New evidence on the impact of antithrombotics in patients submitted to small bowel capsule endoscopy for the evaluation of obscure gastrointestinal bleeding.
Objectives. Small bowel capsule endoscopy (SBCE) plays a decisive role in the obscure gastrointestinal bleeding (OGIB) diagnosis. Antithrombotics may increase bleeding risk in patients with preexistent lesions or through direct mucosal aggression. We aimed to correlate antithrombotics usage with lesions with bleeding potential found in SBCE. Methods. Retrospective single-center study including 274 consecutive SBCE performed over 7 years for OGIB. The lesions were classified as P0 (no bleeding potential), P1 (uncertain bleeding potential: erosions), and P2 (high bleeding potential: angioectasias, ulcers, and tumors). We assessed antiplatelet and anticoagulant drug use during the 60 days preceding SBCE. Results. One-third of the patients were under antithrombotic therapy. The diagnostic yield of SBCE for P2 lesions was 30.0%. Angioectasias (20.4%) were the most frequently observed lesions. There was a significant correlation between anticoagulant drug use and a higher incidence of P2 lesions in the small bowel (43.2% versus 26.5%; OR = 2.11, P = 0.026). We found no significant correlation between antiplatelets and lesions with bleeding potential in SBCE. Conclusions. Small bowel lesions with high bleeding potential were more frequently detected when the patient was on anticoagulant drugs, resulting in a twofold risk. Antiplatelet drugs were not associated with small bowel lesions.


Is there a correlation between molecular markers and response to neoadjuvant chemoradiotherapy in locally advanced squamous cell esophageal cancer?
To evaluate the expression of epidermal growth factor receptor (EGFR), p53, p21 and thymidylate synthase (TS) in a pretherapy biopsy specimen of locally advanced squamous cell esophageal cancer and correlate these markers with response to neoadjuvant chemoradiotherapy. Sixty-two patients with histopathologically proven locally advanced (T3 or greater) squamous cell esophageal cancer were enrolled. The expression of EGRF, p53, p21 and TS markers was assessed with immunohistochemistry. Semiquantitative assessment of expression of these markers was performed based on the percent of the stained cells. Radiotherapy (45-50.4 Gy) was delivered concomitantly with 5-fluorouracil (5-FU)/leucovorin (LV)/cisplatin (CIS) chemotherapy. Five to 6 weeks after chemoradiation, response to treatment was assessed. Medically fit and operable patients were operated. The resected material underwent histopathological evaluation of tumor expansion, histological classification after initial multimodality treatment (yp TNM), residual status and tumor regression grade (TRG). Out of 62 patients enrolled, 41 (66%) were evaluated for molecular markers. Clinical response rate was 43.9%. Out of 41 patients, 12 (29%) underwent surgery. TRG 1 was noted in 58% of the patients. In a pretherapy tumor specimen, positive expression was noted in 80, 90, 80 and 71% for EGFR, p53, p21 and TS, respectively. We noted no statistically significant difference neither between tumor marker expression and clinical response to chemoradiation, nor between tumor marker expression and TRG. We registered no difference in response to treatment between EGFR, TS, p21 and p53 positive and negative staining.


Analysis of synovial fluid visfatin level in temporomandibular joint disorders.
Background: Biochemical analysis of synovial fluid (SF) is an important means of understanding the pathogenesis of temporomandibular disorder (TMD) and confirming diagnoses made using traditional methods. Objective: The aim of this study was to determine whether or not SF visfatin levels can serve as a biochemical marker in the diagnosis of TMD. Method: Sixty samples of SF were obtained from 60 patients with internal derangement (ID) or osteoarthritis (OA). Visfatin in the SF was examined by enzyme-linked immunosorbent assay (ELISA). Result: Visfatin levels showed positive correlations with TMD pain and ID stage and a negative correlation with maximum mouth opening. In addition, Visfatin levels in joints with OA changes in the condyle were significantly higher in comparison to joints with no OA changes. Conclusion: Within the limitations of this study, it can be concluded that visfatin may play a role in the pathogenesis of TMD.


Effective identification of Gram-negative bacterial type III secreted effectors using position-specific residue conservation profiles.
Type III secretion systems (T3SSs) are central to the pathogenesis and specifically deliver their secreted substrates (type III secreted proteins, T3SPs) into host cells. Since T3SPs play a crucial role in pathogen-host interactions, identifying them is crucial to our understanding of the pathogenic mechanisms of T3SSs. This study reports a novel and effective method for identifying the distinctive residues which are conserved different from other SPs for T3SPs prediction. Moreover, the importance of several sequence features was evaluated and further, a promising prediction model was constructed. Based on the conservation profiles constructed by a position-specific scoring matrix (PSSM), 52 distinctive residues were identified. To our knowledge, this is the first attempt to identify the distinct residues of T3SPs. Of the 52 distinct residues, the first 30 amino acid residues are all included, which is consistent with previous studies reporting that the secretion signal generally occurs within the first 30 residue positions. However, the remaining 22 positions span residues 30-100 were also proven by our method to contain important signal information for T3SP secretion because the translocation of many effectors also depends on the chaperone-binding residues that follow the secretion signal. For further feature optimisation and compression, permutation importance analysis was conducted to select 62 optimal sequence features. A prediction model across 16 species was developed using random forest to classify T3SPs and non-T3 SPs, with high receiver operating curve of 0.93 in the 10-fold cross validation and an accuracy of 94.29% for the test set. Moreover, when performing on a common independent dataset, the results demonstrate that our method outperforms all the others published to date. Finally, the novel, experimentally confirmed T3 effectors were used to further demonstrate the model's correct application. The model and all data used in this paper are freely available at http://cic.scu.edu.cn/bioinformatics/T3SPs.zip.


Phase I and II trial of five-day infused 5-fluorouracil and radiation in advanced cancer of the head and neck.
Eighteen patients with advanced epithelial cancers of the head and neck region were studied for their tolerance and response to combined cycles of 120-hour infused 5-fluorouracil (5-FU) and external-beam radiation therapy. 5-FU infusions were given under conditions where radiosensitization would be expected at the higher infusion doses. Coincident radiation treatments were given as four sequential daily fractions of 250 rad each administered during days 1 through 4 of each five-day infusion cycle. The patients were rested for at least nine days after each cycle or longer until toxicity was resolved. The regimen was then repeated in each patient for a total of five treatment cycles. Thereafter therapy was consolidated, usually by boost radiation without drug. In sequential patient subsets the infusion load was progressively escalated in a phase I format. The complete response rate for stage IV patients was 75% with survival benefit compared to prior results. 5-FU dose-dependent combined modality loco-regional toxicity was demonstrated without significant enhancement of systemic toxicity of any form; 5-FU dose-dependent enhanced responsiveness and survival benefit is also suggested. Further scheduling and response studies of 5-FU under radiosensitizing conditions appear warranted.


Epidermoid carcinoma arising from within an epidermoid inclusion cyst.
The unusual occurrence of epidermoid carcinoma within an inclusion cyst arising on the forehead of a patient is documented. The importance of any irregular change or clinically abnormal behavior in such a lesion is underscored and the necessity for routine histological examination of all tissue excised is reaffirmed.


Comprehensive single-cell transcriptional profiling defines shared and unique epithelial injury responses during kidney fibrosis.
The underlying cellular events driving kidney fibrogenesis and metabolic dysfunction are incompletely understood. Here, we employed single-cell combinatorial indexing RNA sequencing to analyze 24 mouse kidneys from two fibrosis models. We profiled 309,666 cells in one experiment, representing 50 cell types/states encompassing epithelial, endothelial, immune, and stromal populations. Single-cell analysis identified diverse injury states of the proximal tubule, including two distinct early-phase populations with dysregulated lipid and amino acid metabolism, respectively. Lipid metabolism was defective in the chronic phase but was transiently activated in the very early stages of ischemia-induced injury, where we discovered increased lipid deposition and increased fatty acid β-oxidation. Perilipin 2 was identified as a surface marker of intracellular lipid droplets, and its knockdown in vitro disrupted cell energy state maintenance during lipid accumulation. Surveying epithelial cells across nephron segments identified shared and unique injury responses. Stromal cells exhibited high heterogeneity and contributed to fibrogenesis by epithelial-stromal crosstalk.


Dynamic radiostereometric analysis for evaluation of hip joint pathomechanics.
Dynamic RSA (dRSA) enables non-invasive 3D motion-tracking of bones and may be used to evaluate in-vivo hip joint kinematics including hip pathomechanics such as femoroacetabular impingement (FAI) and the biomechanical effects of arthroscopic cheilectomy and -rim trimming (ACH). The study aim was to evaluate the kinematic changes in the hip joint after ACH. Seven non-FAI affected human cadaveric hips were CT-scanned and CT-bone models were created. dRSA recordings of the hip joints were acquired at five frames/s during passive flexion, adduction to stop, and internal rotation to stop (FADIR). ACH was performed and dRSA was repeated. dRSA images were analyzed using model-based RSA. Hip joint kinematics before and after ACH were compared pairwise. The volume of removed bone was quantified and compared to the postoperative range of motion (ROM). Mean hip internal rotation increased from 19.1 to 21.9° (p = 0.04, Δ2.8°, SD 2.7) after ACH surgery. Mean adduction of 3.9° before and 2.7° after ACH surgery was unchanged (p = 0.48, Δ-1.2°; SD 4.3). Mean flexion angles during dRSA tests were 82.4° before and 80.8° after ACH surgery, which were similar (p = 0.18, Δ-1.6°, SD = 2.7). No correlation between volume of removed bone and ROM was observed. A small increase in internal rotation, but not in adduction, was observed after arthroscopic cheilectomy and -rim trimming in cadaver hips. The hip flexion angle of the FADIR test was reproducible. dRSA kinematic analysis is a new and clinically applicable method with good potential to evaluate hip joint kinematics and to test FAI pathomechanics and other surgical corrections of the hip.


Reforming graduate medical education.
Because of the traditional subordination of education to service, graduate medical education (GME) in the United States has never realized its full educational potential. This article suggests 4 strategies for reasserting the primacy of education in GME: limit the number of patients house officers manage at one time, relieve the resident staff of noneducational chores, improve educational content, and ease emotional stresses. Achieving these goals will require regulatory reform, adequate funding, and institutional competency in the use of educational resources. Modern medicine grows ever more complex. The need to address the deficiencies of GME is urgent.


Electronic temperatures, densities, and plasma x-ray emission of a 14.5 GHz electron-cyclotron resonance ion source.
We have performed a systematic study of the bremsstrahlung emission from the electrons in the plasma of a commercial 14.5 GHz electron-cyclotron resonance ion source. The electronic spectral temperature and the product of ionic and electronic densities of the plasma are measured by analyzing the bremsstrahlung spectra recorded for several rare gases (Ar, Kr, and Xe) as a function of the injected power. Within our uncertainty, we find an average temperature of approximately 48 keV above 100 W, with a weak dependency on the injected power and gas composition. Charge state distributions of extracted ion beams have been determined as well, providing a way to disentangle the ionic density from the electronic density. Moreover x-ray emission from highly charged argon ions in the plasma has been observed with a high-resolution mosaic-crystal spectrometer, demonstrating the feasibility for high-precision measurements of transition energies of highly charged ions, in particular, of the magnetic dipole (M1) transition of He-like of argon ions.


Climate change amplifies the interactions between wind and bark beetle disturbances in forest landscapes.
Growing evidence suggests that climate change could substantially alter forest disturbances. Interactions between individual disturbance agents are a major component of disturbance regimes, yet how interactions contribute to their climate sensitivity remains largely unknown. Here, our aim was to assess the climate sensitivity of disturbance interactions, focusing on wind and bark beetle disturbances. We developed a process-based model of bark beetle disturbance, integrated into the dynamic forest landscape model iLand (already including a detailed model of wind disturbance). We evaluated the integrated model against observations from three wind events and a subsequent bark beetle outbreak, affecting 530.2 ha (3.8 %) of a mountain forest landscape in Austria between 2007 and 2014. Subsequently, we conducted a factorial experiment determining the effect of changes in climate variables on the area disturbed by wind and bark beetles separately and in combination. iLand was well able to reproduce observations with regard to area, temporal sequence, and spatial pattern of disturbance. The observed disturbance dynamics was strongly driven by interactions, with 64.3 % of the area disturbed attributed to interaction effects. A +4 °C warming increased the disturbed area by +264.7 % and the area-weighted mean patch size by +1794.3 %. Interactions were found to have a ten times higher sensitivity to temperature changes than main effects, considerably amplifying the climate sensitivity of the disturbance regime. Disturbance interactions are a key component of the forest disturbance regime. Neglecting interaction effects can lead to a substantial underestimation of the climate change sensitivity of disturbance regimes.


A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal tear model.
Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis (OA) as a viscosupplement, yet it only provides short-term benefit because HA is cleaved by hyaluronidase and cleared out of the joint after several days. Therefore, we developed a new polymer biolubricant based on poly-oxanorbornane carboxylate to enhance joint lubrication for a prolonged time. Rheological and biotribological studies of the biolubricant reveal viscoelastic properties and coefficient of friction equivalent and superior to that of healthy synovial fluid, respectively. Furthermore, in an ex vivo bovine cartilage plug model, the biolubricant exhibits superior long-term reduction of friction and wear prevention compared to saline and healthy synovial fluid. ISO 10993 biocompatibility tests demonstrate that the biolubricant polymer is non-toxic. In an in vivo rat medial meniscal tear OA model, where the performance of the leading HA viscosupplement (Synvisc-one®) is comparable to the saline control, treatment with the biolubricant affords significant chondroprotection compared to the saline control.


Cardiovascular abnormalities in the Marfanoid hypermobility syndrome.
Two patients are described who had the body habitus of the Marfan syndrome, cutaneous hyperextensibility, and atrophic "cigarette paper" scars. One had mild joint hypermobility and the other had generalized ligamentous laxity. Both individuals are considered to be examples of the Marfanoid hypermobility syndrome, a generalized heritable connective tissue disease with features of, but genetically distinct from, the Marfan and Ehlers-Danlos syndromes. One patient had a "floppy" mitral valve and the other had an aortic aneurysm due to cystic medionecrosis of the aorta; both findings provide evidence that cardiovascular disease may be a significant feature of this syndrome.


Overcoming solvent saturation-transfer artifacts in protein NMR at neutral pH. Application of pulsed field gradients in measurements of 1H-15N Overhauser effects.
Artifacts due to solvent saturation-transfer effects result in incorrect measurements of 1H-15N heteronuclear NOE (HNOE). These artifacts are commonly observed in aqueous protein solutions at neutral pH. We describe the application of pulsed field gradients (PFGs) together with long recycle delays in overcoming errors in HNOE measurements which arise from H2O solvent preirradiation and solvent saturation transfer. Even in the absence of explicit solvent irradiation, the HNOE pulse sequence itself results in a nonequilibrium spin-state distribution of solvent nuclei which can then be transferred by chemical exchange into amide-proton sites. This effect can be avoided by using PFGs for suppression of solvent H2O together with a recycle delay sufficiently long for the magnetization of water to relax back to equilibrium values during the preparation period. These effects were studied in 15N-enriched human type alpha transforming growth factor at pH 7.1. Comparisons of PFG-HNOE experiments with and without selective H2O irradiation and with different recycle times provide estimates of the effects of solvent irradiation on HNOE measurements, which are different for different amide nitrogen-15 nuclei. The amplitudes of these artificial HNOE enhancements are roughly correlated with solvent accessibilities of amide sites in the three-dimensional structure of hTGF alpha.


Lipopolysaccharide-reactive B cells against bromelain-treated mouse erythrocytes: preferential migration to and survival in the peritoneal cavity.
The ratio of lipopolysaccharide (LPS)-reactive B cells specific for bromelain-treated mouse erythrocytes (BrMRBC) to general LPS-reactive B cells is far higher in the peritoneal cavity of normal mice than in their spleen. To investigate the high concentration of anti-BrMRBC LPS-reactive B cells in the peritoneal cavity, spleen and peritoneal cells from (CBA/N X C3H/He)F1 female normal mice were injected intravenously and intraperitoneally into F1 male X-linked immunodeficient mice. Both groups of B cells in the intravenously transferred cell population were able equally to home in the spleen, but only anti-BrMRBC LPS-reactive B cells could be detected migrating into the peritoneal cavity. About half the anti-BrMRBC LPS-reactive B cells in the intraperitoneally transferred cell population could be recovered from the peritoneal cavity, but general LPS-reactive B cells were eliminated rather rapidly from the peritoneal cavity. Neither group of B cells could be detected migrating from the peritoneal cavity into the spleen. These findings suggest that the high concentration of anti-BrMRBC LPS-reactive B cells in the peritoneal cavity may be caused by their preferential ability to penetrate into the peritoneal cavity through circulation and survive there.


The Value of CT 3D Reconstruction in the Classification and Nursing Effect Evaluation of Ankle Fracture.
To study the application value of ankle fracture classification and diagnosis. In this paper, the clinical data of 100 cases of ankle fracture patients admitted from May 2020 to May 2021 were analyzed by CT 3D reconstruction. All patients received surgical treatment and underwent spiral CT 3D reconstruction and X-ray examination before surgery. The results showed that 20 cases (20.00%) of the 100 cases were PER, 24 cases (24%) of the 100 cases were PAB, 31 cases (31%) of the 100 cases were SER, and 25 cases (25%) of the 100 cases were SAB, respectively. The diagnostic accuracy of CT 3D reconstruction for different types of ankle fracture is higher than that of X-ray, and the differences are statistically significant (P < 0.05). CT 3D reconstruction is applied in the early diagnosis of ankle fracture, which can accurately detect the classification of patients. It has important clinical application value and can be used as the first choice for the early classification diagnosis of ankle fracture.


[The role of the students' research groups in the formation of the system of values as a personality trait of the future doctor].
This publication was designed to report the experience gained by the Department of Ear, Throat and Nose Diseases at I.M. Sechenov First Moscow State Medical University in the matters concerning the education of the students involved in the activities of research groups. The main causes for which the senior students should be attracted to doing research work in the framework of the university-based scientific societies are considered. Special emphasis is laid on the role of the students' research groups in the formation of the system of values as a personality trait of the future doctor. The experience gained during the recent years with the organization of inter-institutional students' competitions (otorhinolaryngological olympiads) is discussed.


Sequential acquisition of R-plasmids in vivo by Salmonella typhimurium.
Salmonella typhimurium, resistant only to trimethoprim and sulphamethoxazole, was isolated from the faeces and blood of a chronic alcoholic patient in acute renal failure. The isolates harboured an 18 Md non-conjugative plasmid. He was dialysed peritoneally and treated with ampicillin; four days later there was no clinical improvement and his peritoneal dialysis fluid (PDF) had become infected. Salm. typhimurium was isolated from faeces and PDF. Both isolates were additionally resistant to ampicillin and contained two plasmids (55 Md and 18 Md). Therapy was changed to chloramphenicol and gentamicin was added to the PDF. Two weeks later Salm. typhimurium was again isolated from PDF and faeces. The PDF isolate was unchanged but 4% of the colonies isolated from this faecal specimen were resistant to chloramphenicol and had acquired an additional 62 Md plasmid. From all PDF and faecal specimens two different strains of Escherichia coli and one strain of Klebsiella pneumoniae were isolated which contained plasmids indistinguishable, on the basis of molecular weight and transferable resistance markers, from those acquired by Salm. typhimurium. The transferability of these plasmids in vitro to E. coli K12 and to the patient's initial Salm. typhimurium was studied and the results discussed.


Informal settlements and a relational view of health in Nairobi, Kenya: sanitation, gender and dignity.
On an urban planet, slums or informal settlements present an increasing challenge for health promotion. The living conditions in complex informal settlements interact with how people navigate through their daily lives and political institutions to shape health inequities. In this article, we suggest that only a relational place-based characterization of informal settlements can accurately capture the forces contributing to existing urban health inequities and inform appropriate and effective health promotion interventions. We explore our relational framework using household survey, spatial mapping and qualitative focus group data gathered in partnership with residents and non-governmental organizations in the Mathare informal settlement in Nairobi, Kenya. All data interpretation included participation with local residents and organizations. We focus on the inter-relationships between inadequate sanitation and disease, social, economic and human rights for women and girls, who we show are most vulnerable from poor slum infrastructure. We suggest that this collaborative process results in co-produced insights about the meanings and relationships between infrastructure, security, resilience and health. We conclude that complex informal settlements require relational and context-specific data gathering and analyses to understand the multiple determinants of health and to inform appropriate and effective healthy city interventions.


Routine use of the thallium-technetium scan prior to parathyroidectomy.
The merit of the preoperative localization of parathyroid tumors with thallium-technetium subtraction imaging is a subject of current debate in the treatment of primary hyperparathyroidism. Eighty patients with hyperparathyroidism underwent preoperative subtraction scintigraphy with 201Tl Cl and 99mTcO4; scan results were correlated with the operative identification and histopathology of the resected parathyroid tissue. The true-positive, false-positive and false-negative rates of these scans were compared between patients with tumors in normal and ectopic anatomic locations and between patients undergoing an initial and reoperative neck exploration. The scan was clearly valuable in patients with one or more prior neck explorations. True-positive scans were obtained in seven (77%) of nine such patients. The scan was also valuable in patients who had ectopic tumors (six mediastinal, seven intrathyroid, and two in the carotid sheath). Twelve (80%) of these 15 ectopic tumors were correctly localized either prior to their first operation or before subsequent explorations. In contrast, only 33 (50%) of 65 patients had a true-positive scan prior to their first operation and when the tumor was not in an ectopic location. In summary, in this series, the thallium-technetium scan was correct in only 50 per cent of patients undergoing an initial operation. However, it was positive in 77 per cent of patients who had at least one prior neck exploration and in 80 per cent of patients with an ectopic parathyroid tumor. These results support the selective use of this valuable imaging and localization tool.


PC4 serves as a negative regulator of skin wound healing in mice.
Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model. A PC4 knock-in mouse model (PC4+/+) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay. The PC4+/+ mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4+/+ skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4+/+ mice in vitro. This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.


De novo protein design by an energy function based on series expansion in distance and orientation dependence.
Despite many successes, de novo protein design is not yet a solved problem as its success rate remains low. The low success rate is largely because we do not yet have an accurate energy function for describing the solvent-mediated interaction between amino acid residues in a protein chain. Previous studies showed that an energy function based on series expansions with its parameters optimized for side-chain and loop conformations can lead to one of the most accurate methods for side chain (OSCAR) and loop prediction (LEAP). Following the same strategy, we developed an energy function based on series expansions with the parameters optimized in four separate stages (recovering single-residue types without and with orientation dependence, selecting loop decoys and maintaining the composition of amino acids). We tested the energy function for de novo design by using Monte Carlo simulated annealing. The method for protein design (OSCAR-Design) is found to be as accurate as OSCAR and LEAP for side-chain and loop prediction, respectively. In de novo design, it can recover native residue types ranging from 38% to 43% depending on test sets, conserve hydrophobic/hydrophilic residues at ∼75%, and yield the overall similarity in amino acid compositions at more than 90%. These performance measures are all statistically significantly better than several protein design programs compared. Moreover, the largest hydrophobic patch areas in designed proteins are near or smaller than those in native proteins. Thus, an energy function based on series expansion can be made useful for protein design. The Linux executable version is freely available for academic users at http://zhouyq-lab.szbl.ac.cn/resources/.


Bronchiolitis obliterans organising pneumonia: a consequence of breast radiotherapy.
The authors describe a case of 51-year-old woman who presented with breathlessness following radiotherapy for breast carcinoma. A chest radiograph and thoracic CT scan revealed extensive airspace consolidation affecting right upper and lower lobes. A trans-bronchial biopsy revealed evidence of foamy macrophages and fibroblastic plugs within alveoli, consistent with organising pneumonia. Indirect immunofluorescence microscopy revealed evidence of antiepithelial antibodies. Gradual but complete resolution occurred without any specific treatment. This case highlights the importance of considering radiation induced bronchiolitis obliterans organising pneumonia in the context of parenchymal shadowing following radiotherapy. Although corticosteroids are widely recommended for treatment, this case illustrates that organising pneumonia may resolve spontaneously.


The Influence of Weight Bias on Processes and Outcomes in Negotiation.
In two studies, using a mix of samples, we examined the influence of weight bias on behaviors in competitive, potentially high stakes situations. As predicted, weight bias directed focal actors' treatment of counterparts in a negotiation. Negotiators made lower value offers to overweight counterparts relative to average-weight counterparts. In addition, overweight counterparts also received more negative messages over the course of their negotiation and were evaluated less favorably after the negotiation than average-weight counterparts.


IL-23R gene confers susceptibility to Behcet's disease in a Chinese Han population.
IL-23 has been shown to be involved in the pathogenesis of Behcet's disease (BD) through promoting IL-17 production. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population. Four single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, rs 1343151 and rs17375018 were genotyped in 338 BD patients and 407 age, sex and ethnically matched healthy controls using a PCR restriction fragment length polymorphism assay. A significantly increased prevalence of the homozygous rs17375018 GG genotype and G allele was found in BD patients compared with controls (corrected p (p(c))<0.001,odds ratio (OR) 1.86, 95% CI 1.39 to 2.49; p(c)<0.001, OR 1.57, 95% CI 1.25 to 1.98, respectively). The frequencies of the AA genotype and A allele of the SNP rs11209032 were significantly higher in BD patients compared with controls (p(c)=0.024, OR 1.69, 95% CI 1.21 to 2.35; p(c)<0.001, OR 1.48, 95% CI 1.21 to 1.82, respectively). In addition, the results showed a significantly decreased frequency of the AGCG haplotype in BD patients compared with controls (p(c)=0.0016, OR 0.59, 95% CI 0.45 to 0.77). This study, for the first time, identified a strong association of an SNP of IL-23R, rs17375018, with BD. The results also suggested that both rs11209032 AA and rs17375018 GG of IL-23R are predisposing genotypes for BD and that the AGCG haplotype may provide protection against BD.


Hemolysis, Elevated Liver Enzymes, and Low Platelets, Severe Fetal Growth Restriction, Postpartum Subarachnoid Hemorrhage, and Craniotomy: A Rare Case Report and Systematic Review.
Introduction. Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a relatively uncommon but traumatic condition occurring in the later stage of pregnancy as a complication of severe preeclampsia or eclampsia. Prompt brain computed tomography (CT) or magnetic resonance imaging (MRI) and a multidisciplinary management approach are required to improve perinatal outcome. Case. A 37-year-old, Gravida 6, Para 1-0-4-1, Hispanic female with a history of chronic hypertension presented at 26 weeks and 6 days of gestational age. She was noted to have hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome accompanied by fetal growth restriction (FGR), during ultrasound evaluation, warranting premature delivery. The infant was delivered in stable condition suffering no permanent neurological deficit. Conclusion. HELLP syndrome is an uncommon and traumatic obstetric event which can lead to neurological deficits if not managed in a responsive and rapid manner. The central aggravating factor seems to be hypertension induced preeclamptic or eclamptic episode and complications thereof. The syndrome itself is manifested by hemolytic anemia, increased liver enzymes, and decreasing platelet counts with a majority of neurological defects resulting from hemorrhagic stroke or subarachnoid hemorrhage (SAH). To minimize adverse perinatal outcomes, obstetric management of this medical complication must include rapid clinical assessment, diagnostic examination, and neurosurgery consultation.


Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy.
Cancer is a worldwide health problem. Personalized treatment represents a future advancement for cancer treatment, in part due to the development of targeted therapeutic drugs. These molecules are expected to be more effective than current treatments and less harmful to normal cells. The discovery and validation of new targets are the foundation and the source of these new therapies. The neurotensinergic system has been shown to enhance cancer progression in various cancers such as pancreatic, prostate, lung, breast, and colon cancer. It also triggers multiple oncogenic signaling pathways, such as the PKC/ERK and AKT pathways. In this review, we discuss the contribution of the neurotensinergic system to cancer progression, as well as the regulation and mechanisms of the system in order to highlight its potential as a therapeutic target, and its prospect for its use as a treatment in certain cancers.


Effect of radiation and freezing on [3H]DNA of Yersinia enterocolitica.
Freezing of the enteropathogenic bacterium Yersinia enterocolitica to -18 and -75 degrees C caused 7 and 42% cell death, respectively, and 0.329 and 0.588 single-strand breaks per 10(8) daltons of DNA, respectively, while radiation to one D10 dose (10% cell survival) combined with freezing to 2 to 0, -18, and -75 degrees C induced 0.05, 0.75, and 5.04 single-strand breaks, respectively. The increase in the effectiveness of radiation with respect to the yield of single-strand breaks at -18 and -75 degrees C is contrary to expectation and seems to be due to arrest of repair of single-strand breaks by these low temperatures.


Functional loss of ARID1A is tightly associated with high PD-L1 expression in gastric cancer.
Notwithstanding remarkable treatment success with anti-PD-1 monoclonal antibody, oncogenic mechanism of PD-L1 regulation in gastric cancer (GC) remains poorly understood. We hypothesized that ARID1A might be related to tumor PD-L1 expression in GC. We found that tumor PD-L1 positivity was associated with loss of ARID1A and showed trend toward better survival of patients with various molecular subtypes of GC (experimental set, n = 273). Considering heterogeneous ARID1A expression, we validated this using whole tissue sections (n = 159) and found that loss of ARID1A was correlated with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and PD-L1 positivity. Furthermore, for patients with MSI-H tumors, the degree of PD-L1 expression was significantly higher in ARID1A-deficient tumors. After ARID1A knockdown in GC cell lines, total and membranous PD-L1 protein, and PD-L1 mRNA levels were increased based on Western blot, flow cytometry, and qRT-PCR, respectively. With IFN-γ treatment, PD-L1 expression was significantly increased both in ARID1A-deficient cancer cells and controls, but the increase was not more pronounced in the former. Loss of ARID1A increased PD-L1 via activating AKT signaling, while LY294002 (PI3K inhibitor) decreased PD-L1 levels. Furthermore, we found that 3 MSI-H tumors showing highest expression of PD-L1 had simultaneous KRAS mutation and loss of ARID1A, suggesting a possible synergistic role boosting PD-L1. Our results strongly indicate that loss of ARID1A is tightly associated with high PD-L1 expression in GC. These results would increase our understanding of the oncogenic mechanism of PD-L1 regulation in GC, and also help to find the optimal candidates for immunotherapy.


Emergency department response to domestic violence--California, 1992.
A 1993 national poll found that 34% of adults in the United States report having witnessed a man beating his wife or girlfriend and that 14% of women report that a husband or boyfriend has been violent with them (1). Studies suggest that as many as 30% of women treated in emergency departments (EDs) have injuries or symptoms related to physical abuse (2). A national health objective for the year 2000 is for at least 90% of hospital EDs to have protocols for routinely identifying, treating, and referring victims of sexual assault and spouse abuse (objective 7.12) (3). The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has also recommended that accredited EDs have policies, procedures, and education in place to guide staff in the treatment of battered adults (4). To assess progress toward the national health objective for the year 2000 and the JCAHO standards, all active EDs in California were surveyed during November-December 1992 about their policies and practices for the treatment of battered adults. This report presents findings of this survey.


Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences.
Variations in maternal care have been associated with long-term changes in neurochemistry and behaviour in adult rats. Rats receiving high levels of licking and grooming as pups are less fearful and more maternal than rats receiving low levels of maternal licking and grooming. Central pathways for oxytocin and vasopressin have been implicated in the neurobiology of anxiety and social behaviours. We assessed whether variations in maternal care were associated with differences in oxytocin receptors (OTR) or vasopressin (V1a) receptors in the brains of adult offspring. In the central nucleus of the amygdala and bed nucleus of the stria terminalis, OTR binding was increased in adult females, but not adult males, that had received high levels of maternal licking and grooming as pups. Conversely, amygdala V1a receptor binding was increased in males, but not females, that had received high levels of maternal licking and grooming. These findings suggest that variations in maternal care may influence the expression of oxytocin and vasopressin receptors in a gender-specific manner.


Geriatric patients on a substance abuse consultation service.
The authors describe the demographic and substance use characteristics of older adults (N=310) evaluated by a hospital-based substance abuse consultation service during a 6-year period and compares them to younger adults evaluated by the service. Older adults were more likely to use alcohol and less likely to be injection drug users and heroin, cocaine, or polysubstance users. Elderly patients were also more likely to be admitted for cardiac or gastrointestinal conditions and less likely to be admitted for infections. We estimated that only 1% of older adults admitted to the hospital were referred for substance abuse consultations. Our results suggest that substance use disorders in elderly patients are underdiagnosed and undertreated in the hospital setting.


Prognostic factors in periodontal therapy and their association with treatment outcomes.
During the incipient steps of periodontal treatment, clinicians are usually asked to predict the prognosis of teeth with compromised periodontium. The aim of this literature review was to investigate the association between periodontal Prognosis, Tooth Loss and risk indicators, such as smoking and genetics. Results showed that the definition of good prognosis has much higher predictability than the one for questionable prognosis. Several risk indicators for periodontal prognosis and tooth loss are discussed as well as different definitions of questionable prognosis and their success in predicting tooth loss. In conclusion, the major focus of future studies should be to construct simplified prognostic models with high predictability that will increase the confidence of dentists and periodontists when assigning teeth prognosis.


Lisinopril dihydrate: single-crystal x-ray structure and physicochemical characterization of derived solid forms.
Screening for new solid forms of the antihypertensive lisinopril was performed by recrystallization of the commercial form, lisinopril dihydrate, from various solvents and by exposing the product of its dehydration to a series of vapors under controlled conditions. Modifications other than the dihydrate encountered in the study included new anhydrous and amorphous forms, with intrinsic dissolution rates significantly greater than that of the dihydrate. Further physicochemical characterization included constant and programmed temperature powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, and Fourier transform infrared spectroscopy. In the course of this study, the single-crystal X-ray structure of lisinopril dihydrate, [a = 14.550(2), b = 5.8917(8), c = 14.238(2) Å, β = 112.832(3)° at T = 173(2) K, space group P21 , Z = 2], was determined for the first time, revealing its double zwitterionic character in the solid state.


The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants.
To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic group's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.


Concepts in antibody phage display.
This paper introduces the reader to antibody phage display and its use in combinatorial biochemistry. The focus is on overviewing phage display formats, library design and selection technology, which are the prerequisites for the successful isolation of specific antibody fragments against a diverse set of target antigens.


[Dystrophin gene expression in patients with Duchenne muscular dystrophy after myoblast transplantation].
Based on originally designed technique of myoblast cultivation and in accordance with the approved by the Russian Ministry of Health "one muscle treatment" protocol of myoblast transplantation to the Duchenne muscular dystrophy patients, the first in Russia clinical trial of this gene correction method was carried out. Immonologically related myoblast cultures (30 to 90 million cells per patient) were injected after all preliminary procedures into tibialis anterior muscles of four boys selected from a group of volunteer recipients (Duchenne muscular dystrophy patients) based on the analysis of a number of surface antigens in donor-recipient pairs. The condition of the patients remained satisfactory during the whole period of post-transplantation follow-up (from 6 months to 1.5 years). Six months after myoblast transplantation the presence of donor DNA or dystrophin synthesis was demonstrated in muscle biopsies of three out of four patients. This result confirms efficacy and safety of the procedure used.


Chatbots in the fight against the COVID-19 pandemic.
We are all together in a fight against the COVID-19 pandemic. Chatbots, if effectively designed and deployed, could help us by sharing up-to-date information quickly, encouraging desired health impacting behaviors, and lessening the psychological damage caused by fear and isolation. Despite this potential, the risk of amplifying misinformation and the lack of prior effectiveness research is cause for concern. Immediate collaborations between healthcare workers, companies, academics and governments are merited and may aid future pandemic preparedness efforts.


Chemical Transformation of Lead Halide Perovskite into Insoluble, Less Cytotoxic, and Brightly Luminescent CsPbBr3/CsPb2Br5 Composite Nanocrystals for Cell Imaging.
Lead halide perovskite nanocrystals (NCs) have been widely investigated owing to their potential applications as optoelectronic devices. However, these materials suffer from poor water stability, which make them impossible to be applied in biomedicine. Here, insoluble CsPbBr3/CsPb2Br5 composite NCs were successfully synthesized via simple water-assisted chemical transformation of perovskite NCs. Water plays two key roles in this synthesis: (i) stripping CsBr from CsPbBr3/Cs4PbBr6 and (ii) modifying the coordination number of Pb2+ (six in CsPbBr3 and Cs4PbBr6 vs eight in CsPb2Br5). The as-prepared CsPbBr3/CsPb2Br5 composite NCs not only retain the photoluminescence quantum yield (up to 80%) and a narrow full width to half-maximum of 16 nm, but also present excellent water stability and low cytotoxicity. With these properties, the CsPbBr3/CsPb2Br5 composite NCs were demonstrated as efficient fluorescent probes in live HeLa cells. We believe that our finding not only provides a new method to prepare insoluble, narrow-band, and brightly luminescent CsPbBr3/CsPb2Br5 composite NCs, but also extend the potential applications of lead halides in biomedicine.


The relationship among sexual attitudes, sexual fantasy, and religiosity.
Recent research on the impact of religiosity on sexuality has highlighted the role of the individual, and suggests that the effects of religious group and sexual attitudes and fantasy may be mediated through individual differences in spirituality. The present study investigated the role of religion in an ethnically diverse young adult sample (N = 1413, 69% women) using religious group as well as several religiosity domains: spirituality, intrinsic religiosity, paranormal beliefs, and fundamentalism. Differences between religious groups in conservative sexual attitudes were statistically significant but small; as predicted, spirituality mediated these effects. In contrast to the weak effects of religious group, spirituality, intrinsic religiosity, and fundamentalism were strong predictors of women's conservative sexual attitudes; for men, intrinsic religiosity predicted sexual attitude conservatism but spirituality predicted attitudinal liberalism. For women, both religious group and religiosity domains were significant predictors of frequency of sexual fantasies while, for men, only religiosity domains were significant predictors. These results indicate that individual differences in religiosity domains were better predictors of sexual attitudes and fantasy than religious group and that these associations are moderated by gender.


Enhanced cell density cultivation and rapid expression-screening of recombinant Pichia pastoris clones in microscale.
Cultivation of yeast Pichia pastoris in the microtiter plate, for optimisation of culture conditions, and expression screening of transformants has gained significance in recent years. However, in the microtiter plate, it has been challenging to attain cell densities similar to well-aerated shake-flask culture, due to the poor mixing resulting in oxygen limitation. To solve this problem, we investigated the influence of multiple cultivation parameters on P. pastoris cell growth, including the architecture of 96-deepwell plate (96-DWP), shaking throw diameter, shaking frequency, culture volume/well, and media composition. In the optimised conditions, a cell density of OD600 ~50 (dry cell weight ~13 g/L) with >99% cell viability was achieved in the casamino acids supplemented buffered-minimal-media in 300 to 1000 μl culture volume/well. We have devised a simplified method for coating of the culture supernatant on the polystyrene surface for immunoassay. Clones for secretory expression of envelope domain III of dengue virus serotype-1 under the control of inducible and constitutive promoter were screened using the developed method. Described microscale cultivation strategy can be used for rapid high-throughput screening of P. pastoris clones, media optimization, and high-throughput recombinant protein production. The knowledge gained through this work may also be applied, to other suspension cultures, with some modifications.


Tissue destruction resulting from the interaction of cytotoxic T cells and their targets.
In vitro and in vivo-generated cytotoxic T lymphocytes (CTL) specific for major and minor histocompatibility antigens evoked antigen-specific full-thickness skin necrosis when injected intradermally into allogeneic mice in a variety of strain combinations. In addition, CTL-target-cell mixtures injected intradermally into hosts syngeneic to the CTL also evoked destruction of host tissue. These "innocent bystander" reactions were evoked with alloreactive CTL as well as with CTL directed against hapten (TNP)-modified and virus (influenza A)-infected target cells. Unlike the direct reactions, the bystander reactions in histocompatibility-antigen systems occurred in spite of H-2 incompatibility of the CTL, admixed target cells, and the hosts. One explanation for these results, currently under investigation, is that some bystander reactions may occur without MHC restriction. In aggregate, our findings indicate that nonspecific as well as antigen-specific reactions initiated by CTL-target-cell interactions may contribute to tissue destruction in allograft rejection, in severe forms of delayed-type hypersensitivity, and in certain viral infections.


The persistence toxicity of four insecticides against adult Hippodamia varigata (Coleptera: Cocinellidae).
In order to investigate the effects of four insecticides on Hippodomia variegata (Coleoptera: Coccinellidae), the predator of Aphis fabae, an experiment was carried out using IOBC/wprs method. Persistence toxicity of insecticides has been evaluated in the greenhouse condition. The insecticides abamectin 1.8 EC, deltamethrin 2.5 EC, imidacloprid 350 SC, and proteus OD 110 were used at recommended field rates. The insecticides were applied on broad bean foliage using a hand sprayer, until run-off. Contact toxicity of aged residues of insecticides on adult predator was evaluated using the cage-method. The trials were laid out in randomized complete design (CRD) with 3 replicates and an untreated check. The arcsine transformation was used for analysis. The mortality of adult predator, after 24 h contact with fresh residues of abamectin, deltamethrin, imidacloprid and proteus were 53.4, 52.1, 63.4 and 65.1%, respectively. After 5 days the effect of residues decreased so that the adult mortality diminished to 32.4, 36.5, 56.1 and 57.5% for mentioned above insecticides. 15-day old residues lead to 8.8, 23.1, 56.3 and 57.5%; and 31-day old residues lead to 8.8, 22.7, 29.5 and 41.7% mortality for these insecticides, respectively. Based on this study, abamectin and deltamethrin with persistence less than 5 d are classified as short lived (Class A) while imidacloprid and proteus with persistence between 16 to 31d, classified as moderately persistent (Class C) compounds.


Energy restriction-induced changes in body composition are age specific in mice.
Restricting energy intake while supplying adequate micronutrients slows aging and extends maximal lifespan, whereas loss of body weight with exercise training does not. Our goal was to test the hypothesis that weight loss via energy restriction (ER) alters body composition in a way that is: 1) distinct from exercise-induced weight loss; and 2) conserved regardless of the age at which ER is initiated. An experimental model was developed where matched losses in weight could be induced with 6 mo of ER (approximately 55% of ad libitum energy intake) or voluntary exercise on a running wheel in adult (12 mo) male C57BL/6 mice and a similar amount of ER-induced weight loss could be induced in aged mice (24 mo). Using dual-energy X-ray absorptiometry, we determined that ER and exercise in the 12-mo-old mice caused nearly identical changes in the amount and distribution of adipose tissue in the 12-mo group, with 70-75% of overall weight loss due to fat loss. Decreased prostate and epididymal fat weights were similar with ER and exercise, and heart weight was unaffected by either intervention. In contrast to the adult mice, in aged mice, ER caused primarily a loss of lean body mass including the heart, with no decreased prostate or fat pad weight. Bone mineral density was decreased by ER but not exercise in the adult mice, an effect not seen in the aged mice. Our data refute the hypothesis that ER causes a unique change in body composition that is conserved across age and suggest that fat loss may not be an essential component of the anti-aging effects of ER.


Nursing as a sign of hope and contradiction in the land of the children of Abraham.
Israel, the Gaza Strip, and the West Bank share a small land area and the birthplace of three of the world's great monotheistic religions: Judaism, Christianity, and Islam. It is a land of paradoxes: ancient and modern, religious and secular. Nursing in this unique geographic and historical place struggles with many of the same issues and challenges facing nursing in other modern countries, but it also shines with dramatic episodes of nursing's ability to be a sign of hope and contradiction.


Pyrrolidine dithiocarbamate ameliorates endothelial dysfunction in thoracic aorta of diabetic rats by preserving vascular DDAH activity.
Endothelial dysfunction plays a pivotal role in the development of diabetic cardiovascular complications. Accumulation of endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity have been involved in diabetic endothelial dysfunction. This study was to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on impairment of endothelium-dependent vasodilatation in diabetic rats and its potential mechanism. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (60mg/kg), and PDTC (10mg/kg) was given in drinking water for 8 weeks. Blood glucose and serum ADMA concentrations were measured in experimental rats. Recombinant adenovirus encoding human DDAH2 gene were constructed and ex vivo transferred to isolated rat aortas. The maximal relaxation (Emax) and half maximal effective concentration (EC50) of aortic rings response to accumulative concentrations of acetylcholine and vascular DDAH activity were examined before and after gene transfection. Diabetic rats displayed significant elevations of blood glucose and serum ADMA levels compared to control group (P<0.01). Vascular DDAH activity and endothelium-dependent relaxation of aortas were inhibited, as expressed by the decreased Emax and increased EC50 in diabetic rats compared to control rats (P<0.01). Treatment with PDTC not only decreased blood glucose and serum ADMA concentration (P<0.01) but also restored vascular DDAH activity and endothelium-dependent relaxation, evidenced by the higher Emax and lower EC50 in PDTC-treated diabetic rats compared to untreated diabetic rats (P<0.01). Similar restoration of Emax, EC50 and DDAH activity were observed in diabetic aortas after DDAH2-gene transfection. These results indicate that PDTC could ameliorate impairment of endothelium-dependent relaxation in diabetic rats. The underlying mechanisms might be related to preservation of vascular DDAH activity and consequent reduction of endogenous ADMA in endothelium via its antioxidant action. This study highlights the therapeutic potential of PDTC in impaired vasodilation and provides a new strategy for treatment of diabetic cardiovascular complications.


Effects of angiotensins of the motility of human sperm.
The effects of angiotensins on the motility of highly washed human sperm were examined by multiple exposure photography system. The addition of low doses (0.1-10 ng/ml) of angiotensin II (AT II) stimulated the forward velocity of sperm without increasing the percentage of motility. On the contrary, high concentration (1.0 micrograms/ml) of AT II suppressed the motility. The direct effect of angiotensin I (AT I) on the motility was observed under the presence of SQ 14225, a specific inhibitor of angiotensin I converting enzyme (ACE). At I (0.1-100 ng/ml) gave no influence on the motility, whereas that of high dose (1.0 ug/ml) suppressed the motility in the same manner as the corresponding dose of AT II. The action of AT II on the motility was completely suppressed under the coexistence of saralasin, a specific antagonist against AT II. This fact indicated that the action of AT II on the sperm appeared through the specific receptor on sperm.


Nickel-promoted oxidative domino Csp3-H/N-H bond double-isocyanide insertion reaction to construct pyrrolin-2-ones.
The first nickel-catalyzed oxidative domino Csp3-H/N-H double isocyanide insertion reaction of acetamides with isocyanides has been developed for the synthesis of pyrrolin-2-one derivatives. A wide range of acetamides bearing various functional groups are compatible with this reaction system by utilizing Ni(acac)2 as a catalyst. In this transformation, isocyanide could serve as a C1 connector and insert into the inactive Csp3-H bond, representing an effective way to construct heterocycles.


Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.
Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function.


Respecting the privacy of hospitalized patients: An integrative review.
Privacy is a complicated and obscure concept, which has special meanings in the healthcare environment; therefore, it is essential for healthcare providers to fully understand this concept. However, there is no universally accepted definition for this concept in the texts, and it has been interpreted differently, based on its application. To analyze and provide a clear and scientific definition for respect of privacy of hospitalized patients and identify the common aspects of this concept. This study was conducted using the Whittemore and Knafl's modified framework as a conceptual analysis method. Ethical consideration: This study was approved by the Research Council of the University of Social Welfare and Rehabilitation Sciences. We have respected the ethical requirements required regarding the sources and authorship. Research context and data sources: Using integrative review, a search was performed using national and international databases, including CINAHL, Scopus, Medline, Web of Science, and ISI (with no date restriction). The keywords employed during the search process were "privacy of patients," "confidentiality," "and patients' rights." In total, 1345 articles were retrieved from the databases. After the elimination of repetitive studies and with regard to the study objectives, 124 articles, 3 books, and 4 theses were entered into the study. The data were analyzed using the conventional content analysis approach. The results were extracted in the form of four, seven, and two themes related to attributes such as physical, informational, social, and psychological and the antecedents and consequences of respecting patient privacy, respectively. Respect for hospitalized patient privacy contains multiple dimensions. Factors affecting the achievement of this concept include individual backgrounds, nature of the disease, and rule of paternalism. The fulfillment of patient privacy leads to such consequences as protection and improvement of human dignity as well as improved communication between the patient and the health team.


The cancer Warburg effect may be a testable example of the minimum entropy production rate principle.
Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 36 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle with regard to the function of the Warburg effect. The production of free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) per mole linearly varies with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0.9. Hence, calculation shows that, in respect to pure respiration, the predominant fermentative metabolism decreases around 10% the production of entropy per mole of glucose consumed in cancer cells. We hypothesize that increased fermentation could allow cancer cells to accomplish the Prigogine theorem of the trend to minimize the rate of production of entropy. According to the theorem, open cellular systems near the steady state could evolve to minimize the rates of entropy production that may be reached by modified replicating cells producing entropy at a low rate. Remarkably, at CO2 concentrations above 930 ppm, glucose respiration produces less entropy than fermentation, which suggests experimental tests to validate the hypothesis of minimization of the rate of entropy production through the Warburg effect.


[The usefulness of uterine artery doppler velocimetry in high risk pregnancy diagnostic (PIH and/or IUGR)].
High risk pregnancy was defined as developing of pregnancy induced hypertension or/and growth retardation in the course of gestation. The main aim of the study is to analyze the usefulness of uterine artery doppler velocimetry in high risk pregnancy diagnostic. 610 single pregnancies were included in the study. First group of normal pregnancies where -530 single normal pregnancies between 19 and 39 gestation weeks. S/D, RI & PI in both uterine arteries were assessed. There were assessed flow velocity waveforms also for detection of notches. At the next stage an examined group with 80 pregnant women was formed where in the course of gestation pregnancy induced hypertension and/or fetal growth retardation. 24 hour monitoring of the blood pressure in the examined group was performed. Obtained data from both groups was calculated and statistically analyzed. Mean values for flow velocity waveform indices were estimated for both groups: controls S/D 2,35 (SD 0,61), RI 0,56 (SD 0,11), PI 0,96 (SD 0,32), examined group S/D 2,99 (SD 1,16), RI 0,63 (SD 0,12), PI 1,26 (SD 0,51). There is significant difference between values for all flow parameters p < 0,001. In the control group we observed notches in 11,8% of all women and in the examined (hypertension and/or growth restriction) group in 81,3% (p<0,001). The sensitivity is 81,3% and specificity 88,2%. MoMRIs for both uterine arteries were calculated to compare data from control and examined group. In the examined group 41,3% RI results were above calculated MoM and there is significant difference between both groups (p <0,001). The sensitivity is 41,3% and specificity 89,5%. In the group of the hypertensive pregnant women where mean systolic blood pressure in 24 hour monitoring was above 130 mm Hg we observed notches in 61,1% of flow velocity waveforms in uterine arteries. In the group of normal pregnancies there were 11,8% notches and there is significant difference between both groups (p<0,001). The uterine artery velocimetry values of S/D, RI, PI decrease with the progression of gestation. There are no significant differences between right and left uterine artery doppler velocimetry. There are significant differences for values and percentage of notches in both groups. Extremely high rate of notches is observed in the group with most elevated blood pressure (daily mean value over 130mm Hg). It is possible to calculate obstetrical risk assessing values for blood flow in uterine arteries in pregnancy. It can be helpful to estimate methods detecting elevated risk for hypertension and/or growth retardation in pregnancy.


The RNA interference proteins and vasa locus are involved in the silencing of retrotransposons in the female germline of Drosophila melanogaster.
RNA interference (RNAi) is considered as a defense against expansion of transposable elements. The proteins related to RNA helicase and Argonaute families are involved in RNAi process in different organisms. It was shown that Argonaute AUBERGINE and putative RNA helicase SPINDLE-E proteins were essential for RNAi in Drosophila. Here, we describe the role of aubergine (aub) and spindle-E (spn-E) genes in the control of LTR retrotransposon copia and nonLTR telomeric Het-A and I retrotransposons in ovaries. spn-E mutation causes a drastically increased lacZ expression driven by copia LTR. For the first time we show the involvement of AUBERGINE protein and VASA RNA helicase, essential for oocyte patterning, in the retrotransposon silencing. spn-E, vasa and aub mutations cause similar accumulation of both I element and Het-A transcripts in the developing oocyte. VASA and AUBERGINE proteins are known as components of perinuclear ribonucleoprotein particles in germ cells, and spn-E mutation disturbs protein content of the particles. We suggest participation of these proteins in the same silencing pathway.


Cell surface antigens on rat islet tumors.
To examine the antigenic properties of the rat pancreatic beta cell tumor, RIN, we used a cell surface enzyme-linked immunosorbent assay (CELISA). Monoclonal antibodies of known specificity are used to validate the assay, and the results show that antibodies directed at glycoproteins and glycolipids are detected by this technique. The principal glycolipid targets are found in the ganglio and lacto series of glycosphingolipids, and not in the globo series. When the CELISA was used to study sera from type I diabetics, no differences in binding of control and diabetic samples were detected at low dilutions of serum. However, at higher serum dilutions (1/30 to 1/120) binding of IgG antibodies from type I diabetics was greater than that observed with normal sera. Similar reactivity was not detected in these sera when rat hepatocytes were used as targets in the CELISA. Prolonged culture of RIN cells, however, resulted in the loss of reactivity with sera from type I subjects, and is associated with a corresponding decrease in expression of cell surface gangliosides. Accordingly, subclones selected for ganglioside expression were used to compare anti-RIN binding in type I diabetics with that of normal controls and unaffected siblings. The results indicate that some rat islet tumors express antigenic determinants recognized by anti-islet antibodies associated with type I diabetes. Both nonspecific interaction at low serum dilutions and variable expression of cell surface antigens may explain the difficulties encountered when these cells are used for diagnostic purposes. An objective assay such as the CELISA may help to avoid these problems.


Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity.
The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC-MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS). Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50) of 12.2 μg/mL and 12.9 μg/mL, respectively) and inhibited the production of nitric oxide (NO) evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL). These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems.


Seasonal variation of persistent organochlorine accumulation in birds from Lake Baikal, Russia, and the role of the south Asian region as a source of pollution for wintering migrants.
Concentrations of persistent organochlorines (OCs) such as polychlorinated biphenyls (PCBs), DDT and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), and chlordane compounds (CHLs) were determined in whole body soft tissue homogenates and in muscles of resident and migratory birds collected from Lake Baikal, Russia. The residue pattern in both resident and migratory birds was in the following order: PCBs > DDTs > HCHs > CHLs. OC concentrations in migratory birds varied, depending on the feeding habit. The maximum levels of OCs were found in piscivores, followed by insectivores, omnivores, and herbivores. OC residue levels in Lake Baikal birds were lower than those in the Great Lakes region as well as in other lakes in Europe and Japan. Concentrations of HCHs and DDTs in most of the migratory birds collected in the spring were higher than for those collected in the autumn, indicating a notable accumulation in wintering grounds. Compilation and analysis of the available data in fish and birds from Asia suggested that the tropical and subtropical regions in south Asian countries may be a source of pollution for the wintering accumulation of migratory birds from Lake Baikal. Relatively higher compositions of alpha- and gamma-HCH in total HCHs, p,p'-DDT in total DOTs were observed in some migratory species, indicating recent exposure to HCHs and DDTs in Lake Baikal or wintering areas. PCB isomer patterns were different between residents and migrants, with the predominance of lower chlorinated congeners in migratory species, suggesting recent PCB accumulation in stopover sites during wintering. TEQ concentrations of toxic non- and mono-ortho coplanar PCBs in common terns from Lake Baikal were comparable to those reported in some species from Japan, the United States, and Europe. Relative contributions of non-ortho coplanar congeners to toxic equivalents (TEQs) were predominant, in which CB-126 accounted for the highest toxicity contribution. Estimated TEQ concentrations in the common tern from Lake Baikal exceeded the levels associated with enzyme induction in bald eagles. To our knowledge, this is the first comprehensive study showing the seasonal variations of OC accumulation in the birds from Lake Baikal.


Acute myeloid leukemia in Turkish children with Fanconi anemia. One center experience in the period between 1964-1995.
Fanconi's anemia(FA) is an autosomal recessive disorder characterized by a progressive pancytopenia,variable congenital abnormalities and an increased risk for the development of acute myeloid leukemia (AML). The objective of this study is to evaluate AML in the patients with FA diagnosed and followed-up in the Department of Pediatric Hematology at Ankara University School of Medicine in the period between 1964-1995. A total of 39 patients within the age range 2-14 years( mean 8.2±3.16),28 male and 11 female were diagnosed as FA on the basis of congenital abnormalities,pancytopenia, bone marrow hypoplasia and diepoxybutane induced chromosomal abnormalities that observed in all patients The hereditary and familial basis of FA was apparent in this series.Common abnormalities were growth retardation,cefe'- au- laitspots,hyperpigmentation,microcephaly, finger and thumb deformities,mental retardation and hypogenitalismus Four AML (10.2%) were observed in our series.Cytogenetic analysis of these cases revealed 46/ XX,dup(3)(q22;q26) t(7;17) (p11;p11) in one where it was unsuccessful in three.Two cases could not achieve remission and died.The other two achieved complete remission and remained in remission for2 and 6 months. Acute myelomonocytic type in three cases and acute monocytic type in one patient were diagnosed in our series. The patients with FA should be followed with regard to AML and solid tumors. AML and solid tomors should be taken into the consideration as the first manifestation of FA.


Successful percutaneous extraction of malpositioned pacemaker lead in the left ventricle after proper dabigatran treatment.
Malpositioned pacemaker lead in the left ventricle (LV) is a rare procedural complication, which causes a special risk of thromboembolic events. Hence, prompt identification and early management of misplaced leads inside the LV is critical. Herein, we present a case of malpositioned pacemaker lead with transient ischemic attacks after the pacemaker implantation. The misplaced ventricular lead was discovered during regular echocardiography. Both leads were extracted percutaneously after dabigatran treatment. To our knowledge, this is the first report of uncomplicated percutaneous extraction of an inadvertently placed LV lead after dabigatran treatment. No neurologic events during a follow-up of 4 years.


Analysis of behavioral disability and construction of a disability scale for the elderly in Shanghai.
With the gradual aging of China's population development, the number of disabled elderly has increased significantly. In order to better solve the problem of life care for these elderly people, it is necessary to conduct in-depth and detailed research on the specific conditions of disabled elderly people, in order to differentiate different conditions for care and set appropriate insurance provisions. Based on the detailed analysis of the basic behavioral ability of the elderly, and referring to the International Disability standards, this paper refines the three basic living ability indicators of physiological behavior, cognitive behavior and interpersonal behavior, and integrates the cultural elements of assimilation, continuity, fusion and cohesion with Chinese characteristics. A more systematic and perfect five-level disability scale which conforms to the national conditions of China is designed. The disability of the elderly in Shanghai was investigated with the newly constructed scale, and a detailed analysis and five-level division were made. Experiments show that the results of this study can more effectively establish the disability level of the elderly in China.


Covalent Microporous Polymer Nanosheets for Efficient Photocatalytic CO2 Conversion with H2 O.
It is still a challenging target to achieve photocatalytic CO2 conversion to valuable chemicals with H2 O as an electron donor. Herein, 2D imide-based covalent organic polymer nanosheets (CoPcPDA-CMP NSs), which integrate cobalt phthalocyanine (CoPc) moiety for reduction half-reaction and 3,4,9,10-perylenetetracarboxylic diimide moiety for oxidation half-reaction, are constructed as a Z-scheme artificial photosynthesis system to complete the overall CO2 reduction reaction. Owing to the outstanding light absorption capacity, charge separation efficiency, and electronic conductivity, CoPcPDA-CMP NSs exhibit excellent photocatalytic activity to reduce CO2 to CO using H2 O as a sacrificial agent with a CO production rate of 14.27 µmol g-1 h-1 and a CO selectivity of 92%, which is competitive to the state-of-the-art visible-light-driven organic photocatalysts towards the overall CO2 reduction reaction. According to a series of spectroscopy experiments, the authors also verify the photoexcited electron transfer processes in the CoPcPDA-CMP NSs photocatalytic system, confirming the Z-scheme photocatalytic mechanism. The present results should be helpful for fabricating high-performance organic photocatalysts for CO2 conversion.


Ultrastretchable, transparent triboelectric nanogenerator as electronic skin for biomechanical energy harvesting and tactile sensing.
Rapid advancements in stretchable and multifunctional electronics impose the challenge on corresponding power devices that they should have comparable stretchability and functionality. We report a soft skin-like triboelectric nanogenerator (STENG) that enables both biomechanical energy harvesting and tactile sensing by hybridizing elastomer and ionic hydrogel as the electrification layer and electrode, respectively. For the first time, ultrahigh stretchability (uniaxial strain, 1160%) and transparency (average transmittance, 96.2% for visible light) are achieved simultaneously for an energy-harvesting device. The soft TENG is capable of outputting alternative electricity with an instantaneous peak power density of 35 mW m-2 and driving wearable electronics (for example, an electronic watch) with energy converted from human motions, whereas the STENG is pressure-sensitive, enabling its application as artificial electronic skin for touch/pressure perception. Our work provides new opportunities for multifunctional power sources and potential applications in soft/wearable electronics.


Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound.
Because the antigenic changes occurring after in vivo treatment of murine lymphoma cells with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) were suggested to result from DTIC-induced somatic mutation(s), quinacrine dihydrochloride, an antimutagenic compound, was tested for possible antagonistic activity related to this phenomenon. The increased immunogenicity of L1210Ha leukemia occurring at the first transplant generation of DTIC-treated histocompatible (BALB/cCr x DBA/2Cr)F1 male mice or the appearance of strong lymphoma-associated transplantation antigens at transplant generation 6 was prevented by simultaneous administration of quinacrine. However, the compound did not modify the antitumor or immunodepressive activity of DTIC in the mouse. We concluded that the selective antagonistic effect of quinacrine on DTIC-mediated immunogenic changes (DMIC) supported the hypothesis that the molecular mechanism of DMIC could be related to somatic mutation(s).


Extensive DNA polymorphism within and between two strains of Trichostrongylus colubriformis.
The isolation and characterization of a library of short (< 1 kbp) DNA probes suitable for restriction fragment length polymorphism (RFLP) analysis of Trichostrongylus colubriformis are described. More than 70% of these probes contained repetitive DNA sequences, implying that repetitive DNA is widely dispersed in the T. colubriformis genome. Analysis of one laboratory and one field strain for RFLPs using non-repetitive probes showed that there is extensive genetic heterogeneity within each strain (17 of 21 probe X enzyme combinations detected multiple bands on genomic Southern blots, consistent with the existence of multiple alleles) and also considerable polymorphism between strains (18 of the 62 bands detected were strain specific). The laboratory strain was not significantly less polymorphic than the field strain, suggesting that a relatively small, restricted population size is sufficient for the maintenance of the polymorphism observed. The possible applications of these data in the epidemiology and population genetics of the parasite are discussed.


Hybrid procedure to treat aortic arch aneurysm combined with aortic arch coarctation and left internal carotid artery aneurysm (Case Report).
Aortic arch aneurysm is a rare condition but carries a high risk of rupture. We report one case of aortic arch aneurysm combined with aortic arch coarctation and left internal carotid artery aneurysm, which is extremely rare. Left internal carotid artery aneurysm resection and revascularization, carotid and carotid graft bypass combined with endovascular stent graft and embolization with coils were successfully performed. There were no any complaints and complications at 8 months follow-up. The follow-up CTA demonstrated thrombus formation in the aneurysm lumen, no endoleak and the aortic arch and bypass graft were all patent. We feel that hybrid procedure may be a valuable therapeutic alternative when treating this type of lesion. However, long-term clinical efficacy and safety have yet to be confirmed.


Effect of naked neck gene (NA) and frizzle gene (F) on immunocompetence in chickens.
1. A total of 98 birds belonging to 4 genetic groups from two specialised populations--heterozygous naked neck (NA*NA/NA*N) and normally feathered (NA*N/NA*N) from one specialised population and heterozygous frizzle (F*F/F*N) and normally feathered (F*N/F*N) from another specialised population--were evaluated for general immunocompetence by assessing antibody response to SRBC, haemolytic complement level in the serum, in-vivo cell mediated immune (CMI) response to Concanavalin-A (Con-A) and a phagocytic index at 10-12 weeks of age. 2. The naked neck gene did not seem to influence the antibody response to SRBC, CMI to Con-A or the phagocytic index. However, significantly higher haemolytic complement level in serum was observed in birds carrying a copy of the NA mutation as compared to the normally feathered birds. 3. Similar trends were observed for the frizzle gene.


Apoptosis and apoptosis-associated gene products related to the response to neoadjuvant chemotherapy for gastric cancer.
To evaluate the effect of neoadjuvant chemotherapy on gastric cancer, we examined the correlation between induction of apoptosis and expression of p53, Bcl-2, and Bax. Eighty-five patients with advanced gastric cancer were retrospectively divided into the following two groups: 54 patients received 5-fluorouracil (5-FU) at 300 mg/body/day for 14 days and cisplatin (CDDP) at 15 mg/body/day for 2 days as group A; 31 patients without any preoperative chemotherapy as group B. According to histological changes in tumors due to neoadjuvant chemotherapy, the therapeutic effects on tumors were evaluated. The apoptotic index (AI) of group A was significantly higher than that of group B (1.12+/-0.40 vs. 0.67+/-0.24; p<0.01). In group A, the AI of p53-positive cases was significantly lower than that of negative cases (0.92+/-0.32 vs. 1.39+/-0.32; p<0.01). The AI of histological responders was significantly higher than that of non-responders (1.34+/-0.35 vs. 1.02+/-0.38; p<0.01). There was no significant correlation between AI and expression of Bcl-2 or Bax. In group A, histological responders, Bcl-2 positive, and high AI patients had better prognosis, respectively. In conclusion, neoadjuvant chemotherapy for gastric cancer enhanced induction of apoptosis, and AI might be useful to evaluate the effect of neoadjuvant chemotherapy.


[The clinical significance of the immunoenzyme determination of trophoblastic beta 1-glycoprotein].
The authors analyze the diagnostic potentialities of measurements of trophoblastic beta 1-glycoprotein (TBG) in trophoblastic diseases, in normal pregnancy, threatened abortion, and ectopic pregnancy. Two laboratory tests for the diagnosis of pregnancy are compared: gravidodiagnosticum test and enzyme immunoassay of TBG. The findings have demonstrated a number of important advantages of enzyme immunoassay of the serum TBG. Measurements of urinary TBG are useless for the early diagnosis of pregnancy, because the protein level is low and does not correlate with a gestation period.


Cytokine gene polymorphisms and breast cancer susceptibility and prognosis.
Single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes are associated with differential levels of cytokine expression. We hypothesized that these SNPs might influence breast tumour development and progression by affecting the efficiency of the antitumour immune response and/or pathways of angiogenesis. A total of 144 female breast cancer patients and 263 cancer-free population controls were genotyped for the interleukin (IL)-1beta-511 (T/C), IL-6 -174 (G/C), tumour necrosis factor (TNF)-alpha-308 (A/G), IL-10 -1082 (A/G), IL-8 -251 (A/T) and vascular endothelial growth factor (VEGF) -1154 (A/G) SNPs, using amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and TaqMan (Applied Biosystems, Foster City, CA, USA) 5' nuclease assays for allelic discrimination. No significant associations were seen. Patient-control comparisons revealed a non-significant trend for association between the TNF-alpha-308 GG genotype and breast cancer compared to controls (79.7 vs. 68.2%, P = 0.03, Pc = 0.54). Stratification of the patient group according to the Nottingham Prognostic Index and individual prognostic factors revealed trends for association between IL-6 -174 GC and IL-8 -251 AA genotypes and markers of poor prognosis (P = 0.04, Pc = 0.72 and P = 0.02, Pc = 0.36, respectively). There were also trends for associations between VEGF -1154 AG and IL-1beta-511 TC genotypes and markers of good prognosis (P = 0.02, Pc = 0.36 and P = 0.05, Pc = 0.90, respectively). These results suggest that the role of cytokine promoter SNPs in both susceptibility to and prognosis in breast cancer requires further investigation in a larger study.


The evaluation of residual antimicrobial activity on hands and its clinical relevance.
A model for evaluation of the residual activity of agents used for hygienic hand disinfection, which relates closely to the "in-use" setting, is described. We looked for residual activity following hand disinfection by a standard method with soap and water and four skin disinfectants in common use. Two test organisms known to have caused cross-infection and having clinically-significant antibiotic resistance were used: a strain of vancomycin-resistant Enterococcus faecium and one of gentamicin-multiply-resistant Enterobacter cloacae. Both organisms survived well on artificially inoculated hands. Residual activity on previously disinfected hands against both test organisms was most marked for alcoholic chlorhexidine ('Hibisol') which showed a 4 log10 reduction within 1 min of inoculation. Chlorhexidine digluconate skin cleanser ('Hibiscrub') and povidone-iodine surgical scrub ('Betadine') also had marked residual activity, but less than alcoholic chlorhexidine. 60% Isopropanol showed no residual activity and, except for marginal activity against E. cloacae, soap and water showed little residual activity. The residual activity of alcoholic chlorhexidine may be useful to control cross-infection with those multiply-resistant strains which survive well on fingers previously washed with soap and water.


Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in Patients with Indication for Oral Anticoagulation: Data from a Single Center Registry.
Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention.


A time- and dose-dependent STAT1 expression system.
The signal transducer and activator of transcription (STAT) family of transcription factors mediates a variety of cytokine dependent gene regulations. STAT1 has been mainly characterized by its role in interferon (IFN) type I and II signaling and STAT1 deficiency leads to high susceptibility to several pathogens. For fine-tuned analysis of STAT1 function we established a dimerizer-inducible system for STAT1 expression in vitro and in vivo. The functionality of the dimerizer-induced STAT1 system is demonstrated in vitro in mouse embryonic fibroblasts and embryonic stem cells. We show that this two-vector based system is highly inducible and does not show any STAT1 expression in the absence of the inducer. Reconstitution of STAT1 deficient cells with inducible STAT1 restores IFNgamma-mediated gene induction, antiviral responses and STAT1 activation remains dependent on cytokine stimulation. STAT1 expression is induced rapidly upon addition of dimerizer and expression levels can be regulated in a dose-dependent manner. Furthermore we show that in transgenic mice STAT1 can be induced upon stimulation with the dimerizer, although only at low levels. These results prove that the dimerizer-induced system is a powerful tool for STAT1 analysis in vitro and provide evidence that the system is suitable for the use in transgenic mice. To our knowledge this is the first report for inducible STAT1 expression in a time- and dose-dependent manner.


Development of the nitrone-based spin trap agent NXY-059 to treat acute ischemic stroke.
The only current FDA-approved treatment for acute ischemic stroke is thrombolysis with tissue plasminogen activator (tPA). However, there are numerous shortcomings to tPA treatment including an increased incidence of intracerebral hemorrhage (ICH) and a short therapeutic window (3-6 h). In recent years, studies have attempted to identify new therapeutics that might be neuroprotective following ischemic strokes. Free radical scavenging spin trap agents have been proposed as potential candidates for stroke therapy because of the hypothesized role of free radicals in the progression of stroke and ischemia-induced neurodegeneration. Novel spin trap agents like (disodium-[(tert-butylimino) methyl] benzene-1,3-disulfonate N-oxide (NXY-059) are of particular interest, not only because they are broad-spectrum nitrone-based free radical scavengers, but also because of their safety profile in humans. Moreover, the rationale for developing NXY-059 for the treatment of acute ischemic stroke is further supported by the drug's reported neuroprotective effects. In addition, NXY-059 may represent a useful adjunct stroke therapy to tPA, since preclinical studies have demonstrated that NXY-059 increases the therapeutic window for tPA and lowers the occurrence of tPA-induced ICH.


Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio).
We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent.


Mycotic Pulmonary Artery Aneurysm Mimicking a Rasmussen Aneurysm.
Mycotic aneurysms arising from the pulmonary arteries are rare; only a few cases have been reported. Staphylococcus and Streptococcus species are the most common causative pathogens. Mycotic aneurysms are seldom clinically apparent unless as a sequela of adverse procedural complications. They carry high morbidity and mortality if not treated expeditiously. We present the case of a 37-year-old male with bacteremia and bronchopneumonia associated with a pulmonary artery mycotic aneurysm. The case was confounded by clinical features mimicking a Rasmussen aneurysm. We discuss distinctive imaging features, disease mechanism, typical presentation, and management. While mycotic aneurysms are uncommon, certain clinical scenarios warrant consideration of the diagnosis, such as a history of intravenous drug use, bacterial endocarditis, and immunocompromise. Rapid identification is critical to prevent life-threatening complications such as vessel rupture. Computed tomography allows for an accurate and timely diagnosis, and interventional embolization is a fast, minimally invasive curative treatment. Given similar risk factors and presentation, a mycotic aneurysm can be indistinguishable from a Rasmussen aneurysm; therefore, appropriate precautions should be taken while adequate microbiologic assessment is performed.