Influences of size and surface coating of gold nanoparticles on inflammatory activation of macrophages.
The widely used engineered nanoparticles have presented non-negligible immunotoxicity and specific patterns of inflammatory-activating behaviors, which remain to be revealed in a more systematic way. In this work, gold nanoparticles (GNPs) with 3 different diameters were prepared, and then were further modified with poly(ethylene glycol) (PEG) or chicken ovalbumin (OVA) to achieve different surface properties. Both types of GNPs had sizes of 12, 35, and 60nm and possessed negatively charged surface, showing good colloidal stability in cell culture medium, respectively. The conjugated amount of OVA was around 110ng/mm2 regardless of the particle size. All the particles showed neglectable influence on viability of RAW246.7 macrophages when cocultured in vitro. The GNPs of larger size or conjugated with OVA were internalized with significantly larger amount. While the OVA-coated GNPs induced higher secretion of tumor necrosis factor-α, interleukin-6, and interleukin-1β, the PEG coating did not induce significant inflammatory response especially when the size of NPs was larger than 35nm. Comparatively, smaller GNPs induced stronger inflammatory responses regardless of their surface-conjugated molecules.


Development, validation and application of an HPLC method for reduced vitamin C qualification in HBOCs solution.
A rapid and sensitive high-performance liquid chromatography (HPLC) method for vitamin C (Vc) determination was developed in hemoglobin-based oxygen carriers (HBOCs) solution. After polymerized hemoglobin precipitation, Vc could be tested out within 5 min. The standard curve was linear in Vc quantity of 0.00-3.00 μg. Vc recovery was 103.56-108.68%, and relative standard deviation values of the repeatability and precision were below 1.00%. The limits of detection and limits of quantification were 0.002 ppm and 0.01 ppm, respectively. Furthermore, the application of established HPLC methods in methemoglobin reduction by Vc under different pH indicated that higher pH values could accelerate the reduction. This study suggested the potential application of established HPLC method in HBOCs research and development.


Passive transfer of maternal antibodies and their existence in eggs, larvae and fry of Indian major carp, Labeo rohita (Ham.).
Lack of immune competence in the early stages of life leads to severe mortality in larval stages of different fish species including Indian major carp (IMC). Investigation through indirect enzyme linked immunosorbent assay (ELISA) and agglutination test revealed a significant increase in specific serum antibody response in the brood fish of Indian major carp, Labeo rohita (Ham.) following immunisation with a virulent Aeromonas hydrophila bacterin 1 month prior to breeding, which was transferred to larvae through the egg. No significant differences (P > 0.05) in mean antibody levels in larvae at the 1st and 2nd weeks post-hatch was recorded while a slight rise in antibody level was observed in 3-week-old fry, perhaps due to exposure to A. hydrophila present in the aquatic environment. Immunised brood fish serum, egg and larval extracts in non-reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and subsequent western blot analysis revealed an antibody molecule of approximate molecular weight 210 kDa. On challenge with virulent A. hydrophila, a significant reduction in mortality was recorded in immunised larvae and fry (58.0, 43.75 and 37.14% in the 1st, 2nd and 3rd week, respectively) relative to control fish (87.0, 79.0 and 76.4% in 1st, 2nd and 3rd week, respectively). The present study indicated the role of maternally derived antibody in protection of hatchlings of Indian major carp against specific pathogens.


Biohumanities: rethinking the relationship between biosciences, philosophy and history of science, and society.
We argue that philosophical and historical research can constitute a "Biohumanities" that deepens our understanding of biology itself engages in constructive "science criticism," helps formulate new "visions of biology," and facilitates "critical science communication." We illustrate these ideas with two recent "experimental philosophy" studies of the concept of the gene and of the concept of innateness conducted by ourselves and collaborators. We conclude that the complex and often troubled relations between science and society are critical to both parties, and argue that the philosophy and history of science can help to make this relationship work.


Clinical Significance of CD66b Expression in Non-Small Cell Lung Cancer.
We studied the expression of CD66b (a protein of the cancer-embryonic antigen family, expressed mainly in neutrophils) in tumor and stromal cells of non-small cell lung cancer (93 samples). The number of CD66b+ neutrophils is not associated with clinical and morphological parameters of the tumors and the disease prognosis. However, CD66b is expressed in the tumor cells of most studied samples. CD66b expression is also associated with the histological type of tumor and its localization. Increased expression of CD66b in tumor cells indicated a more favorable prognosis, which allows using this protein as a prognostic marker and as a potential target for the immunotherapy.


Long-term effects of conversion from cyclosporine to rapamycin on testicular function and morphology in a rat transplantation model.
The purpose of this study was to investigate the long-term effects of conversion from cyclosporine (CsA) to rapamycin on testicular function and morphology in a rat transplantation model compared with the continuous administration of CsA. Fisher 344 kidneys were orthotopically transplanted into Lewis recipients. Four Fisher 344 to Lewis allograft groups were treated posttransplantation as follows: Group 1, CsA treatment to week 8 followed by rapamycin from week 8-24; Group 2, CsA from transplantation to week 24; Group 3, CsA from transplantation to week 8 then vehicle from weeks 8-24, and Group 4, control vehicle from transplantation to week 24. A fifth group (Group 5) underwent syngeneic isografts (Lewis to Lewis) with no drug treatment. At 24 week, we measured serum creatinine and sex hormones and harvested the right testis for histological analysis. All rats showed normal serum creatinine levels. Testosterone was significantly lower in Group 1 versus Group 5 (0.85 ± 0.09 vs 1.05 ± 0.17 ng/mL; P = .008). Groups 2, 3 and 4 displayed higher testosterone values than Group 1 but lower than Group 5. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also higher in Group 1 versus the other groups, but the differences were not significant. The histological damage score was significantly higher in Groups 1, 2, 3, and 4 versus Group 5 (1.8 ± 0.8), but the highest one was observed in Group 1 (8.3 ± 1.6). Electron microscopy showed more severe testicular ultrastructural damage in Group 1. Conversion from CsA to rapamycin resulted in more severe damage to testicular function and structure than the continuous use of CsA in a rat kidney transplantation model.


Immunotyping of Chlamydia psittaci by indirect immunofluorescence antibody test with monoclonal antibodies.
Monoclonal antibodies against pigeon and budgerigar strains of Chlamydia psittaci were used to classify the immunotypes of C. psittaci strains by an indirect immunofluorescence antibody (IFA) test. Thirty-three C. psittaci strains from pigeons and 24 from budgerigars were divided into three immunotypes (P-I, P-II, and P-III) and (B-I, B-II, and B-III), respectively. Two strains from human psittacosis patients were identified as P-III and B-I, coinciding with the epidemiological evidence of each human infection. Two strains from psittacine birds, a parrot and a parakeet, were identical to the B-II immunotype. Other mammalian strains were quite distinct from avian strains in their IFA reaction with the monoclonal antibodies.


Myxoma of the mandible with unusual radiographic appearance.
Myxoma of the jaws is a fairly frequent bone tumor classified as a benign odontogenic neoplasm. The radiographic picture varies according to its evolution and, it many cases, diagnosis is not easy. A new case with an unusual radiographic appearance is reported. On occlusal radiographic examination the tumor showed multiple spicules of bone with a classic "sun-ray" effect. Only two similar cases were found in the literature. Oral and maxillofacial surgeons should be aware of this unusual presentation so that a misdiagnosis of malignant bone tumor is not made.


Applicability and clinical relevance of the transfer function method in the assessment of baroreflex sensitivity in heart failure patients.
We sought to assess applicability, clinical correlates, and prognostic value of the transfer function method for measuring baroreflex sensitivity (TF-BRS). Abnormalities in autonomic reflexes play an important role in the development and progression of chronic heart failure (CHF). Simple and non-invasive techniques for clinical measurement of such reflexes are desirable. In 317 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 years [48 to 59 years], New York Heart Association [NYHA] functional class II to III: 88%, left ventricular ejection fraction [LVEF]: 27% [22% to 33%]) we recorded electrocardiograms and non-invasive arterial pressure during paced breathing to measure TF-BRS. Owing to a high number of ectopic beats, TF-BRS could be computed in 72% of the patients; TF-BRS was lower in NYHA functional class III to IV and mitral regurgitation 2 to 3 (p < 0.0005 for both). Correlation with LVEF and standard deviation of all normal-to-normal intervals was 0.18 and 0.31 (p < 0.001 for both). During a mean follow-up of 26 months, 23% of the patients experienced a cardiac event. A depressed TF-BRS (< or =3.1 ms/mm Hg) was significantly associated with the outcome (hazard ratio 3.2, 95% confidence interval [CI] 1.7 to 6.0, p = 0.0003). Patients with a missing TF-BRS had a high event rate (36%). Combining this information with available TF-BRS measurements, a new prognostic index could be computed in 97% of the patients that significantly predicted the outcome after adjustment for clinical and functional variables (hazard ratio 2.5, 95% CI 1.3 to 4.6 p = 0.004). In CHF patients in sinus rhythm, TF-BRS conveys relevant clinical and prognostic information, but its measurability is markedly affected by ectopic activity. Nevertheless, a TF-BRS-based risk index carrying significant and independent prognostic information can be computed in almost all patients.


Synthesis and antimicrobial activity studies of ortho-chlorodiarylamines and heteroaromatic tetracyclic systems in the benzo[b]thiophene series.
ortho-Chlorodiarylamines in the 2,3,7-trimethylbenzo[b]thiophene series were prepared in high yields (70-85%) by C-N palladium-catalyzed cross-coupling using P(t-Bu)(3) as ligand and NaOt-Bu as base. A palladium-assisted C-C intramolecular cyclization of the coupling products gave thienocarbazoles and the dechlorinated diarylamines. Studies of antimicrobial activity of the compounds obtained, against representative species of bacteria (Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus and Bacillus subtilis) and fungi (Candida albicans), were performed. We have also included in the biological assays some pyridine derivatives previously prepared by us, and it was possible to establish some structure-activity relationships (SARs).


Testosterone destroys the transcortin-receptor complex.
Dissociation of the complex of transcortin receptor with immobilized transcortin in the presence of 10(-5) M testosterone has been shown with the use of affinity chromatography on transcortin-Sepharose. The specificity of this effect is confirmed by its abrogation in the presence of cortisol. The testosterone effect has been used for the elution of transcortin receptor from affinity column. The receptor retained transcortin-binding capacity after the elution and removal of testosterone. Characteristics of the receptor obtained by testosterone elution were identical with those of the transcortin eluted preparation.


Introducing a simple method of maxillary sinus volume assessment based on linear dimensions.
Measuring sinus volume in a general practice clinic is a complex and time-consuming procedure, requiring experience in the use of radiological methods In the presented research, the automatically estimated maxillary sinus volume was compared with maxillary sinus volume assessed with mathematical formulas used to calculate the volume of spheres and pyramids. The starting point for the statistical analysis were specific measurements of the sinuses. We wanted to discover which geometric shape has the volume that is nearest to the automatically estimated volume. The study was performed using samples of CT scans of pediatric patients age 1-17. The dimensions (maximal width, maximal height, maximal length) were used for manual calculations. For the automatic volume calculation, the CT Image Segmentation algorithm (Syngo Via for Oncology, Siemens) was used. Pearson's correlation coefficient was applied to analyse the interrelationship between automatically and manually calculated volume of maxillary sinus. It was statistically established that the "sphere", "pyramid" and "mean" manually calculated maxillary sinus volume were accurate and strongly correlated with the automatically estimated maxillary sinus volume. The volume of the sphere corresponds better with the automatic measurements than the volume of the pyramid. The variations are significant and they were made reliable with the application of a statistical test. It is quick and easy to calculate the maxillary sinus volume based on its linear dimensions instead of applying advanced software. The manual method for maxillary sinus volume calculation requires three linear measurements of the sinus (length, width, and height) and can be recommended if the automatically estimated volume cannot be obtained.


Identification and characterization of a chitin deacetylase from a metagenomic library of deep-sea sediments of the Arctic Ocean.
The chemical and biological compositions of deep-sea sediments are interesting because of the underexplored diversity when it comes to bioprospecting. The special geographical location and climates make Arctic Ocean a unique ocean area containing an abundance of microbial resources. A metagenomic library was constructed based on the deep-sea sediments of Arctic Ocean. Part of insertion fragments of this library were sequenced. A chitin deacetylase gene, cdaYJ, was identified and characterized. A metagenomic library with 2750 clones was obtained and ten clones were sequenced. Results revealed several interesting genes, including a chitin deacetylase coding sequence, cdaYJ. The CdaYJ is homologous to some known chitin deacetylases and contains conserved chitin deacetylase active sites. CdaYJ protein exhibits a long N-terminal and a relative short C-terminal. Phylogenetic analysis revealed that CdaYJ showed highest homology to CDAs from Alphaproteobacteria. The cdaYJ gene was subcloned into the pET-28a vector and the recombinant CdaYJ (rCdaYJ) was expressed in Escherichia coli BL21 (DE3). rCdaYJ showed a molecular weight of 43kDa, and exhibited deacetylation activity by using p-nitroacetanilide as substrate. The optimal pH and temperature of rCdaYJ were tested as pH7.4 and 28°C, respectively. The construction of metagenomic library of the Arctic deep-sea sediments provides us an opportunity to look into the microbial communities and exploiting valuable gene resources. A chitin deacetylase CdaYJ was identified from the library. It showed highest deacetylation activity under slight alkaline and low temperature conditions. CdaYJ might be a candidate chitin deacetylase that possesses industrial and pharmaceutical potentials.


[Pneumonectomy: an alternative to sleeve resection in lung cancer patients?].
Lung cancer is localized in the upper lobes in more than half of the cases. The risk of tumor infiltration of centrally located structures, such as bronchi and vessels are enhanced due to the anatomic topography. Pneumonectomy competes with sleeve resection for the surgical resection of centrally located tumors. The present review deals with the question if pneumonectomy should be considered as an alternative to sleeve resection for the treatment of lung cancer. Primary pneumonectomy does not provide any advantage even in advanced nodal disease. Extended lymph node dissection is not a contraindication for sleeve resections. Local recurrence rate is lower after sleeve resections despite the same radicality for both surgical treatment options. Mortality and morbidity rates are significantly lower for sleeve resections. Sleeve resections are associated with prolonged survival and better quality of life even in elderly patients.


Contribution to the faunistics of shore bugs (Hemiptera: Heteroptera: Leptopodomorpha) in the Palaearctic Region and the Himalayas.
New distributional data on 33 species of the infraorder Leptopodomorpha (3 species of the family Leptopodidae and 30 species and subspecies of Saldidae) from the Palaearctic Region and Himalayas are provided. The following new or confirmed records are listed: Chartoscirta cocksii (Curtis, 1835) from Kosovo; Halosalda halophila (Jakovlev, 1876), Saldula amplicollis (Reuter, 1891) and Saldula xanthochila (Fieber, 1859) from Iran; Macrosaldula jakowleffi (Reuter, 1891) from Nepal and Pakistan; Macrosaldula scotica (Curtis, 1835) from Uzbekistan; Macrosaldula variabilis (Herrich-Schaeffer, 1835), Saldula lindskogi Vinokurov, 2004, Saldula opacula (Zetterstedt, 1838) from Afghanistan; Micracanthia ornatula (Reuter, 1881) from Oman; Saldula fucicola (J. Sahlberg, 1870) from Bosnia and Herzegovina and Bulgaria; Saldula lindbergi Lindskog, 1975 from Lebanon; Saldula melanoscela (Fieber, 1859) from Iran and Montenegro; Saldula palustris (Douglas, 1874) and Saldula pilosella hirsuta (Reuter, 1888) from Montenegro; Saldula orthochila (Fieber, 1859) from Afghanistan and Pakistan; Saldula pallipes (Fabricius, 1794) from Montenegro and Nepal; Saldula pilosella pilosella (Thomson, 1871) from Libya; and Saldula saltatoria (Linnaeus, 1758) from Iran and Nepal. A tabular checklist of Leptopodomorpha of Afghanistan, Iran and Pakistan is also provided.


Assessment of Quality of Life After Ventilation Tube Insertion Using Otitis Media 6-Item (OM-6) Questionnaire.
To assess the impact of Ventilation tube insertion on the quality of life of children with otitis media with effusion using OM-6 questionnaire. The present prospective study was conducted in the Department of ENT, SMGS Hospital on 65 children suffering from Otitis Media with Effusion-OME (diagnosed by otoscopy and tympanometry after 3-month follow-up) over a period of 1 year from December 2020 to December 2021. Caregivers of all 65 children were subjected to Otitis Media 6-Item (OM-6) questionnaire at the time of admission (preoperative). All 65 children were subjected to ventilation tube insertion (Shephard Grommet) under general anaesthesia. Post-operatively at 6 weeks of ventilation tube insertion, caregivers were again asked to fill OM-6 questionnaire. The mean pre-operative overall OM6 score was 4.59 ± 1.02 and mean postoperative overall OM6 score was 2.22 ± 0.83, the difference being statistically significant (p < 0.05). Out of the six domains of OM6 questionnaire, the highest mean preoperative-postoperative difference was seen in Caregiver Concern (2.76), followed by Physical suffering (2.55). The least mean preoperative-postoperative difference was seen in Speech impairment (0.88). According to our study, there is statistically significant improvement in quality of life in children with OME, after insertion of ventilation tube.


Analysis of the singing voice handicap index for elderly choristers.
To analyze the singing voice handicap index in elderly choristers and verify its relationship with the profile, habits and health conditions of the participants. 110 individuals aged 60 years or older, participating in amateur choirs, were included. Choir singers were interviewed in order to verify data such as age, time in choir singing, vocal classification, and the presence of habits and health conditions adverse to voice production. Subsequently, they answered the questionnaire "Singing Voice Handicap Index (SVHI)", which assesses the individual's self-perception in relation to experiences in the use of the singing voice. The SVHI score had a median of 25, with a minimum score of 0 and a maximum score of 86. The most scored items were related to physical aspects in the use of singing voice: "I am unable to use my 'high voice'" (Q10) and "My throat is dry when I sing"(Q13). It was found that older adults over 75 years of age had a greater voice handicap when compared to younger ones (p=0.020). Choir singers classified as contralto also had a higher SVHI score (p=0.023), as well as individuals who reported drinking little water (p=0.007). The choristers in this study presented a singing voice handicap index compatible with healthy singing voices. When verifying the relationship of the SVHI score with the characteristics of the participants and with respect to habits and health conditions, it was found that the elderly choir singers over 75 years old, the contralto choir singers, and those who claimed to drink little water had higher scores for the singing voice handicap.


Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome.
Isolated restriction endonuclease fragments of the herpes simplex virus type 1 (HSV-1) genome were introduced into hamster embryo cells to identify DNA sequences capable to transforming the cells with respect to acquisition of properties correlated with tumorigenicity. One of the fragments generated by cleavage of HSV-1 DNA with the restriction endonuclease Xba I was found to induce transformation at a frequency of about 10 colonies per quantity of fragment recovered from 1 microgram of uncut DNA; fractions containing the other Xba I fragments failed to induce transformation reproducibly, although occasional colonies were detected. The fragment with transforming activity (Xba I-F) is 15.5 X 10(6) daltons in molecular weight and is located between 0.30 and 0.45 map units on the HSV-1 genome. The Xba I-F transformants obtained were selected for their ability to replicate in low concentrations of serum; in addition, they were found to attain high saturation densities in the presence of 10% serum and to form colonies in semisolid medium. Moreover, the transformed cells produced at least one of the viral gene products (a membrane glycoprotein) encoded in the fragment used for transformation, indicating not only that viral DNA was incorporated into the cells, but also that viral genes were expressed.


Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax.
All extant core-eudicot plants share a common ancestral genome that has experienced cyclic polyploidizations and (re)diploidizations. Reshuffling of the ancestral core-eudicot genome generates abundant genomic diversity, but the role of this diversity in shaping the hierarchical genome architecture, such as chromatin topology and gene expression, remains poorly understood. Here, we assemble chromosome-level genomes of one diploid and three tetraploid Panax species and conduct in-depth comparative genomic and epigenomic analyses. We show that chromosomal interactions within each duplicated ancestral chromosome largely maintain in extant Panax species, albeit experiencing ca. 100-150 million years of evolution from a shared ancestor. Biased genetic fractionation and epigenetic regulation divergence during polyploidization/(re)diploidization processes generate remarkable biochemical diversity of secondary metabolites in the Panax genus. Our study provides a paleo-polyploidization perspective of how reshuffling of the ancestral core-eudicot genome leads to a highly dynamic genome and to the metabolic diversification of extant eudicot plants.


Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma.
The effectiveness of stereotactic radiosurgery (SRS) for recurrent glioblastoma (rGBM) remains uncertain. SRS has been associated with a high risk of radionecrosis in gliomas. To determine the safety of dose escalation of single-fraction radiosurgery for rGBM in the setting of bevacizumab therapy. We conducted a prospective trial to determine the safety and synergistic benefit of higher doses of SRS administered with bevacizumab for rGBM. A single dose of bevacizumab was given prior to SRS and continued until progression. Dose-limiting toxicity was evaluated in successive cohorts of 3 patients. Seven males and 2 females entered the study. The maximum linear diameter of the enhancing tumor was 2.58 cm (2.04-3.09). Prescription dose was escalated from 18 to 22 Gy. The radiosurgery target was chosen before the first dose of bevacizumab, about 1 wk prior to SRS treatment. Pre-SRS bevacizumab treatment was associated with a reduction of the mean volume of the enhancing lesion from 4.7 to 2.86 cm3 on the day of SRS (P = .103). No patient developed an acute side effect related to SRS treatment. The combination of SRS and bevacizumab resulted in a partial response in 3 patients and stable disease in 6 patients. Median progression-free and overall survival were 7.5 and 13 mo, respectively. A single dose of bevacizumab prior to SRS permitted safe prescription dose escalation up to 22 Gy for rGBM. Further evaluation of the efficacy of SRS for rGBM should be performed in the setting of bevacizumab treatment.


Single bead IR monitoring of a novel benzimidazole synthesis.
A novel and efficient solid-phase synthesis of benzimidazoles and the monitoring of all conversions in this synthesis are reported.


The sensitivity of room-air pulse oximetry in the detection of hypercapnia.
To estimate the sensitivity of room-air pulse oximetry in the detection of moderate hypercapnia. In this retrospective case-control study, charts were reviewed from patients with and without moderate hypercapnia (Pa co 2 >50 mm Hg), as determined by analysis of arterial blood gas samples obtained in the ED. Test characteristics (sensitivity, specificity, and likelihood ratios [LR) for room-air pulse oximetry < or = 96% to detect hypercapnia were calculated, as were confidence intervals. A total of 349 charts were eligible for abstraction-92 cases and 257 controls. A room-air pulse oximetry reading < or = 96% detected 88 of 92 cases of hypercapnia. Test characteristics were as follows (with 95% confidence interval): sensitivity, 0.96 (0.89-0.99); specificity, 0.39 (0.33-0.45), LR of a room-air pulse oximetry value >96%, 0.1 (0.04-0.3); and LR of a room-air pulse oximetry value < or = 96%, 1.6 (1.4-1.7). Room-air pulse oximetry detects moderate hypercapnia with high sensitivity.


Bradykinin receptors in the guinea-pig taenia caeci are similar to proposed BK3 receptors in the guinea-pig trachea, and are blocked by HOE 140.
1. Bradykinin (BK) receptors of the guinea-pig taenia caeci were compared with those of the guinea-pig trachea, a preparation proposed to possess novel BK3 receptors. 2. Bradykinin-evoked contractile responses were unaffected in both preparations by the selective BK1 receptor antagonist [des-Arg9,Leu8]-BK (1 microM-10 microM). The BK2 receptor antagonists, D-Arg-[Hyp3,D-Phe7]-BK and D-Arg-[Hyp3,Thi5,8,D-Phe7]-BK, both had low affinities (apparent pKB estimates less than 6) which did not differ significantly between the two preparations (P greater than 0.05). In contrast, the novel bradykinin receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE 140) potently antagonized responses to bradykinin with relatively high affinity (apparent pKB = 8.42 +/- 0.15 and 8.94 +/- 0.16 in the taenia caeci, and trachea, respectively). 3. We conclude that the bradykinin receptors in the guinea-pig taenia caeci have similar recognition properties to those present in the guinea-pig trachea, and in this respect the taenia caeci represents a useful preparation for the further study of proposed novel BK3 receptors.


A Comparative Study to Evaluate Difficult Intubation Using Ratio of Patient Height to Thyromental Distance, Ratio of Neck Circumference to Thyromental Distance and Thyromental Height in Adult Patients in Tertiary Care Centre.
Patients' airway assessment is one of the foremost responsibility of every anaesthesiologist. Several preoperative predictive methods have been studied by various authors to find the best difficult airway predictor. We conducted this study to compare three methods to predict difficulty of laryngoscopic endotracheal intubation viz Ratio of patient Height to Thyro-Mental Distance (RHTMD), Ratio of Neck Circumference to Thyro-Mental Distance (RNCTMD) and Thyro-Mental Height (TMHT) in adult patients. This prospective observational study was conducted on 330 adult patients, ASA staus I and II, aged 18-60 years of either sex, weighing 50-80 kg scheduled for elective surgeries under general anaesthesia. Patient's height, weight, Body Mass Index (BMI) was recorded and thyromental distance, neck circumference, TMHT were measured preoperatively. Laryngoscopic view was graded according to Cormack- Lehane (CL) Grade. Predictive indices and optimal cut-off values were calculated using ROC curve analysis. Difficulty in laryngoscopic endotracheal intubation was encountered in 12.42% patients. The sensitivity, specificity, positive predictive value, negative predictive value and Area Under Curve (AUC) for TMHT were 100%, 95.2%, 75.54%, 100%, 0.982; for RHTMD were 75.6%, 72.7%, 28.18%, 95.45%, 0.758 and for RNCTMD were 82.9%, 65.4%, 25.37%, 96.42%, 0.779 respectively. There was no statistically significant difference to predict difficulty of laryngoscopic intubation between any of them (P < .05). Among these 3 parameters, TMHT was found to be the best preoperative method to predict difficult laryngoscopic endotracheal intubation with highest predictive indices and AUC. The RNCTMD was found to be more sensitive and useful method than RHTMD to predict difficulty of laryngoscopic endotracheal intubation.


Plasma carotenoids and tocopherols and risk of myocardial infarction in a low-risk population of US male physicians.
Increased intake of carotenoids and vitamin E may protect against myocardial infarction (MI). However, prospective data on blood levels of carotenoids other than beta-carotene and vitamin E (tocopherol) and risk of MI are sparse. We conducted a prospective, nested case-control analysis among male physicians without prior history of cardiovascular disease who were followed for up to 13 years in the Physicians' Health Study. Samples from 531 physicians diagnosed with MI were analyzed together with samples from paired control subjects, matched for age and smoking, for 5 major carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene), retinol, and alpha- and gamma-tocopherol. Overall, we found no evidence for a protective effect against MI for higher baseline plasma levels of retinol or any of the carotenoids measured. Among current and former smokers but not among never-smokers, higher baseline plasma levels of beta-carotene tended to be associated with lower risk (P for interaction=0.02). Men with higher plasma levels of gamma-tocopherol tended to have an increased risk of MI (P for trend=0.01). These prospective data do not support an overall protective relation between plasma carotenoids or tocopherols and future MI risk among men without a history of prior cardiovascular disease.


Effects of Rhei Undulati Rhizoma on lipopolysaccharide-induced neuroinflammation in vitro and in vivo.
Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders. In this study, we investigated whether RUR modulates inflammatory processes in lipopolysaccharide (LPS)-stimulated BV2 microglia cells and the mouse brain. RUR exerted anti-neuroinflammatory effects by inhibiting the production of nitric oxide and reactive oxygen species induced by LPS via the downregulation of transcription factors such as inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) without causing cytotoxicity. RUR also regulated mitogen-activated protein kinase pathway by inhibiting phosphorylation of p38 and c-Jun N-terminal kinases and translocation of nuclear factor kappa B. Moreover, RUR attenuated LPS-induced glial activation and COX-2 expression in the substantia nigra and hippocampus of the mouse brain. These results indicate that RUR is a potential candidate to treat neurodegenerative diseases by regulating neuroinflammation.


Aspirin reduces endothelial cell senescence.
We report here the effect of aspirin on the onset of replicative senescence. Endothelial cells that were cultured until cumulative population doublings 40 showed clear signs of aging. Incubation with aspirin inhibited senescence-associated beta-galactosidase activity and increased telomerase activity. Along with the delayed onset of senescence, aspirin decreased reactive oxygen species and increased nitric oxide (NO) and cGMP levels. Furthermore, aspirin reduced the elaboration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, and up-regulated the activity of dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA. These effects were specific in that other nonsteroidal anti-inflammatory drugs, such as ibuprofen or acetaminophen, did not prevent the onset of endothelial senescence. The NO synthase inhibitor l-NAME, but not its inactive d-enantiomer, led to complete inhibition of aspirin-delayed senescence. These findings demonstrate that aspirin delays the onset of endothelial senescence by preventing a decrease in NO formation/generation. This might provide a therapeutic strategy aimed at blocking aging-induced NO inhibition.


Drug-Eluting-Balloon Angioplasty in Tunisian population versus Everolimus-platinum-chrome-stent for de-novo coronary lesion.
Drug-eluting balloon (DEB) angioplasty is a well-established treatment modality for in-stent restenosis, however its safety and efficacy in de-novo lesion especially in large vessel remains undetermined. Theoretically, DEB sight to eliminate stent thrombosis and reduce restenosis rates by leaving no metal behind. To compare the results of angioplasty of de novo lesions by DEB (SEQUENT PLEASE) versus DES (Promus Premier and Promus Elite) in a Tunisian population. THE ENDPOINTS will be primarily the Late Lumen Loss at 12 months and secondarily the Major Cardiovascular Event rate (MACE) at 12 months. This is a randomized controlled non-inferiority trial including 290 patients with chronic coronary disease or non-ST elevation myocardial infarction with de novo lesions. After coronarography, angiographic parameters concerning lesion location and quantitative analysis will be collected. Patients will be treated with DEB or DES according to their allocation group. Before removal of the guide, post-procedural angiographic parameters will be evaluated. Follow-up will be performed for 12 months and an angiographic examination will be performed either as an emergency or at 12 months. The significance level will be 5%. A univariate analysis will be performed to search for predictive factors of MACE. Ethical considerations will be undertaken and respected. The study will run for 15 months starting August 25, 2021 Trial registration: NCT05516446.


Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers.
Beta blockers improve cardiac function and prolong survival in patients with systolic chronic heart failure (CHF). However, the exact mechanisms underlying these benefits are uncertain. Specifically, it is unclear whether a close relation exists between heart rate (HR) reduction and clinical outcomes with these agents. This hypothesis was therefore tested within randomized controlled trials of beta blockers in systolic CHF. Left ventricular ejection fraction (LVEF) and HR values at baseline and study end were obtained from available beta-blocker randomized clinical trials. The relation between change in HR and all-cause mortality as well as the LVEF was determined using regression analysis. Thirty-five trials, which included 22,926 patients with a mean follow-up duration of 9.6 months, were analyzed for all-cause mortality, the LVEF, and HR. There was a close relation between all-cause annualized mortality rate and HR (adjusted R2 = 0.51, p = 0.004). A strong correlation between change in HR and change in LVEF (adjusted R2 = 0.48, p = 0.000) was also observed. When only trials with >100 patients were included, an even tighter correlation was seen (adjusted R2 = 0.60, p = 0.0004). In conclusion, these analyses indicate that a major contributor to the clinical benefits of beta-blocker therapy in systolic CHF may be the HR-lowering effect of these agents. Therefore, the magnitude of HR reduction may be more important than the achievement of target dose in beta-blocker treatment of systolic CHF.


The syndrome of normal electrocardiograms, accessory pathways and paroxysmal tachycardias.
Tachycardias may be associated with the pre-excitation syndrome, a short PR interval or a prolonged QT interval. This report describes seven patients whose electrocardiograms (ECGs) did not reveal any of the above-named conditions. All of the patients presented with syncopal episodes, and the history of palpitations was elicited in five of the patients. His bundle electrogram studies in all of the patients showed an essentially unchanged AH interval with atrial pacing rates up to 180 beats/min. This can only be explained by a total bypass of the AV node. Two of the patients were also paced from the ventricle, and an unchanged pacing stimulus to A wave interval was observed. This signifies in these patients a functioning bypass pathway in the retrograde direction as well. Thus it would appear that pre-excitation cannot by eliminated as a diagnostic possibility even if the ECG is normal.


Cloud point extraction-HPLC method for determination and pharmacokinetic study of flurbiprofen in rat plasma after oral and transdermal administration.
A method based on cloud-point extraction (CPE) was developed for the determination of flurbiprofen (FP) in rat plasma after oral and transdermal administration by high-performance liquid chromatography coupled with UV detection (HPLC-UV). The non-ionic surfactant Genapol X-080 was chosen as the extract solvent. Variables parameter affecting the CPE efficiency were evaluated and optimized. Chromatography separation was performed on a Diamond C(18) column (4.6 mm i.d. x 250 mm, 10 microm particle size) by isocratic elution with UV detection at 254 nm. The assay was linear over the range of 0.2-50 and 0.1-10 microg/ml for oral and transdermal administration, respectively, and the lower limit of quantification (LLOQ) was 0.1 microg/ml. The extraction recoveries were more than 84.5%, the accuracies were within +/-3.8%, and the intra- and inter-day precisions were less than 10.1% in all cases. After strict validation, the method indicated good performance in terms of reproducibility, specificity, linearity, precision and accuracy, and it was successfully applied to the pharmacokinetic study of flurbiprofen in rats after oral and transdermal administration.


Automatic methods for alveolar bone loss degree measurement in periodontitis periapical radiographs.
Periodontitis involves progressive loss of alveolar bone around the teeth. Hence, automatic alveolar bone loss measurement in periapical radiographs can assist dentists in diagnosing such disease. In this paper, we propose an automatic length-based alveolar bone loss measurement system with emphasis on a cementoenamel junction (CEJ) localization method: CEJ_LG. The bone loss measurement system first adopts the methods TSLS and ABLifBm, which we presented previously, to extract teeth contours and bone loss areas from periodontitis radiograph images. It then applies the proposed methods to locate the positions of CEJ, alveolar crest (ALC), and apex of tooth root (APEX), respectively. Finally the system computes the ratio of the distance between the positions of CEJ and ALC to the distance between the positions of CEJ and APEX as the degree of bone loss for that tooth. The method CEJ_LG first obtains the gradient of the tooth image then detects the border between the lower enamel and dentin (EDB) from the gradient image. Finally, the method identifies a point on the tooth contour that is horizontally closest to the EDB. Experimental results on 18 tooth images segmented from 12 periodontitis periapical radiographs, including 8 views of upper-jaw teeth and 10 views of lower-jaw teeth, show that 53% of the localized CEJs are within 3 pixels deviation (∼ 0.15 mm) from the positions marked by dentists and 90% have deviation less than 9 pixels (∼ 0.44 mm). For degree of alveolar bone loss, more than half of the measurements using our system have deviation less than 10% from the ground truth, and all measurements using our system are within 25% deviation from the ground truth. Our results suggest that the proposed automatic system can effectively estimate degree of horizontal alveolar bone loss in periodontitis radiograph images. We believe that our proposed system, if implemented in routine clinical practice, can serve as a valuable tool for early and accurate diagnosis of alveolar bone loss in periodontal diseases and also for assessing the status of alveolar bone following various types of non surgical and surgical and regenerative therapy. For overall system improvement, a more objective comparison by using transgingival bone measurement with a periodontal probe as the ground truth and enhancing the localization algorithms of these three critical points are the two major tasks.


Age-related macular degeneration: is polypoidal choroidal vasculopathy recognized and treated?
To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). Retrospective chart review. 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.


Development and evaluation of a double antibody sandwich ELISA for the detection of human sDC-SIGN.
sDC-SIGN is the soluble form of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN, CD209), which is a molecule involved with pathogen recognition and immune regulation. However, there is no commercially available ELISA kit for detecting human sDC-SIGN, and the normal range of this molecule is unknown. Here, we describe an ELISA for detecting human sDC-SIGN with high specificity. First, sDC-SIGN protein was expressed and purified. Monoclonal and polyclonal antibodies were then raised against the purified protein and subsequently characterized. A sandwich ELISA was developed using polyclonal antibodies specific for sDC-SIGN for capture and a biotin-labeled monoclonal antibody specific for sDC-SIGN for detection of protein. This method has sensitivity up to 0.2 ng/ml. Using this ELISA, we found that the concentration of sDC-SIGN in sera of healthy volunteers ranges from 0-319 ng/ml with a mean concentration of 27.14 ng/ml. Interestingly, the concentration of sDC-SIGN in sera from patients with cancer or chronic hepatitis B virus (CHB) infection was lower than that of health controls. The mean concentrations of sDC-SIGN in cancer patients and chronic hepatitis B virus infection patients were 3.2 ng/ml and 3.8 ng/ml, respectively. We developed a sandwich ELISA for detecting human sDC-SIGN and demonstrated its use by assessing sera concentrations of sDC-SIGN in patients with cancer and chronic CHB infection compared to that of healthy controls.


Expression of anchorin CII mRNA by cultured chondrocytes.
The establishment of a cell culture system promoting chondrocyte differentiation has been utilized to better characterize phenotypic stages of chondrogenesis at the cellular level. Although the expression of the type II collagen gene has been studied during "in vitro" chondrocyte differentiation, little is known about the expression of the gene coding for its receptor: anchorin CII. The modulation of the anchorin mRNA steady state level in chick embryo chondrocytes at different developmental stages is described here.The anchorin mRNA level was low in dedifferentiated chondrocytes, progressively increased after the cell transfer into suspension (a condition promoting differentiation), reached its maximal value after 4 weeks and decreased after 5 weeks.Therefore anchorin CII mRNA reaches its maximum level in hypertrophic stage II chondrocytes.


Alternative reading frame selection mediated by a tRNA-like domain of an internal ribosome entry site.
The dicistrovirus intergenic region internal ribosome entry site (IRES) utilizes a unique mechanism, involving P-site tRNA mimicry, to directly assemble 80S ribosomes and initiate translation at a specific non-AUG codon in the ribosomal A site. A subgroup of dicistrovirus genomes contains an additional stem-loop 5'-adjacent to the IRES and a short open reading frame (ORFx) that overlaps the viral structural polyprotein ORF (ORF2) in the +1 reading frame. Using mass spectrometry and extensive mutagenesis, we show that, besides directing ORF2 translation, the Israeli acute paralysis dicistrovirus IRES also directs ORFx translation. The latter is mediated by a UG base pair adjacent to the P-site tRNA-mimicking domain. An ORFx peptide was detected in virus-infected honey bees by multiple reaction monitoring mass spectrometry. Finally, the 5' stem-loop increases IRES activity and may couple translation of the two major ORFs of the virus. This study reveals a novel viral strategy in which a tRNA-like IRES directs precise, initiator Met-tRNA-independent translation of two overlapping ORFs.


Investigation of melt agglomeration process with a hydrophobic binder in combination with sucrose stearate.
The melt agglomeration process of lactose powder with hydrogenated cottonseed oil (HCO) as the hydrophobic meltable binder was investigated by studying the physicochemical properties of molten HCO modified by sucrose stearates S170, S770 and S1570. The size, size distribution, micromeritic and adhesion properties of agglomerates as well as surface tension, contact angle, viscosity and specific volume of molten HCO, with and without sucrose stearates, were examined. The viscosity, specific volume and surface tension of molten HCO were found to be modified to varying extents by sucrose stearates which are available in different HLB values and melt properties. The growth of melt agglomerates was promoted predominantly by an increase in viscosity, an increase in specific volume or a decrease in surface tension of the molten binding liquid. The agglomerate growth propensity was higher with an increase in inter-particulate binding strength, agglomerate surface wetness and extent of agglomerate consolidation which enhanced the liquid migration from agglomerate core to periphery leading to an increased surface plasticity for coalescence. The inclusion of high concentrations of completely meltable sucrose stearate S170 greatly induced the growth of agglomerates through increased specific volume and viscosity of the molten binding liquid. On the other hand, the inclusion of incompletely meltable sucrose stearates S770 and S1570 promoted the agglomeration mainly via the reduction in surface tension of the molten binding liquid with declining agglomerate growth propensity at high sucrose stearate concentrations. In addition to being an agglomeration modifier, sucrose stearate demonstrated anti-adherent property in melt agglomeration process. The properties of molten HCO and melt agglomerates were dependent on the type and concentration of sucrose stearate added.


Extracellular vesicular lncRNA FAL1 promotes hepatocellular carcinoma cell proliferation and invasion by inducing macrophage M2 polarization.
Current evidence finds that circulating exosomal lncRNA focally amplified lncRNA on chromosome 1 (FAL1) promotes the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of serum extracellular vesicular FAL1 in HCC progression remains elusive. Here, we extracted extracellular vesicles (EVs) from serum samples of HCC patients and healthy volunteers, and found that FAL1 was highly enriched in the serum EVs of HCC patients. Then, macrophages were treated with EVs alone or together with small interfering RNA against FAL1 (si-FAL1). The data indicated that FAL1-enriched EVs induced macrophage M2 polarization, while silencing FAL1 in macrophages antagonized the role of EVs. Moreover, HepG2 cells were co-cultured with the conditioned macrophages, and co-culturing with EVs-incubated macrophages promoted HepG2 cell proliferation, invasion, cell cycle progression, and colony formation, and inhibited cell apoptosis and sorafenib sensitivity, while interfering FAL1 in macrophages reversed these effects. Consistently, ectopic expression of FAL1 in macrophages also induced macrophage M2 polarization, and co-culture of FAL1-overexpressing macrophages with HepG2 cells facilitated the malignant progression of HepG2 cells. Furthermore, co-culturing HepG2 cells with EVs-incubated macrophages activated the Wnt/β-catenin signaling pathway, and treatment with a Wnt/β-catenin pathway inhibitor IWP-2 partially neutralized the effect of EVs-incubated macrophages on HepG2 cell malignant behaviors. Additionally, FAL1 enriched EVs-incubated macrophages markedly increased mouse xenograft tumor growth. In conclusion, extracellular vesicular lncRNA FAL1 promotes macrophage M2 polarization and further activates the Wnt/β-catenin signaling pathway in HCC cells, thus promoting HCC progression.


Use of the Airtraq as the primary technique to manage anticipated difficult airway: a report of three cases.
The Airtraq laryngoscope (Prodol Meditec S.A., Vizcaya, Spain) is a new disposable optical laryngoscope designed to facilitate intubation in an uncomplicated or difficult airway. Its distinctive shape and its optical system can provide a full view of the glottis without the need to align the oropharyngeal axis. The use of this device as the primary technique to manage the airway of three patients with a previous history of difficult intubation related to difficult laryngoscopy is presented.


Primary orbital leiomyosarcoma. A case report and review of the literature.
An 82-year-old woman presented with a five-week history of painless proptosis. Results of clinical evaluation, including computed tomography, were consistent with a benign orbital tumor. Biopsy followed by surgical resection disclosed leiomyosarcoma. We reviewed the literature and studied the clinical spectrum of this rare disease of the orbit.


Biochemical characterization of two Cdc6/ORC1-like proteins from the crenarchaeon Sulfolobus solfataricus.
The biological role of archaeal proteins, homologous to the eukaryal replication initiation factors of cell division control (Cdc6) and origin recognition complex (ORC1), has not yet been clearly established. The hyperthermophilic crenarchaeon Sulfolobus solfataricus (referred to as Sso) possesses three Cdc6/ORC1-like factors, which are named Sso Cdc6-1, Cdc6-2 and Cdc6-3. This study is a report on the biochemical characterization of Sso Cdc6-1 and Cdc6-3. It has been found that either Sso Cdc6-1 or Cdc6-3 behave as monomers in solutions by gel filtration analyses. Both factors are able to bind to various single-stranded and double-stranded DNA ligands, but Sso Cdc6-3 shows a higher DNA-binding affinity. It has also been observed that either Sso Cdc6-1 or Cdc6-3 inhibit the DNA unwinding activity of the S. solfataricus homo-hexameric mini-chromosome maintenance (MCM)-like DNA helicase (Sso MCM); although they strongly stimulate the interaction of the Sso MCM with bubble-containing synthetic oligonucleotides. The study has also showed, with surface plasmon resonance measurements, that Sso Cdc6-2 physically interacts with either Sso Cdc6-1 or Sso Cdc6-3. These findings may provide important clues needed to understand the biological role that is played by each of these three Cdc6 factors during the DNA replication initiation process in the S. solfataricus cells.


A Single Intrathecal or Intraperitoneal Injection of CB2 Receptor Agonist Attenuates Bone Cancer Pain and Induces a Time-Dependent Modification of GRK2.
The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain. Female Sprague-Dawley rats, weighing 160-180 g, were utilized to establish a model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. JWH-015, a selective CB2 agonist, was injected intrathecally or intraperitoneally on postoperative day 10. Bone cancer-induced pain behaviors-mechanical allodynia and ambulatory pain-were assessed on postoperative days -1 (baseline), 4, 7, and 10 and at post-treatment hours 2, 6, 24, 48, and 72. The expressions of spinal CB2 and GRK2 protein were detected by Western Blotting on postoperative days -1 (baseline), 4, 7, and 10 and at post-treatment hours 6, 24, and 72. The procedure produced prolonged mechanical allodynia, ambulatory pain, and different changes in spinal CB2 and GRK2 expression levels. Intrathecal or intraperitoneal administration of JWH-015 alleviated the induced mechanical allodynia and ambulatory pain, and inhibited the downregulation of spinal GRK2 expression. These effects were in a time-dependent manner and reversed by pretreatment of CB2 selective antagonist AM630. The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain. Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.


Twenty-Three-Hour-Stay Colectomy Without Increased Readmissions: An Analysis of 1905 Cases from the National Surgical Quality Improvement Program.
Isolated case series from highly specialized centers suggest the feasibility of a 23-h hospital stay after colectomy. We sought to determine preoperative variables associated with discharge within 23 h after colectomy to identify patients best suited for a short-stay model. The American College of Surgeons NSQIP Colectomy-Targeted database was used to identify patients who underwent elective colectomy from 2012 to 2017. All cases with missing length of stay or inpatient death were excluded. Patients with a postoperative hospital stay ≤1 day were identified. Univariate and multivariate analyses were conducted to identify factors associated with early discharge. A total of 1905 patients were discharged within 23 h after surgery (1.6%). These patients were noted to be younger (59 versus 61 years, p < 0.001) and less likely to have insulin-dependent diabetes (3.0 versus 4.4%, p < 0.001), preoperative dyspnea (2.2 versus 6.0%, p < 0.001), COPD (3.0 versus 4.2%, p = 0.011), and hypertension (40.7 versus 46.9%, p < 0.001) than patients who stayed longer. Shorter operative time (OR 0.986, 95% CI 0.985-0.987, p < 0.001), minimally invasive techniques (OR 2.969, 95% CI 2.686-3.282, p < 0.001), lack of ostomy (OR 0.614, 95% CI 0.478-0.788, p < 0.001), and lack of ureteral stenting (OR 0.641, 95% CI 0.500-0.821, p < 0.001) were associated with early discharge in multivariable analysis. There was no increased incidence of readmission in patients discharged within 23 h. Twenty-three-hour-stay colectomy is feasible on a national level and does not result in an increased incidence of readmission. Patients undergoing elective procedures without significant medical comorbidities may be eligible for early discharge. Preoperative factors may be used to select patients best suited for this short-stay model.


The Evolving Role of Radiotherapy for Head and Neck Cancer.
The length and quality of head and neck cancer survivorship continues to meaningfully improve. Radiotherapy has been central to this process through advances in treatment delivery, fractionation schemas, radiosensitizing systemic therapy, and thoughtful interplay with technical surgical improvements. The future looks brighter still, with ongoing progress in targeted biologic therapy, immuno-oncology, and molecular-genetic tumor characterization for personalized treatment. Head and neck cancer, a disease once fraught with nihilism and failure, is evolving into a major success story of modern multidisciplinary cancer care.


Chloroquine Inhibits Ca(2+) Signaling in Murine CD4(+) Thymocytes.
Bitter-tasting chloroquine can suppress T cell activation by inhibiting Ca(2+) signaling. However, the mechanism of inhibition remains largely unclear. In this study, CD4(+) T cells were isolated from the thymus, and the calcium content of CD4(+) thymocytes was measured using fura-2 AM and a TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used to assess the effects of chloroquine on the intracellular Ca(2+) content of CD4(+) T cells. In murine CD4(+) thymocytes, chloroquine decreased the TG-triggered intracellular Ca(2+) increase in a dose-dependent manner. In the absence of chloroquine under Ca(2+)-free conditions (0 mM Ca(2+) and 0.5 mM EGTA), TG induced a transient Ca(2+) increase. After restoration of the extracellular Ca(2+) concentration to 2 mM, a dramatic Ca(2+) increase occurred. This elevation was completely blocked by chloroquine and was markedly inhibited by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the TG-induced transient Ca(2+) increase under Ca(2+)-free conditions was eliminated in the presence of chloroquine. Chloroquine also blocked the dialyzed inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca(2+) increase. However, chloroquine was not able to decrease the caffeine-induced Ca(2+) increase. These data indicate that chloroquine inhibits the elevation of intracellular Ca(2+) in thymic CD4(+) T cells by inhibiting IP3 receptor-mediated Ca(2+) release from intracellular stores and TRPC3 channel-mediated and/or STIM/Orai channel-mediated Ca(2+) influx.


Surface protection method for the magnetic core using covalent organic framework shells and its application in As(III) depth removal from acid wastewater.
Fe3O4-based materials are widely used for magnetic separation from wastewater. However, they often suffer from Fe-leaching behavior under acidic conditions, decreasing their activity and limiting sustainable practical applications. In this study, covalent organic frameworks (COFs) were used as the shell to protect the Fe3O4 core, and the Fe3O4@COF core-shell composites were synthesized for As(III) removal from acid wastewater. The imine-linked COFs can in situ grow on the surface of the Fe3O4 core layer by layer with [COFs/Fe3O4]mol ratio of up to 2:1. The Fe-leaching behavior was weakened over a wide pH range of 1-13. Moreover, such composites keep their magnetic characteristic, making them favorable for nanomaterial separation. As(III) batch adsorption experiments results indicated that, when COFs are used as the shell for the Fe3O4 core, a balance between As(III) removal efficiencies and the thickness of the COF shell exists. Higher As(III) removal efficiencies are obtained when the [COFs/Fe3O4]mol ratios were < 1.5:1, but thicker COF shells were not beneficial for As(III) removal. Such composites also exhibited better As(III) removal performances in the pH range of 1-7. Over a wide pH range, the zeta potential of Fe3O4@COF core-shell composites becomes more positive, which benefits the capture of negative arsenic ions. In addition, thinner surface COFs were favorable for mass transfer and facilitating the reaction of Fe and As elements. Our study highlights the promise of using COFs in nanomaterial surface protection and achieving As(III) depth removal under acidic conditions.


Zinc deficiency with reduced mastication impairs spatial memory in young adult mice.
Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency and reduced mastication, but not body weight, may inhibit recovery of impaired spatial learning. A zinc-sufficient diet is pivotal for maintaining spatial memory.


Molecular evidence of genetic modification of Sinorhizobium meliloti: enhanced PCB bioremediation.
The genome of the nitrogen-fixing soil bacterium Sinorhizobium meliloti does not possess genes for bioremediation of aromatic pollutants. It has the well-known ability to interact specifically with the leguminous alfalfa plant, Medicago sativa. Our previous work has shown enhanced degradation of the nitroaromatic compound 2,4-dinitrotoluene (DNT) when a plasmid containing degradative genes was introduced in it. In this study we report molecular evidence of the transfer of a polychlorinated biphenyl (PCB)-biodegradative plasmid pE43 to S. meliloti strain USDA 1936. Several standard analytical tests and plant growth chamber studies were conducted to test the ability of S. meliloti to degrade 2',3,4-PCB congener. Alfalfa plant alone was able to degrade 30% of PCBs compared with control. No enhanced dechlorination was noted when alfalfa plant was grown with wild-type S. meliloti, and when alfalfa plant was grown with the S. meliloti electrotransformants (genetically modified) dechlorination of PCBs was more than twice that when alfalfa plant was grown with wild-type S. meliloti. When alfalfa plant was grown with uncharacterized mixed culture (containing nodule formers), almost equally significant PCB degradation was observed. The significance of this work is that the naturally occurring nitrogen-fixing soil bacterium S. meliloti (genetically modified) has the ability to enhance fertility of soil in association with the leguminous alfalfa plant while simultaneously enhancing bioremediation of PCB-contaminated soils. Enhanced bioremediation of PCB and robust alfalfa plant growth was also noted when uncharacterized mixed cultures containing alfalfa plant nodule formers were used.


[Results of research on the microflora of the conjunctiva with either chemotherapeutically pretreated eyes or eyes not influenced by drugs concerning the question of the preoperative prophylaxis against infections (author's transl)].
In this study the results of 396 smears of conjunctiva are analysed concerning the microflora of chemotherapeutically pretreated eyes in comparison with eyes not treated. The results of microbiological culture indicate only a small statistically unsignificant difference in regard to the quantitity of sterile smears as well as the distribution of bacteria of both research groups. The discussion is on the question of unaimed preoperative prophylaxis of infection as conditio sine qua non before intraocular procedures on eyes free of phlogistic irritation.


Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset.
Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1-18.6 mo), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2-4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65-74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.


Evaluation of Machine Learning Methods Developed for Prediction of Diabetes Complications: A Systematic Review.
With the rising prevalence of diabetes, machine learning (ML) models have been increasingly used for prediction of diabetes and its complications, due to their ability to handle large complex data sets. This study aims to evaluate the quality and performance of ML models developed to predict microvascular and macrovascular diabetes complications in an adult Type 2 diabetes population. A systematic review was conducted in MEDLINE®, Embase®, the Cochrane® Library, Web of Science®, and DBLP Computer Science Bibliography databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Studies that developed or validated ML prediction models for microvascular or macrovascular complications in people with Type 2 diabetes were included. Prediction performance was evaluated using area under the receiver operating characteristic curve (AUC). An AUC >0.75 indicates clearly useful discrimination performance, while a positive mean relative AUC difference indicates better comparative model performance. Of 13 606 articles screened, 32 studies comprising 87 ML models were included. Neural networks (n = 15) were the most frequently utilized. Age, duration of diabetes, and body mass index were common predictors in ML models. Across predicted outcomes, 36% of the models demonstrated clearly useful discrimination. Most ML models reported positive mean relative AUC compared with non-ML methods, with random forest showing the best overall performance for microvascular and macrovascular outcomes. Majority (n = 31) of studies had high risk of bias. Random forest was found to have the overall best prediction performance. Current ML prediction models remain largely exploratory, and external validation studies are required before their clinical implementation. Open Science Framework (registration number: 10.17605/OSF.IO/UP49X).


Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production.
Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia-reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg-1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min-1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.


Comparison of In-Plane Stress Development in Sol-Gel- and Nanoparticle-Derived Mesoporous Metal Oxide Thin Films.
By using an evaporation-induced self-assembly (EISA) process, mesoporous metal oxide thin films are prepared via molecular precursors undergoing a sol-gel transition or by using nanoparticle dispersions as the starting materials. Both methods are employed together with PIB50-b-PEO45 as the structure-directing agent to produce porous TiO2 and ZrO2 thin films with spherical mesopores of around 14 nm in diameter. These nanoparticle- and sol-gel-derived films were investigated in terms of the intrinsic in-plane stress development during the heat treatment up to 500 °C to evaluate the impact of solvent evaporation, template decomposition and crystallization on the mechanical state of the film. The investigation revealed the lowest intrinsic stress for the nanoparticle-derived mesoporous film, which is assigned to the combination of the relaxing effects of the utilized diblock copolymer and the interparticular gaps between the precrystalline nanoparticles. Furthermore, the residual in-plane stress was studied after annealing steps ranging from 300 to 1000 °C and cooling down to room temperature. Here, TiO2 nanoparticle-derived mesoporous films possess a lower residual stress than the sol-gel-derived mesoporous films, while in the case of ZrO2 films, sol-gel-derived coatings reveal the smallest residual stress. The latter is based on the lower thermal expansion coefficient of the dominant monoclinic crystal phase compared to that of the silicon substrate. Hence, the present crystal structure has a strong influence on the mechanical state. The observation in this study helps to further understand the stress-related mechanical properties and the formation of mesoporous metal oxides.


Presence of a non-NMDA glutamate receptor subtype in the sympathetic nervous system of neonatal swine.
For the first time, the GluR-1 subtype of AMPA receptor was identified in the sympathetic nervous system of neonatal swine, an animal model of human development and heart disease. The rationale was to seek evidence of a role ascribed to glutamate in cardiorespiratory regulation in the laboratory rat. The receptor was demonstrated with the avidin-biotin immunoperoxidase technique by using an affinity-purified polyclonal antibody judged to be specific to Glu-R1 in several species. Glu-R1 immunoreactivity was regionally distributed in the thoracic spinal gray, and present intracellularly in neurons and within the surrounding neuropil. Sympathetic preganglionic neurons in the intermediolateral cell column of upper and lower thoracic spinal segments were intensely labeled and surrounded by labeled neuropil. High concentrations of Glu-R1 distinguished laminae II: substantia gelatinosa and the outer region of lamina III. Laminae I and V of the dorsal horn but not IV contained immunolabeled neurons. Arrays of moderately immunoreactive perikarya extended from an intermediate zone of laminae VII to the central gray. Glia and perivascular processes were not labeled, confirming previous observations [Tachibana, M., Wenthold, R.J., Morioka, H., Petralia, R.S., 1994. Light and electron microscopic immunocytochemical localization of AMPA-selective glutamate receptors in the rat spinal cord. J. Comp. Neurol. 344, 431-454]. Neuronal staining patterns corroborated evidence in rats indicating a postsynaptic localization of Glu-R1 associated with plasma membranes and cytoplasmic organelles [Martin, L.J., Blackstone, C.D., Levey, A.I., Huganir, R.L., Price, D.L., 1993. AMPA glutamate receptor subunits are differentially distributed in rat brain. Neuroscience 53, 327-358.; Rubio, M.E., Wenthold, R.J., 1997. Glutamate receptors are selectively targeted to postsynaptic sites in neurons. Neuron 18, 939-950]. Our data predict a role for L-glutamate in postnatal development of cardiorespiratory reflexes in swine.


Assembly of Tat-dependent [NiFe] hydrogenases: identification of precursor-binding accessory proteins.
The Escherichia coli twin-arginine translocation (Tat) system serves to export fully folded protein substrates across the bacterial cytoplasmic membrane. Respiratory [NiFe] hydrogenases are synthesised as precursors with twin-arginine signal peptides and transported as large, cofactor-containing, multi-subunit complexes by the Tat system. Cofactor insertion and assembly of [NiFe] hydrogenases requires coordination of networks of accessory proteins. In this work we utilise a bacterial two-hybrid assay to demonstrate protein-protein interactions between the uncharacterised chaperones HyaE and HybE with Tat signal peptide-bearing hydrogenase precursors. It is proposed that the chaperones act at a 'proofreading' stage in hydrogenase assembly and police the protein transport pathway preventing premature targeting of Tat-dependent hydrogenases.


Aggregation-induced emission fluorescent probes for lipid droplets-specific bioimaging of cells and atherosclerosis plaques.
Visualizing lipid droplets (LDs) using fluorescence imaging is highly desirable for the diagnosis and treatment of atherosclerotic heart diseases. However, the imaging performance of the current commercial lipid probes is unsatisfactory. In this study, we prepared two probes (TTM and MeO-TTM) with aggregation-induced emission (AIE) properties for LD imaging with efficiency. Interestingly, TTM and MeO-TTM showed low emissions in H2O but their emissions were significantly increased in oil. Moreover, TTM and MeO-TTM showed great biocompatibility and intracellular LDs would be specifically illuminated by these probes with good resistance to photobleaching. In addition, TTM and MeO-TTM also exhibited great imaging performance in studying the spatial distribution of LDs in mouse atherosclerotic plaques. This work not only provides a simple tool for studying atherosclerosis but also hopes to enhance the development of fluorescent probes for LDs-specific imaging applications.


IL6-mediated suppression of miR-200c directs constitutive activation of inflammatory signaling circuit driving transformation and tumorigenesis.
Abnormal inflammatory signaling activation occurs commonly in cancer cells. However, how it is initiated and maintained and its roles in early stages of tumorigensis are largely unknown. Here, we report that the monocyte-derived MCP-1-induced transformation of immortal breast epithelial cells is triggered by transient activation of MEK/ERK and IKK/NF-κB pathways and maintained by constitutive activation of a feed-forward inflammatory signaling circuit composed of miR-200c, p65, JNK2, HSF1, and IL6. Suppression of miR-200c by IL6 constitutively activates p65/RelA and JNK2, and the latter phosphorylates and activates HSF1. In turn, HSF1 triggers demethylation of the IL6 promoter that facilitates the binding of p65 and c-Jun, which together drive constitutive IL6 transcription. Importantly, this signaling circuit is manifest in human cancer cells and in a mouse model of ErbB2-driven breast cancer, where IL6 loss significantly impairs tumorigenesis. Therefore, targeting this signaling circuit represents an effective therapeutic avenue for breast cancer prevention and treatment.


Mast cells are critically involved in serum-mediated vascular leakage in chronic urticaria beyond high-affinity IgE receptor stimulation.
Chronic urticaria (CU) is one of the most common skin disorders whose pathogenic mechanisms are not fully clarified. Autoimmune aetiology can be ascribed to 45% of patients with CU, and basophil histamine release is positive in 40% of cases. Our aim was to use a novel approach to evaluate the serum permeabilizing effect to identify the mediators of endothelial cell (EC) leakage and to define the role of mast cells (MCs) in the process. Permeabilizing activity of sera from 19 patients with CU and 11 healthy blood donors was evaluated by measuring serum-induced degranulation of two MC lines, expressing (LAD2) or lacking (HMC-1) the IgE receptor. Mast cell supernatant (SN) was then incubated with an EC monolayer, and endothelial permeability was evaluated by Fluorescein isothiocyanate-bovine serum albumin leakage in a transwell system. All 19 patient sera failed to induce direct EC leakage, but 15/19 and 17/19 promoted degranulation of HMC-1 and LAD2, respectively. Interestingly, 85% of autologous serum skin test-negative sera were able to cause MC degranulation. Also, 17/19 SNs from HMC-1 and all SNs from LAD2 incubated with CU sera increased endothelial permeability. Endothelial cell leakage remained unchanged after Ig depletion and was prevented by antihistamine, platelet-activating factor or leukotriene antagonist. Our study shows that CU sera are able to degranulate MCs through an IgE- and IgG-independent mechanism. The nature of histamine-releasing factors involved is still unclear, but our finding opens new ways to the understanding of the pathogenesis of CU, particularly in patients not showing circulating autoantibodies to FcεRI or IgE.


Bilateral Locked Posterior Fracture-Dislocation of the Shoulder After Epileptic Seizures Secondary to Cavernous Hemangioma: A Case Report and Literature Review.
BACKGROUND Posterior shoulder dislocation is an uncommon injury, accounting for less than 5% of all glenohumeral dislocations. Bilateral locked posterior shoulder fracture-dislocation is an extremely rare entity with an incidence of 0.6 cases/100 000 people/year. A few reports have been published in the literature, predominantly associated with epileptic seizures. CASE REPORT We present a rare case of a 55-year-old male patient with a history of epileptic seizures, who presented with bilateral, locked, posterior fracture-dislocation of the shoulder following an epileptic seizure. The patient was diagnosed with a cavernous hemangioma, which caused his epileptic episode. He was treated operatively, with a modified McLaughlin procedure performed on both sides, at 1 stage, by 2 surgical teams. The cavernous hemangioma was also resected 2 months later. After a follow-up period of 18 months, no recurrent episodes of instability or dislocation were identified. Full range of motion was present on both sides, with good clinical and radiological outcomes. We also conducted a literature review to elucidate the causes of this rare incidence, along with diagnostic workup and treatment options. We were able to identify 36 cases, involving 72 shoulders of bilateral posterior fracture-dislocations in 30 case reports and 2 case series. CONCLUSIONS Bilateral posterior fracture-dislocation of the shoulder is uncommon. Treatment strategy depends on the chronicity, involvement of the humeral head, and the patient's age and functional level. The target is to restore shoulder anatomy and maintain a functional range of motion.


Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series.
Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagonists led to the discovery of compounds with increased intrinsic permeability. This effort led to the identification of a potent CCR5 antagonist which exhibited an improved in vivo pharmacokinetic profile.


Determining the clinical significance of the PROMIS physical function score in the setting of femur fractures.
To adequately utilize patient reported outcome scores in the clinical setting, accurate determination of a cohort-specific minimal clinically important differences (MCID) is necessary. The purpose of this study was to assess MCID for Patient Reported Outcome Information System Physical Function Scores (PROMIS®) Physical Function (PF) in a sample of patients who have undergone operative fixation for femur fractures. All patients at a single Level 1 trauma center who were treated for operative femur fractures were identified by Current Procedural Terminology (CPT) codes (27,244, 27,245, 27,506, 27,507). PROMIS PF was collected as part of routine clinical care via computer adaptive testing (CAT). MCID calculations were performed using both anchor-based and distribution-based methods. A total of 182 patients with 723 score observations were included in the overall distribution-based analysis and 131 patients with 309 score observations were included in the anchor-based analysis. In the overall cohort, the average age was 53.1 (SD 22.3), and 45% of participants were female. MCID for PROMIS PF scores was 5.43 in the distribution-based method and 5.18 in the anchor-based method. Overall scores in the distribution group improved from mean of 27.4 (SD 7.0) at the first postoperative visit to a mean of 36.7 (SD 10.0) at a subsequent follow up visit. Overall scores in the anchor group improved from mean of 26.7 (SD 7.3) at the first postoperative visit to a mean of 37.5 (SD 9.3) at a subsequent follow up visit. This study identifies two MCID values (5.18, 5.43) based on two calculation methods for PROMIS physical function scores in the operative femur fracture population. This data could be helpful in targeting postoperative patients who fall below expected norms or in allowing clinical correlation with changes in surgical practice.


One-pot synthesis of polysubstituted indoles from aliphatic nitro compounds under mild conditions.
Polysubstituted indoles can be prepared directly from functionalized nitroalkanes under very mildly acidic conditions in a simple, one-pot, two-stage procedure.


A retrospective review of nosocomial infections in an acute rehabilitative and chronic population at a large skilled nursing facility.
This study was undertaken to analyze infection rate, risk for acquisition of infection, and spectrum of infectious disease in two distinct sub-populations within a large, metropolitan, long-term care skilled nursing facility (LTCSNF). A retrospective chart review over an 18-month period. A large, metropolitan LTCSNF. 786 acute rehabilitative patients and 554 chronic patients. The study compared infection rate, risk for acquisition of infection, and the microbiology of the most common infections in the two sub-populations. Analyses comparing the infection rate in the rehabilitative population with the infection rate in the chronic population were performed by multiple regression. The dependent variable in these analyses was the number of infections. The length of time that the patient was at risk for infection was included as a covariate. Approximately 75% of patients in both groups were women. The median age was 80 years in the rehabilitative group, 85 years in the chronic group. Urinary tract infection, pneumonia, skin/soft tissue infection were the most common infections in both groups. Five hundred forty-seven patients in the rehabilitative group and 479 patients in the chronic group had three or more underlying diseases. Enterobacteriaceae organisms were the most common isolates in urinary tract infectious episodes in both groups; mixed flora were the most common isolates for pneumonia and skin/soft tissue episodes in both groups. The calculated rate of infection for the rehabilitative and chronic groups was not significantly different (P = > 0.05). In concordance with other studies, urinary tract infection, respiratory infections, and skin and soft tissue infections were the most common in the long-term care facility. Analyses of two distinct populations within a single, large, teaching nursing facility revealed, however, that the rate of infection was not significantly different between the groups and that length of stay or presence of underlying disease was not predictive of infection.


Comparison of Reactive Sites in 2(1H)-Quinolone Derivatives for the Detection of Biologically Important Sulfur Compounds.
Novel fluorescent probes based on 2(1H)-quinolone skeleton containing a malonate group (Q1-Q3) were synthesized and proposed for biothiols detection. Their chemical reactivity toward thiols was compared to the reactivity of derivative having a dicyanovinyl group (Q4) as a reactive site. The detailed photophysical properties of these compounds were assessed through the determination of absorption and fluorescence spectra, fluorescence quantum yield, and fluorescence lifetime. In the presence of biothiols, an increase in the fluorescence intensity of compounds Q1-Q3 and a hypsochromic shift in their emission bands were observed. In contrast, the compound with the dicyanovinyl group (Q4) in the presence of biothiols and cyanide ion showed the quenching of fluorescence, while a fluorescence "turn on" effect was observed toward reactive sulfur species.


Exhaustive physical exercise and acid hydrolase activity in mouse skeletal muscle. A histochemical study.
Adult, untrained NMRI mice were exhausted on a motor-driven treadmill by an intermittent-type running programme. Serial cryostate sections for the staining of NADH-tetrazolium reductase, beta-glucuronidase, beta-N-acetylglucosaminidase, and beta-glycerophosphatase activities and for making hematoxylin-eosin staining were cut from m. quadriceps femoris 1, 2, 3, 5, 7, and 15 days after physical exhaustion. A strong increase in the activities of beta-glucuronidase and beta-N-acetylglucosaminidase was observed 7 days after exhaustion and the activity changes, which were similar for the both glycosidases, were more prominent in the highly oxidative red compared to less oxidative white fibres. Activity granules were more numerous in the perinuclear than the interfibrillar area of red fibres. Spots were arranged like longitudinal chains between myofibrils. Activity in connective tissue was usually observed only in animals exhausted 3--7 days earlier. Simultaneous activity in fibres exceeded that in connective tissue. beta-Glycerophosphatase activity was not, by the method used, seen in histologically "healthy" or normal-looking fibres. In samples taken 2--5 days after exhaustion some degenerating and necrotic fibres were observed. Inflammatory reaction was also observed being at its strongest five days after loading when mononuclear cells were seen inside necrotic fibres. The number of regenerating muscle cells was most abundant 7 days after exhaustion. It is suggested that temporary hypoxia, which accompanies exhaustive physical exercise in skeletal muscle, upsets the energy metabolism and homeostasis of fibres and causes the observed histological and histochemical alterations, which possess features typical of both lethal and sublethal acute cell injury.


[Aggressive fibromatosis of the penis (desmoid tumor)].
To describe an additional case of desmoid tumor of the penis. The incidence, etiopathogenesis, symptoms, diagnosis and treatment of this condition are discussed. A 70-year-old male consulted at the emergency services for pain and urinary symptoms. Physical examination showed no regional lymphadenopathy. Patient assessment by ultrasound and CT disclosed a penile lesion. Treatment was by wide local excision. Control evaluation at 3, 6 and 12 months showed normal findings and the patient remains asymptomatic. Wide local excision is advocated as the treatment of choice for desmoid tumor of the penis.


Metaiodobenzylguanidine and hyperglycemia augment tumor response to isolated limb perfusion in a rodent model of human melanoma.
Perfusate acidification with dilute hydrochloric acid augments tumor response rates in a rodent model of isolated limb perfusion (ILP). This study investigates the combination of metaiodobenzylguanidine (MIBG), a mitochondrial inhibitor, and systemic hyperglycemia as a strategy to selectively acidify tumors and thereby sensitize them to ILP. Human melanoma xenografts were implanted into the hind limbs of athymic rats. When tumors reached 12 to 15 mm in diameter, animals were randomized to ILP with or without melphalan, with or without systemic MIBG, and hyperglycemia of 485 +/- 35 mg/dL. Intratumoral pH was measured during MIBG and glucose treatment by using magnetic resonance spectroscopy. MIBG at 30 mg/kg plus hyperglycemia decreased intracellular pH by.6 units and extracellular pH by.8 units. MIBG at 22.5 mg/kg plus hyperglycemia decreased intracellular and extracellular pH by.4 and.5 units, respectively. Tumor growth was unaffected by systemic MIBG and hyperglycemia alone. When MIBG at 30 mg/kg and hyperglycemia were combined with ILP, tumor growth was delayed for 33 days after control ILP and for 44 days after melphalan ILP. However, this dose of MIBG was complicated by a 40% mortality rate after ILP. MIBG at 22.5 mg/kg, in combination with MIBG in the perfusate, did not cause mortality and delayed tumor growth by 51 days after melphalan ILP. MIBG and hyperglycemia improve tumor response rates after ILP in a rodent model of human melanoma. Selective tumor acidification with MIBG and hyperglycemia may offer added benefit to current regional perfusion strategies.


HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity.
Both cytotoxic T cells and helper T cells are important in immune responses against pathogens and malignant cells. In hematological malignancies which express HLA class II molecules, immunotherapy may be directed to HLA class II restricted antigens. We investigated whether it is possible to engineer HLA class II restricted T cells with both antigen-specific cytolytic activity and the capacity to produce high amounts of cytokines. CD4+ and CD8+ peripheral-blood-derived T cells were retrovirally transduced with the HLA class II restricted minor histocompatibility antigen dead box RNA helicase Y (DBY)-specific TCR. The TCR-transduced CD4+ T cells exerted DBY-specific cytolytic activity, produced Th0, Th1, or Th2 cytokines, and proliferated upon DBY-specific stimulation. TCR-transduced CD8+ T cells exerted cytolytic activity which equaled the level of cytolytic activity of the TCR-transferred CD4+ T cells. Cotransfer of CD4 enhanced the cytolytic activity of the TCR-transduced CD8+ T cells, but introduction of CD4 was not sufficient to generate DBY-specific CD8+ T cells with the capacity to produce high amounts of cytokines. In this study, we demonstrated the feasibility to engineer T cells with antigen-specific cytolytic activity, as well as the ability to produce significant amounts of cytokines, by TCR transfer to CD4+ T cells.


Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform.
High density lipoprotein (HDL) is an important natural nanoparticle that may be modified for biomedical imaging purposes. Here we developed a novel technique to create unique multimodality HDL mimicking nanoparticles by incorporation of gold, iron oxide, or quantum dot nanocrystals for computed tomography, magnetic resonance, and fluorescence imaging, respectively. By including additional labels in the corona of the particles, they were made multifunctional. The characteristics of these nanoparticles, as well as their in vitro and in vivo behavior, revealed that they closely mimic native HDL.


Monoclonal antibodies against synthesized short peptides corresponding to human AA amyloid protein.
Monoclonal antibodies (McAbs) were raised against the synthesized short peptides corresponding to 37-47 residues in amino acid sequence of human AA protein. The McAbs reacted immunohistochemically to amyloid tissues from cow, mouse, swan, and human AA amyloidosis. We concluded that the McAbs were useful for identification of AA type amyloidosis of various species, and that the 37-47 residues were effective antigenic sites in AA protein.


Time-dependent improvement in functional outcome following Oxford medial unicompartmental knee arthroplasty. A prospective longitudinal multicenter study involving 96 patients.
10-year survival rates after unicompartmental knee replacement (UKR) have been up to 97% in single-center studies, but they have been as low as 80% in studies from arthroplasty registers. Few studies have evaluated short-term functional outcome and its improvement with time. We determined the time course of functional outcome as evaluated by the knee injury and osteoarthritis outcome score (KOOS) over the first 2 years after Oxford medial UKR. In a prospective multicenter study, we included 99 unselected knees (96 patients, mean age 65 (51-80) years, 57 women) operated with Oxford medial UKR at 3 hospitals in the southeast of Norway between November 2003 and October 2006. Data were collected by independent investigators preoperatively and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. KOOS and range of motion (ROM) were determined at all follow-ups. Mean KOOS values for pain and activities of daily living were improved already after 6 weeks, and increased between each time point up to 2 years postoperatively. However, no statistically significant improvements were seen after 6 months. Mean active and passive ROM gradually improved up to 2 years after UKR, and were then better than before surgery. Most of the expected improvements in pain and function after UKR are achieved within 6 months of surgery. Only minimal improvement can be expected beyond this time.


Synthesis and evaluation of artificial taxoids with antitumor and multi-drug resistance reversing activities.
Artificial taxoids were synthesized and subjected to evaluation of their ability of multi-drug resistance reversing and antitumor activities. While the taxoid 4 could not increase cellular accumulation of vincristine in multi-drug resistant tumor cells, the C4-hydroxy analog 15 showed significant effect. However, these compounds showed weak activities on growth inhibition of cancer cells.


Temporal changes in open-field activity following progressive lesions of entorhinal cortex: evidence for enhanced recovery.
Simultaneous bilateral lesions of the entorhinal cortex typically result in an increase in locomotor activity followed by a decline toward control levels. The present investigation evaluated the effects of "progressive" or "serial" entorhinal lesions on open-field activity. Progressive lesions were made by destroying either the medial or lateral portion of entorhinal cortex bilaterally during one operation and then destroying the remaining portion 11-15 days later. By contrast, serial lesions were made by destroying the entorhinal cortex totally on one side during one operation and then destroying the contralateral side 15 days later. Progressive lesions enhanced the rate and extent of the decline in activity, whereas serial lesions did not. Interoperative testing experience did not appreciably alter the pattern of changes in activity following either type of lesion. The present results indicate that progressive (but not serial) lesions of entorhinal cortex enhance behavioral recovery, and that the degree of recovery following such lesions may be related to the spatial and temporal pattern of sprouting in the hippocampus.