Reproducibility of echocardiographic assessment of 2D-derived longitudinal strain parameters in a population-based study (the STANISLAS Cohort study).
Global peak systolic longitudinal strain (PLS) derived from speckle tracking echocardiography (STE) is a widely used left ventricular deformation parameter. Modern ultrasound systems with improved temporal resolution and new software now allow automated multilayer analysis; however, there is limited evidence regarding its reproducibility. We performed intra- and inter-observer analyses within a population-based cohort study using conventional quantitative strain analysis (GE Healthcare). Fifty patients (49 ± 14 years) were randomly selected among the fourth visit of the STANISLAS Cohort. Multilayer PLS (transmural, subendocardial, and subepicardial), and strain rate (peak systolic, early and late diastolic) were evaluated. Peak systolic shortening (PSS) and early positive systolic strain (EPS) were calculated, as well as post-systolic index (PSI) and pre-stretch index (PST), two additional strain-derived parameters. Intra-observer intraclass correlation coefficients (ICC) were >0.75 for all analyzed parameters. The mean relative intra-observer differences were <5% for all considered parameters, and their 1.96 SDs were <15% for multilayer PLS, strain rate and PSS, but not for EPS, PSI and PST. Inter-observer ICCs were >0.70 (the majority being >0.80). The mean relative inter-observer differences were <7.5% for all considered parameters, with 1.96 SDs of relative differences being <21% for multilayer PLS, strain rate and PSS, but not for EPS, PSI and PST. In this population-based study, in subjects without or with a limited number of cardiovascular risk factors and no previous cardiovascular events, deformation parameters were found to be highly reproducible, except for EPS, PSI and PST, which showed moderately higher variability. Quantitative strain analysis appears to be an effective clinical and research tool, providing insights regarding longitudinal deformation using a simple three-step post-processing procedure.


[Cryopreservation of early human embryo stages].
A short review of freezing procedures applied to early human embryos is given. It is noted that human embryos survived freezing and thawing at a developmental stage of 1. cell to blastocyst. But it seems to be necessary to use for any developmental stage of early embryo a special freezing and thawing method. Embryo survival is correlated with their morphologic features where as neither age of embryos nor developmental stage were involved in freezing and thawing ability.


Scientific Rationale for Combined Immunotherapy with PD-1/PD-L1 Antibodies and VEGF Inhibitors in Advanced Hepatocellular Carcinoma.
A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported. This is groundbreaking because nivolumab and pembrolizumab, both programmed cell death-1 (PD-1) antibodies, have failed to show efficacy as first- and second-line therapeutics, respectively, in phase III clinical trials. Immunotherapy with a combination of atezolizumab and bevacizumab resulted in better survival than treatment with sorafenib for the first time since sorafenib was approved in 2007. The high efficacy of the combination of PD-1/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) antibodies is not only due to their additive effects on tumor growth, but also to their reprogramming of the immunosuppressive microenvironment into an immunostimulatory microenvironment. These results were confirmed in a phase Ib trial that showed significantly longer progression-free survival in the atezolizumab plus bevacizumab group than in patients that received atezolizumab alone. These results demonstrate that immunotherapy with a combination of PD-1/PD-L1 and VEGF inhibitors is effective and may result in a reprogramming of the tumor microenvironment. The results of an ongoing phase III trial of a PD-1 antibody in combination with the VEGF receptor tyrosine kinase inhibitor (TKI) are highly anticipated.


The journey between brain and gut: A systematic review of psychological mechanisms of treatment effect in irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by abdominal pain and altered bowel habits. It is estimated to affect 10-22% of the UK population. The use of psychological interventions in IBS is increasingly empirically supported, but little is known about the mechanism of psychological treatment approaches. The present systematic review aimed to investigate the mechanisms of psychological treatment approaches applied to IBS. The systematic review included studies conducting mediation analysis in the context of psychological interventions for IBS, focusing on the outcomes of symptom severity and/or quality of life (QoL). Nine studies in total were included in the review. Eight of the studies assessed mediation in the context of cognitive behavioural-based interventions, and one study assessed mediation in a mindfulness-based stress reduction intervention. Results indicate that change in illness-specific cognitions is a key process by which psychological treatments may have an effect on the outcomes of symptom severity and QoL. Furthermore, results suggest that whilst GI-specific anxiety may also be a key mechanism of treatment effect, it would appear that general or state anxiety is not. Although less commonly included in mediation analysis, illness-specific behaviours may also have a mediating role. A mediational model amalgamating the results of studies is proposed to illustrate the findings of the review. The model depicts the process by which psychotherapy changes illness-specific cognitions, behaviours, and anxiety to achieve reduction in symptom severity. Statement of contribution What is already known on this subject? Cognitive behavioural therapy (CBT) is the predominant psychological treatment for irritable bowel syndrome (IBS), although there is some research supporting other treatments such as mindfulness and hypnotherapy. Mediation analysis in the context of psychological treatments for IBS has just begun to explore possible mechanisms of treatment effect especially within CBT studies. Some studies include anxiety in a basic mediation analysis, whilst others include cognitions with inconsistent results for each. What does this study add? Reviews mediators included in mediation analysis and the methods used for mediation analysis Proposes a mediation model informed by the results of the review for future studies to investigate Provides clinical implications for the targeting of cognitions and behaviours rather than general anxiety.


A stereotaxic atlas for the telencephalon of the Siamese fighting fish (Betta splendens).
1. A stereotaxic technique for electrode positioning in the telencephalic nuclei of the Siamese Fighting fish (Betta splendens) is described. 2. The forebrain atlas was based on paraffin-embedded, in situ-sectioned, Nissl-stained material. Brain measurements were corrected for tissue shrinkage due to histological procedures. The atlas and methods have already been tested and have shown good accuracy and reproducibility.


A Comprehensive Evaluation of Factors Affecting Healing, Range of Motion, Strength, and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair.
Rotator cuff repair (RCR) leads to improved patient outcomes, which may or may not coincide with biological healing of the tendon. Many patient factors may play a role in subjective and objective patient outcomes of surgery. To evaluate the effect of various patient factors and tendon healing on range of motion, strength, and functional outcomes after arthroscopic RCR. Case-control study; Level of evidence, 3. We reviewed patients who underwent arthroscopic RCR. Postoperative endpoints included physical examination, repeat magnetic resonance imaging (MRI), and patient-reported outcome measures. The Short Form-36 (SF-36) was also completed at enrollment. Physical examination included range of motion and strength testing. Preoperative tear characteristics and postoperative healing on MRI were recorded. Associations between these characteristics and rotator cuff healing were determined. Multivariate models investigated factors affecting healing and final outcomes. A total of 81 patients had MRI before and a minimum of 1 year after RCR. Patient-reported outcomes were available for all patients at mean 2.7 years (range, 1-7.7 years) after RCR. Seventy-five patients had physical examination data. Patients were less likely to heal if they had tears involving multiple tendons (P = .037), tears >2.2 cm (P = .037), tears retracted >2.0 cm (P = .006), and tears with cumulative Goutallier grade ≥3 (P = .003). Patients who healed were stronger on manual muscle testing in forward elevation (P < .001) and external rotation (P = .005) and on forward elevation isometric testing (P = .033), and they reported better patient-reported outcomes (P ≤ .01) at final follow-up. In multivariate models, tendon healing was associated with less pain (P = .019) and better patient-reported outcomes (all P ≤ .006). Lower SF-36 mental component summary (MCS) score was associated with increased pain (P = .025) and lower final American Shoulder and Elbow Surgeons score (P = .035), independent of healing status. Larger, more retracted tears with greater fatty infiltration are less likely to heal per MRI. Patients who do not heal are weaker and have worse patient-reported outcome measures. Lower SF-36 MCS score was associated with poorer patient-reported outcomes independent of tendon healing.


Effects of the IDH1 R132H Mutation on the Energy Metabolism: A Comparison between Tissue and Corresponding Primary Glioma Cell Cultures.
The R132H mutation in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is the most important prognostic factor for the survival of glioma patients. Subsequent studies led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. To further study these changes, appropriate glioma models are required that accurately mimic in vivo metabolism. To investigate how metabolism is affected by in vitro cell culture, we here compared surgically obtained snap-frozen glioma tissues with their corresponding primary glioma cell culture models with a previously developed targeted mass spectrometry proteomic assay. We determined the relative abundance of a panel of metabolic enzymes. Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. However, these metabolic profiles were not reflected in the paired glioma primary cell cultures. We suggest that culture conditions and tumor microenvironment play a crucial role in maintaining the in vivo metabolic situation in cell culture models. For this reason, new models that more closely resemble the in vivo microenvironment, such as three-dimensional cell co-cultures or organotypic multicellular spheroid models, need to be developed and investigated.


Singular value decomposition applied to the compression of T3 amplitude for the coupled cluster method.
We apply the singular value decomposition to compress the degrees of freedom of T3 amplitude for the CCSDT-1 method (compressed CCSDT-1). This method enables us to make the number of the T3 amplitudes less than that of the T2 amplitudes, making CCSDT-1 calculations much less expensive without losing accuracy. We perform test calculations on some atoms and molecules to investigate the applicability of this method. Computational results for the electronic energies as well as timings of these calculations are presented.


Anterior bone block: treatment of calcaneus deformity after failed soft-tissue operations.
Calcaneus deformity is almost always the result of a neural disorder. It is progressive, disabling, and resistant to bracing and usually requires surgery. In immature feet, soft-tissue operations are the procedures of choice but have the disadvantage of recurrence due to stretching of soft tissues. However, bony operations will lead to growth center damage. Anterior bone block corrects the deformity without damaging the growth centers.


GNL3 and SKA3 are novel prostate cancer metastasis susceptibility genes.
Prostate cancer (PC) is very common in developed countries. However, the molecular determinants of PC metastasis are unclear. Previously, we reported that germline variation influences metastasis in the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of PC. These mice develop prostate tumors similar to a subset of poor outcome, treatment-associated human PC tumors. Here, we used TRAMP mice to nominate candidate genes and validate their role in aggressive human PC in PC datasets and cell lines. Candidate metastasis susceptibility genes were identified through quantitative trait locus (QTL) mapping in 201 (TRAMP × PWK/PhJ) F2 males. Two metastasis-associated QTLs were identified; one on chromosome 12 (LOD = 5.86), and one on chromosome 14 (LOD = 4.41). Correlation analysis using microarray data from (TRAMP × PWK/PhJ) F2 prostate tumors identified 35 metastasis-associated transcripts within the two loci. The role of these genes in susceptibility to aggressive human PC was determined through in silico analysis using multiple datasets. First, analysis of candidate gene expression in two human PC datasets demonstrated that five candidate genes were associated with an increased risk of aggressive disease and lower disease-free survival. Second, four of these genes (GNL3, MAT1A, SKA3, and ZMYM5) harbored SNPs associated with aggressive tumorigenesis in the PLCO/CGEMS GWAS of 1172 PC patients. Finally, over-expression of GNL3 and SKA3 in the PC-3 human PC cell line decreased in vitro cell migration and invasion. This novel approach demonstrates how mouse models can be used to identify metastasis susceptibility genes, and gives new insight into the molecular mechanisms of fatal PC.


SGLT-2 inhibitors reduce the risk of cerebrovascular/cardiovascular outcomes and mortality: A systematic review and meta-analysis of retrospective cohort studies.
Despite Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been associated with a reduced risk of heart failure in patients with type 2 diabetes mellitus (T2DM), the effect observed for other cardiovascular (CV) and cerebrovascular outcomes differed among clinical trials. Different observational studies have investigated the effects of SGLT2 inhibitors on these outcomes and mortality. The present meta-analysis aimed to assess the effects of SGLT2 inhibitors on the risk of CV (major adverse CV event - MACE, non-fatal myocardial infarction, or hospitalization for heart failure) and cerebrovascular (stroke) outcomes. A systematic review was conducted in Pubmed from January 1, 2012 to November 31, 2020. Only retrospective cohort studies including as control group users of dipeptidyl peptidase-4 (DPP-4) inhibitors or non-SGLT2 inhibitors were retained and analysed separately. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Of the 158 references identified, 20 articles were selected for meta-analysis, of which 13 considered the comparison with DPP-4 inhibitors and 7 the comparison with non-SGLT2 inhibitors. The pooled intention-to-treat analysis showed a reduced risk of stroke with SGLT2 inhibitors compared to DPP-4 inhibitors (Hazard ratio HR, 0.89; 95%CI, 0.82-0.96; I2 = 25%; p = 0.25) and non-SGLT2 inhibitors (HR, 0.83; 95%CI, 0.77-0.91; I2 = 11%; p = 0.34). Finally, SGLT2 inhibitors were also associated with a reduced risk of CV outcomes and mortality in all comparisons. Our data support contemporary society recommendations to prioritise the use of SGLT2 inhibitors in patients with T2DM and at high risk for CV complications.


Identification of cysteine protease inhibitors as new drug leads against Naegleria fowleri.
Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. PAM occurs principally in healthy children of less than 13 years old with a history of recent exposure to warm fresh water. While as yet not a reportable disease, the Centers for Disease Control and Prevention (CDC) documents a total of 143 cases in the United States. Only four patients have survived. Infection results from water containing N. fowleri entering the nose, followed by migration of the amebae to the brain. Within the brain, N. fowleri infection results in extensive necrosis, leading to death in 3-7 days. Mortality among patients with PAM is greater than 95%. The drugs of choice in treating PAM are the antifungal amphotericin B, and the antileishmanial, miltefosine. However neither drug is FDA-approved for this indication and the use of amphotericin B is associated with severe adverse effects. Moreover, very few patients treated with amphotericin B have survived PAM. Therefore, development of new, safe and effective drugs is a critical unmet need to avert future deaths of children. The molecular mechanisms underlying the pathogenesis of PAM are poorly understood but it is known that cysteine proteases of N. fowleri play a role in the progression of PAM. We therefore assessed the in vitro activity of the synthetic vinyl sulfone cysteine protease inhibitor, K11777, and 33 analogs with valine, phenylalanine or pyridylalanine at P2 position, against cysteine protease activity in the lysate of N. fowleri. Inhibitors with phenylalanine or pyridylalanine at P2 position were particularly effective in inhibiting the cysteine protease activity of N. fowleri cell lysate with IC50 ranging between 3 nM and 6.6 μM. Three of the 34 inhibitors also showed inhibitory activity against N. fowleri in a cell viability assay and were 1.6- to 2.5-fold more potent than the standard of care drug miltefosine. Our study provides the first evidence of the activity of synthetic, small molecule cysteine protease inhibitors against N. fowleri.


[Laparoscopic adrenalectomy].
In the last few years, laparoscopic adrenalectomy has become widely used in the management of adrenal disease. We reviewed our experience of 24 patients who underwent laparoscopic adrenalectomy between 1998 and 2006. Surgery was indicated for Cushing's syndrome in 46% of the patients, aldosteronoma in 25%, incidentaloma in 21% and pheochromocytoma in 8%. A lateral transabdominal approach was employed in all patients. The mean age of the patients was 50.4 years (17 women and 7 men). Left unilateral adrenalectomy was performed in 63% of the patients, right unilateral adrenalectomy in 29% and bilateral adrenalectomy in 8%. The conversion rate was 4%. The mean operating time was 134 minutes in unilateral approaches and 245 minutes in bilateral approaches. The mean size of the gland was 4 cm. The complications rate was 4% and there was no mortality. Disease control was achieved in 96% of the patients after a mean follow-up of 49 months. Laparoscopic adrenalectomy should be considered the procedure of choice for the surgical management of benign adrenal disease.


Association of serum adipocyte-specific Fatty Acid binding protein with Fatty liver index as a predictive indicator of nonalcoholic Fatty liver disease.
Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects. A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day). Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001). The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006). After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012). This study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.


Pancreatic metastasis from papillary thyroid cancer: a case report and literature review.
Pancreatic metastasis from papillary thyroid cancer (PTC) is extremely rare; only 18 cases have been reported in the literature. However, several reviews have highlighted similar characteristics between metastatic and primary pancreatic tumors. The patient was a 51-year-old male with a history of total thyroidectomy, modified radical neck dissection, and radioactive iodine ablation for PTC in 2014. Nodules suspected of metastasis were found in both lungs on chest computed tomography (CT). However, after 6 months, a follow-up chest CT showed no increase in size; thus, a follow-up observation was planned. Six years after his initial diagnosis, abdominal CT and pancreas magnetic resonance imaging revealed a 4.7 cm cystic mass with a 2.5 cm enhancing mural nodule in the pancreas tail. We diagnosed the pancreatic lesion as either metastatic cancer or primary pancreas cancer. The patient underwent distal pancreato-splenectomy. After surgery, the pathological report revealed that the mass was metastatic PTC. Pancreatic metastasis from PTC indicates an advanced tumor stage and poor prognosis. However, pancreatectomy can increase the survival rate when the lesion is completely resectable. Therefore, surgical resection should be considered as a treatment for pancreatic metastasis from PTC.


Recovery of precious metals from waste streams.
As there is a high potential for microbe-based technologies to bring the recovery of metals from waste streams to an ecologically friendly and financially reasonable level, it is worth to invest efforts into the advancement of these biotechnologies in the future.


Unique hydrogen bonds between 9-anthracenyl hydrogen and anions.
Unique hydrogen bonds of the 9-H of anthracene moieties in hosts 1 and 2 with fluoride and pyrophosphate ions were observed on the basis of the (1)H NMR experiments. Furthermore, hosts 1 and 2 act as a colorimetric sensor and a fluorescent chemosensor for the recognition of fluoride ion, respectively.


Inconsistency of the tibia test for estimating growth hormone in crude pituitary extracts.
The complement fixation immunoassay (CFIA) was used for quantitating growth hormone (GH) in crude anterior pituitary extracts from rats subjected to thyroidectomy with or without cortisol and exogenous GH administration. The results obtained from this study were compared with pertinent bioassay (tibia test) results or correlated with the pituitary acidophil cell counts. Whereas it has been reported that pituitary GH levels are normal by the tibia test at 2 weeks after thyroidectomy, the highly specific CFIA method showed an actual 87% decrement which correlated well with the reduction in acidophilis. In addition, the apparently normal content of GH after cortisol administration to thyroidectomized rats, as measured by the tibia test, was contradictory to the very low acidophil population and to the marked reduction in pituitary GH content as measured by the CFIA. Furthermore, theoretical tibia responses illustrate the inconsistency of the bioassay in different experimental conditions. If, as previously suggested, the content of thyrotrophin (TSH) in the crude pituitary extracts renders the bioassay of GH a dubious procedure, then the superiority of immunoassay is obvious.


Immunization with HIV-1 trimeric SOSIP.664 BG505 or founder virus C (FVCEnv) covalently complexed to two-domain CD4S60C elicits cross-clade neutralizing antibodies in New Zealand white rabbits.
Background: An ongoing challenge in HIV-1 vaccine research is finding a novel HIV-1 envelope glycoprotein (Env)-based immunogen that elicits broadly cross-neutralizing antibodies (bnAbs) without requiring complex sequential immunization regimens to drive the required antibody affinity maturation. Previous vaccination studies have shown monomeric Env and Env trimers which contain the GCN4 leucine zipper trimerization domain and are covalently bound to the first two domains of CD4 (2dCD4S60C) generate potent bnAbs in small animals. Since SOSIP.664 trimers are considered the most accurate, conformationally intact representation of HIV-1 Env generated to date, this study further evaluated the immunogenicity of SOSIP.664 HIV Env trimers (the well characterized BG505 and FVCEnv) covalently complexed to 2dCD4S60C. Methods: Recombinant BG505 SOSIP.664 and FVCEnv SOSIP.664 were expressed in mammalian cells, purified, covalently coupled to 2dCD4S60C and antigenically characterized for their interaction with HIV-1 bnAbs. The immunogenicity of BG505 SOSIP.664-2dCD4S60C and FVCEnv SOSIP.664-2dCD4S60C was investigated in New Zealand white rabbits and compared to unliganded FVCEnv and 2dCD4S60C. Rabbit sera were tested for the presence of neutralizing antibodies against a panel of 17 pseudoviruses. Results: Both BG505 SOSIP.664-2dCD4S60C and FVCEnv SOSIP.664-2dCD4S60C elicited a potent, HIV-specific response in rabbits with antibodies having considerable potency and breadth (70.5% and 76%, respectively) when tested against a global panel of 17 pseudoviruses mainly composed of harder-to-neutralize multiple clade tier-2 pseudoviruses. Conclusion: BG505 SOSIP.664-2dCD4S60C and FVCEnvSOSIP.664-2dCD4S60C are highly immunogenic and elicit potent, broadly neutralizing antibodies, the extent of which has never been reported previously for SOSIP.664 trimers. Adding to our previous results, the ability to consistently elicit these types of potent, cross-neutralizing antibody responses is dependent on novel epitopes exposed following the covalent binding of Env (independent of sequence and conformation) to 2dCD4S60C. These findings justify further investment into research exploring modified open, CD4-bound Env conformations as novel vaccine immunogens.


Southern limits of distribution of the intertidal gobies Chaenogobius annularis and C. gulosus support the existence of a biogeographic boundary in southern Japan (Teleostei, Perciformes, Gobiidae).
Understanding the distributional patterns of individual animal groups with respect to coastal topology and the local physical environment provides essential foundational frameworks for marine zoogeography. In the northwestern Pacific waters of Japan, the distributional pattern of some cool-temperate species of marine fishes suggests the existence of a biogeographic boundary corresponding to a long sandy shore on the eastern coast of Kyushu, southern Japan. The existence of this hypothetical biogeographic boundary was tested by mapping the southern distributional limit of two species of cool-temperate intertidal gobies, Chaenogobius annularis and C. gulosus, which are endemic to East Asia and common in rock pools within their range in the Japanese Archipelago. Distribution and abundance were assessed by survey of museum collections from south-east Kyushu (i.e., the entire coasts of Kagoshima and Miyazaki prefectures); and a quantitative survey of the abundance of these gobies in rock pools at various sites around the hypothesized boundary on the eastern coast of Kyushu, including the subtropical Tanega-shima Island. The museum collection survey showed different distribution patterns between the two species: C. annularis was distributed along the entire coasts of south-east Kyushu including subtropical islands, whereas C. gulosus was distributed along these coasts, including one site on a subtropical island, except for an area south of the hypothesized boundary on the eastern coast of Kyushu. The density and occurrence rates of C. annularis in rock pools decreased with latitude, it being absent from a subtropical island, and C. gulosus was not detected from sites south of the hypothesized boundary. The qualitative survey showed that the southernmost records of C. annularis and C. gulosus were the adjacent subtropical islands (Yaku-shima and Tanega-shima islands respectively), although the quantitative survey suggested that their normal range of distribution was limited to the southern part of the Kyushu mainland. A combination of qualitative and quantitative survey methods in the present study highlighted that the southernmost record of a certain species may not necessarily indicate the true limit of its distribution. The distribution of C. gulosus supports the existence of the hypothetical biogeographic boundary, and the different distribution patterns of the two species may be caused by differences in their early life histories.


An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia.
Accurate diagnosis of dysplasia and adenocarcinoma in patients with Barrett esophagus is critical for clinical decision-making and patient management. IMP3 is an oncofetal protein and has been demonstrated to be associated with aggressive tumor behavior. The aim of this study was to establish the expression pattern and diagnostic value of IMP3 in Barrett esophagus, dysplasia, and carcinoma. A total of 217 cases (resection, n=56; biopsy, n=161) with 302 lesions (invasive esophageal adenocarcinoma, n=147; metastatic esophageal adenocarcinoma, n=14; high-grade dysplasia of the esophagus, n=52; low-grade dysplasia of the esophagus gland, n=21; and Barrett esophagus, n=68) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic granular staining in 138 of 147 (94%) of invasive esophageal adenocarcinomas, 13 of 14 (93%) of metastatic esophageal adenocarcinomas, and 49 of 52 (94%) of high-grade dysplasias. In contrast, 3/21 (14%) of low-grade dysplasia and 5/68 (7%) Barrett esophagus were positive for IMP3. Expression of IMP3 was not found in adjacent benign squamous and glandular mucosa. Our findings indicate that IMP3 is a highly sensitive and specific biomarker for the diagnosis of invasive esophageal adenocarcinoma and high-grade dysplasia. The data also suggest that IMP3, an oncofetal protein, may play an important role in malignant transformation in esophageal adenocarcinoma.


Flexible control of light trapping and localization in a hybrid Tamm plasmonic system.
A hybrid Tamm plasmonic system is proposed to investigate light manipulation at near-infrared frequency. The numerical results reveal that two remarkable absorption peaks are generated due to the different types of resonant modes excited in the structure, which can be well explained theoretically by guided-mode resonance (GMR) and Tamm plasmon polaritons. It is found that the electromagnetic energy can be easily trapped in different parts of the structure. More importantly, strong interaction between the two modes can be achieved by adjusting the structure period or incident angle, resulting in obvious mode hybridization and exhibiting unique energy-transfer characteristics. In addition, the active modulation of GMR-based absorption can be controlled in a continuous type by tuning the polarization angle or in a jump type by adjusting the chemical potential of graphene. This work should be useful for developing many high-performance optoelectronic devices, including sensors, modulators, detectors, etc.


Solution-Processed, Ultrathin Solar Cells from CdCl3(-)-Capped CdTe Nanocrystals: The Multiple Roles of CdCl3(-) Ligands.
Solution-processed CdTe solar cells using CdTe nanocrystal (NC) ink may offer an economically viable route for large-scale manufacturing. Here we design a new CdCl3(-)-capped CdTe NC ink by taking advantage of novel surface chemistry. In this ink, CdCl3(-) ligands act as surface ligands, sintering promoters, and dopants. Our solution chemistry allows obtaining very thin continuous layers of high-quality CdTe which is challenging for traditional vapor transport methods. Using benign solvents, in air, and without additional CdCl2 treatment, we obtain a well-sintered CdTe absorber layer from the new ink and demonstrate thin-film solar cells with power conversion efficiency over 10%, a record efficiency for sub-400 nm thick CdTe absorber layer.


Dos and don'ts for hospital cleaning.
More evidence is emerging on the role of cleaning and decontamination for reducing hospital-acquired infection. Timely and adequate removal of environmental pathogens leads to measurable clinical benefits for patients. This article considers studies published from 2013 examining hospital decontamination technologies and evidence for cost-effectiveness. Novel biocides and cleaning products, antimicrobial coatings, monitoring practices and automated equipment are widely accessible. They do not necessarily remove all environmental pathogens, however, and most have yet to be comprehensively assessed against patient outcome. Some studies are confounded by concurrent infection control and/or antimicrobial stewardship initiatives. Few contain data on costs. As automated dirt removal is assumed to be superior to human effort, there is a danger that traditional cleaning methods are devalued or ignored. Fear of infection encourages use of powerful disinfectants for eliminating real or imagined pathogens in hospitals without appreciating toxicity or cost benefit. Furthermore, efficacy of these agents is compromised without prior removal of organic soil. Microbiocidal activity should be compared and contrasted against physical removal of soil in standardized and controlled studies to understand how best to manage contaminated healthcare environments.


Total thyroidectomy: safe and adequate treatment for papillary microcarcinoma of the thyroid gland.
Total thyroidectomy: safe and adequate treatment for papillary microcarcinoma of the thyroid gland. The purpose of this study was to evaluate the incidence of and surgical approach in patients with papillary thyroid microcarcinoma (PTMC; thyroid cancer s10 mm) when these patients underwent surgery for presumed benign thyroid conditions. Between January 2006 and December 2013, 1460 adult patients underwent partial or total thyroidectomy for presumed benign thyroid conditions in the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, University Hospital in Martin, Slovakia. Of this population, 78 patients with incidental PTMC were further studied. Incidental papillary microcarcinoma was more frequently detected in patients with multinodular goitre (P = 0.034) or Hashimoto's thyroiditis (P=0.00 13) than in patients with other thyroid diseases. Multifocal and bilateral occurance of PTMC was identified in 26% and 18% of patients, respectively. The initial surgical procedure was -hemithyroidectomy in 23% of patients. All patients initially treated with hemithyroidectomy underwent completion thyroidectomy 10-32 days (median 19 ±7 days) after initial surgery. There were no significant differences in postoperative complications (recurrent laryngeal nerve injury, hypoparathyroidism) between patients with hemithyroidectomy and patients with total thyroidectomy at the first operation (P = 0.647). Completion surgery in patients with hemithyroidectomy was not followed by a significant increase in the incidence of complications (P=0.228). Incidental PTMC is more often detected in patients that undergo surgery for multinodular goitre and Hashimoto's thyroiditis. Total thyroidectomy constitutes a safe and adequate surgical approach in patients with PTMC.


The role of self-to-object updating in orientation-free performance on spatial-memory tasks.
A single view of a room-sized path produces an orientation-specific memory representation, yet when memory is tested at a location on the path, orientation-free performance is observed. Either a virtual-views or an updating hypothesis can account for orientation-free performance by attributing it, respectively, to an orientation-free long-term-memory representation or to a working-memory representation of the body's updated location relative to the path. Experiments 1 and 2 test these hypotheses by manipulating the test-site location and the complexity of the trajectory from the study site to the test site. Experiment 3 tests orientation to the test space as a function of trajectory complexity. Results support a virtual-views explanation for the orientation-free performance of males and an updating explanation for females.


Molecular detecting of piroplasms in feeding and questing Ixodes ricinus ticks
The purpose of this study was to detect piroplasms, which are pathogens of veterinary and zoonotic importance in ticks, that were collected from ponies and field vegetation and to determine the role of Shetland ponies as potential reservoir hosts for piroplasms. A total of 1737 feeding and 371 questing Ixodes ricinus collected from horses or vegetation were tested for the presence of Babesia and Theileria DNA. Piroplasm 18S rRNA gene amplification was conducted, and the obtained amplicons were sequenced. Babesia DNA was detected in only three ticks (one tick collected from a pony and two collected from vegetation), and all of the obtained sequences had 100% similarity to B. divergens. Theileria DNA was not present in the examined ticks. Thus, the above results indicate that ponies are probably not essential hosts for the detected species of piroplasms. Piroplasm species typical for horses (Babesia caballi and Theileria equi) were not detected because I. ricinus is not their vector. The low infection rate of I. ricinus with B. divergens shows that the disease risk for the local horse population and people associated with pony horses is low, but it demonstrates their possible role as a source of human infection in northern Poland.


Safety and utilization of blood components as therapeutic delivery systems.
In recent years, natural blood components have been extensively studied as the advanced therapeutic delivery systems. The blood components which can potentially be used as the therapeutic delivery systems include different types of cells, such as erythrocytes and lymphocytes, macromolecular complexes such as lipoproteins and antibody or albumin conjugates and other molecules. This review article covers the progress in this topic, specifically, including the safety issues and the utilization of these component. It can be seen through the literature that the blood components as the therapeutic delivery systems have a number of advantages over traditional pharmaceutical products. The efficacy and practice of the applications, however, require significant amount of development work in the near future.


Endovascular Aortic Repair After Proximal Stent Graft Migration of a Modified Frozen Elephant Trunk.
We describe the endovascular repair for a proximal endograft migration following a modified frozen elephant trunk (mFET) repair for a retrograde type A dissection (retro-A AD). A 40-year-old man presented with a type B aortic dissection that progressed to a retro-A AD. He was emergently taken to the operating room for an mFET repair. Computed tomography (CT) angiogram on the day of discharge revealed that the proximal end of the endograft migrated through the primary intimal tear resulting in obstruction of true lumen flow. The patient returned to the catheterization lab for endovascular repair utilizing a through-and-through wire to extend the endograft proximally and a left carotid-subclavian artery bypass. This complication highlights the importance of postoperative CT surveillance and the endovascular technique utilized to restore aortic true lumen flow.


Temporary Tumor Shrinkage Following Enfortumab Vedotin Therapy for Metastatic Urothelial Carcinoma After Radical Cystectomy With Neoadjuvant Chemotherapy: A Case Report.
A 39-year-old Japanese male patient presented with a chief complaint of gross hematuria persistent for two months. However, no relevant findings in the patient's medical and family history were observed. He was diagnosed with muscle-invasive bladder cancer, clinical stage T2bN0M0. After four courses of neoadjuvant chemotherapy with gemcitabine and cisplatin, the tumor size reduced by approximately 30%. The patient underwent robot-assisted radical cystectomy with standard lymph node dissection followed by intracorporeal ileal conduit reconstruction. Histologically, the tumor was diagnosed as a high-grade urothelial carcinoma invading the fatty tissue surrounding the bladder and metastasizing to the lymph nodes, with a pathological stage of ypT3aypN2M0. Four months after surgery, multiple metastases were detected, and treatment with pembrolizumab was initiated immediately. However, the patient did not respond to pembrolizumab. Therefore, a third-line treatment with enfortumab vedotin (EV) was initiated. Thereafter, the metastatic lesion shrank quickly, and the metastatic lesions almost disappeared after two courses of EV administration. Although new metastases were observed at other sites, there has been no regrowth to date. EV-related adverse events were not observed during follow-up. Eighteen months after the surgery, the patient remains alive with multiple metastases. Therefore, the sequence of treatment should be considered to maximize the therapeutic effect of EV, and, consequently, administering EV as early as possible may be important.


Solvent controlled intramolecular electron transfer in mixtures of 1-butyl-3-methylimidizolium tetrafluoroborate and acetonitrile.
Time-resolved emission techniques were used to study the excited-state intramolecular electron transfer of 9-(4-biphenyl)-10-methylacridinium (BPAc+) in mixtures of 1-butyl-3-methylimidizolium tetrafluoroborate ([Im41][BF4])+ acetonitrile (ACN), a mixture previously shown to be of nearly constant polarity and nearly ideal mixing behavior. Reaction times (τ rxn) track solvation times (τ solv) as a function of mixture composition over a range of more than 3 orders of magnitude in τ solv. This same correlation extends to a variety of neat dipolar solvents and ionic liquids. Reaction times are ∼2-fold larger than τ solv over most of the range studied but appear to reach a limiting value of ∼3 ps in the fastest solvents.


A biomimetic coupled circuit based microphone array for sound source localization.
An equivalent analog circuit is designed to mimic the coupled ears of the fly Ormia ochracea for sound source localization. This coupled circuit receives two signals with tiny phase difference from a space closed two-microphone array, and produces two signals with obvious intensity difference. The response sensitivity can be adjusted through the coupled circuit parameters. The directional characteristics of the coupled circuit have been demonstrated in the experiment. The miniature microphone array can localize the sound source with low computational burden by using the intensity difference. This system has significant advantages in various applications where the array size is limited.


Characterization of biofilm of a rotating biological contactor treating synthetic wastewater.
A four-stage rotating biological contactor (RBC) was designed and operated to treat synthetic wastewater containing 1,000 mg/l chemical oxygen demand (COD) and 112 mg/l NH(4)(+)-N. A mixed culture bacterial biofilm was developed consisting of a heterotrophic bacterium Paracoccus pantotrophus, nitrifiers and other heterotrophs. Applying the peculiar characteristics of P. pantotrophus of simultaneous heterotrophic nitrification and aerobic denitrification, high simultaneous removal of carbon and nitrogen could be achieved in the fully aerobic RBC. The microbial community structure of the RBC biofilm was categorized based on the nitrate reduction, biochemical reactions, gram staining and morphology. The presence of P. pantotrophus within the RBC biofilm was confirmed with an array of biochemical tests. Isolates from the four stages of RBC were grouped into complete denitrifiers, incomplete denitrifiers and non-denitrifiers. This categorization showed a higher relative abundance of P. pantotrophus in the first stage as compared with subsequent stages, in which other nitrifiers and heterotrophs were significantly present. High total nitrogen removal of upto 68% was in conformity with observations made using microbial categorization and biochemical tests. The high relative abundance of P. pantotrophus in the biofilm revealed that it could successfully compete with other heterotrophs and autotrophic nitrifiers in mixed bacterial biomass.


A comprehensive review of inflammatory bowel disease focusing on surgical management.
The two main diseases of inflammatory bowel disease are Crohn's disease and ulcerative colitis. The pathogenesis of inflammatory disease is that abnormal intestinal inflammations occur in genetically susceptible individuals according to various environmental factors. The consequent process results in inflammatory bowel disease. Medical treatment consists of the induction of remission in the acute phase of the disease and the maintenance of remission. Patients with Crohn's disease finally need surgical treatment in 70% of the cases. The main surgical options for Crohn's disease are divided into two surgical procedures. The first is strictureplasty, which can prevent short bowel syndrome. The second is resection of the involved intestinal segment. Simultaneous medico-surgical treatment can be a good treatment strategy. Ulcerative colitis is a diffuse nonspecific inflammatory disease that involves the colon and the rectum. Patients with ulcerative colitis need surgical treatment in 30% of the cases despite proper medical treatment. The reasons for surgical treatment are various, from life-threatening complications to growth retardation. The total proctocolectomy (TPC) with an ileal pouch anal anastomosis (IPAA) is the most common procedure for the surgical treatment of ulcerative colitis. Medical treatment for ulcerative colitis after a TPC with an IPAA is usually not necessary.


Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis.
There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.


Quantifying social asymmetric structures.
Many social phenomena involve a set of dyadic relations among agents whose actions may be dependent. Although individualistic approaches have frequently been applied to analyze social processes, these are not generally concerned with dyadic relations, nor do they deal with dependency. This article describes a mathematical procedure for analyzing dyadic interactions in a social system. The proposed method consists mainly of decomposing asymmetric data into their symmetric and skew-symmetric parts. A quantification of skew symmetry for a social system can be obtained by dividing the norm of the skew-symmetric matrix by the norm of the asymmetric matrix. This calculation makes available to researchers a quantity related to the amount of dyadic reciprocity. With regard to agents, the procedure enables researchers to identify those whose behavior is asymmetric with respect to all agents. It is also possible to derive symmetric measurements among agents and to use multivariate statistical techniques.


[THE CHOICE OF SURGICAL TREATMENT METHOD FOR THE DEEP VEINS THROMBOSIS IN SYSTEM OF VENA CAVA INFERIOR].
There were analyzed the results of examination and treatment of 455 patients, suffering deep veins thrombosis in a system of vena cava inferior, of whom 175 (38.5%) were operated on. Inclusion of ultrasound duplex scanning, roentgencontrast phlebography, multispiral computer tomography with intravenous contrasting, radionuclide phleboscintigraphy into complex of clinic-instrumental examination of the patients gives possibility to estimate the disorders of the main trunk and collateral venous blood flow in the deep veins thrombosis, as well as to substantiate indications and choice of the operative treatment method.


Metal-Organic Framework Derived Ultrafine Sb@Porous Carbon Octahedron via In Situ Substitution for High-Performance Sodium-Ion Batteries.
Alloying-type anode materials are regarded as promising alternatives beyond intercalation-type carbonaceous materials for sodium storage owing to the high specific capacities. The rapid capacity decay arising from the huge volume change during Na+-ion insertion/extraction, however, impedes the practical application. Herein, we report an ultrafine antimony embedded in a porous carbon nanocomposite (Sb@PC) synthesized via facile in situ substitution of the Cu nanoparticles in a metal-organic framework (MOF)-derived octahedron carbon framework for sodium storage. The Sb@PC composite displays an appropriate redox potential (0.5-0.8 V vs Na/Na+) and excellent specific capacities of 634.6, 474.5, and 451.9 mAh g-1 at 0.1, 0.2, and 0.5 A g-1 after 200, 500, and 250 cycles, respectively. Such superior sodium storage performance is primarily ascribed to the MOF-derived three-dimensional porous carbon framework and ultrafine Sb nanoparticles, which not only provides a penetrating network for rapid transfer of charge carriers but also alleviates the agglomeration and volume expansion of Sb during cycling. Ex situ X-ray diffraction and in situ Raman analysis clearly reveal a five-stage reaction mechanism during sodiation and desodiation and demonstrate the excellent reversibility of Sb@PC for sodium storage. Furthermore, post-mortem analysis reveals that the robust structural integrity of Sb@PC can withstand continuous Na+-ion insertion/extraction. This work may provide insight into the effective design of high-capacity alloying-type anode materials for advanced secondary batteries.


Neoadjuvant chemotherapy with sequential anthracycline-docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem).
Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy. Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety. 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer. Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.


c-Krox, a transcriptional regulator of type I collagen gene expression, is preferentially expressed in skin.
We have cloned a mouse cDNA that is a member of the Krox gene family and encodes a protein we have named c-Krox. The c-Krox protein contains three zinc fingers of the Cys2His2 type. c-Krox binds specifically to a guanine-rich cis-acting element present twice in the promoter element of the mouse alpha 1(I) collagen gene. Study of c-Krox gene expression shows that c-Krox is markedly enriched in skin, one of the two major sites of type I collagen synthesis, but is absent in bone, the other main type I collagen-producing tissue, indicating that type I collagen gene expression is differentially regulated in skin and bone. DNA transfection experiments in mouse NIH 3T3 fibroblasts, cells that express the c-Krox gene, or in Drosophila S2 cells, which do not express c-Krox, reveal that c-Krox can activate transcription of a reporter gene linked to several copies of its binding site in the alpha 1(I) collagen promoter. Thus, c-Krox is only the second member of the Krox family for which a target gene has been identified. The selective spatial pattern of expression of its mRNA and its transcription activation ability suggest that c-Krox may be an important regulator of type I collagen skin specific expression in physiologic conditions and in fibrotic diseases such as scleroderma.


Effect of glutaraldehyde on hemoglobin: functional aspects and Mössbauer parameters.
Glutaraldehyde is widely used for the cross-linking of hemoglobin for blood substitute research or for technological purposes. The effects of this reagent on the biochemical properties of hemoglobin were correlated with Mössbauer data. Human hemoglobin was cross-linked by glutaraldehyde as soluble polymers and insoluble particles. Effects of cross-linking on oxygen affinity, oxidation-reduction potential, autoxidation kinetics, and thermal stability were studied. Stability of cross-linked hemoglobin was specifically studied by Mössbauer spectroscopy. Oxygen affinity is increased, redox potential is decreased, autoxidation rates are increased, and stability towards thermal denaturation is increased. The regeneration of partially denatured hemoglobin by glutaraldehyde cross-linking is shown. Effects of cross-linking on biochemical properties are explained by the hypothesis of the opening of the heme pocket on the distal-histidine side and the concomitant charge transfer from the iron to the oxygen.


Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.
Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD) values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0) and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC). SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.


Diffusion-Weighted Imaging Shows a False-Negative Finding for Bone Marrow Involvement on 18F-FDG PET/MRI in a Patient With Malignant Lymphoma After Blood Transfusion.
Iron overload is a major complication in blood transfusion procedures. This report presents a case of malignant lymphoma, in which the findings of bone marrow involvement were discordant between F-FDG PET imaging studies and MRI with diffusion-weighted imaging studies. In this case, the PET imaging studies were positive for malignant lymphoma, whereas the MRI studies were negative. Iron deposition in the reticuloendothelial system due to posttransfusion iron overload was considered to be the cause of the decrease in signal intensity on diffusion-weighted imaging, resulting in a false-negative finding on MRI.


Antisense anti-MDM2 oligonucleotides as a novel approach to the treatment of glioblastoma multiforme.
Overexpression of the MDM2 oncogene is one of the molecular characteristics of gliomas. In this study we determined the therapeutic effects of an antisense anti-MDM2 oligonucleotide administered alone or in combination with the clinically used chemotherapeutic agents Paclitaxel and Irinotecan. In cultured cells with various p53 status, U87-MG (p53wt/wt), A172 (p53wt/mt) and T98G (p53mt/mt), the antisense oligonucleotide, produced a dose- and sequence-dependent reduction in MDM2 expression and elevation in p53 (in U87-MG and A172 cells) and p21 levels (in all three cell lines), resulting in an increase in apoptosis and cytotoxicity. Synergistic effects on p53 and p21 levels between the oligonucleotide and chemotherapeutic agents were also observed in vitro. In in vivo studies with U87-MG xenografts, the oligonucleotide inhibited tumor growth and improved the therapeutic efficacy of paclitaxel and irinotecan 39- and 63-fold, respectively. In conclusion, inhibiting MDM2 expression could be a novel pharmacological approach to glioblastoma therapy.


Reflexivity, reflection, and the change process in offender work.
This study explores the therapeutic engagement experiences of men who have sexually offended against children and who are involved in a prototypical prison-based group treatment programme. The study examined factors relating to the therapeutic engagement of the offender in treatment, and in particular, the impact of the "out-of-group" time between sessions. The findings, although tentative, suggest that between formal therapy sessions, clients of the programme make significant movement either toward or away from engagement in the therapy. The implications of these processes with respect to clinical practice and the development of offender services are discussed.


Effects of substance abuse on hallucination rates and treatment responses in chronic psychiatric patients.
Few data systematically document the effects of illicit drug exposure on psychotic illness. We examined the effect of substance abuse on rates and treatment responses of hallucinations in a chronic psychiatric population. 113 cooperative patients consecutively admitted to a state psychiatric hospital were administered the Structured Clinical Diagnostic Interview for DSM-III-R, a Hallucination Interview, and an inventory of past and current substances of abuse. Demographic information was obtained on 104 of 108 patients who declined interview. Medication dosage was analyzed for one third of the interviewed sample; hospital records, nursing reports, contacts with relatives, and urine drug screens were used to confirm information from patient interviews. Hallucination rates and response were compared by diagnostic groups (chi-square). Noninterviewed patients had more frequent hospitalizations, more patients diagnosed with psychosis not otherwise specified or schizoaffective disorder, and fewer females with comorbid substance abuse than the study population. Among interviewed subjects, those with substance abuse and psychiatric illness had first admissions at an earlier age than patients with no substance abuse (p = .005). Schizophrenics experienced higher rates of visual (p = .04) and olfactory (p = .05) hallucinations when using illicit drugs. Substance abuse was associated with decreased treatment responsiveness of auditory (p < .03) and tactile (p < .004) hallucinations in schizophrenic or manic patients. Compared with nonparanoid patients, there was a trend for paranoid schizophrenics with substance abuse to experience more frequent visual (p = .09) and tactile (p = .06) and more refractory auditory (p = .08) hallucinations. No differences in medication dosages were found between patients with treatment-responsive and treatment-refractory hallucinations. Abused substances may interact selectively with primary psychiatric illness to increase rates and treatment resistance of specific hallucination modalities; etiologies are discussed.


Silicon nanowire radial p-n junction solar cells.
We have demonstrated a low-temperature wafer-scale etching and thin film deposition method for fabricating silicon n-p core-shell nanowire solar cells. Our devices showed efficiencies up to nearly 0.5%, limited primarily by interfacial recombination and high series resistance. Surface passivation and contact optimization will be critical to improve device performance in the future.


[Which general practitioner requests cardiologic consultation?].
Since health care costs continue to rise, the Regions and the Local Health Boards needs to draw up their plans, and permanent training initiatives must be undertaken for physicians, it was decided to see if and which personal and professional characteristics influence primary physicians in their requests for cardiological consultation. It is, in fact, well known that the attitudes of doctors not only affect the health of the population, but also the cost of such health to the community. Assessment of calls for heart examinations on the part of general practitioners attached to a local health board showed that neither age nor sex, nor the fact of working solely for the health service, nor the number of patients on a doctor's panel made any appreciable difference with respect to cardiological consultations. It was noted, however, that doctors whose only activity consisted of general practice under the health service called for fewer consultations than their colleagues with other activities, and that older physicians measured blood pressure less frequently and tended to give shorter descriptions of their findings to the cardiologist. The survey tended to show that the decision to send a patient to a cardiologist was probably more influenced by the characteristics of his complaint and his condition, and the medical attendant's clinical and psychological convictions than on such factors as age, sex, number of persons looked after, and working solely for the general health service.


Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective.
Multidrug resistance is one of the most serious problems in the treatment of epilepsy that is likely to have a complex genetic and acquired basis. Various experimental data support the hypothesis that over-expression of antiepileptic drug (AED) transporters may play a pivotal role in drug resistance. Hyyt 6however, key questions concerning their functionality remain unanswered. The idea that P-glycoprotein, encoded by the ABCB1 gene, might mediate at least part of the drug resistance was met with both enthusiasm and skepticism. As in oncology, initial optimism has been clouded subsequently by conflicting results. The first study reporting a positive association between genetic variation in the P-glycoprotein and multidrug-resistant epilepsy was published in 2003. Since then, several other genetic association studies have attempted to verify this result. However, taken overall, the role of P-glycoprotein in drug resistance in epilepsy still remains uncertain. We intend to critically review the inherent problems associated with epilepsy pharmacogenetic studies in general and with ABCB1 polymorphisms studies in particular. The lessons learnt from the ABCB1 studies can help us to guide future association genetics studies to investigate AED resistance, and thereby taking us closer to the cherished dream of personalized AED therapy.


Hematoxylin procedure for staining mature pollen grains in maize with dimethylsulfoxide as a clearing agent.
Observing nuclei of mature pollen grains in maize is extremely difficult because the starch granules surrounding the nuclei are deeply stained. The cytoplasm of hematoxylin stained pollen grains becomes clear when DMSO and gentle heating are used. By separating the staining and clearing processes, uniformly stained pollen grains were consistently obtained. Using this method, 2,000 pollen grains were examined and it was determined that 99.5% were in the normal tricellular state, while pentacellular pollen, bicellular pollen and pollen grains with two vegetative nuclei were observed in the remaining 0.5%.


Large Magneto-piezoelectric Effect in EuMnBi2 Single Crystal at Low Temperatures.
Magneto-piezoelectric effect (MPE) refers to generation of strain in response to electric currents in magnetic metals which lack both time-reversal and space-inversion symmetries. A recent experimental paper demonstrated the MPE in the antiferromagnetic metal EuMnBi2 at 77 K, but the limited temperature range of the MPE measurement hampered detailed discussion on the MPE. Here we extend the measurement temperature range down to liquid He temperature, and studied the dependences of the MPE on the laser position, frequency and amplitude of electric currents, and temperature in the very low temperature range. We show that the MPE signal is enhanced at low temperatures and reaches a maximum magnitude in the antiferromagnetically ordered states of both Eu and Mn ions. An effective piezoelectric coefficient for the MPE at 4.5 K is estimated to be as large as 3500 pC/N, which is much larger than piezoelectric coefficients of typical piezoelectric ceramics, although the magnitude of real MPE displacements should be limited due to strong Joule heating at high electric currents. The present results may open up a new strategy to realize new lead-free piezoelectric materials.


Fundamental shift in vitamin B12 eco-physiology of a model alga demonstrated by experimental evolution.
A widespread and complex distribution of vitamin requirements exists over the entire tree of life, with many species having evolved vitamin dependence, both within and between different lineages. Vitamin availability has been proposed to drive selection for vitamin dependence, in a process that links an organism's metabolism to the environment, but this has never been demonstrated directly. Moreover, understanding the physiological processes and evolutionary dynamics that influence metabolic demand for these important micronutrients has significant implications in terms of nutrient acquisition and, in microbial organisms, can affect community composition and metabolic exchange between coexisting species. Here we investigate the origins of vitamin dependence, using an experimental evolution approach with the vitamin B(12)-independent model green alga Chlamydomonas reinhardtii. In fewer than 500 generations of growth in the presence of vitamin B(12), we observe the evolution of a B(12)-dependent clone that rapidly displaces its ancestor. Genetic characterization of this line reveals a type-II Gulliver-related transposable element integrated into the B(12)-independent methionine synthase gene (METE), knocking out gene function and fundamentally altering the physiology of the alga.


The Prevalence of Autoimmune Diseases in Patients with Primary Open-Angle Glaucoma Undergoing Ophthalmic Surgeries.
To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. Retrospective, cross-sectional study. Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27-5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P < 0.001). In a case-only analysis involving the eye with worse glaucoma, there was no statistical difference in visual field mean deviation or retinal nerve fiber layer (RNFL) thickness in POAG patients with AiD (n = 30) and without AiD (n = 142, P > 0.13, for both). A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.


Atomic-scale mass sensing using carbon nanotube resonators.
Ultraminiaturized mass spectrometers are highly sought-after tools, with numerous applications in areas such as environmental protection, exploration, and drug development. We realize atomic scale mass sensing using doubly clamped suspended carbon nanotube nanomechanical resonators, in which their single-electron transistor properties allows self-detection of the nanotube vibration. We use the detection of shifts in the resonance frequency of the nanotubes to sense and determine the inertial mass of atoms as well as the mass of the nanotube. This highly sensitive mass detection capability may eventually enable applications such as on-chip detection, analysis, and identification of compounds.


Concordance between microsatellite instability testing and immunohistochemistry for mismatch repair proteins and efficient screening of mismatch repair deficient gastric cancer.
Microsatellite instability (MSI) testing, an established technique that has gained prominence in recent years for its predictive potential regarding the efficacy of immune checkpoint inhibitors, is used to evaluate DNA mismatch repair (MMR) deficiency (dMMR). As with other methods, the immunohistochemistry (IHC) of MMR proteins is also widely adopted. Although both techniques have been validated, their concordance rate remains unknown, particularly regarding non-colorectal cancer. Therefore, the aim of the present study was to explore and elucidate their concordance in the context of gastric cancer (GC). A total of 489 surgically resected primary GC tissues were analyzed to compare the results yielded by the MSI test and those from IHC. Of 488 GC cases, 56 (11.5%) exhibited a loss of MMR proteins, whereas 52 (10.7%) were classified as high-frequency MSI (MSI-H). The concordance rate between these two categories was 99.2%. The microsatellite markers BAT26 and MONO27 demonstrated 100% sensitivity and 99.5% specificity in detecting dMMR GC. In addition, histopathological analysis revealed that MSI-H was more prevalent in GCs exhibiting coexisting Tub2 and Por1 subtypes. However, four discordant cases were observed. All four cases were microsatellite-stable cases but exhibited loss of MLH1 protein expression with hypermethylation of the MLH1 promoter. The results of the present study highlight that while there is a strong concordance between MSI and IHC testing results for determining dMMR status, IHC testing may offer superior efficacy in detecting dMMR.


Gemcitabine-induced Gli-dependent activation of hedgehog pathway resists to the treatment of urothelial carcinoma cells.
Patients with urothelial carcinoma (UC) experience gemcitabine resistance is a critical issue. The role of hedgehog pathway in the problem was explored. The expressions of phospho-AKTser473, phospho-GSK3βser9 and Gli2 were up-regulated in gemcitabine-resistant NTUB1 (NGR) cells. Without hedgehog ligands, Gli proteins can be phosphorylated by GSK3β kinase to inhibit their downstream regulations. Furthermore, the GSK3β kinase can be phosphorylated by AKT at its Ser9 residue to become an inactive kinase. Therefore, overexpression of AKT1, Flag-GSKS9D (constitutively inactive form) or active Gli2 (GLI2ΔN) in NTUB1 cells could activate Gli2 pathway to enhance migration/invasion ability and increase gemcitabine resistance, respectively. Conversely, overexpression of Flag-GSKS9A (constitutively active form) or knockdown of Gli2 could suppress Gli2 pathway, and then reduce gemcitabine resistance in NGR cells. Therefore, we suggest gemcitabine-activated AKT/GSK3β pathway can elicit Gli2 activity, which leads to enhanced migration/invasion ability and resistance to gemcitabine therapy in UC patients. The non-canonical hedgehog pathway should be evaluated in the therapy to benefit UC patients.


[Intracardiac hemodynamics in patients with isolated chronic obstructive pulmonary disease and coronary heart disease].
Analysis of intracardiac hemodynamics is presented in patients with isolated stage II, III and IV chronic obstructive pulmonary disease (COPD) in the period of exacerbation and in those having COPD with concomitant coronary heart disease (stable angina of functional class II). Retrospective evaluation included 100 medical histories. Color Doppler echoCG was performed and parameters of systolic and diastolic function of both ventricles measured. Results of correlation analysis of systolic and diastolic function of left and right ventricles are presented along with the data on blood pressure in the right chambers of the heart.


Challenging the role of calibration, validation and sensitivity analysis in relation to models of health care processes.
Many applications of Operational Research in the context of health care involve processes of calibration, validation and sensitivity analysis. Indeed these processes seem to have such an elevated status that their absence is often regarded as a marker that a study is somehow substandard. Undoubtedly this may be the case, however there may also be circumstances where it is perfectly reasonable not to use such methods. This paper concerns general principles underlying mathematical modelling, particularly in contexts where data for calibration are either poor quality or non-existent. The discussion challenges the view that modelling should necessarily be subject to formulaic calibration, validation and sensitivity analysis processes in an attempt to achieve or establish 'accuracy'. Some models are used purely to deduce the logical consequences of a set of beliefs and in this context, the need for validation is at best questionable. If calibration and sensitivity analysis are to be carried out, there is a need to be clear about what the objective is in such analyses.


Efficacy of HUMN criteria for scoring the micronucleus assay in human lymphocytes exposed to a low concentration of p,p'-DDT.
The cytokinesis-block micronucleus (CBMN) assay is one of the standard cytogenetic tools employed to assess chromosomal damage subsequent to exposure to genotoxic/cytotoxic agents, and is widely applicable to plant, animal and human cells. In the present study, the CBMN assay was used to assess the baseline damage in binuclear human peripheral blood lymphocytes exposed to 25 microg/L p,p'-DDT for 1, 2, 24, and 48 h by measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. These new scoring criteria facilitated the detection of different types of clastogenic and aneugenic effects induced by this type of pollutant. With these criteria, CBMN can also be used to measure nucleoplasmic bridges which are considered to be consequences of chromosome rearrangements and nuclear buds which are biomarkers of altered gene amplification and gene dosage. The total number of micronuclei observed in binuclear human peripheral blood lymphocytes of the exposed samples (ranging from 32 to 47) was significantly greater (P < 0.05) than that detected in the unexposed (0 time) control sample, where the total number of micronuclei was 7. The number of nucleoplasmic bridges and nuclear buds obtained after 24 and 48 h was also significantly (P < 0.05) greater in the samples treated with p,p'-DDT than in the unexposed control samples. Thus, our results confirmed the usefulness of the new criteria applicable for the CBMN assay employed in measuring the DNA damage and its role of a sensitive cytogenetic biomarker.


Toward evidence-based prescribing at end of life: a comparative review of temazepam and zolpidem for the treatment of insomnia.
A comparative review of temazepam and zolpidem use in managing insomnia in the hospice patient was undertaken to determine whether treatment with temazepam is a more cost-effective approach for this patient population. A MEDLINE search was conducted to identify pertinent literature, including clinical trials and reviews that involved temazepam or zolpidem. Published data was used as background information and provided in the discussion. This retrospective analysis, conducted from June 2002 through November 2002, focused on the prescribing patterns of temazepam and zolpidem in our hospice practice setting. We examined the reasons for discontinuation of each agent, along with the frequency of therapeutic change from temazepam to zolpidem. The top 10 ICD-9 codes associated with each treatment modality were investigated to determine any prescribing patterns. A total of 4,752 participants were prescribed either temazepam or zolpidem during this six-month period. Of the 4,065 patients prescribed temazepam 9.9 percent had the agent discontinued, whereas, 13.0 percent of those taking zolpidem (n = 687) terminated therapy. Reasons for discontinuation included change in dose, incomplete efficacy, change in patient status, adverse drug reaction, cultural/social issues and "other." Analyses of prescribing patterns and the reasons for termination of each drug therapy were completed and compared with results found in the primary literature. Due to the limited financial resources available for hospice care, our goal is to provide the most clinically appropriate and cost-effective agents for hospice patients. With the lack of data pertaining to the hospice patient, physicians often are faced with challenges in deciding the most appropriate therapy. They may prefer one agent over another based on current medical opinion rather than sound clinical evidence. After review of the primary literature and the prescribing patterns in our setting, there is currently no evidence in our patient population to support that zolpidem is superior to benzodiazepines for the treatment of insomnia.


The post-natal development of holocrine epidermal specializations in gekkonid lizards.
The abdominal escutcheon, and certain aspects of pre-anal organ morphology, have been studied in Sphaerodactylus spp. and Gekko vittatus respectively. These epidermal modifications are male characteristics. The sphaerodactyline escutcheon becomes larger by the peripheral addition of specialized scales with increasing size of the individuals: this relationship is much more clearcut in S. cinereus than in the notatus species group (sensu Shreves, '68), and the possible reasons for this are discussed. The number of pre-anal organs varies between populations of G. vittatus, but within populations remains constant throughout life. Individual organs increase steadily in size throughout life. These data are discussed with reference to current interpretations of gekkonid gland evolution, and of factors controlling epidermal cell proliferation and differentiation.


Development of High-Performance Polymer Electrolyte Membranes through the Application of Quantum Dot Coatings to Nafion Membranes.
Proton exchange membrane water electrolysis (PEMWE) generates oxygen and hydrogen at the anode and cathode, respectively, by conducting protons generated at the anode to the cathode through a proton exchange membrane (PEM). The performance of PEMWE can be improved with faster catalytic reactions at each electrode; thus, the development of a PEM with excellent ionic conductivity and physicochemical stability is essential. Nafion, a type of perfluoro-sulfonic acid polymer, is the most widely used PEM material. However, despite its excellent conductivity and chemical stability, it exhibits high hydrogen permeability due to its structural characteristics. Quantum dots (QDs) have a hydrophilic functional group that can act as an ion conductor and are extremely compatible with the hydrophilic cluster of Nafion due to their characteristic nanosized structure. In this study, various compositions of N-doped carbon quantum dots (CQDs) containing hydrophilic functional groups were coated on a Nafion-212 membrane. The resulting series of CQD-coated Nafion membranes exhibited improvements in morphology and ionic conductivity as well as reductions in hydrogen permeability. In particular, the Nafion membrane coated with 0.75 wt % of N-doped CQD (CQD-cNafion-0.75) exhibited improved mechanical properties and higher oxidation stability compared to Nafion-212. It also displayed higher ionic conductivity of 240.3 mS cm-1 at 80 °C and reduced hydrogen permeability (about 10% reduction) compared to Nafion-212. In addition, the performance of single-cell PEMWE using the CQD-cNafion-0.75 membrane was found to be approximately 1.2 times higher than Nafion-212.


Multiple-dose comparison of suprofen, aspirin, and placebo in the treatment of musculoskeletal pain.
The effectiveness and safety of suprofen 200 mg, aspirin 650 mg, and placebo in the treatment of moderate to severe pain were compared in a 72-hour multiple-dose, double-blind, parallel, randomized study in 75 adults suffering from musculoskeletal pain. Suprofen was superior to aspirin and placebo for pain relief, total pain relief scores, pain severity, activity impairment, comparative evaluation of activity impairment, and comparative evaluation of pain and sleep, with differences achieving statistical significance for most parameters at the 24- to 72-hour evaluation points. 1 mild, transient side effect occurred in the suprofen group, 3 in the placebo group, and 4 of moderate intensity in the aspirin group. The effectiveness of multiple-dose treatment of musculoskeletal pain with suprofen 200 mg is superior to that of aspirin and placebo.


Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation.
Sip1, a Smad-binding zinc-finger homeodomain transcription factor, has essential functions in embryonic development, but its role in individual tissues and the significance of its interaction with Smad proteins have not been fully characterized. In the lens lineage, Sip1 expression is activated after lens placode induction, and as the lens develops, the expression is localized in the lens epithelium and bow region where immature lens fibers reside. The lens-lineage-specific inactivation of the Sip1 gene was performed using mice homozygous for floxed Sip1 that carry a lens-specific Cre recombinase gene. This caused the development of a small hollow lens connected to the surface ectoderm, identifying two Sip1-dependent steps in lens development. The persistence of the lens stalk resembles a defect in Foxe3 mutant mice, and Sip1-defective lenses lose Foxe3 expression, placing Foxe3 downstream of Sip1. In the Sip1-defective lens, beta-crystallin-expressing immature lens fiber cells were produced, but gamma-crystallin-expressing mature fiber cells were absent, indicating the requirement for Sip1 activity in lens fiber maturation. A 6.2 kb Foxe3 promoter region controlled lacZ transgene expression in the developing lens, where major and minor lens elements were identified upstream of -1.26 kb. Using transfection assays, the Foxe3 promoter was activated by Sip1 and this activation is further augmented by Smad8 in the manner dependent on the Smad-binding domain of Sip1. This Sip1-dependent activation and its augmentation by Smad8 occur using the proximal 1.26 kb promoter, and are separate from lens-specific regulation. This is the first demonstration of the significance of Smad interaction in modulating Sip1 activity.


[Clinical efficacy and radiation exposure analysis of vertebroplasty and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture].
Taking the classic bilateral puncture vertebroplasty as a reference, to evaluate the clinical efficacy of vertebroplasty of the curved-angle puncture device, analyze the radiation exposure of patients and surgeons during the operation and summarize the protective measures. The clinical data of 49 patients with osteoporotic vertebral compression fractures admitted from March 2018 to September 2019 were retrospectively analyzed. According to the different surgical puncture methods, 49 patients were divided into vertebroplasty group (using classic bilateral puncture) and curved vertebroplasty group (using curved angle puncture). Among them, there were 26 cases in vertebroplasty group, including 7 males and 19 females, aged (73.25±6.36) years, 2 cases in thoracic segment, 21 cases in thoracolumbar segment, and 3 cases in lumbar segment. In curved vertebroplasty group, there were 23 cases, including 6 males and 17 females, aged (73.09±6.52) years, 3 cases in thoracic segment, 19 cases in thoracolumbar segment, and 1 case in lumbar segment. The operation time and the amount of injected bone cement in the two groups were recorded. Visual analogue scale (VAS) and modified Oswestry Disability Index (ODI) were respectively used to assess the pain degree and lumbar function, the postoperative bone cement leakage or other complications were observed. The radiation doses of the two groups of patients and surgeons were compared. All 49 patients were followed up for 10-22 (14.55±3.83) months. Eleven cases in vertebroplasty group and 9 cases in curved vertebroplasty group occurred bone cement leakage after surgery, and there was no statistically significant difference between two groups. VAS scores of vertebroplasty group were 6.23±0.68 before operation and 1.69±0.47 at 1 day after operation, respectively, modified ODI were (72.59±3.25)% and (33.59±2.85)%. The preoperative and postoperative VAS scores of curved vertebroplasty group were 6.46±0.56 and 1.57±0.49, respectively, modified ODI were (73.21±3.18)% and (33.17±2.37)%. The postoperative pain degree and lumbar function of the two groups were significantly improved, but the difference between the groups was not statistically significant. The operation time of curved vertebroplasty group and vertebroplasty group were (17.27±9.58) min and(23.19±8.56) min, and the amount of injected bone cement were (4.91±1.49) ml and (6.58±1.42) ml. Obviously, curved vertebroplasty group has more advantages in operation time and the amount of injected bone cement. In curved vertebroplasty group, the radiation dose of the operator was (0.53±0.05) mSv and the patient was (10.64±1.65) mSv;in vertebroplasty group, the operator was (0.59±0.08) mSv andthe patient was (13.52±1.81) mSv. The radiation dose of patients in curved vertebroplasty group was significantly lower than that of the vertebroplasty group, but there was no statistically significant difference in the operator between two groups. Both puncture methods can achieve satisfactory clinical results, but curved angle puncture can optimize the distribution of bone cement and reduce the radiation dose of patients.


Gold Nanopopcorn Attached Single-Walled Carbon Nanotube Hybrid for Rapid Detection and Killing of Bacteria.
We report a strategy to fabricate a rapid and stable surface-enhanced Raman scattering (SERS)-based hybrid nanomaterial using gold nanopopcorns attached single-walled carbon nanotubes (AuNP@f3-SWCNTs) for label-free detection and photothermal killing of bacteria. Herein, previously ester-functionalized single-walled carbon nanotubes (f1-SWCNTs) undergo 1,3-dipolar cycloaddition reaction with in-situ generated nitrile imine under Microwave (MW) irradiation to form a doubly ester terminated SWCNTs cycloadduct (f2-SWCNTs). The ester terminals are further modified with 4-aminothiophenol (4-ATP) under MW-irradiation to form thiol-terminated SWCNTs templates (f3-SWCNTs) that allow gold nanopopcorns (AuNPs) to covalently and uniformly attach at a minimum inter-particle distance thus yielding a hybrid nanomaterial (AuNP@f3-SWCNT) with good aqueous stability and abundant 'hotspots'. Consequently, monoclonal E. coli antibody-conjugated bioassays fabricated with our AuNP@f3-SWCNT substrates (mAb-AuNP@f3-SWCNT) rapidly detect E. coli in water with good selectivity and impressive SERS sensitivity. The detection limit of E. coli 49979, selected as a model to establish proof of principle, was found to be 1.0×102 CFU/mL. Furthermore, the AuNP@f3-SWCNT hybrid nanomaterial offers impressive photothermal pathogen killing effects. The synergy-type enhancement effect arising from the inherent noble properties of the respective components of the hybrid nanomaterial indicate that our AuNP@f3-SWCNT has the potential for further application in multiplex detection in samples.


Nano-TiO2-Catalyzed Dehydrochlorination of 1,1,2,2-Tetrachloroethane: Roles of Crystalline Phase and Exposed Facets.
Nanoscale titanium dioxide ( nTiO2) is one of the most widely used metal oxide nanomaterials. Once released into the environment, nTiO2 may catalyze abiotic transformation of contaminants and consequently affect their fate and effects. Here, we show that the overall catalytic efficiency of nTiO2 for the dehydrochlorination reaction of 1,1,2,2-tetrachloroethane, a commonly used solvent, depends on the crystalline phase and exposed facets of nTiO2, which significantly affect the adsorption capacity and surface catalytic activity of nTiO2. Specifically, under all three pH conditions tested (7.0, 7.5 and 8.0), the overall catalytic efficiency of eight nTiO2 materials (as indicated by the surface-area-normalized reaction kinetic constants) followed the order of rutile > anatase > TiO2(B). For anatase and TiO2(B) materials, the overall catalytic efficiency increased with the increasing percentage of exposed {001} and {010} facets, respectively. Crystalline phase and exposed facets significantly affected adsorption affinities of nTiO2, likely by modulating surface hydrophobicity of nTiO2. Crystalline phase and exposed facets also determined the activity of surface catalytic sites on nTiO2 by dictating the concentration and strength of surface unsaturated Ti atoms, as the deprotonated hydroxyl groups chemisorbed to these reactive Ti atoms served as bases to catalyze the base-promoted reaction.


Comorbid psychiatric and substance abuse disorders: recent treatment research.
Psychiatric comorbidity is defined as the co-occurrence of a psychiatric disorder in a patient with a substance use disorder. Psychiatric disorders in substance abuse patients can antedate the substance use disorder or be a consequence of the substance abuse. There is emerging evidence that drug use in adolescence may alter the onset of certain psychiatric disorders in vulnerable individuals. Patients with concurrent comorbid disorders present special challenges for the substance abuse treatment system in terms of diagnosis and management because each disorder has the capability of exacerbating the other. This manuscript is a summary of an ISAM symposium that featured three speakers who discussed the following topics: 1. Etiology and treatment of comorbid psychiatric and substance use disorders in adolescents; 2. Treatment of ADHD and substance use disorders in adults; 3. Effects of substance abuse on the onset, severity, and treatment of schizophrenia. Recommendations for further research will be presented.


Ferritins and nodulation in Lupinus luteus: iron management in indeterminate type nodules.
An ability to form symbiotic associations with rhizobia and to utilize atmospheric nitrogen makes legumes ecologically successful. High iron content in legume grains, partially relocated from root nodules, is another-nutritional-advantage of this group of plants. The ferritin complex is the major cell iron storage and detoxification unit and has been recognized as a marker of many stress-induced responses. The possible participation of ferritin in nodule formation and functioning was investigated here. Correlation of increased accumulation of both ferritin polypeptide and mRNA with actual in situ localization of ferritin allowed ferritin synthesis in the developing, indeterminate-type root nodules to be related to differentiating bacteroid tissue. This kind of tissue, in contrast to the determinate-type nodules, is present in lupin nodules at almost all stages of their development. Interestingly, it was found that, in this type of nodule, senescence starting in the decaying zones induces ferritin accumulation in younger, still active, tissues. Based on the presented data, and in correlation with previous results, some aspects of the regulation of expression of lupin ferritin genes are also discussed.


Comparative study on transcatheter arterial chemoembolization, portal vein embolization and high intensity focused ultrasound sequential therapy for patients.
To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.