Clinical efficacy of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC).
To evaluate the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). CEUS and angiography were performed in ten cases of ruptured HCC. We evaluated whether this technique allowed us to determine the bleeding point by observing an extravasation of contrast media into the ascites. In four of the ten cases, CEUS demonstrated an extravasation of Levovist into ascites. Angiography showed an extravasation of contrast medium in three of these four cases. In three of the remaining six cases, in which CEUS did not show the presence of contrast medium in ascites, angiography demonstrated an extravasation. In eight cases, it yielded cessation of bleeding. In two cases, embolization was not successful. The bleeding point was not determined by CEUS or angiography in one case. CEUS allows us to differentiate active bleeding (presence of contrast medium in the ascites) from nonactive bleeding.


[Genetic analysis of the indices of gastric acid secretory and proteolytic functions in duodenal ulcer patients].
The phenotypic correlations between pepsinogen, proteases and the debit of acid secretion in patients with the peptic ulcer of duodenum and their parents were studied. It was found that the genetic factors have great influence on the level of pepsinogen and proteases in the basal conditions and under stimulation. In comparison with the general population, we obtained highly reliable increase of the level of pepsinogen and proteases in the groups of patients and their parents.


Post COVID-19 pandemic recovery of intracity human mobility in Wuhan: Spatiotemporal characteristic and driving mechanism.
After successfully inhibiting the first wave of COVID-19 transmission through a city lockdown, Wuhan implemented a series of policies to gradually lift restrictions and restore daily activities. Existing studies mainly focus on the intercity recovery under a macroscopic view. How does the intracity mobility return to normal? Is the recovery process consistent among different subareas, and what factor affects the post-pandemic recovery? To answer these questions, we sorted out policies adopted during the Wuhan resumption, and collected the long-time mobility big data in 1105 traffic analysis zones (TAZs) to construct an observation matrix (A). We then used the nonnegative matrix factorization (NMF) method to approximate A as the product of two condensed matrices (WH). The column vectors of W matrix were visualized as five typical recovery curves to reveal the temporal change. The row vectors of H matrix were visualized to identify the spatial distribution of each recovery type, and were analyzed with variables of population, GDP, land use, and key facility to explain the recovery driving mechanisms. We found that the "staggered time" policies implemented in Wuhan effectively staggered the peak mobility of several recovery types ("staggered peak"). Besides, different TAZs had heterogeneous response intensities to these policies ("staggered area") which were closely related to land uses and key facilities. The creative policies taken by Wuhan highlight the wisdom of public health crisis management, and could provide an empirical reference for the adjustment of post-pandemic intervention measures in other cities.


Optimized sequencing depth and de novo assembler for deeply reconstructing the transcriptome of the tea plant, an economically important plant species.
Tea is the oldest and among the world's most popular non-alcoholic beverages, which has important economic, health and cultural values. Tea is commonly produced from the leaves of tea plants (Camellia sinensis), which belong to the genus Camellia of family Theaceae. In the last decade, many studies have generated the transcriptomes of tea plants at different developmental stages or under abiotic and/or biotic stresses to investigate the genetic basis of secondary metabolites that determine tea quality. However, these results exhibited large differences, particularly in the total number of reconstructed transcripts and the quality of the assembled transcriptomes. These differences largely result from limited knowledge regarding the optimized sequencing depth and assembler for transcriptome assembly of structurally complex plant species genomes. We employed different amounts of RNA-sequencing data, ranging from 4 to 84 Gb, to assemble the tea plant transcriptome using five well-known and representative transcript assemblers. Although the total number of assembled transcripts increased with increasing sequencing data, the proportion of unassembled transcripts became saturated as revealed by plant BUSCO datasets. Among the five representative assemblers, the Bridger package shows the best performance in both assembly completeness and accuracy as evaluated by the BUSCO datasets and genome alignment. In addition, we showed that Bridger and BinPacker harbored the shortest runtimes followed by SOAPdenovo and Trans-ABySS. The present study compares the performance of five representative transcript assemblers and investigates the key factors that affect the assembly quality of the transcriptome of the tea plants. This study will be of significance in helping the tea research community obtain better sequencing and assembly of tea plant transcriptomes under conditions of interest and may thus help to answer major biological questions currently facing the tea industry.


Sequencing and expression pattern of inducible heat shock gene products in the European flat oyster, Ostrea edulis.
Heat shock proteins are a multigene family of polypeptides composed of the constitutively-expressed heat shock cognate (HSC) members and of the stress-inducible (HSP) proteins, whose expression is specifically induced by stress factors. Constitutive and inducible 70 kDa isoforms are reported in vertebrates and invertebrates. HSCs are expressed in all bivalve molluscs studied to date, while the occurrence of strictly heat-inducible HSPs seems a distinctive feature of oysters. To gain more insight into the molecular features of the Ostrea edulis HSP70, we have cloned and sequenced the gene product putatively encoding for the heat-inducible isoform HSP69 and examined the pattern of expression after heat exposure. Four different clones of approximately 1794 bp were obtained that share a high degree of homology with heat-inducible HSP70 from other bivalves. Amino acid sequence comparisons indicated that the main structural features of the heat-inducible HSP70 are highly conserved within the O. edulis HSP70 clones, while lower sequence homology occurred with respect to HSC70 transcripts. Northern blot analysis indicated that HSP69 mRNA was absent in control animals but induced after heat shock (1 h at 32 degrees C or higher). Induction was detectable immediately after heat shock, reaching a maximum after 2 to 3 h of post-stress recovery at 18 degrees C, and decreasing thereafter. A phylogenetic analysis of the HSP70 family members from oyster and other bivalves revealed a substantial conservation in the evolutionary pattern among constitutive and inducible gene products, from invertebrates to higher vertebrates.


Comparison between computer-guided and freehand dental implant placement surgery: A systematic review and meta-analysis.
The purpose of this systematic review was to compare computer-guided (fully guided) and freehand implant placement surgery in terms of marginal bone loss, complications, and implant survival. This review followed the PRISMA guidelines and was registered in the PROSPERO database (CRD42019135893). Two independent investigators performed the search of the PubMed/MEDLINE, Scopus, and Cochrane Library databases for studies published up to April 2020 and identified 1508 references. After a detailed review, only four studies were considered eligible. These studies involved a total of 154 patients with 597 dental implants and a mean follow-up period of 2.25 years. There was no difference between computer-guided surgery and freehand surgery in terms of the marginal bone loss (mean difference -0.11mm, 95% confidence interval (CI) -0.27 to 0.04mm; P=0.16), mechanical complications (risk ratio (RR) 0.85, 95% CI 0.36-2.04; P=0.72), biological complications (RR 1.56, 95% CI 0.42-5.74; P=0.51), and implant survival rate (RR 0.53, 95% CI 0.11-2.43; P=0.41). This meta-analysis demonstrated that both computer-guided and freehand surgeries yielded similar results for marginal bone loss, mechanical and biological complications, and implant survival rate.


Incidence of cardiac arrhythmias with therapeutic versus diagnostic ultrasound and intravenous microbubbles.
The purpose of this study was to determine the type of arrhythmias induced with therapeutic versus diagnostic transthoracic low-frequency ultrasound (TLFUS) transducers in the presence of intravenous microbubbles. Intravenous perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles were infused or given as a bolus injection while TLFUS was applied in the standard parasternal and apical views with either a 1-MHz therapeutic ultrasound transducer or high-mechanical-index diagnostic ultrasound (1.7 MHz). Significantly more ectopy was produced by the therapeutic transducer, especially at higher-intensity settings in the continuous wave mode after bolus injections of PESDA (P < .001 compared with lower intensities and lower continuous infusion rates). Six patients (15%) had either clinical supraventricular tachycardia or nonsustained ventricular tachycardia after intravenous PESDA with therapeutic TLFUS. In comparison, diagnostic high-mechanical-index ultrasound produced only isolated ventricular ectopy and no sustained ventricular arrhythmias. Intravenously injected microbubbles and low-frequency therapeutic transducers operating at longer duty cycles and wide beam widths have the capability of eliciting clinically important arrhythmias in patients at high risk for such events.


Heat loss variations of full-face motorcycle helmets.
Heat loss of 27 full-face motorcycle helmets was studied using a thermal manikin headform. The headform was electrically heated and positioned at the exit of a wind tunnel, so that the air stream flowed onto its front side. All helmets were measured in three sessions in which all the vents were opened or closed consecutively in random order. Average heat loss was calculated from a steady state period, under controlled environmental conditions of 22+/-0.05 degrees C, 50+/-1% RH and 50.4+/-1.1 km h(-1) (14.0+/-0.3 ms(-1)) wind speed. The results show large variations in heat loss among the different helmets, ranging from 0 to 4 W for the scalp section of the headform and 8 to 18 W for the face section of the headform. Opening all the vents showed an increase in heat loss of more than 1 W (2 W) for four (two) helmets in the scalp section and six (one) helmets in the face section. These levels of heat transfer have been shown to be the thresholds for human sensitivity in scalp and face sections. Furthermore, helmet construction features which could be identified as important for heat loss of motorcycle helmets were identified.


Association of glutathione S-transferase T1, M1, and P1 polymorphisms in the breast cancer risk: a meta-analysis.
Several case-control studies investigating the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP1 (rs1695) and the risk of breast cancer have reported contradictory results. We therefore performed a meta-analysis to clarify this issue. An updated meta-analysis using PubMed and Web of Knowledge databases for the eligible case-control studies was performed. Random- or fixed-effects model was used. A total of 10,067 cancer cases and 12,276 controls in 41 independent case-control studies from 19 articles were included in this meta-analysis. Significant increase in risk of breast cancer for Asians was found in GSTM1-null genotype (P=0.012, odds ratio [OR] =1.17, 95% confidence interval [CI] =1.04-1.32) and GSTT1-null genotype (P=0.039, OR =1.19, 95% CI =1.01-1.41). In addition, our results showed that the GSTP1 (rs1695) polymorphisms can significantly increase the risk among Caucasians (P=0.042, OR =1.16, 95% CI =1.01-1.34). Sensitivity analysis and publication bias further confirmed the dependability of the results in this meta-analysis. Our results demonstrate that both GSTM1- and GSTT1-null polymorphisms are associated with an increased risk of breast cancer in Asians and that GSTP1 Val105Ile (rs1695) polymorphism is associated with an increased breast cancer risk in Caucasians.


Structure-based virtual screening and molecular dynamics simulation of SARS-CoV-2 Guanine-N7 methyltransferase (nsp14) for identifying antiviral inhibitors against COVID-19.
The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) calls the whole world into a medical emergency. For tackling Coronavirus Disease 2019 (COVID-19), researchers from around the world are swiftly working on designing and identifying inhibitors against all possible viral key protein targets. One of the attractive drug targets is guanine-N7 methyltransferase which plays the main role in capping the 5'-ends of viral genomic RNA and sub genomic RNAs, to escape the host's innate immunity. We performed homology modeling and molecular dynamic (MD) simulation, in order to understand the molecular architecture of Guanosine-P3-Adenosine-5',5'-Triphosphate (G3A) binding with C-terminal N7-MTase domain of nsp14 from SARS-CoV-2. The residue Asn388 is highly conserved in present both in N7-MTase from SARS-CoV and SARS-CoV-2 and displays a unique function in G3A binding. For an in-depth understanding of these substrate specificities, we tried to screen and identify inhibitors from the Traditional Chinese Medicine (TCM) database. The combination of several computational approaches, including screening, MM/GBSA, MD simulations, and PCA calculations, provides the screened compounds that readily interact with the G3A binding site of homology modeled N7-MTase domain. Compounds from this screening will have strong potency towards inhibiting the substrate-binding and efficiently hinder the viral 5'-end RNA capping mechanism. We strongly believe the final compounds can become COVID-19 therapeutics, with huge international support.[Formula: see text]The focus of this study is to screen for antiviral inhibitors blocking guanine-N7 methyltransferase (N7-MTase), one of the key drug targets involved in the first methylation step of the SARS-CoV-2 RNA capping mechanism. Compounds binding the substrate-binding site can interfere with enzyme catalysis and impede 5'-end cap formation, which is crucial to mimic host RNA and evade host cellular immune responses. Therefore, our study proposes the top hit compounds from the Traditional Chinese Medicine (TCM) database using a combination of several computational approaches.Communicated by Ramaswamy H. Sarma.


Burnout Among Nephrologists in the United States: A Survey Study.
Burnout decreases job satisfaction and leads to poor patient outcomes but remains underinvestigated in nephrology. We explored the prevalence and determinants of burnout among a sample of nephrologists. Cross-sectional. The nephrologists were approached via the American Medical Association Physicians Masterfile, National Kidney Foundation listserv, email, and social media between April and August 2019. The predictors were demographics and practice characteristics. The outcome was burnout, defined as responding "once a week" or more on either 1 of the 2 validated measures of emotional exhaustion and depersonalization or both. Participant characteristics were tabulated. Responses were compared using χ2 tests. Multivariable logistic regression was used to estimate the odds ratios (ORs) of burnout for risk factors. Free text responses were thematically analyzed. About half of 457 respondents were 40-59 years old (n=225; 49.2%), and the respondents were more predominantly men (n=296; 64.8%), US medical graduates (n=285; 62.4%), and in academic practice (n=286; 62.6%). Overall, 106 (23.2%) reported burnout. The most commonly reported primary drivers of burnout were the number of hours worked (n=27; 25.5%) and electronic health record requirements (n=26; 24.5%). Caring for ≤25 versus 26-75 patients per week (OR, 0.34; 95% confidence interval [95% CI], 0.15-0.77), practicing in academic versus nonacademic settings (OR, 0.33; 95% CI, 0.21-0.54), and spending time on other responsibilities versus patient care (OR, 0.32; 95% CI, 0.17-0.61) were each independently associated with nearly 70% lower odds of burnout after adjusting for age, sex, race, and international medical graduate status. The free text responses emphasized disinterested health care systems and dissatisfaction with remuneration as the drivers of burnout. Inability to precisely capture response rate. Nearly one-quarter of the nephrologists in our sample reported burnout. Future studies should qualitatively investigate how the care setting, time spent on electronic medical records, and hours of clinical care drive burnout and explore other system-level drivers of burnout in nephrology.


The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins.
Ricin is a potent cytotoxic protein derived from the higher plant Ricinus communis that inactivates eukaryotic ribosomes. In this paper we have studied the mechanism of action of ricin A-chain on rat liver ribosomes in vitro. Our findings indicate that the toxin inactivates the ribosomes by modifying both or either of two nucleoside residues, G4323 and A4324, in 28 S rRNA. These nucleotides are located close to the alpha-sarcin cleavage site and become resistant to all ribonucleases tested. The examination of the lability of phosphodiester bonds of these nucleotides to both mild alkaline digestion and aniline treatment at acidic pH suggests that the base of A4324 is removed by the toxin. This unique activity of ricin A-chain was also observed when naked 28 S rRNA is used as a substrate, indicating that the toxin directly acts on the RNA. Similar activity on 28 S rRNA is also exhibited by abrin and modeccin, ricin-related toxins, suggesting a general mechanistic pathway for ribosome inactivation by lectin toxins.


Nanoparticles reveal Extreme Size-Sorting and Morphologies in Complex Coacervate Superstructures.
We here provide detailed insight in self-assembled complex coacervate systems exploiting gold nanoparticles for cryoTEM contrast. Nanoparticle-containing dendrimicelles are formed from fifth-generation dendrimer-encapsulated nanoparticles (DENs) and dendrimer-stabilized nanoparticles (DSNs). The complex coacervate structures self-organize in biconcave thin water layers into size-sorted monolayer superstructures. The embedded nanoparticles are a straightforward tool to visualize dendrimicelles and determine the aggregation number and polydispersity. The superstructure shows extreme size-sorting patterns which, contrary to related systems with higher generation dendrimers, consists not only of dendrimicelles but also much bigger complex coacervate nanoassemblies, such as vesicles.


Assessment of cardiac volumes using an isotropic whole-heart dual cardiac phase sequence in pediatric patients.
To evaluate the accuracy of a three-dimensional dual phase (3D DP) whole-heart technique for cardiac volumetric assessment in pediatric patients with cardiac abnormalities. The institutional approved this study, and informed consent was obtained from patients or their guardians. This prospective study involved 31 pediatric patients (mean age, 7.9 years; range, 15 days to 15 years) for the assessment of cardiac abnormalities using cardiovascular MR. A standard protocol was performed for assessing cardiac anatomy and function. For evaluating the 3D DP technique, statistical comparison with a 2D cine multi-slice technique (2D steady-state free-precession [SSFP]) was performed using linear regression, intraclass correlation coefficient, and Bland Altman plots. Left (LV) and right (RV) ventricular cardiac volumes obtained with the 3D DP technique were in strong agreement with those obtained with the 2D SSFP technique for small and large ventricular volumes. The intraclass correlation coefficients (ICC) between both techniques were 0.992 for the LV end-diastolic volume (EDV), 0.983 for the LV end-systolic volume (ESV), 0.952 for the LV-systolic volume (SV), 0.992 for the RV-EDV, 0.992 for the RV-ESV, 0.928 for the RV-SV. Interobserver analysis indicated good reproducibility for both the 2D SSFP and the 3D DP techniques. The 3D DP technique provides as accurate cardiac volumes as the 2D SSFP technique in the pediatric population, but with the added benefits of easier data acquisition and detailed anatomical information of the whole heart and great vessels in a single free-breathing scan.


An eye tracking investigation of color-location binding in infants' visual short-term memory.
Two experiments examined 8- and 10-month-old infants' (N = 71) binding of object identity (color) and location information in visual short-term memory (VSTM) using a one-shot change detection task. Building on previous work using the simultaneous streams change detection task, we confirmed that 8- and 10-month-old infants are sensitive to changes in binding between identity and location in VSTM. Further, we demonstrated that infants recognize specifically what changed in these events. Thus, infants' VSTM for binding is robust and can be observed in different procedures and with different stimuli.


Result publication of Chinese trials in World Health Organization primary registries.
Result publication is the key step to improve the transparency of clinical trials. To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries. We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication. We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2% (156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0% (9/44), and 55.6% (5/9), respectively. The publication rate of trials sponsored by industry (23.8%) was lower than that of sponsored by central and local government (31.7%), hospital (35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar (33.4% versus 33.3%). The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China.


[Relationship between PDGF-A, bFGF and proliferation of smooth muscle cells in vein grafts].
To detect the relationship between platelet-derived growth factor-A (PDGF-A), basic fibroblast growth factor (bFGF), and proliferation of smooth muscle cells in vein grafts. An animal model of autogenous vein graft was established by transplanting internal branch of the jugular vein to the common iliac artery by end-to-end anastomosis. 25 rats were used. The grafted veins were harvested at 6 h, 2 d, 1 w, 2 w and 4 w respectively after the operation. The expression of PDGF-A and bFGF in different stages after grafting procedure was observed immunohistochemically. The expression of PDGF-A peaked at 1 w, paralleled with proliferation of SMC, and was significantly higher than that at 6 h (P < 0.01). The expression of PDGF-A diminished gradually. At 4 w, it was significantly lower than that at 1 w (P < 0.01). bFGF demonstrated bimodal pattern of the expression: the first peak of expression occurred by 2 d and the second peak by 2 w. The difference was significantly compared with other stages. The expression of PDGF-A 1 contributed to migration and proliferation of SMC. Except for contributing to proliferation of SMC, bFGF perhaps took part in endothelization.


Exploring the efficiency of thrombin inhibitors with a quantitative model of the coagulation cascade.
A detailed mathematical description of the coagulation cascade is a challenging task due to a huge set of protein-protein interactions. Simplified models do not permit quantitative description of anticoagulants. The detailed mathematical model presented here was constructed with 98 reactions between 70 species. The model was verified using experimental data on thrombin generation. Four thrombin inhibitors, which have different inhibitory mechanisms, were incorporated into the model. All four thrombin inhibitors delayed prothrombin conversion into thrombin, but did not preclude it. At high inhibitor concentration, thrombin-mediated positive feedback loops were strongly inhibited and the proportion of prothrombin, converted with factor Xa only, was considerably increased. The most potent inhibitor of prothrombin conversion was aptamer NU172, which also binds prothrombin and inhibits its conversion.


Efficacy of left thoracoscopy and blunt mediastinal dissection during the Nuss procedure for pectus excavatum.
The minimally invasive Nuss procedure is emerging as the preferred technique for repair of pectus excavatum. Original methods of pectus bar placement have been modified to improve safety and efficacy and avoid cardiothoracic complications. The currently reported modifications to facilitate retrosternal pectus bar placement include routine use of right thoracoscopy or a subxiphoid incision. The purpose of this article is to describe additional modifications of the Nuss procedure to improve safety and efficacy. A retrospective analysis was performed on 51 patients who have had a thoracoscopic-assisted Nuss procedure at The Children's Hospital, Denver, Colo, between 1999 and 2002. Technical modifications included patient positioning, routine use of left thoracoscopy, and an Endo-kittner. Fifty-one patients have successfully undergone the Nuss procedure using the new modifications. Surgical time ranged from 45 to 120 minutes. There have been no intraoperative or postoperative bleeding complications. There have been 2 large pneumothoraces requiring needle thoracenteses in the operating room before extubation. No chest tubes were required postoperatively. Subjectively, all patients have been satisfied with their surgical correction. Average length of hospital stay was 4 to 6 days. By using left chest thoracoscopy and Endo-kittner dissectors, the risk of cardiothoracic injury can be eliminated. Moreover, other methods to ensure safe substernal dissection are unnecessary.


3D projection and multivariate image analysis for quantitative visual modelling of mixability and rheological behavior of lactose powder.
This study reports the use of multivariate time and image analysis of avalanche videographic data for quantitative visual modelling of mixability. Its usefulness, in mechanistically modelling a powder's rheological behavior in relation to mixing, was evaluated. Particle size distribution (PSD) of a pharmaceutical grade lactose powder was modified to reflect commercially encountered variability. The PSD variants were rheologically distinct and had different mixability. Avalanche testing was performed on the modified lactose powders. Avalanche rheological properties (ARP) profiles and videos were collected for numerical and quantitative visual modelling, respectively. In quantitative visual modelling, videos captured were transformed into serial projected images. Important features of the projected images were extracted as eigen-images, to derive the avalanche rheological visual metric (ARVM). Mixability was modelled as a function of ARP or ARVM and the rotation speed. Relative to the ARP model, the ARVM models were highly interpretable. As a univariate expression of ARP, ARVM also possessed construct validity (r2 greater than 0.99, slope ≥ 0.96). Important rheological features of the lactose powders were holistically visualized within a single eigen-image which enabled the generation of simpler models (5 versus 34 variables for ARP model). The ARVM models predicted mixability of lactose powders with greater accuracy than the ARP model (relative root mean square error of external validation ≤ 3.30% versus 4.96%). Quantitative visual modelling is a viable alternative to purely numerical approaches. Most significantly, the model's interpretability and concreteness enable manufacturers to readily understand the risk posed by PSD variability on manufacturing processes and swiftly take pre-emptive actions, without being mired in multivariate data complexity. In addition, the use of quantitative visual approach in time series imaging, for studying and monitoring industrial processes, could also be explored.


Idiopathic hypertrophic cranial pachymeningitis masquerading as Tolosa-Hunt syndrome.
Idiopathic hypertrophic cranial pachymeningitis is a rare condition. A case of idiopathic hypertrophic cranial pachymeningitis presenting as Tolosa-Hunt syndrome is being reported. The importance of neuroimaging in patients with suspected Tolosa-Hunt syndrome is discussed. Tolosa-Hunt syndrome might represent a focal manifestation of Idiopathic hypertrophic cranial pachymeningitis. Future studies are necessary to further clarify the relationship between these two conditions.


Gold-copper nanoshell dot-blot immunoassay for naked-eye sensitive detection of tuberculosis specific CFP-10 antigen.
Herein, a straightforward and highly specific dot-blot immunoassay was successfully developed for the detection of Mycobacterium tuberculosis antigen (10 kDa culture filtrate protein, CFP-10) via the formation of copper nanoshell on the gold nanoparticles (AuNPs) surface. The principle of dot-blot immunoassay was based on the reduction of Cu2+ ion on the GBP-CFP10G2-AuNPs conjugates, which has gold binding and antigen binding affinities, simultaneously, favouring to appear red dot that can be observed with naked-eye. The dot intensity is proportional to the concentration of tuberculosis antigen CFP-10, which offers a detection limit of 7.6 pg/mL. The analytical performance of GBP-CFP10G2-AuNPs-copper nanoshell dot-blot was superior than that of conventional silver nanoshell. This method was successfully applied to identify the CFP-10 antigen in the clinical urine sample with high sensitivity, specificity, and minimized sample preparation steps. This method exhibits great application potential in the field of nanomedical science for highly reliable point-of-care detection of CFP-10 antigen in real samples to early diagnosis of tuberculosis.


Reoperation following transcatheter aortic valve replacement: Insights from 10 years' experience.
Use of transcatheter aortic valve replacement (TAVR) has demonstrated dramatic growth in the past decade. This study aims to investigate implications of post-TAVR reoperation from our 10-year experience. Between 2011 and 2022, 66 post-TAVR patients underwent a reoperation, consisting of 42 (63.6%) patients with native TAVR and 24 (36.4%) patients with valve-in-valve TAVR (VIV-TAVR) after surgical aortic valve replacement. The aggregate proportion of patients belonging to the low-/intermediate-risk group at the time of TAVR exceeded that of the high-/extreme-risk cohort in 2021. The native TAVR group received a larger TAVR valve, whereas more frequent low-risk status at the time of TAVR than the VIV-TAVR group. Concurrent procedures were highly common during reoperation and isolated surgical aortic valve replacement represented only 18.2% of the entire cohort. The native TAVR group demonstrated significantly higher TAVR explant difficulty index score (2.0 vs 1.0 points; P < .001) and operative mortality (14.2% vs 0%; P = .079) compared with the VIV-TAVR group. The 8-year cumulative incidence of reoperation was 1.9% and 14.1% (subdistribution hazard ratio, 8.0; 95% CI, 4.1-15.9; P < .001) in the native and VIV-TAVR group, respectively. Furthermore, cumulative incidence of valve reintervention, combining reoperations and redo TAVRs, was 3.3% and 19.0% (subdistribution hazard ratio, 6.2; 95% CI, 3.6-10.9; P < .001). Low-/intermediate-risk patients are emerging as the predominant group necessitating reoperations. Native TAVR was associated with lower postimplant reintervention rates, albeit with higher reoperative technical difficulty and mortality. Conversely, VIV-TAVR was associated with higher reintervention, but demonstrated lower technical difficulty and mortality for reoperation.


Emulsification/internal gelation as a method for preparation of diclofenac sodium-sodium alginate microparticles.
Emulsification/internal gelation has been suggested as an alternative to extrusion/external gelation in the encapsulation of several compounds including non-steroidal anti-inflammatory drugs such as diclofenac sodium. The objective of the present study was a trial to formulate diclofenac sodium as controlled release microparticles that might be administered once or twice daily. This could be achieved via emulsification/internal gelation technique applying Box-Behnken design to choose these formulae. Box-Behnken design determined fifteen formulae containing specified amounts of the independent variables, which included stirring speed in rpm (X1), drug:polymer ratio (X2) and the surfactant span 80% (X3). The dependent variables studied were cumulative percent release after two hours (Y1), four hours (Y2) and eight hours (Y3). The prepared microparticles were characterized for their production yield, sizes, shapes and morphology, entrapment efficiency and Diclofenac sodium in vitro release as well. The results showed that the production yield of the prepared diclofenac sodium microparticles was found to be between 79.55% and 97.41%. The formulated microparticles exhibited acceptable drug content values that lie in the range 66.20-96.36%. Also, the data obtained revealed that increasing the mixing speed (X1) generally resulted in decreased microparticle size. In addition, scanning electron microscope images of the microparticles illustrated that the formula contains lower span concentration (1%) in combination with lower stirring speed (200 rpm) which showed wrinkled, but smooth surfaces. However, by increasing surfactant concentration, microspheres' surfaces become smoother and slightly porous. Kinetic treatment of the in vitro release from drug-loaded microparticles indicated that the zero order is the drug release mechanism for the most formulae.


Letters.
MAGGOTS - A PERSONAL EXPERIENCE ABPI TECHNIQUES VAPOUR-PERMEABLE DRESSINGS PRESSURE SORES AND SPINAL CORD INJURY DANGERS OF TOWEL CLIPS.


The Nesbit procedure for Peyronie's disease.
We treated 8 patients with severe Peyronie's disease with the Nesbit procedure. All patients had had partial to full erections and all had been unable to achieve vaginal penetration because of pronounced curvature of the penis. After penile straightening all patients were able to resume normal coitus. We recommend the Nesbit procedure as the first step in the surgical treatment of patients with Peyronie's disease who have severe penile deformity but good erections.


Rosiglitazone attenuates amyloid beta and glial fibrillary acidic protein in the hippocampus and neuroinflammation associated learning and memory impairments in rats.
The aim of the current study was to investigate the beneficial effects of rosiglitazone (Rosi) on amyloid beta(Aβ) and glial fibrillary acidic protein (GFAP) in the hippocampus and neuroinflammation-associated learning and memory impairments in rats. The rats were grouped and treated as follows: (1) Control in which saline and vehicle were administered instead of LPS and Rosi respectively. (2) Lipopolysaccharide (LPS) group in which LPS was dissolved in saline and injected (1 mg/kg) intraperitoneally. Vehicle was administered instead of Rosi in this group. (3-5) LPS+ Rosi 1, LPS+ Rosi 3, and LPS+ Rosi 5 groups in them 1, 3, or 5 mg/kg of Rosi respectively was administered 30 min before LPS. The treatments were done for two weeks. In the first week, Rosi or its vehicle was injected 30 min before LPS. In the second week, the treatments were the same as the first week and behavioral tests were also carried out in the second week. The hippocampal tissues were finally detached for biochemical assessment. The results showed that Rosi reversed increased levels of Aβ, GFAP, interleukin (IL)- 6, tumor necrosis factor-α (TNF-α), nitric oxide (NO) metabolites, and malondialdehyde (MDA) due to LPS injection. Rosi also reversed attenuating effects of LPS on IL-10 and thiol concentration and activities of catalase (CAT) and superoxide dismutase (SOD). In the Morris water maze test, the LPS group had a longer latency to find the platform while spent a shorter time spent in the target quadrant in the probe trial than the control group. In the passive avoidance test, the animals of the LPS group had a shorter delay to enter the dark chamber than the animals of the control group. Treatment with Rosi reversed these parameters. The findings showed Rosi attenuated Aβ, GFAP, and oxidative stress in the hippocampus and neuroinflammation-associated learning and memory impairments in rats.


A comparison of late reactions to antigen and exercise.
Immediate and late asthmatic reactions may occur after inhalation of specific antigens such as house dust mites or pollens. Recently, similar dual reactions have been found to occur after asthma induced by exercise. The immediate reaction to an antigen is believed to be due to the release of preformed and newly formed mediators derived primarily from mast cells via IgE antibodies. The late reaction also appears to be the result of an IgE reaction but involves inflammation in which cells play a role. The late reaction to antigen is often more severe than the immediate reaction and may be followed by a prolonged period of "nonspecific" bronchial hyperreactivity. By contrast, the late reaction to exercise is usually less severe than the immediate reaction. Both immediate and late exercise reactions are also associated with peaks of neutrophil chemotactic factor activity. Cromolyn sodium administered before challenge modifies both the immediate and the late response to antigen and exercise. Glucocorticoids block the late but not the early reaction to antigens. Their effect on the late exercise reaction is not yet known. Albuterol prevents the initial reaction to both exercise and antigen and may modify the late reaction to exercise as well.


The electrical and sodium transport characteristics of sutured premalignant mouse colon.
Depolarization of the plasma membrane and increased sodium influx have both been suggested as mitogenic signals. Following bowel resection the intestinal suture line has been reported a fertile site for tumor recurrence. Whether alterations in cell surface signaling occur at suture lines has not been previously examined the electrical changes of sodium transport occurring at a suture line in an animal model of large bowel cancer. Forty-eight female CF1 mice underwent colotomies with repair utilizing silk or chromic sutures. Twenty-four mice underwent sham operations to serve as controls. The mice were injected subcutaneously with the carcinogen DMH (1,2-dimethylhydrazine) 20 mg/kg or an identical volume of 0.9% saline for 6 weeks and were sacrificed 1 week after the last injection. The sites of the sutured colotomies or a piece of distal colon from the sham-operated mice were mounted in a modified Ussing chamber and the electrical properties and unidirectional sodium fluxes were measured. The potential difference (pd) across the distal colon was not significantly different in any suture group compared to that in sham-operated controls when treated with saline (pd sham, -2.3 +/- 0.2 mV (mean +/- SEM); silk, -1.7 +/- 0.3 mV, chromic, -1.9 +/- 0.3 mV, P greater than 0.05, unpaired Student t test). The potential difference was significantly lowered in both suture groups compared to sham operated animals after treatment with DMH (pd sham, -2.6 +/- 0.3 mV; silk, -1.5 +/- 0.2 mV, P less than 0.05; chromic, -1.6 +/- 0.4 mV, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Haplotyping by capillary electrophoresis.
The investigation of the genetic background and phenotype structures of complex diseases, such as cardiovascular or psychiatric disorders and tumors, is one of the most scrutinized fields of the post genomic era. Besides the multiplex analysis of genetic markers and polymorphisms throughout the whole genome, more and more attention is focused on the interaction between the etiological factors of these traits. Haplotype determination, rather than multiplex genotyping seems to be one of the first building blocks of this endeavor. This review focuses on the importance and theoretical background of haplotyping, and summarizes the recent examples of novel and emerging haplotyping techniques by capillary gel electrophoresis based DNA fragment analysis, a powerful tool for the examination of the inheritance of complex traits.


Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity.
Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4'-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3' (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 muM. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3'-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.


Dynamic Change of Shanks Gene mRNA Expression and DNA Methylation in Epileptic Rat Model and Human Patients.
Synaptic protein shanks (SH3 and multiple ankyrin repeat domains protein, Shank) have emerged as an important mediator of synaptic remodeling. Synaptic remodeling is a common pathogenic process in various neurological disorders including epilepsy. However, the expression and function of shanks gene in epileptogenesis has not been investigated to date. Herein, we investigated the expression of shanks (shank1/2/3) mRNA expression in both epileptic rats and epilepsy patients. Furthermore, methyl target sequencing was applied to explore the relationship between shank mRNA expression and DNA methylation in both rats and human patients. In general rat model, shank1/2/3 mRNA was downregulated at acute stage, upregulated at latent stage, and returned to the basal level at chronic stage. Ten CpG sites of shank1 was found differentially methylated, out of which 6 were hypermethylated. Seventeen CpG sites of shank3 were differentially methylated, out of which 8 were hypermethylated. In human epilepsy patients, decreased shank2 mRNA was detected from the brain tissue, with DNA hypermethylation dominant from both brain (18 out of 30) and blood tissue (58 out of 80), indicating the regulation role of DNA methylation on shank2 expression. In conclusion, our finding suggests the participation of the shanks gene in the pathophysiology of seizure, out of which 2 shank3 CpG sites (Chr7: 130473419, and Chr7: 130473405) may play an important role in shank3 expression at both the acute and latent stages in the SE rat model.


Poly(arabitol phosphate) teichoic acid in the cell wall of Agromyces cerinus subsp. cerinus VKM Ac-1340T.
On the basis of NMR studies and analysis of the products of acid and alkaline hydrolyses the following structures were established for the repeating units of poly(arabitol phosphate) teichoic acid: alpha-6-deoxy-L-Talp-(1-->3)-beta-D-GLcpNAc-(1-->2)-alpha-L-Rha p-(1-->4(2)-D- Arabitol-PO4 and beta-D-GlcpNAc-(1-->2)-alpha-L-Rhap-(1-->4(2)-D-arabitol-PO4. The molar ratio of these units is about 1.2:1.0, respectively. Poly(arabitol phosphate) teichoic acid is here reported in bacterial cells walls for the first time.


Irrigation depth far exceeds water uptake depth in an oasis cropland in the middle reaches of Heihe River Basin.
Agricultural irrigation in the middle reaches of the Heihe River Basin consumes approximately 80% of the total river water. Whether the irrigation depth matches the water uptake depth of crops is one of the most important factors affecting the efficiency of irrigation water use. Our results indicated that the influence of plastic film on soil water δ(18)O was restricted to 0-30 cm soil depth. Based on a Bayesian model (MixSIR), we found that irrigated maize acquired water preferentially from 0-10 cm soil layer, with a median uptake proportion of 87 ± 15%. Additionally, maize utilised a mixture of irrigation and shallow soil water instead of absorbing the irrigation water directly. However, only 24.7 ± 5.5% of irrigation water remained in 0-10 cm soil layer, whereas 29.5 ± 2.8% and 38.4 ± 3.3% of the irrigation water infiltrated into 10-40 cm and 40-80 cm layers. During the 4 irrigation events, approximately 39% of the irrigation and rainwater infiltrated into soil layers below 80 cm. Reducing irrigation amount and developing water-saving irrigation methods will be important strategies for improving the efficiency of irrigation water use in this area.


Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS): peering into the cup of Jamshid.
The complex process underlying the development of blood-induced joint disease remains mysterious. Novel technologies such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) to examine protein signatures may provide clues into the process.


Evaluation of the applicability of the current CDC pediatric ventilator-associated events (PedVAE) surveillance definition in the neonatal intensive care unit population.
There is limited data on pediatric ventilator-associated events (PedVAE) in the neonatal intensive care unit (NICU) setting, since the CDC mandated state reporting of these events in January 2019. This study sought to describe PedVAE rates and characteristics in the NICU population. Single-center case-control study of infants requiring mechanical ventilation in a 39-bed level IV NICU between January 1, 2018 and December 31, 2020. Baseline infant demographic, respiratory support and antibiotic use data was obtained and comparisons were performed between patients with potential PedVAEs and those without events. Two hundred and nine infants were mechanically ventilated. Two of the 126 patients ventilated for ≥4 days met CDC criteria for PedVAEs with a total of 3 events, and 32 (25%) received antibiotics with escalation of respiratory support, primarily for tracheitis. NICU-specific data on PedVAE is limited. Only 2 infants in the study period met the current CDC criteria for PedVAE with a rate of 0.9 events per 1000 ventilator days. The current CDC PedVAE definition might be inadequate to identify actionable VAEs to inform prevention efforts in the NICU population, and alternate indices could better characterize these events.


Gay and bisexual men in Kampala, Uganda.
HIV/AIDS disproportionately affects gay and bisexual men around the world; however, little is known about this population in sub-Saharan Africa. We conducted a respondent-driven sampling survey of gay and bisexual men in Kampala, Uganda (N = 224). Overall, 61% reported themselves as "gay" and 39% as "bisexual". Gay and bisexual men were 92% Ugandan; 37% had unprotected receptive anal sex in the last six months, 27% were paid for sex, 18% paid for sex, 11% had history of urethral discharge. Perception that gay and bisexual men are at risk for HIV infection was low. Gay and bisexual men in Kampala are overwhelmingly Ugandan nationals from all parts of society. Recognition of gay and bisexual men in local HIV prevention programs and education messages are urgently needed. Our study demonstrates that gay and bisexual men in Uganda are willing to identify themselves and participate in research.


Radial Motion Estimation of Myocardium in Rats with Myocardial Infarction: A Hybrid Method of FNCCGLAM and Polar Transformation.
Ultrasound elastography is a novel approach of evaluating regional myocardial systolic function and detecting infarcted area. This study aims to evaluate the radial motion of myocardial infarction (MI) area in left ventricular parasternal short axis (PSAX) view using a hybrid method of fast normalized cross-correlation and global analytic minimization (FNCCGLAM) and polar transformation. Fifteen rats were randomly selected for sham group, MI group and ischemia-reperfusion (IR) group (N = 5 for each group). The ultrasound radiofrequency data of the PSAX view of rat heart were acquired. After polar transformation of the data, the infarcted myocardium with the change of mechanical property was tracked over one myocardial systolic phase by the proposed method in comparison with fast normalized cross-correlation (FNCC) and dynamic programming analytic minimization (DPAM). To obtain a clear visualization of the myocardium, the inverse polar transformation was performed. The results indicated that the use of FNCCGLAM refined the myocardial displacements to obtain high-quality myocardial elastographic map with a higher contrast-to-noise ratio and dynamically tracked the infarcted myocardial segment with a higher success rate in comparison with FNCC and DPAM. It was found that the radial systolic motion of the infarcted anterior segment in the MI group reduced significantly (p < 0.05) in comparison with the sham group, while the systolic function of that myocardial segment in the IR group recovered at some extent. The results in this study suggest that FNCCGLAM is superior to FNCC and DPAM with the improved accuracy and robustness of motion estimation and has potentials as displacement estimator in ultrasound elastography.


Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancer.
Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin(R)) has become a valuable therapeutic option for patients with Her-2/neu-overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu-overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy.


Monitoring AML1-ETO and CBFbeta-MYH11 transcripts in acute myeloid leukemia.
The core-binding factor (CBF) leukemias comprise acute myeloid leukemia (AML) with t(8;21) and inv(16)/t(16;16), characterized by the presence of the AML1-ETO and CBFbeta-MYH11 fusion genes, respectively. These leukemia-associated genes can now be sensitively and reliably quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) techniques and thus can serve as molecular targets for monitoring residual leukemia. Studies to date suggest that quantitative monitoring of minimal residual disease (MRD) in CBF-positive AML is useful in distinguishing patients at high risk of relapse from those in durable remission. Preliminary results of MRD monitoring by real-time RT-PCR in this subset of AML patients are promising and provide the basis for further evaluation by quantitative analysis in large prospective clinical trials.


Targeted effects of ketamine on perceptual expectation during mediated learning in rats.
While neural correlates of hallucinations are known, the mechanisms have remained elusive. Mechanistic insight is more practicable in animal models, in which causal relationships can be established. Recent work developing animal models of hallucination susceptibility has focused on the genesis of perceptual expectations and perceptual decision-making. Both processes are encompassed within mediated learning, which involves inducing a strong perceptual expectation via associative learning, retrieving that memory representation, and deciding whether this internally generated percept is predictive of an external outcome. Mediated learning in rodents is sensitive to many psychotomimetic manipulations. However, we do not know if these manipulations selectively alter learning of perceptual expectations versus their retrieval because of their presence throughout all task phases. Here, we used mediated learning to study the targeted effect of a psychotomimetic agent on the retrieval of perceptual expectation. We administered (R,S)-ketamine to rats selectively during the devaluation phase of a mediated learning task, when the representation of the expected cue is retrieved, to test the hypothesis that internally generated perceptual experiences underlie this altered mediated learning. We found that ketamine increased only mediated learning at a moderate dose in rats, but impaired direct learning at the high dose. These results suggest that ketamine can augment retrieval of perceptual expectations and thus this may be how it induces hallucination-like experiences in humans. More broadly, mediated learning may unite the conditioning, perceptual decision-making, and even reality monitoring accounts of psychosis in a manner that translates across species.


Peptide probes containing a non-hydrolyzable phosphotyrosine-mimetic residue for enrichment of protein tyrosine phosphatases.
We developed peptide probes containing a non-hydrolyzable phosphotyrosine mimetic, 4-[difluoro(phosphono)methyl]-L-phenylalanine (F2 Pmp) for the enrichment of protein tyrosine phosphatases (PTPs). We found that different F2 Pmp probes can enrich different PTPs, depending on the probe sequence. Furthermore, proteins containing a Src homology 2 (SH2) domain were enriched together. Importantly, probes containing phosphotyrosine instead of F2 Pmp failed to enrich PTPs due to dephosphorylation during the pulldown step. This enrichment approach using peptides containing F2 Pmp could be a generic tool for tyrosine phosphatome analysis without the use of antibodies.


Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics.
The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation. The reliability of the methods used in these experiments is also compared.


Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine.
An enantioselective HPLC method has been developed and validated for the stereospecific analysis of N-ethyl-3,4-methylenedioxyamphetamine (MDE) and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA). These compounds have been analyzed both from human plasma and urine after administration of 70 mg pure MDE-hydrochloride enantiomers to four subjects. The samples were prepared by hydrolysis of the o-glucuronate and sulfate conjugates using beta-glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange phase. A chiral stationary protein phase (chiral-CBH) was used for the stereoselective determination of MDE, HME and MDA in a single HPLC run using sodium dihydrogenphosphate, ethylendiaminetetraacetic acid disodium salt and isopropanol as the mobile phase (pH 6.44) and fluorimetric detection (lambda(ex) 286 nm, lambda(em) 322 nm). Moreover, a suitable internal standard (N-ethyl-3,4-methylenedioxybenzylamine) was synthesized and qualified for quantitation purposes. The method showed high recovery rates (>95%) and limits of quantitation for MDE and MDA of 5 ng/ml and for HME of 10 ng/ml. The RSDs for all working ranges of MDE, MDA and HME in plasma and urine, respectively, were less than 1.5%. After validation of the analytical methods in plasma and urine samples pharmacokinetic parameters were calculated. The plasma concentrations of (R)-MDE exceeded those of the S-enantiomer (ratio R:S of the area under the curve, 3.1) and the plasma half time of (R)-MDE was longer than that of (S)-MDE (7.9 vs. 4.0 h). In contrast, the stereochemical disposition of the MDE metabolites HME and MDA was reversed. Concentrations of the (S)-metabolites in plasma of volunteers were much higher than those of the (R)-enantiomers.


Left ventricular thrombus sans overt cardiac pathology.
A 25-year-old man presenting with peripheral and cerebral emboli was incidentally detected as having a left ventricular mass on two-dimensional echocardiographic examination of the heart. In absence of any obvious structural heart disease or hypercoagulable state, the mass was presumptively diagnosed as left ventricular myxoma. The patient was operated on, and histopathology revealed the mass to be a thrombus. The cause and pathogenesis of the left ventricular thrombus, differential diagnosis, and management are discussed. The rarity of the case is highlighted.


Postmortem validation of imaging-derived formulas for prediction of fetal lung volume.
To determine the validity of existing imaging-derived formulas for predicting the fetal lung volume (FLV). In a consecutive series of postmortem lungs without pulmonary anomalies, the observed FLV (FLV(obs)) after inflation was correlated with individual fetal variables used in imaging-derived formulas. In addition, FLV(obs) was correlated with the predicted FLV calculated according to these same formulas. Postmortem FLV(obs) showed a strong correlation with estimated fetal body weight, biparietal diameter, and head circumference (r > 0.9). The correlation of FLV(obs) with gestational age, femur length, and liver weight was less strong (0.8 < r < 0.9). The correlation was strongest for midgestation fetuses (between 22 and 32 weeks' gestation). The predicted FLV calculated using formulas based on fetal body weight, biparietal diameter, and head circumference showed the strongest correlation with the actual FLV(obs) (r > 0.9). Postmortem FLV(obs) strongly correlates with fetal body weight, biparietal diameter, and head circumference, especially in midgestation fetuses. Regression formulas based on these fetal variables provide the most accurate prediction of FLV.


Structure, mechanism, and specificity of a eukaryal tRNA restriction enzyme involved in self-nonself discrimination.
tRNA restriction by anticodon nucleases underlies cellular stress responses and self-nonself discrimination in a wide range of taxa. Anticodon breakage inhibits protein synthesis, which, in turn, results in growth arrest or cell death. The eukaryal ribotoxin PaT secreted by Pichia acaciae inhibits growth of Saccharomyces cerevisiae via cleavage of tRNA(Gln(UUG)). We find that recombinant PaT incises a synthetic tRNA(Gln(UUG)) stem-loop RNA by transesterification at a single site 3' of the wobble uridine, yielding 2',3'-cyclic phosphate and 5'-OH ends. Incision is suppressed by replacement of the wobble nucleobase with adenine or guanine. The crystal structure of PaT reveals a distinctive fold and active site, essential components of which are demonstrated by mutagenesis. Pichia acaciae evades self-toxicity via a distinctive intracellular immunity protein, ImmPaT, which binds PaT and blocks nuclease activity. Our results highlight the evolutionary diversity of tRNA restriction and immunity systems.


Estimation of herd incidence of infection with bovine virus diarrhoea virus (BVDV) in herds previously without animals persistently infected with BVDV.
On a previous occasion, all animals in 9 herds had been bled for bovine virus diarrhoea virus (BVDV) and antibodies. No animals persistently infected (PI) with BVDV were detected. Three years later 10 animals in each herd were tested again. By this time 60 out of 90 previously seronegative animals had seroconverted. Seroconversions had occurred in 8 of the 9 herds corresponding to a incidence risk of herd infection of 0.52 per year. The incidence risk of seroconversions in individual animals was 0.31. Examination of young stock for antibodies and determination of antibody titer in bulk milk were good indicators for ongoing infections in the herds. The number of herd infections seemed to be higher than could be explained from purchase of PI animals.


A prospective study of risk and protective factors for substance use among impoverished women living in temporary shelter settings in Los Angeles County.
Alcohol and drug use are significant public health problems facing homeless women, but few prospective studies have examined risk and protective factors for substance use in this population. This 6-month prospective study identified psychosocial, behavioral, and economic predictors of drinking to intoxication, crack use, and marijuana use in a probability sample of 402 women living in temporary shelter settings in Los Angeles County with a simple majority of homeless residents (92% of these women had a history of homelessness). Engaging in sexual risk behavior and having depressive symptoms were risk factors for more frequent intoxication, marijuana use, and crack use. Drinking to intoxication was additionally predicted by perceived HIV susceptibility, lower social support, more avoidant and less active coping, and lower self-esteem. Additional predictors of marijuana use included partner alcohol misuse and less social support, whereas more frequent crack use was additionally predicted by partner alcohol misuse, lack of economic resources, and more avoidant and less active coping. These findings suggest that effective substance use programs may need an integrative approach that addresses other types of risk behaviors, assists women in strengthening their support networks and learning effective coping skills, and provides access to basic services (e.g., housing, health care). For women in relationships, there may be a further need to address issues of partner substance use.


[Genetic Polymorphism of Durum Wheat (Triticum durum Desf.) Accessions of Azerbaijan].
The genetic diversity of 110 durum wheat genotypes of Azerbaijan was evaluated by ISSR markers. A total of 107 fragments were determined, ranging from 9 to 18 per locus. ISSR primers have revealed a high level of polymorphism (average 82%) among different durum wheat varieties and botanical varieties. The ISSR markers used in the study were quite informative and made it possible to distinguish all durum wheat accessions from each other. Cluster analysis based on ISSR data classified the accessions into 11 major groups. No linkage was observed between the collection site and genetic structure of the samples. On the other hand, a few accessions were detected as unique genotypes and tended to form separate clusters. The estimated gene diversity value was high, both within the whole collection and within the different groups of botanical varieties.


Hospital-Based Cancer Incidence in Nepal from 2010 to 2013.
Cancer is one of the leading causes of death throughout the world. Analyzing the incidence of cancer by site, sex and age is essential to detect the burden of cancer. Throughout the twelve hospital based cancer registries of Nepal, a total of 29,802 cancer cases with known age, were registered from January 1st 2010 to 2013 December 31st. The purpose of this retrospective study is to present the incidence of all cancer sites in both males and females for this period. This paper reviews data from all the hospital based cancer registries over a four-year period. This retrospective study has illustrated the number of cases, frequencies and crude incidence of all cancers by sex and site. For statistical analysis, SPSS (version 23.0) and Microsoft Excel 2010 were used. Over the four-year period from January 1st 2010 to 2013 December 31st the major cancer in males was identified as follows: lung cancer (17.5%) followed by stomach cancer (7.6 %) and larynx cancer (5.4%). Among females, for the same four-year period, the three common cancers were identified as cervix (18.9 %) followed by breast (15.6 %) and lung (10.2%). This retrospective study concluded that cancer is being increased by calendar years both in males and females however, the incidence of cancer is higher in females compared to males. .


The impact of scientific information on ecosystem management: making sense of the contextual gap between information providers and decision makers.
Scientific information is not always effectively incorporated into decision-making processes. This phenomenon seems to hold even when the information is aligned with an articulated need, is generated according to sound scientific procedures, and is packaged with end-user preferences in mind. We propose that contextual or cultural differences contribute significantly to the misalignment in communication between those who generate information and those who seek information for improved management of natural resources. The solution is to cultivate shared understanding, which in turn relies on acknowledgment and sharing of diverse values and attitudes. This constitutes a difficult challenge in a culturally diverse environment. Whereas cultural diversity represents wealth in experiences, knowledge and perspectives it can constrain the potential to develop the shared understandings necessary for effective integration of new information. This article illustrates how a lack of shared understanding among participants engaged in a resource-management process can produce and perpetuate divergent views of the world, to the extent that information and knowledge flows are ineffective and scientific information, even when requested, cannot be used effectively. Four themes were distilled from interviews with management and scientific staff of a natural resource-management agency in South Africa. The themes are used to illustrate how divergent views embedded in different cultures can discourage alignment of effort toward a common purpose. The article then presents a sense-making framework to illustrate the potential for developing shared understandings in a culturally diverse world.


Identification of a pH-Sensitive Switch in VSV-G and a Crystal Structure of the G Pre-fusion State Highlight the VSV-G Structural Transition Pathway.
VSV fusion machinery, like that of many other enveloped viruses, is triggered at low pH in endosomes after virion endocytosis. It was suggested that some histidines could play the role of pH-sensitive switches. By mutating histidine residues H22, H60, H132, H162, H389, H397, H407, and H409, we demonstrate that residues H389 and D280, facing each other in the six-helix bundle of the post-fusion state, and more prominently H407, located at the interface between the C-terminal part of the ectodomain and the fusion domain, are crucial for fusion. Passages of recombinant viruses bearing mutant G resulted in the selection of compensatory mutations. Thus, the H407A mutation in G resulted in two independent compensatory mutants, L396I and S422I. Together with a crystal structure of G, presented here, which extends our knowledge of G pre-fusion structure, this indicates that the conformational transition is initiated by refolding of the C-terminal part of the G ectodomain.


Tuning the bioactivity of bone morphogenetic protein-2 with surface immobilization strategies.
Bone morphogenetic protein-2 (BMP-2) involved therapy is of great potential for bone regeneration. However, its clinical application is restricted due to the undesirable bioactivity and relevant complications in vivo. Immobilization of recombinant BMP-2 (rhBMP-2) is an efficient strategy to mimic natural microenvironment and retain its bioactivity. Herein, we present evidences indicating that osteoinductive capacity of rhBMP-2 can be regulated via variant immobilizing approaches. Three representative superficial immobilizing models were employed to fabricate rhBMP-2-immobilized surfaces including physical adsorption (Au/rhBMP-2), covalent grafting (rhBMP-2-SAM-Au) and heparin binding (Hep-SAM-Au/rhBMP-2) (SAM: self-assembled monolayer). Loading capacity, releasing behavior, osteogenic differentiation and signaling pathways involved, as well as the cellular recognition of rhBMP-2 under various immobilization modes were systematically investigated. As a result, disparate immobilizing approaches not only have effects on loading capacity, but also lead to disparity of osteoinduction at the same dosage. Notably, heparin could reinforce the recognition between rhBMP-2 and its receptors (BMPRs) whereas weaken its binding to its antagonist Noggin. Owing to this "selective" binding feature, the favorable osteoinduction and maximum ectopic bone formation can be achieved with the heparin-binding approach. In particular, manipulation of orientation-mediated BMP-2-cell recognition efficiency may be a potential target to design more therapeutic efficient rhBMP-2 delivery system. STATEMENT OF SIGNIFICANCE: Bone morphogenetic protein-2 (BMP-2) is crucial in bone regeneration. However, its clinical application is challenged due to its shorten half-life and supra-physiological dose associated complications. In this study, three representative superficial immobilizing patterns were fabricated through physical adsorption, covalent grafting and electrostatic interaction with heparin respectively. We provided evidences indicating an dose-dependent osteoinductive capacity of immobilized BMP-2. Further, a possible mechanism of rhBMP-2-cell recognition at the interface was presented, highlighting the superior effect of heparin on rhBMP-2 bioactivity. Finally, We proposed a dual mechanism of tuning the bioactivity of immobilized rhBMP-2 through surface immobilization approaches: regulation of the saturated loading capacity and orientation-mediated rhBMP-2-cell recognition. These results provide novel insights into designing criterion of efficient delivery vehicle for rhBMP-2.


Metformin in the treatment of obese children and adolescents at risk of type 2 diabetes.
Metformin is the first-line treatment for type 2 diabetes (T2D) in adults, children and young people, particularly in obese or overweight patients. Many studies have demonstrated that metformin is associated with weight reduction in adults and in prevention or delay of T2D onset in those who are at increased risk. In 2012, metformin was recommended by the UK National Institute for Health and Care Excellence as a treatment option in adults aged 18 years or over, who remain at high risk of T2D, despite participation in an intensive lifestyle-change programme. Prevalence of childhood obesity is increasing and is associated with elevated long-term risk of T2D and other adverse cardio-metabolic events; however, consensus is lacking on intervention strategies aimed at reducing this risk. This article discusses the rationale and evidence for the use of metformin in obese children and young people at high risk of T2D.


Scapular muscular activity with shoulder impingement syndrome during lowering of the arms.
To compare isolated electromyographic (EMG) activity of the serratus anterior, upper, middle, and lower trapezius, as well as the coactivation of the upper and middle trapezius/serratus anterior in subjects with and without shoulder impingement syndrome (IS), during lowering of the arms. Cross-sectional study. University laboratory. Twenty young adults, 10 with unilateral IS degree I or II (mean age 28.6 +/- 5.89 years) and 10 without any complaints or history of previous shoulder lesions (mean age 29.0 +/- 5.35 years), matched by gender, age, and levels of physical activity. Isolated EMG activity of the serratus anterior, upper, middle, and lower trapezius, as well as the coactivation of the upper trapezius and middle trapezius/serratus anterior. The EMG activity was quantified by root mean square calculations and normalized by maximal voluntary isometric contractions. Significant differences between groups were found only for the coactivation of the middle trapezius/serratus anterior (F = 6.81; P = 0.02). No significant differences were found between sides (F = 0.05; P = 0.83) nor for interactions between sides and groups (F = 3.85; P = 0.07). These findings pointed out the importance of evaluating the lowering of the arms in individuals with IS and suggested that measures of coactivation, besides reflecting the real purpose of the muscular actions during functional activities, are more sensitive to detect changes between groups. The evaluation of the coactivation of the middle trapezius/serratus anterior should be included in clinical assessment of individuals with IS and investigations on the etiology and progression of IS.


A Manganese-Based Metal-Organic Framework as a Cold-Adapted Nanozyme.
The development of cold-adapted enzymes with high efficiency and good stability is an advanced strategy to overcome the limitations of catalytic medicine in low and cryogenic temperatures. In this work, inspired by natural enzymes, a novel cold-adapted nanozyme based on a manganese-based nanosized metal-organic framework (nMnBTC) is designed and synthesized. The nMnBTC as an oxidase mimetic not only exhibits excellent activity at 0 °C, but also presents almost no observable activity loss as the temperature is increased to 45 °C. This breaks the traditional recognition that enzymes show maximum activity only under specific psychrophilic or thermophilic condition. The superior performance of nMnBTC as a cold-adapted nanozyme can be attributed to its high-catalytic efficiency at low temperature, good substrate affinity, and flexible conformation. Based on the robust performance of nMnBTC, a low-temperature antiviral strategy is developed to inactivate influenza virus H1N1 even at -20 °C. These results not only provide an important guide for the rational design of highly efficient artificial cold-adapted enzymes, but also pave a novel way for biomedical application in cryogenic fields.


Oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages.
The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex consisting of a receptor, an adaptor protein, and procaspase-1 that induces the secretion of the mature form of IL-1β in response to microbial infection and danger signals. Activation of the NLRP3 inflammasome induced by endogenous danger signal molecules is closely linked to the development and progress of chronic inflammatory diseases. The oxidation of phospholipids occurs upon cellular stress and damage, resulting in the accumulation of oxidized phosphatidylcholines (oxPAPC) such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-phosphocholine (POVPC) at inflammatory sites. In this study, we investigated whether oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages, leading to the secretion of IL-1β. POVPC induced the degradation of procaspase-1 to caspase-1(p10), the cleavage of pro-IL-1β to IL-1β, and oligomerization of ASC in primary mouse bone marrow-derived macrophages. POVPC-induced production of caspase-1, and IL-1β was abolished in macrophages derived from NLRP3- or caspase-1-deficient mice. In an air pouch model and a peritonitis model in mice, POVPC injection resulted in the production of caspase-1(p10), IL-1β, and IL-18 in wild-type, but not in NLRP3-deficient, mice. POVPC-induced inflammasome activation was mediated by mitochondrial reactive oxygen species resulting from intracellular Ca2+ signaling and mitochondrial destabilization. Our results demonstrate that endogenously produced oxidized phosphatidylcholines such as POVPC induce the activation of NLRP3 inflammasome, leading to the production of IL-1β in macrophages. The results provide an insight to understand how the oxidized lipids endogenously produced upon cellular stress and tissue damage contribute to the inflammatory reaction at pathologic sites.


Low attenuation lesions in the midline posterior fossa: differential diagnosis.
A wide variety of cystic appearing or low attenuation lesions in the midline posterior fossa can so closely resemble one another as to render specific histologic diagnosis from CT scans alone fraught with error. Absorption coefficients often overlap and are too nonspecific to infer consistently accurate histologic diagnosis. It is virtually impossible to separate cystic from noncystic, benign from malignant, and neoplastic from non-neoplastic lesions by absorption coefficients alone.


Fermentation of xylose into acetic acid by Clostridium thermoaceticum.
For optimum fermentation, fermenting xylose into acetic acid by Clostridium thermoaceticum (ATCC 49707) requires adaptation of the strain to xylose medium. Exposed to a mixture of glucose and xylose, it preferentially consumes xylose over glucose. The initial concentration of xylose in the medium affects the final concentration and the yield of acetic acid. Batch fermentation of 20 g/L of xylose with 5 g/L of yeast extract as the nitrogen source results in a maximum acetate concentration of 15.2 g/L and yield of 0.76 g of acid/g of xylose. Corn steep liquor (CLS) is a good substitute for yeast extract and results in similar fermentation profiles. The organism consumes fructose, xylose, and glucose from a mixture of sugars in batch fermentation. Arabinose, mannose, and galactose are consumed only slightly. This organism loses viability on fed-batch operation, even with supplementation of all the required nutrients. In fed-batch fermentation with CSL supplementation, D-xylulose (an intermediate in the xylose metabolic pathway) accumulates in large quantities.


Association of clozapine treatment and rate of methamphetamine or amphetamine relapses and abstinence among individuals with concurrent schizophrenia spectrum and amphetamine use disorder: A retrospective cohort study.
Preliminary evidence suggest clozapine is associated with more favorable impact on concurrent substance use disorder related outcomes in patients with concurrent schizophrenia spectrum disorders (SSD). At the same time, there is a dearth of evidence with regards to clozapine outcomes in the context of concurrent methamphetamine or amphetamine use disorder (MAUD). To examine whether clozapine use decreases rate of methamphetamine or amphetamine (MA) relapses and increases the likelihood of maintaining abstinence from any MA use. A descriptive-analytic retrospective cohort study was conducted on individuals with SSD-MAUD in an inpatient provincial treatment and rehabilitation center for concurrent disorders. Antipsychotic exposure was categorized as "on clozapine" or "on other antipsychotic(s)." Data were collected using electronic health records. Logistic regression was used to examine association of clozapine treatment with likelihood of complete abstinence from MA use for the duration of antipsychotic exposure. Negative binomial regression was used to examine association of clozapine treatment with rate of MA relapses for the duration of antipsychotic exposure. The majority of the 87 included patients were male. Ethnicity was diverse, with the largest groups self-identifying as Indigenous and European. Clozapine use was both associated with increased likelihood of maintaining abstinence from MA use (adjusted odds ratio (aOR) = 3.05, 95% confidence intervals (CI) = 1.15-8.1, p = 0.025), and decreased rate of MA relapses (aRR = 0.45, 95% CI = 0.25-0.82, p = 0.009) for the duration of antipsychotic exposure. Co-prescription of psychostimulants was associated with increased rate of MA relapses (aRR = 2.43, 95% CI = 1.16-5.10, p = 0.019). In this study, clozapine use compared with other antipsychotics in SSD was associated with improved outcomes related to severe concurrent MAUD. Co-prescription of psychostimulant medications was associated with a poor outcome.


The comorbidity burden and disease phenotype in pre-capillary pulmonary hypertension: The contributing role of obstructive sleep apnea.
Pre-capillary pulmonary hypertension (PH) with risk factors for left ventricular diastolic dysfunction, described as an atypical phenotype of "mixed" pre- and post-capillary PH, has become a research focus. However, the relationship between obstructive sleep apnea (OSA), a known risk factor for cardiometabolic conditions, and comorbidity burden and disease phenotype in PH remains unclear. This study aimed to investigate the effect of the presence and severity of OSA on the left ventricular function, comorbidity burden and disease phenotype in pre-capillary PH patients. We retrospectively examined 450 consecutive pre-capillary PH patients undergoing cardiorespiratory polygraphy and right heart catheterization between May 2020 to November 2021 at Fuwai Hospital. The prevalence of OSA was 34.2%, and the presence and severity of OSA in pre-capillary PH patients was associated with increased left heart mass index (P < 0.001), pulmonary arterial wedge pressure (P = 0.06) and H2FPEF score (P < 0.001). After adjustment for confounding factors, the severity of OSA measured as apnea-hypopnea index (AHI) was an independent risk factor associated with obesity, systemic hypertension, diabetes mellitus and an atypical phenotype (OR: 1.054, P = 0.004) in pre-capillary PH. A dose-response relationship was also identified between sleep parameters (AHI, oxygen desaturation index, the percentage of sleep time with oxygen saturation<80%) and the number of key comorbidities. Patients with ≥3 comorbidities (atypical phenotype) were older, experienced negative alterations in left ventricular structure and function, and were at a higher risk of OSA. OSA is relatively prevalent in pre-capillary PH patients, independently associated with the presence of a variety of comorbidities and the atypical phenotype of PH. These findings highlight the importance of OSA as a modifiable target for optimal treatment in PH with comorbidities.


Suppression of macrophage lysosomal enzymes after Leishmania donovani infection.
In order to have an insight into the role of host lysosomal enzymes in the intracellular survival of Leishmania parasites, the activities of beta-galactosidase, alpha-mannosidase, and N-acetyl-beta-D-glucosaminidase were studied in peritoneal macrophages of hamsters infected with L. donovani. There was a significant decrease of all three lysosomal enzymes after infection. Heat-killed or formalin-treated parasites failed to inhibit the enzymes, instead a slight stimulation was observed. Purified excreted factor from promastigotes had no effect on the enzymes except beta-galactosidase which was inhibited up to 20%. Inhibition of enzymes was not due to increased secretion after infection. The absence of induction of any endogenous macrophage inhibitor was confirmed by mixed experiments. The levels of 5'-nucleotidase and lactate dehydrogenase remained unchanged after infection. Thus, the inhibition of lysosomal enzymes appears to be the effect of infection process and reflects to actua decrease rather than increased secretion or the action of any inhibitors present in Leishmania promastigotes.


Treatment of small cell lung cancer in the elderly.
Since both the incidence of lung cancer and the proportion of the population over age 65 are increasing rapidly in North America, we undertook a retrospective review of elderly patients with small cell lung cancer (SCLC) in an attempt to assess the effect of age on treatment decisions, response, survival, and toxicity. Retrospective chart view. Oncology Unit of a university-affiliated teaching hospital. There were 123 patients age > 70 years treated from 1976-88. Chemotherapy consisted of either cyclophosphamide, doxorubicin, and vincristine, or etoposide and cisplatin. There were 74 patients aged 70-74, 35 aged 75-80, and 14 aged 80 years or older. No significant differences existed between the groups in sex, stage, performance status, or presence of co-morbid disease. Median survivals for patients with limited and extensive disease were 11.9 and 5.2 months, respectively (P = < 0.0001), with no significant difference for patients in any age group (P = 0.4). For both limited and extensive disease, survival correlated strongly with the treatment received. Twenty-five patients received no treatment (median survival 1.1 months), 20 had radiation only (median 7.8 months), and 27 patients had < 3 cycles of chemotherapy (median 3.9 months). Median survival for the 50 patients who had 4-6 cycles was 10.7 months (limited disease 15.0 months, extensive disease 8.61 months). In the Cox Model, survival correlated strongly with stage of disease and chemotherapy treatment (P < 0.0001), but only marginally with performance status (P < 0.077). Of the 77 patients who had chemotherapy, less than 50% in all age groups completed six cycles. Only two patients completed chemotherapy without a single dose reduction, and 76.7% required more than two reductions. Chemotherapy should not be withheld from elderly patients with SCLC on the basis of age. The survival of patients who receive chemotherapy is significantly longer than that of untreated patients even though frequent dose reductions for toxicity may be required. The survival benefit is due to treatment effect and is not due to a selection bias in the cohort of patients chosen for therapy.


Epidemiologic features of overseas imported malaria in the People's Republic of China.
With the dramatic increase in international travel among Chinese people, the risk of malaria importation from malaria-endemic regions threatens the achievement of the malaria elimination goal of China. Epidemiological investigations of all imported malaria cases were conducted in nine provinces of China from 1 Nov, 2013 to 30 Oct, 2014. Plasmodium species, spatiotemporal distribution, clinical severity, preventive measures and infection history of the imported malaria cases were analysed using descriptive statistics. A total of 1420 imported malaria cases were recorded during the study period, with P. falciparum (723 cases, 50.9 %) and P. vivax (629 cases, 44.3 %) being the two predominant species. Among them, 81.8 % of cases were in Chinese overseas labourers. The imported cases returned from 41 countries, mainly located in Africa (58.9 %) and Southeast Asia (39.4 %). About a quarter (25.5 %, 279/1094) of counties in the nine study provinces were affected by imported malaria cases. There were 112 cases (7.9 %) developing complicated malaria, including 12 deaths (case fatality rate: 0.8 %). Only 27.8 % of the imported cases had taken prophylactic anti-malarial drugs. While staying abroad, 27.7 % of the cases had experienced two or more episodes of malaria infection. The awareness of clinical manifestations and the capacity for malaria diagnosis were weak in private clinics and primary healthcare facilities. Imported malaria infections among Chinese labourers, returned from various countries, poses an increasing challenge to the malaria elimination programme in China. The risk of potential re-introduction of malaria into inland malaria-free areas of China should be urgently addressed.


Ablation of EWS-FLI1 by USP9X inhibition suppresses cancer cell growth in Ewing sarcoma.
The neomorphic transcription factor EWS-FLI1 is a key driver of Ewing sarcoma. Ablation of EWS-FLI1 may present a promising therapeutic strategy for this malignancy. Here we found that the deubiquitinase, ubiquitin specific peptidase 9 X-linked (USP9X) stabilizes EWS-FLI1 protein expression in Ewing sarcoma. We show that USP9X binds the ETS domain of EWS-FLI1 in Ewing sarcoma cells and deubiquitinates EWS-FLI1 and that USP9X and EWS-FLI1 protein expression is correlated in clinical Ewing sarcoma specimens. We found that treatment of Ewing sarcoma cells with the USP9X inhibitor WP1130 mediates rapid EWS-FLI1 degradation in vitro and in vivo which coincides with reduced growth of Ewing sarcoma cells and tumors. Our results suggest that USP9X might be a potential therapeutic target to mediate EWS-FLI1 depletion in Ewing sarcoma.


Mild vitamin A deficiency and childhood morbidity--an Indian experience.
Over 1500 preschool urban Indian children were followed weekly for morbidity from 12 to 18 mo. Examination for mild xerophthalmia (Bitot's spots and night blindness) was done initially and at 6 and 12 mo. Children with mild xerophthalmia at the start of a 6-mo interval developed respiratory disease in the interval twice as often as children with normal eyes at the start of the interval. No association was found between mild xerophthalmia and incidence of diarrhea.


Isolated myelosarcoma development in an adolescent chronic myeloid leukemia patient with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).
Additional chromosomal abnormalities are found in 5-20% of patients during chronic phase of chronic myeloid leukemia and in 60-80% preceding or accompanying blast crisis. These abnormalities are important in disease progression and, because they may occur before hematological and clinical symptoms, can be taken as a prognostic indicator. An adolescent with chronic myeloid leukemia initially presented with extreme thrombocytosis, increased megakaryopoiesis with dysmorphic features, and focal myelofibrosis in bone marrow examinations and then developed isolated myelosarcoma 1 year after onset, with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).


Cold gas in the Milky Way's nuclear wind.
The centre of the Milky Way hosts several high-energy processes that have strongly affected the inner regions of our Galaxy. Activity from the super-massive black hole at the Galactic Centre, which is coincident with the radio source Sagittarius A*, and stellar feedback from the inner molecular ring1 expel matter and energy from the disk in the form of a galactic wind2. Multiphase gas has been observed within this outflow, including hot highly ionized3,4 (temperatures of about 106 kelvin), warm ionized5,6 (104 to 105 kelvin) and cool atomic7,8 (103 to 104 kelvin) gas. However, so far there has been no evidence of the cold dense molecular phase (10 to 100 kelvin). Here we report observations of molecular gas outflowing from the centre of our Galaxy. This cold material is associated with atomic hydrogen clouds travelling in the nuclear wind8. The morphology and the kinematics of the molecular gas, resolved on a scale of about one parsec, indicate that these clouds are mixing with the warmer medium and are possibly being disrupted. The data also suggest that the mass of the molecular gas outflow is not negligible and could affect the rate of star formation in the central regions of the Galaxy. The presence of this cold, dense and high-velocity gas is puzzling, because neither Sagittarius A* at its current level of activity nor star formation in the inner Galaxy seems to be a viable source for this material.


Tropical fish medicine. Bacterial culture and evaluation of diseases of fish.
Bacteria are ubiquitous in nature. Fish are constantly exposed to bacteria, and usually only succumb to an infection after having been exposed to prolonged periods of stress. Before making a diagnosis of a bacterial disease, it is necessary to eliminate the possibility of environmental or parasitic problems. Environmental factors may act as stressors and can predispose a fish to bacterial disease while affecting the fish simultaneously. Clinical signs caused by the various bacterial pathogens are very similar. Therefore, to make a definitive bacterial diagnosis, it is necessary to culture and identify the organisms involved.


The Role of Kidney Supportive Care and Active Medical Management Without Dialysis in Supporting Well-Being in Kidney Care.
People living with kidney failure often experience a higher symptom burden (including anxiety and depression) and lower quality of life than patients with other serious chronic diseases. The end of life for these patients is characterized by high intensity of treatment (such as intensive care unit stays) and lack of support for family. Kidney supportive care, which emphasizes quality of life, person-centered care, and holistic care for the person and their family, is an approach that improves well-being by aligning care with the patient's preferences and goals. Kidney supportive care encompasses identifying seriously ill patients, eliciting patient values and goals through shared decision making and advance care planning, assessing and managing symptoms, communicating prognosis, offering active medical management without dialysis, and planning and managing care transitions, especially at the end of life. Models, strategies, and tools for incorporating kidney supportive care and active medical management without dialysis into existing workflows are available. However, barriers to implementation in the United States include clinician knowledge gaps, current workflows, and financial incentives, which make it difficult to break from the de facto default practice of starting dialysis for patients with kidney failure regardless of age, frailty, or debilitating condition. Policy changes are needed to fully implement kidney supportive care in the United States.


[Hypoglycemia insulin test in the assessment of the hypothalamic-pituitary-adrenal function].
Recent advances in sensitivity and specificity of hormone immunoanalysis and their automatization have brought about changes in clinical laboratories that led us to review the need for some endocrine dynamic tests. The specific aim of this study was to determine the basal cortisol values predicting a normal or impaired response to the insulin hypoglycemia test (ITT). We retrospectively analysed cortisol responses to ITT in 320 subjects. Moreover, we studied the impact the use of a new strategy has on economic cost, by means of a relative value unit (RVU) calculation. No patient with a basal cortisol < 6 g/dl (13%) responded to the test whereas all those with a basal cortisol > 18 g/dl responded in full. The rest of patients exhibited a basal cortisol level between 6-18 g/dl, 39% of them responding and 16% showing an inadequate response. Baseline and peak cortisol concentrations were strongly correlated (r = 0.74; p < 0.0001). The cost of ITT was 131.6 RVU as compared to 17.8 RVU for cortisol. Basal cortisol levels below 6 g/dl or above 18 g/dl make the test unnecessary. Cortisol measurement by automated methods, along with subsequent reduced assay times, allows us to apply new diagnosis strategies. Considering that the cost of ITT is 15 fold higher than that of single cortisol measurement, the potentially generated saving is significant.


Headache caused by a single lesion of multiple sclerosis in the periaqueductal gray area.
We report a severe acute headache that occurred in conjunction with a solitary fresh lesion of multiple sclerosis in the periaqueductal gray region of a 16-year-old girl. This unique natural event supports the recent proposition, based on observations of patients with implanted electrodes, that perturbations of the periaqueductal gray region can produce headache. It also suggests that headaches accompanying attacks of multiple sclerosis are due to disturbances in particular regions of the brain.


Highly conserved alpha-toxin sequences of avian isolates of Clostridium perfringens.
Clostridium perfringens causes necrotic enteritis in chickens, and alpha-toxin has been suggested to be a key virulence determinant. Analysis of the alpha-toxin of 25 chicken-derived C. perfringens strains demonstrated high homology to mammal-derived strains rather than to the only avian-derived C. perfringens alpha-toxin sequence reported previously.