (64d) male and female fetuses were delivered by hysterotomy from anesthetized sows, and body/organ weights were measured. Left ventricles of fetal hearts were excised and frozen for measurement of expression of complex (I-V) subunits, fusion (Mfn2/OPA1) and fission (DRP1/Fis1) proteins, and enzymatic rates of I and IV from isolated mitochondrial proteins. Chronic HPX decreased fetal body weight and increased relative placenta weight regardless of timing. Early-onset HPX increased I, III, and V subunit levels, increased complex I but decreased IV activities in males but not females (all P < 0.05). Late-onset HPX decreased (P < 0.05) I, III, and V levels in both sexes but increased I and decreased IV activities in males only. Both HPX conditions decreased cardiac mitochondrial DNA content in males only. Neither early- nor late-onset HPX had any effect on Mfn2 levels but increased OPA1 in both sexes. Both HPX treatments increased DRP1/Fis1 levels in males. In females, early-onset HPX increased DRP1 with no effect on Fis1, whereas late-onset HPX increased Fis1 with no effect on DRP1. We conclude that both early- and late-onset HPX disrupts the expression/activities of select complexes that could reduce respiratory efficiency and shifts dynamics toward fission in fetal hearts. Thus, intrauterine HPX disrupts the mitochondrial phenotype predominantly in male fetal hearts, potentially altering cardiac metabolism and predisposing the offspring to heart dysfunction.


Overview of the relationship between use of progestogen-only contraceptives and bone mineral density.
To summarise the available epidemiological evidence regarding the relationship between the use of progestogen-only contraceptives and bone mineral density. Overview of the published epidemiological literature. Overall, 17 studies of the use of progestogen-only contraceptives and bone mineral density were identified, involving 1529 women exposed to progestogen-only contraceptives and 2086 controls. Sixty-eight percent of the data relate to the effects of use of depot medroxyprogesterone acetate. Average bone mineral density was reduced in current users of depot medroxyprogesterone acetate compared with non-users, although density in users was within one standard deviation of the mean in non-users. There was significant heterogeneity between the results of different studies (P < 0.0001). The reduction in bone mineral density appeared to be greater at the lumbar spine, femoral neck and ultradistal forearm than at the midshaft of the ulna. Studies involving women with a longer average duration of use of depot medroxyprogesterone acetate displayed greater reductions in bone mineral density compared with studies of women with shorter durations of use. Based on limited data, no difference in bone mineral density was observed between former and never users of depot medroxyprogesterone acetate. Results regarding the effect of levonorgestrel implants were conflicting. Studies of progestogen-only oral contraceptives and the progesterone vaginal ring were small and restricted to lactating women. Women currently using depot medroxyprogesterone acetate have a lower average bone mineral density than non-users. The magnitude of this effect is uncertain but appears to be greater with longer durations of use.


Pediatric Nurse Performance on a Medication Dosage Calculation Assessment Tool.
Nurses who care for children must be competent to perform medication dosage calculations because most pediatric doses are weight based and obtained from adult formulations. The purpose of the study was to describe and compare nurse performance on a medication dosage calculation assessment tool, considering work unit, years experience, and certification status. A secondary analysis of data from 851 Registered Nurses (RN) was completed. Multiple regression was used to model the effect of work unit, certification, and experience on score. The mean assessment tool score was 92.4 (47-100). The work unit and the interaction between certification status and experience were significant in relation to score on the calculation assessment.


SsrA (tmRNA) acts as an antisense RNA to regulate Staphylococcus aureus pigment synthesis by base pairing with crtMN mRNA.
SsrA RNA (small stable RNA A), also known as tmRNA and 10Sa RNA, functions both as tRNA and mRNA through its unique structure. The carotenoid pigment is the eponymous feature of human pathogen Staphylococcus aureus. Here, we found that the pigment of the mutant strain with ssrA deletion was increased. Furthermore, it was demonstrated that ssrA could act as an antisense RNA aside from its well-known biological function, and crtMN, encoding two essential enzymes for the pigment synthesis, was identified as target of ssrA. Further investigation showed ssrA could specifically base pair with the RBS (ribosomal binding site) region of the crtMN mRNA. Our results revealed a new mechanism by which ssrA regulated the biosynthesis of pigment in S. aureus.


Since surgery isn't getting any easier, why is reimbursement going down? An update from the SGO taskforce on coding and reimbursement.
In 2015, there was an 18% reduction in the Relative Value Units (RVUs) that the Center for Medicare and Medicaid Services (CMS) assigned to the Current Procedural Terminology (CPT) code 58571 (Laparoscopy, surgical, with total hysterectomy, for uterus 250g or less; with removal of tube(s) and/or ovary(s)→TLH+BSO). The other CPT codes for laparoscopic hysterectomy and laparoscopic supracervical hysterectomy (58541-58544 and 58570-58573) lost between 12 and 23% of their assigned RVUs. In 2016, the laparoscopic lymph node dissection codes 38570 (Laparoscopy, surgical; with retroperitoneal lymph node sampling (biopsy), single or multiple), 38571 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy), and 38572 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy and para-aortic lymph node sampling (biopsy), single or multiple) lost between 5.5 and 16.3% of their RVU's. The goals of this article from the Society of Gynecologic Oncology (SGO) Task force on Coding and Reimbursement are 1) to inform the SGO members on why CMS identified these codes as a part of their misvalued services screening program and then finalized a reduction in their payment levels; and 2) outline the role individual providers have in CMS' methodology used to determine the reimbursement of a surgical procedure.


A randomized, open-label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft-tissue sarcoma.
Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.


Neonatal development of intestinal neuroimmune interactions.
Interactions between the enteric nervous system (ENS), immune system, and gut microbiota regulate intestinal homeostasis in adults, but their development and role(s) in early life are relatively underexplored. In early life, these interactions are dynamic, because the mucosal immune system, microbiota, and the ENS are developing and influencing each other. Moreover, disrupting gut microbiota and gut immune system development, and potentially ENS development, by early-life antibiotic exposure increases the risk of diseases affecting the gut. Here, we review the development of the ENS and immune/epithelial cells, and identify potential critical periods for their interactions and development. We also highlight knowledge gaps that, when addressed, may help promote intestinal homeostasis, including in the settings of early-life antibiotic exposure.


Mass and mechanical sensitivity of otoliths.
It has been suggested that the changes of otolith mass during the otolith development in altered gravity conditions as well as the growth of otoliths in fishes in normal conditions are determined by the feedback between the otolith dynamics and the processes that regulate otolith growth. This hypothesis originates from the pendulum model of an otolith (de Vries, 1950), in which otolith mass is a parameters. The validity of this hypothesis is tested by comparing the pendulum model with a simplified spatially distributed model of an otolith. It was shown that when the otolith plate (otoconial layer) was spatially distributed and fixed to the macular surface, the mechanical sensitivity of the otolith does not depend on the total otolith mass and its longitudinal dimensions. It is determined by otolith thickness, Young's modulus, and the viscosity of the gel layer of the growing otolith. These parameters may change in order to secure otolith sensitivity under altered dynamic conditions (e.g., in microgravity). Possible hypotheses regarding the relationship between the otolith growth, otolith dynamics and animal growth are proposed and discussed here.


A Low-Cost Miniature Histotripsy Transducer for Precision Tissue Ablation.
A miniature, 10 mm aperture histotripsy transducer with an f-number of 0.7 was fabricated using an elliptically shaped aluminum lens, which was epoxy-bonded to an air-backed 5.0 MHz, PTZ-5A, 1-3 dice-and-fill piezoelectric composite, and the lens coupled to water using a quarter-wavelength matching layer of Parylene-C. A Krimholtz-Leedom-Matthaei model of the device and curved lens was developed. The epoxy layer resulted in an increased power output at 6.8 MHz compared to the 5 MHz composite design. Cavitation was observed in water by driving the composite with a 173 V single-cycle, unipolar 6.8 MHz pulse at a pulse repetition frequency of 50 Hz, and a bubble cloud 264 long by 124 wide was measured. A coregistered imaging and ablation device was also fabricated and characterized. The coregistered device was modified to include a mm square hole through the center, allowing access for a high-frequency imaging array, and both imaging and ablation are demonstrated in cerebral tissue with this device. Radial -3 dB beam widths were measured as 0.145 and 0.116 mm, and axial -3 dB depths of field were 0.698 and 0.752 mm for the noncoregistered and coregistered transducers, respectively. Total material cost for the transducer and pulser board is below $200 USD.


Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67.
The proliferative activity of 133 human tumors of the nervous system was investigated by means of immunohistochemistry using the monoclonal antibody Ki-67 in order to evaluate the usefulness of this method for histopathological tumor grading. Ki-67 recognizes a proliferation-associated nuclear antigen present in human cells during all active phases of the cell cycle but absent in the G0 phase [Gerdes J, Schwab U, Lemke H, Stein H (1983) Int J Cancer 31:13-20]. In 28 WHO grade I and II gliomas of all major types Ki-67 indices were generally low with mean values ranging from less than 1% in pilocytic astrocytomas to 4.2% in grade II oligodendrogliomas. Individual cases of grade II astrocytomas and oligodendrogliomas had, however, values up to 8.5%. In 13 primary anaplastic gliomas of WHO grade III consistently higher statistical means were obtained with values ranging from 8.6% for anaplastic astrocytomas to 14.2% for anaplastic mixed gliomas. Interestingly, 18 WHO grade IV glioblastomas demonstrated a mean value of only 7%, which is probably due to the pronounced phenothypic heterogeneity in this tumor group. This heterogeneity results in enormous intra- and intertumor variability in Ki-67 indices (range less than 1%-22.1%). Investigation of 17 recurrent gliomas revealed mean values for Ki-67 ranging from 1.7% for three WHO grade II astrocytomas up to 48.5% obtained in two highly anaplastic recurrent astrocytomas corresponding to WHO grade IV. Other tumors of the nervous system evaluated included 9 medulloblastomas (mean 17.9%, range 5.0%-42.0%), 17 benign meningiomas (mean 1.1%, range 0%-5%), 15 metastatic carcinomas (mean 16.5%, range less than 1%-46.0%), and individual tumors of various types. Our results indicate that Ki-67 immunohistochemistry can add useful additional information for histopathological grading which, by supplementing and refining the traditional WHO grading system, might lead to a better assessment of the biological behaviour of human tumors of the nervous system.


Plasmodium vivax gametocyte protein Pvs230 is a transmission-blocking vaccine candidate.
The malaria transmission-blocking vaccine (TBV) aims to interfere the development of malaria parasite in the mosquito and prevent further transmission in the community. So far only two TBV candidates have been identified in Plasmodium vivax; ookinete surface proteins Pvs25 and Pvs28. The pvs230 (PVX_003905) is reported as an ortholog of Pfs230, a gametocyte/gamete stage TBV candidate in Plasmodium falciparum, however its candidacy for TBV has never been tested. Therefore here, we have investigated whether Pvs230 can be a TBV candidate using P. vivax samples obtained from Thailand. The mouse antiserum raised against the plasmid expressing CRDs I-IV of Pvs230 detected Pvs230 protein in the lysate of P. vivax gametocyte in western blot analysis under non-reducing condition. From the localization of Pvs230 on the outer most regions of gametocyte in the immunofluorescence assay, it appears that Pvs230 is localized on the surface of gametes. Importantly, the anti-Pvs230 mouse serum significantly reduced the number of P. vivax oocysts developed in the mosquito midgut. Moreover, the polymorphism in Pvs230 CRDs I-IV is limited suggesting that it may not be an impediment for the utilization of Pvs230 as an effective TBV candidate. In conclusion, our results show that Pvs230 is a transmission-blocking vaccine candidate of P. vivax.


Transcriptome and the gut microbiome analysis of the impacts of Brucella abortus oral infection in BALB/c mice.
Brucellosis is a zoonotic infectious disease caused by Brucella spp, which could cause serious economic losses to animal husbandry and threaten human public health. Ingestion of contaminated animal products is a common way to acquire Brucella infection in humans, while research on effect of oral Brucella infection on host gut microbiota and the gene expression in intestinal tissues is limited. In the present study, 16S rRNA sequencing and RNA sequencing were conducted to explore gut microbiota and expression profiles of mRNAs in the colon of BALB/c mice, which were infected by Brucella abortus 2308. The fecal samples were collected at 7 and 28 days post infection to observe changes in the gut microbiota during Brucella infection. In the alpha diversity analysis, significantly increased Chao 1 index was observed at 28 days after Brucella infection. The Bray-Curtis distancebased principal coordinate analysis indicated that the WT group showed a separation from the Brucella infection groups. In addition, analysis of composition of microbes revealed that Prevotellaceae_NK3B31_group were more abundant in 1 week and 4 week infection groups, while Turicibacter was only more abundant in 4 week infection group. Based on the RNA-seq assay, a total of 45 differentially expressed genes were detected between Brucella abortus infection group and control group. Furthermore, KEGG pathway enrichment analysis showed that protein processing in endoplasmic reticulum, Legionellosis, Spliceosome, Hippo signaling pathway and Influenza A were significantly enriched in response to Brucella abortus infection. Our finding will help to improve the knowledge of the mechanisms underlying Brucella infection and may provide novel targets for future treatment of this pathogen infection.


Disability in the Individual ADL, IADL, and Mobility among Older Adults: A Prospective Cohort Study.
To examine the risk of disability in 15 individual ADL, IADL, and mobility in older adults by age; and to assess the association of multimorbidity, gender, and education with disability. A prospective cohort study. The sample included 805 community-dwelling older people aged 60+ living in the Netherlands. Disability was assessed using the Katz-15 Index of Independence in Basic Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and one mobility item. Disability in any of these activities was defined as the inability to perform the activity without assistance. The risk of disability by age for each individual ADL, IADL, and for mobility was assessed using Generalized mixed models. Disability in activities as household tasks, traveling, shopping, and continence had the highest risk and increased rapidly with age. The risk traveling disability among people aged 65 with two comorbidities increase from 9% to 37% at age 85. Disability in using the telephone, managing medications, finances, transferring, and toileting, had a very low risk and hardly increased with age. Compared to those without chronic conditions, those with ≥ 3 chronic conditions had a 3 to 5 times higher risk of developing disability. Males had a higher risk of disability in managing medication (P=0.005), and preparing meals (P=0.019), whereas females had a higher risk of disability with traveling (P=0.001). No association between education and disability on the individual ADL, IADL, and mobility was observed. Older adults were mostly disabled in physical related activities, whereas disability in more cognitive related activities was less often experienced. The impact of multimorbidity on disability in each activity was substantial, while education was not.


The effect of chronic ritanserin and clorgyline administration on 5-HT2 receptor linked inositol phospholipid hydrolysis.
We have previously shown that chronic administration of the 5-hydroxytryptamine (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 5-HT2 receptor number in rat cerebral cortex. This study investigates the effects of acute and chronic ritanserin administration, on 5-HT2 receptor linked inositol phospholipid hydrolysis in rat cortical slices and compares it with the effect of a chronic clorgyline regimen. [3H]Myo-inositol (50 microCi) was used to label inositol phospholipids. Their subsequent hydrolysis in the presence or absence of 5-HT was determined by the accumulation of [3H]myoinositol monophosphate ([3H]InsP). Addition of 5 nM ritanserin to slices had no effect on basal or 5-HT stimulated [3H]InsP accumulation whereas 100 nM ritanserin blocked the stimulated response by 65%. Acutely, ritanserin (15 mg/kg i.p.) completely blocked 5-HT stimulated [3H]InsP accumulation. Chronic ritanserin or clorgyline treatment had no effect on basal levels of [3H]InsP accumulation compared to controls (mean value 3125 +/- 298 dpm/mg protein). Ritanserin increased 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT and this effect was significant at 100 microM 5-HT. Clorgyline had no significant or consistent effect on 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 5-HT. Thus the effects of both chronic clorgyline and ritanserin administration on 5-HT2 linked inositol phospholipid hydrolysis do not correlate with their effects on 5-HT2 receptor number (Bmax). The situation is further complicated since ritanserin significantly increases phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) labelling whereas clorgyline significantly increases PtdIns and PtdIns4P labelling. The implications of this are discussed.


Polysaccharide-based hydrogels: New insights and futuristic prospects in wound healing.
Polysaccharides elicit enormous and promising applications due to their extensive obtainability, innocuousness, and biodegradability. Various outstanding features of polysaccharides can be employed to fabricate biomimetic and multifunctional hydrogels as efficient wound dressings. These hydrogels mimic the natural extracellular matrix and also boost the proliferation of cells. Owing to distinctive architectures and abundance of functional groups, polysaccharide-derived hydrogels have exceptional physicochemical properties and unique therapeutic interventions. Hydrogels designed using polysaccharides can effectively safeguard wounds from bacterial attack. This review includes wound physiology and emphasises on numerous polysaccharide-based hydrogels for wound repair applications. Polysaccharide hydrogels for different wound types and diverse therapeutic agents loaded in hydrogels for wound repair with recent patents are portrayed in the current manuscript, debating the potential of fascinating hydrogels for effective wound healing. More research is required to engineer multifaceted advanced polysaccharide hydrogels with tuneable and adjustable properties to attain huge potential in wound healing.


Exploring the elevation dynamics of rumen bacterial communities in Barn feeding cattle from 900 to 3,600 meters by full-length 16S sequencing.
The diversity and abundance of rumen microorganisms serve as indicators not only of the host's digestive and metabolic capacity but also of its health status. The complex microbial communities in the rumen are influenced to varying degrees by environmental adaptability. In this study, we collected 24 rumen fluid samples from 24 healthy male cattle in three regions of Yunnan, China. Using 16S rRNA amplicon sequencing data analysis, we examined the variations in rumen microorganisms among cattle fed at altitudes of 900 m, 1800 m, and 3,600 m. Altitude-related environmental factors did not surpass phylogeny as the main driving force behind the convergent evolution of yellow cattle rumen microbiome composition. However, they did have an impact on the alpha diversity of the rumen microbiome and the coevolution of the core microbiome. The change in altitude noticeably influenced the diversity and richness of the rumen microbiota, highlighting the environmental effect of altitude. As altitude increased, there was an observed increase in the abundance of Firmicutes and Bacteroidetes, while the abundance of ruminal Proteobacteria and Kiritimatiellaeota decreased. Importantly, at the genus level, the core genus exhibited distinct dynamic changes as altitude increased. Ruminants exhibit the ability to adapt their gut type in accordance with altitude, thereby optimizing energy utilization, especially in high-altitude settings. These discoveries offer valuable insights into the coevolution of host-microbe interactions during ruminant adaptation to various altitudinal environments.


Changes in opalescence and fluorescence properties of resin composites after accelerated aging.
Opalescence and fluorescence properties and the correlated translucency and masking effect of resin composites may change after aging. The objective of this study was to determine the changes in opalescence and fluorescence properties of resin composites after accelerated aging for 150 kJ/m2. Changes in translucency and masking effect were also determined. Color and spectral distribution of seven resin composites (A2 shade, 1-mm thick) were measured in the reflectance and transmittance modes under ultraviolet light (UV)-included and excluded conditions. Opalescence parameter (OP) was calculated as the difference in yellow-blue (Deltab*) and red-green (Deltaa*) coordinates between the reflected and transmitted colors under UV-included and excluded conditions. For the fluorescence evaluation, color differences (FL-Ref and FL-Trans) by the inclusion or exclusion of the UV-component of the standard illuminant D65 in the reflectance and transmittance modes were calculated. Under UV-included and excluded conditions, the translucency parameter (TP) was calculated, and the masking effect (ME) was calculated as the color difference between a specimen over a black tile and black tile itself. Repeated-measures 2-way analysis of variance at the significance level of 0.05 was performed for the values before and after aging. OP values in UV-included and excluded conditions did not change significantly after aging. FL-Ref and FL-Trans, TP values and ME values in UV-included and excluded conditions changed significantly after aging (p<0.05). The ranges of changes after aging in DeltaE*ab units were: OP, -0.50 to 0.74; FL, -1.19 to 0.15; TP, -1.37 to 0.13; and ME, -0.49 to 0.33. Opalescence of resin composites did not change but fluorescence was not detected after accelerated aging for 150 kJ/m2. Translucency and masking effect changed significantly after aging.


Vedolizumab response in inflammatory bowel disease. Two years of follow-up.
vedolizumab is an α4β7 integrin antagonist. The aim of this study was to evaluate the clinical response and remission rates with vedolizumab. this was a retrospective study of inflammatory bowel disease (IBD) patients who received vedolizumab between 2016 and 2019. Response and remission rates were analyzed at three, six, 12, 18 and 24 months after induction. fifty-five patients were included. Clinical remission rates in CD and UC at three, six, 12, 18 and 24 months were 19.35 %, 26.67 %, 30.43 %, 30 %, 38.89 % and 29.17 %, 26.09 %, 19.05 %, 26.67 % and 20 %, respectively. vedolizumab is effective for induction and maintenance of clinical remission, both in Crohn's disease and ulcerative colitis.


Increased duration and similar outcomes of V-V ECLS in patients with COVID-19 ARDS compared to non-COVID ARDS: Single center experience.
Veno-venous extracorporeal life support (V-V ECLS or V-V ECMO) has been adopted as a rescue support in severe cases of COVID-19 ARDS. Initial reports on the use of V-V ECLS in COVID-19 patients reported very high mortality rates (57%-94%), but subsequent studies showed much lower rates (30%-40%). The aim of this study is to analyze demographic features, clinical course and outcomes of COVID-19 treated with V-V ECLS during the Italian 'third wave', in which the alpha variant was prevalent in the country. Single-center, retrospective observational study conducted at the ECLS referral center of a teaching hospital in Italy from January 1st, 2021 and October 31st, 2021. Between January and October 2021, 18 consecutive adult patients who underwent V-V ECLS for severe ARDS due to COVID-19 were enrolled. Thirteen patients (72.2%) were male, and their median age was 50 years; the median P/F ratio before V-V ECLS initiation was 43 mm Hg (IQR, 40; 56), and the median RESP score was 0.5 (IQR, -2.25; 1.0). The mortality rate at 90 days was 55.6, compared to 55.7% in non-COVID patients in our center (p > 0.05); the median duration of ECLS was 29 days (IQR, 11; 32), compared to 10 days (IQR, 8; 15), in non-COVID patients (p = 0.004). Incidence of complications was high. In patients with COVID-19 ARDS receiving V-V ECLS, unadjusted mortality was similar to pre-pandemic V-V ECLS cases, while the duration of ECLS was almost three times longer and with frequent complications. This could be partly explained by the selection of very sick patients at the baseline that evolved to multiorgan failure during the course of ECLS.


Antimicrobial activity of the resins obtained from the roots and stems of Cedrus libani and Abies cilicica.
The antimicrobial activity of the ethanol extract of resins obtained from the roots and stems of Cedrus libani and Abies cilicica was investigated using a disc diffusion method. Results revealed that crude extracts of the resins of both plants are highly effective against tested microorganisms by preventing their growth to a greater extent.


Diagnostic value of computed tomography colonography (CTC) after incomplete optical colonoscopy.
This study evaluated the role of computed tomography colonography (CTC) in patients who previously underwent incomplete optical colonoscopy (OC). We analyzed the impact of colonic lesions in intestinal segments not studied by OC and extracolonic findings in these patients. Between January 2014 and May 2015, 61 patients with a history of abdominal pain and incomplete OC examination were studied by CTC. CTCs were performed by 320-row CT scan in both the supine and the prone position, without intravenous administration of contrast medium. In all patients both colonic findings and extracolonic findings were evaluated. Among the study group, 24 CTC examinations were negative for both colonic and extracolonic findings while 6 examinations revealed the presence of both colonic and extracolonic findings. In 24 patients CTC depicted colonic anomalies without extracolonic ones, while in 7 patients it showed extracolonic findings without colonic ones. CTC is a noninvasive imaging technique with the advantages of high diagnostic performance, rapid data acquisition, minimal patient discomfort, lack of need for sedation, and virtually no recovery time. CTC accurately allows the evaluation of the nonvisualized part of the colon after incomplete OC and has the distinct advantage to detect clinically important extracolonic findings in patients with incomplete OC potentially explaining the patient's symptoms and conditioning their therapeutic management. CTC accurately allows the assessment of both colonic and extracolonic pathologies representing a useful diagnostic tool in patients for whom complete OC is not achievable.


A case series of spotted fever rickettsiosis with neurological manifestations in Sri Lanka.
Spotted fever group (SFG) rickettsial infections are increasingly detected in Sri Lanka. We describe 17 patients with SFG who developed neurological manifestations. The cases were studied prospectively from 2008 at the Teaching Hospital, Peradeniya. An immunofluorescent antibody assay (IFA) was used to confirm the diagnosis. All had an IFA IgG titer ranging from 1/64 to 1/4096 and a positive IFA IgM titer against Rickettsia conorii antigen; in 10 (59%) cases the IgG titers were ≥ 1/256 (definitive cases). The median age of the patients was 62 years (range 26-82 years); 10 were male and seven female. The median duration of fever was 12 days (range 4-35 days). Neurological manifestations on admission were drowsiness or confusion in 14 (82%) and a semi-comatose state in three (18%). Rigidity of the limbs occurred in 14 (82%), bradykinesia and resting tremors in 12 (71%), which persisted after defervescence, neck stiffness in seven (42%), weakness of the limbs in five (29%), deafness in two (12%), and stupor in three (18%). Electroencephalograms in three (18%) showed generalized slow waves. Cerebrospinal fluid examination showed a cellular reaction, predominantly lymphocytes, in three cases. Two patients died (fatality rate 12%). We have documented for the first time the neurological features of SFG rickettsioses in the Central Province, Sri Lanka. These were predominantly extrapyramidal features in patients of older age.


Detection of Salmonella enterica in pigs at slaughter and comparison with human isolates in Italy.
In 2013-2014, 201 pigs belonging to 67 batches were tested for Salmonella in their mesenteric lymph nodes (MLN) in one abattoir of Northern Italy. For each batch, faecal material was collected at lairage by swabbing the pen floor for approximately 1600 cm(2). The aim of this study was to investigate the prevalence of Salmonella in MLN of pigs at slaughter, to assess Salmonella contamination at lairage and to evaluate the effect of lairage duration on its prevalence. Serotyping, XbaI PFGE typing and antimicrobial testing of the isolates were performed. Pig and human Salmonella isolates of the same region of Italy were compared to evaluate possible correlations. Salmonella enterica was isolated from 19.9% of the MLN and 49.3% of the environmental faecal samples. Nine different serovars were identified among 75 S. enterica isolates. In MLN Salmonella Derby was the most common (52.5%), followed by S. enterica 4,[5],12:i:- (17.5%) and Salmonella Rissen (10.0%). In faecal samples S. Derby was prevalent (51.4%), followed by S. enterica 4,[5], 12:i:- (20.0%) and Salmonella Brandenburg (14.3%). Lairage holding varied between 1 and ≥ 12 h (median value: 2.5h). In pigs held for 1-3h, 14.1% were positive for Salmonella in MLN but the prevalence reached 31.8% when they were held for ≥ 12 h. The contamination of MLN was statistically different (p=0.0045) between the two groups, thus confirming the role of long-lasting lairage in Salmonella contamination of pigs. XbaI PFGE typing detected 36 PFGE types. Twenty-three PFGE types were identified among the 40 MLN isolates and 22 PFGE types among the 35 faecal isolates. A total of 11 PFGE types were shared between the MLN of pigs and the lairage environment. Among S. Derby, 6 shared PFGE types between MLN and faeces were found and among S. enterica 4,[5],12:i:- one PFGE type was common between MLN and the faecal samples. Shared profiles between human and swine isolates of S. Derby, S. enterica 4,[5],12:i:-, S. Rissen, Salmonella Manhattan, S. Brandenburg, Salmonella Livingstone, Salmonella London and Salmonella Muenchen were identified. Among S. Derby and S. enterica 4,[5],12:i:- isolates found in pigs, 6/15 profiles (40.0%) and 8/10 (80.0%) were shared with human isolates. High resistance rates to streptomycin (97.3%), sulphonamide compounds (84.0%) and tetracycline (56.0%) were observed. No resistance was detected to ertapenem and meropenem. High proportions of isolates showed intermediate sensitivity to ciprofloxacin (85.3%) and cefotaxime (66.7%). High sensitivity rates were found to chloramphenicol (96.0%) and trimethoprim/sulfamethoxazole (81.3%).


Development of an analytical method for the determination of polybrominated diphenyl ethers in mussels and fish by gas chromatography-Inductively coupled plasma mass spectrometry.
Six congeners of polybrominated diphenyl ethers (PBDEs): BDE 28, BDE 47, BDE 99, BDE 100, BDE 153 and BDE 154, were determined by a reliable and sensitive analytical method based on gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS) in mussel and fish tissue samples. For their extraction, 30min of ultrasound-assisted extraction with a 25% aqueous solution of tetramethylammonium hydroxide (TMAH) and an additional 2h of mechanical shaking with tris(hydroxymethyl)aminomethane (Tris)-citrate buffer and iso-octane were applied. An effective cleaning, with minor solvent consumption, was achieved by passing the extract through a column filled with Florisil. PBDEs in the organic phase were quantified by GC-ICP-MS. Accuracy checks were performed by analyzing reference materials NIST SRM 2974a (freeze-dried mussel tissue) and SRM 1946 (fresh fish tissue homogenate) samples with a standard addition calibration method and by comparative analysis with species-specific isotope-dilution GC-ICP-MS. Good agreement of results between the determined and certified values were obtained (recoveries lied between 94 and 105%). Limits of detection (LODs) expressed on wet weight (ww) basis were 0.003ngg-1 for BDE 28, 0.006ngg-1 for BDE 47, 0.008ngg-1 for BDE 99, 0.004ngg-1 for BDE100, 0.005ngg-1 for BDE 153 and 0.009ngg-1 for BDE 154. The analytical method was applied for the determination of PBDEs in marine mussels and fish samples from the northern Adriatic Sea and fish samples from the Sava River. Among the six PBDEs congeners determined, BDE 47, BDE 100 and BDE 99 were commonly detected in the samples analysed.


Neuropraxia: An Underappreciated Morbidity of Liver Transplantation.
Peripheral nerve injuries can be devastating complications of surgery, potentially resulting in severe functional disability and decreased quality of life. Long surgeries with considerable tissue manipulation, for example, liver transplantation, may present increased risk; however, neuropraxia in transplantation has not been well investigated. This is a retrospective study of all adult patients undergoing liver transplantation at a large academic center between January 2013 and December 2015. Descriptive analyses, logistic regressions, and forward selection procedures were used to determine the odds of developing neuropraxia and associated factors. Of the 283 liver recipients, the mean age was 55.8 y, 35.1% were female, 65.6% were Caucasian, 8.9% were African American, 16.7% were Hispanic, and mean model for end-stage liver disease sodium score at transplant was 24.2 ± 10.9. The underlying etiology was alcohol (26.2%), hepatitis C (34.8%), nonalcoholic steatohepatitis (13.1%), and other (14.2%). The incidence of neuropraxia after liver transplantation was 8.3% (n = 25), with 60% (n = 16) upper extremities, 82% left sided, and 84% male. There was no difference in age, race, body mass index, hypertension, diabetes, hyperlipidemia, or smoking in those with neuropraxia versus those without. In multivariate analysis, neuropraxia was significantly associated with male gender, lower model for end-stage liver disease score, and longer duration of surgery (P < 0.05). Symptoms lasted median 5 d, with a wide range up to 187 d. Neuropraxia-specific treatment (physical therapy or medications) was required in 32% (n = 9). Peripheral nerve injuries are an unexplored complication of liver transplantation. Although transient, a high number (8.2%) of patients developed neuropraxia, negatively affecting their ability for recovery. Exploration of mechanisms for minimizing risk and intraoperative detection and prevention should be considered to mitigate this complication.


Unraveling individual host-guest interactions in molecular recognition from first principles quantum mechanics: Insights into the nature of nicotinic acetylcholine receptor agonist binding.
Drug binding to a protein target is governed by a complex pattern of noncovalent interactions between the ligand and the residues in the protein's binding pocket. Here we introduce a generally applicable, parameter-free, computational method that allows for the identification, quantification, and analysis of the key ligand-residue interactions responsible for molecular recognition. Our strategy relies on Local Energy Decomposition analysis at the "gold-standard" coupled cluster DLPNO-CCSD(T) level. In the study case shown in this paper, nicotine and imidacloprid binding to the nicotinic acetylcholine receptor, our approach provides new insights into how individual amino acids in the active site determine sensitivity and selectivity of the ligands, extending and refining classical pharmacophore hypotheses. By inference, the method is applicable to any kind of host/guest interactions with potential applications in industrial biocatalysis and protein engineering.


Validating and Verifying AI Systems.
AI systems will only fulfill their promise for society if they can be relied upon. This means that the role and task of the system must be properly formulated; that the system must be bug free, be based on properly representative data, and can cope with anomalies and data quality issues; and that its output is sufficiently accurate for the task.


PROMIS pain intensity and interference after pelvic organ prolapse surgery.
Patient-Reported Outcome Measurement Information System (PROMIS) questionnaires provide valid comparisons across disciplines. Pain measures can be used to track functional outcomes. Limited PROMIS pain data exist in gynecological surgery. We sought to use pain intensity and pain interference short forms to assess pain and recovery after pelvic organ prolapse surgery. The PROMIS pain intensity and pain interference questionnaires were given to patients undergoing uterosacral ligament suspension (USLS), sacrospinous ligament fixation (SSLF) or minimally invasive sacrocolpopexy (MISC) at baseline, 1 week, and 6 weeks postoperatively. Clinical minimally important change was defined as a difference of 2-6 T-score points. Mean pain intensity and pain interference T-scores were compared at baseline, 1 week and 6 weeks with ANOVA. Multiple linear regression assessed 1-week scores adjusted for apical suspension type, advanced prolapse, concurrent hysterectomy, concurrent anterior or posterior repair, and concurrent sling. At 1 week, all apical suspension groups showed minimally important change in pain intensity and pain interference T-scores. Between groups at 1 week, pain interference was higher in USLS (66.3±6.6) and MISC (65.5±5.9) than in SSLF (59.2±9.8), p=0.01. Multiple linear regression showed an association of hysterectomy with increases in pain intensity and pain interference. USLS had a higher proportion of concurrent hysterectomy (100%) than SSLF (0%) and MISC (30.8%), p<0.01. No difference was found based on apical suspension type alone. No differences were found in PROMIS pain intensity and pain at 1 week postoperatively after apical suspension procedures.


Astrocytic response in hippocampus and cerebral cortex in an experimental epilepsy model.
Astrocytes are very sensitive to alterations in the brain environment and respond showing a phenomenon known as astroglial reaction. S100beta is an astroglial derived neurotrophic factor, seems to be involved in neuroplasticity. The aim of this work was to study the astrocytic response in rat hippocampus and cerebral cortex after repetitive seizures induced by 3-mercaptopropionic acid (MP) administration. Immunocytochemical studies were performed to analyze GFAP and S100beta expression. Both studied areas showed hypertrophied astrocytes with enlarged processes and increased soma size. Astrocyte hyperplasia was observed only in the cerebral cortex. A significant decrease in the astrocytic S100beta immunostaining occurs after MP treatment. These results indicate that MP administration induces an astroglial reaction with reduced intracellular S100beta level. The observed reduction in astroglial S100beta could be related to the release of this factor to the extracellular space, where it may produce neurotrophic or deleterious effects accordingly to the concentration achieved. The mechanism of this remains to be elucidated.


A simple screening test for acute pancreatitis.
A urinary test strip for amylase (Rapignost-Amylase) was compared with plasma amylase assay in samples of urine and plasma collected on the day of admission to hospital from 23 patients with acute pancreatitis and 38 patients with other causes of acute abdominal pain. Plasma amylase was greater than 1200 IU/l in 24 patients (23 with pancreatitis and 1 with a perforated duodenal ulcer) and all were Rapignost-Amylase positive. Twenty-nine of the remaining patients were Rapignost-Amylase negative, but there were eight "false positives' with plasma amylase levels of 86-474 IU/l. The Rapignost-Amylase test is of potential value to screen for clinically occult acute pancreatitis.


Erythema multiforme: As a complication of allergen-specific immunotherapy.
Here we present a 25-year-old female patient admitted with a complaint of blistering lesions on her face, neck, chest and extremities appearing after the first dosis of specific immunotherapy and diagnosed as erythema multiforme. To our knowledge, there are no papers in the literature reporting erythema multiforme due to specific immunotherapy.


FAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity.
Polo like kinase 4 (Plk4) is a tightly regulated serine threonine kinase that governs centriole duplication. Increased Plk4 expression, which is a feature of many common human cancers, causes centriole overduplication, mitotic irregularities, and chromosomal instability. Plk4 can also promote cancer invasion and metastasis through regulation of the actin cytoskeleton. Herein we demonstrate physical interaction of Plk4 with FAM46C/TENT5C, a conserved protein of unknown function until recently. FAM46C localizes to centrioles, inhibits Plk4 kinase activity, and suppresses Plk4-induced centriole duplication. Interference with Plk4 function by FAM46C was independent of the latter's nucleotidyl transferase activity. In addition, FAM46C restrained cancer cell invasion and suppressed MDA MB-435 cancer growth in a xenograft model, opposing the effect of Plk4. We demonstrate loss of FAM46C in patient-derived colorectal cancer tumor tissue that becomes more profound with advanced clinical stage. These results implicate FAM46C as a tumor suppressor that acts by inhibiting Plk4 activity.


Effects of audiovisual distraction in children with Down syndrome during dental restorations: a randomised clinical trial.
To evaluate the effect of audiovisual distraction on the dental chairside behaviour of children with Down syndrome (DS) during dental restorations and its influence on the operator stress and the duration of the appointment. Study design: This randomised controlled trial included 48 children with DS requiring dental restorations. The study group was treated while wearing video eyeglasses, the control group with conventional behaviour management techniques. The child behaviour was evaluated using the revised Face, Leg, Activity, Cry, Consolability scale (r-FLACC) and the Frankl scale. The operator stress was evaluated using a VAS scale and the duration of the appointment was recorded. In the study group 64% of the children refused to wear the video eyeglasses during the whole duration of the dental treatment, the median r-FLACC score was significantly higher (p= 0.01552; Mann Whitney U test) and significantly more children showed a negative behaviour (68%vs 30%: p =0.011; Chi-square test). Audiovisual distraction using video eyeglasses is not useful in managing the dental chairside behaviour of children with DS.


[Pharmacological correction of neuronal damage in sensomotor zone of frontal cortex under conditions of experimental cerebral blood flow pathology].
The administration of thiotriazoline, emoxypine and magnelong (a combined glycine-magnesium preparation) to animals with acute cerebral circulatory insufficiency showed significant neuroprotective effect in both acute and late ischemic periods, as indicated by the indices of cell density and number and the characteristics of apoptic and destructed neurons approaching those in the group of intact rats. Pyracetam showed cerebroprotective effect only in late ischemic period. Magnelong exhibited the most significant neuroprotective effect, maintaining cell density on the intact control level and reducing the number of apoptotic and destructed neurons.


Electrokinetic characterization of extracellular vesicles with capillary electrophoresis: A new tool for their identification and quantification.
This work reports on the development of the first capillary electrophoresis methodology for the elucidation of extracellular vesicles' (EVs) electrokinetic distributions. The approach is based on capillary electrophoresis coupled with laser-induced fluorescent (LIF) detection for the identification and quantification of EVs after their isolation. Sensitive detection of these nanometric entities was possible thanks to an 'inorganic-species-free' background electrolyte. This electrolyte was made up of weakly charged molecules at very high concentrations to stabilize EVs, and an intra-membrane labelling approach was used to prevent EV morphology modification. The limit of detection for EVs achieved using the developed CE-LIF method reached 8 × 109 EV/mL, whereas the calibration curve was acquired from 1.22 × 1010 to 1.20 × 1011 EV/mL. The CE-LIF approach was applied to provide the electrokinetic distributions of various EVs of animal and human origins, and visualize different EV subpopulations from our recently developed high-yield EV isolation method.


Vasculitides throughout history and their clinical treatment today.
Therapeutic management of the vasculitides is closely linked to modern rheumatologic advances, particularly as it relates to the discovery and first clinical use of glucocorticoids. These compounds were introduced in the late-1940s for the treatment of rheumatoid arthritis, but soon after, clinicians in Europe and the United States realized that they could have a significant positive impact in systemic vasculitides. However, once it was realized that glucocorticoid use was associated with a high degree of morbidity, the search for better immunosuppressive agents with similar efficacy but improved safety profiles was on. During the past several years, several agents have been utilized for the therapeutic management of systemic vasculitides, and the list keeps growing with the development of newer compounds that have retained efficacy but with a better safety profile.


Effects of composition of hydroxyapatite/gray titania coating fabricated by suspension plasma spraying on mechanical and antibacterial properties.
While several metallic implants with bioactive coatings have been developed thus far for treating bone deformations or deterioration, a multifunctional coating with the desired mechanical and antibacterial properties has not been demonstrated. This study aimed to reveal the effect of the composition of hydroxyapatite (HAp)/gray titania coatings on the mechanical and antibacterial properties for biomedical applications. Suspension plasma spray (SPS) aided successful deposition of HAp/gray titania coatings on the surface of titanium substrates. The microstructure of coatings with different compositions was then characterized using scanning electron microscopy, X-ray diffraction, and Raman spectroscopy to identify the crystal structure. All results consistently demonstrated that SPS could transform Ti2O3 into TiO2 with mixed Magneli phases, such as Ti4O7 and Ti3O5, which could typically demonstrate photocatalytic activity. Hardness, Young's modulus, and interfacial strength of composite coatings commonly increased with an increase in the weight percentage of TiO2. A multi-modal damage assessment combining acoustic emission (AE), infrared ray camera (IR), and digital-image-correlation (DIC) was performed to monitor the damage process of HAp composite coating, which successfully revealed initiations of microcracks and nonlinear deformation at interface until fracture. Antibacterial test performed for examining the cytotoxic effects against E. coli under LED light irradiation conditions revealed that SPS HAp/gray titania coating could significantly enhance the antibacterial properties. Enhanced antibacterial properties can be attributed to an increase in the number of Magneli phases and better bacterial adhesion was attributed to hydrophilic properties conferred by submicron-sized particles. Hence, SPS can help fabricate visible light-responsive antibacterial coating, which can be used for medical devices.


Molecular Epidemiology of Stenotrophomonas maltophilia Strains Isolated from Bacteremia in Hospitalized Children.
The aim of this study was to determine the phenotypic and genotypic characteristics of Stenotrophomonas maltophilia isolates obtained from blood culture samples of pediatric patients hospitalized in Borujerd and Hamadan hospitals in western Iran. Oxidase-negative isolates were collected from the blood cultures of pediatric patients. S. maltophilia isolates were identified and confirmed by routine microbiological and molecular testing. Antibiotic susceptibility of the isolates was determined. The phenotypic and genotypic biofilm-forming ability of the isolates were investigated. Molecular typing of all isolates was performed by repetitive element sequence-based polymerase chain reaction. Out of 450 oxidase-negative bacilli, 72 (16.0%) were identified as S. maltophilia isolates. Biofilm assay results showed strong biofilm formation in 19 (26.4%) isolates, moderate in 38 (52.8%), weak in 10 (13.9%), and no biofilm formation in five (6.9%) isolates. Biofilm-associated genes rmlA, rpfF, and spgM were detected respectively in 59 (81.9%), 54 (75.0%), and 72 (100%) of isolates. Antimicrobial susceptibility testing showed that 67 (93.1%) isolates were sensitive to trimethoprim-sulfamethoxazole. All isolates were sensitive to levofloxacin and resistant to ceftazidime. The S. maltophilia isolates were grouped into 14 different types of repetitive sequence by repetitive element sequence-based polymerase chain reaction analysis. The results of this study indicate that S. maltophilia should be considered an important opportunistic pathogen in pediatric units. Different genotypes of S. maltophilia with the ability to form a biofilm (an important virulence factor) were circulating in the hospitals investigated. Levofloxacin and trimethoprim-sulfamethoxazole are recommended to treat S. maltophilia infections.


Rib fracture repair: indications, technical issues, and future directions.
Rib fracture repair has been performed at selected centers around the world for more than 50 years; however, the operative indications have not been established and are considered controversial. The outcome of a strictly nonoperative approach may not be optimal. Potential indications for rib fracture repair include flail chest, painful, movable rib fractures refractory to conventional pain management, chest wall deformity/defect, rib fracture nonunion, and during thoracotomy for other traumatic indication. Rib fracture repair is technically challenging secondary to the human rib's relatively thin cortex and its tendency to fracture obliquely. Nonetheless, several effective repair systems have been developed. Future directions for progress on this important surgical problem include the development of minimally invasive techniques and the conduct of multicenter, randomized trials.


Assessing the uncertainty in QUANTEC's dose-response relation of lung and spinal cord with a bootstrap analysis.
To apply a statistical bootstrap analysis to assess the uncertainty in the dose-response relation for the endpoints pneumonitis and myelopathy reported in the QUANTEC review. The bootstrap method assesses the uncertainty of the estimated population-based dose-response relation due to sample variability, which reflects the uncertainty due to limited numbers of patients in the studies. A large number of bootstrap replicates of the original incidence data were produced by random sampling with replacement. The analysis requires only the dose, the number of patients, and the number of occurrences of the studied endpoint, for each study. Two dose-response models, a Poisson-based model and the Lyman model, were fitted to each bootstrap replicate using maximum likelihood. The bootstrap analysis generates a family of curves representing the range of plausible dose-response relations, and the 95% bootstrap confidence intervals give an estimated upper and lower toxicity risk. The curve families for the 2 dose-response models overlap for doses included in the studies at hand but diverge beyond that, with the Lyman model suggesting a steeper slope. The resulting distributions of the model parameters indicate correlation and non-Gaussian distribution. For both data sets, the likelihood of the observed data was higher for the Lyman model in >90% of the bootstrap replicates. The bootstrap method provides a statistical analysis of the uncertainty in the estimated dose-response relation for myelopathy and pneumonitis. It suggests likely values of model parameter values, their confidence intervals, and how they interrelate for each model. Finally, it can be used to evaluate to what extent data supports one model over another. For both data sets considered here, the Lyman model was preferred over the Poisson-based model.