[Mutational analysis of ASS1, ASL and SLC25A13 genes in six Chinese patients with citrullinemia].
To detect potential mutations in six patients with citrullinemia. Genomic DNA was extracted from peripheral blood samples from the patients. Mutations of the ASS1, ASL and SLC25A13 genes were screened using microarray genotyping combined with direct sequencing. One patient was diagnosed with argininosuccinate lyase deficiency, and has carried a homozygous c.1311T>G (p.Y437*) mutation of the ASL gene. The remaining five patients were diagnosed with neonatal intrahepatic cholestasis due to citrin deficiency, and have respectively carried mutations of the SLC25A13 gene including [c.851-854delGTAT+c.851-854delGTAT], [c.851-854delGTAT+IVS6+5G>A], [c.851-854delGTAT+IVS16ins3kb], [c.851-854delGTAT+IVS6-11A>G] and [c.851-854delGTAT+c.1638-1660dup23]. Among these, the c.1311T>G mutation was first identified in the Chinese population, and the IVS6-11A>G mutation was a novel variation which may affect the splicing, as predicted by Human Splicing Finder software. This study has confirmed the molecular diagnosis of citrullinemia in six patients and expanded the mutational spectrum underlying citrullinemia.


Facilitation of brain stimulation reward by mesencephalic injections of neurotensin-(1-13).
The effects on brain stimulation reward of neurotensin-(1-13) microinjected at different concentrations (2.5, 5, 10 and 20 micrograms/0.5 microliters) into the ventral mesencephalic region containing mesocorticolimbic dopamine neurons were tested in 12 male rats. Neurotensin lowered the stimulation frequency required to sustain threshold levels of responding for brain stimulation reward, suggesting that this neuropeptide is involved in modulating the activity of dopamine neurons that mediate behaviors motivated by positive reinforces. The magnitude of the facilitatory effect of neurotensin on brain stimulation reward was dependent on the concentration injected and to a significant extent also on whether the peptide was administered in an ascending or a descending order of concentration. The different effects of neurotensin depending on the order of administration may suggest long-lasting effects on the responsiveness of neurotensin receptors in this region after injection of high concentrations of the peptide. Subsequent injection of morphine (2.5-5 micrograms/0.5 microliter) into the same site produced a weaker facilitation of brain stimulation reward than expected, suggesting that local damage after multiple central injections or prior injections of neurotensin itself reduced the responsiveness of dopamine neurons to opiates. Taken together, the results are consistent with data indicating that activation of neurotensin receptors in the ventral mesencephalon stimulates dopamine cell firing and axonal dopamine release in limbic terminal fields and suggest that endogenous neurotensin is involved in the control of behavior motivated by positive reinforcement.


Differences in Meat Quality of Six Muscles Obtained from Southern African Large-Frame Indigenous Veld Goat and Boer Goat Wethers and Bucks.
Various meat quality characteristics of six muscles (Longissimus thoracis et lumborum (LTL), Semimembranosus (SM), Biceps femoris (BF), Supraspinatus (SS), Infraspinatus (IS), Semitendinosus (ST)) from large-frame Boer Goats (BG) and Indigenous Veld Goats (IVG: Cape Speckled and the Cape Lob Ear) were studied. Weaner male BG (n = 18; 10 bucks and 8 wethers) and IVG (n = 19; 9 bucks and 10 wethers) were raised on hay and natural grass, and on a commercial pelleted diet to a live weight of 30-35 kg. All goats were slaughtered at a commercial abattoir and the dressed carcasses were chilled at 4 °C within 1 h post mortem. The muscles were dissected from both sides 24 h post mortem and aged for 1 d and 4 d. Variations in meat characteristics such as ultimate pH, water holding capacity (WHC), % purge, myofibril fragment length (MFL), intramuscular fat (IMF), connective tissue characteristics, and Warner-Bratzler shear force (WBSF) were recorded across muscles. Bucks had higher lightness (L*) and hue-angle values, whereas wethers had increased redness (a*) and chroma values. The muscle baseline data will allow informed decisions to support muscle-specific marketing strategies, which may be used to improve consumer acceptability of chevon.


Seasonal variation of total dissolved arsenic and arsenic speciation in a polluted surface waterway.
Seasonal differences in the dissolved arsenic concentration and speciation in a contaminated urban waterway in northwest England have been determined using a coupled ion chromatography-inductively coupled plasma-mass spectrometry (IC-ICP-MS) technique. Waters sampled in the vicinity of an industrial works during relatively dry conditions in April 2000 were found to contain total arsenic concentrations (sigma As) of up to 132 micrograms L-1, more than an order magnitude greater than the 4 micrograms L-1 maximum found in December 2000. The difference in sigma As between the April and December sampling periods is speculated to be largely due to the irregular anthropogenic supply of arsenic to the watercourse. For both sampling periods, the dissolved arsenic was exclusively inorganic in nature and had an As(V)/sigma As ratio of between 0.6 and 0.8. Analysis of samples taken downstream of the industrial site, after the confluence with a relatively As-poor stream, revealed that As(III), As(V) and sigma As concentrations were lower than would be expected from conservative mixing. The As(V)/sigma As ratio was also observed to decrease markedly. The loss of arsenic from solution is thought to be due to adsorption on the iron oxyhydroxide-rich sediment observed to coat the riverbed downstream of the confluence. The reduction in the As(V)/sigma As ratio is believed to be due to the more rapid adsorption of As(V) compared to that of As(III). Deviations from conservative behaviour were more marked during the relatively dry April 2000 sampling period and suggest the increased importance of adsorption processes controlling arsenic availability during this time.


Effects of glycosylation on antigenicity and immunogenicity of classical swine fever virus envelope proteins.
Classical swine fever virus (CSFV) harbors three envelope glycoproteins (E(rns), E1 and E2). Previous studies have demonstrated that removal of specific glycosylation sites within these proteins yielded attenuated and immunogenic CSFV mutants. Here we analyzed the effects of lack of glycosylation of baculovirus-expressed E(rns), E1, and E2 proteins on immunogenicity. Interestingly, E(rns), E1, and E2 proteins lacking proper post-translational modifications, most noticeable lack of glycosylation, failed to induce a detectable virus neutralizing antibody (NA) response and protection against CSFV. Similarly, no NA or protection was observed in pigs immunized with E1 glycoprotein. Analysis of E(rns) and E2 proteins with single site glycosylation mutations revealed that detectable antibody responses, but not protection against lethal CSFV challenge is affected by removal of specific glycosylation sites. In addition, it was observed that single administration of purified E(rns) glycoprotein induced an effective protection against CSFV infection.


Inbreeding depression in benign and stressful environments.
Understanding the consequences of inbreeding has important implications for a wide variety of topics in population biology. Although it is often stated in the literature that the deleterious effects of inbreeding (inbreeding depression) are expected to be more pronounced under stressful than benign conditions, this issue remains unresolved and controversial. We review the current literature on the relationship between the magnitude of inbreeding depression and environmental stress and calculate haploid lethal equivalents expressed under relatively benign and stressful conditions based on data from 34 studies. Inbreeding depression increases under stress in 76% of cases, although this increase is only significant in 48% of the studies considered. Estimates of lethal equivalents are significantly greater under stressful (mean = 1.45, median = 1.02) than relatively benign (mean = 0.85, median = 0.61) conditions. This amounts to an approximately 69% increase in inbreeding depression in a stressful vs a benign environment. However, we find strong lineage effects to be ubiquitous among studies that examine inbreeding depression in multiple environments, and a prevalence of conditionally expressed deleterious effects within lineages that are uncorrelated across environments. These results have important implications for both evolutionary and conservation biology.


Clinical evaluation of ERCP and naobiliary drainage for biliary fungal infection--a report of five cases of severe combined bacterial and fungal infection of biliary tract.
This study studied the use of ERCP and nasobiliary tube in the diagnosis of fungal infection of biliary tract and the efficacy of combined use of local administration via nasobiliary tube and intravenous antifungal treatment for severe biliary tract fungal infection. 5 patients in our series, with age ranging from 47 to 68 y (mean 55.8), were diagnosed as having mixed bacterial and fungal infection of biliary tract as confirmed by smear or/and culture of bile obtained by ERCP and nasobiliary drainage. Besides routine anti-bacteria therapy, all patients received local application of fluconazole through nasobiliary tube and intravenous administration of fluconazole or itraconazole in terms of the results of in vitro sensitivity test. The mean duration of intravenous fluconazole or itraconazole was 30 days (24-40 days), and that of local application of fluconazole through nasobiliary drainage tube was 19 days (8-24 days). During a follow-up period of 3-42 months, all patient's fungal infection of biliary tract was cured. It is concluded that on the basis of typical clinical features of biliary tract infection, fungal detection of smear/culture of bile obtained by ERCP was the key for the diagnosis of fungal infection of biliary tract. Local application antifungal drug combined with intravenous anti-fungal drugs might be an effective and safe treatment for fungal infection of biliary tract.


Excited-state observation of active K-Ras reveals differential structural dynamics of wild-type versus oncogenic G12D and G12C mutants.
Despite the prominent role of the K-Ras protein in many different types of human cancer, major gaps in atomic-level information severely limit our understanding of its functions in health and disease. Here, we report the quantitative backbone structural dynamics of K-Ras by solution nuclear magnetic resonance spectroscopy of the active state of wild-type K-Ras bound to guanosine triphosphate (GTP) nucleotide and two of its oncogenic P-loop mutants, G12D and G12C, using a new nanoparticle-assisted spin relaxation method, relaxation dispersion and chemical exchange saturation transfer experiments covering the entire range of timescales from picoseconds to milliseconds. Our combined experiments allow detection and analysis of the functionally critical Switch I and Switch II regions, which have previously remained largely unobservable by X-ray crystallography and nuclear magnetic resonance spectroscopy. Our data reveal cooperative transitions of K-Ras·GTP to a highly dynamic excited state that closely resembles the partially disordered K-Ras·GDP state. These results advance our understanding of differential GTPase activities and signaling properties of the wild type versus mutants and may thus guide new strategies for the development of therapeutics.


Fatty acid acylation of mucin by gastric mucosa: effects of sofalcone and sucralfate.
The effects of antiulcer drugs, sofalcone and sucralfate, on the activity of gastric mucosal mucus glycoprotein fatty acyltransferase were investigated. The acyltransferase enzyme, contained in the detergent extracts of the microsomal fraction of rat gastric mucosa, was incubated with the deacylated gastric mucin and palmitoyl-CoA substrates in the presence and absence of drugs, and the formed fatty acid acylated glycoprotein product was quantitated. In the absence of drugs, the enzymatic activity increased proportionally with increased concentrations of both substrates and of enzyme, and gave an apparent Km value of 5.6 X 10(-7) M. Introduction of sofalcone to the reaction mixtures led to an enhancement in the rate of mucus glycoprotein acylation. The rate of enhancement was proportional to sofalcone concentration up to 1.0 X 10(-5) M, with an apparent Km value of 3.7 X 10(-7) M. In contrast to sofalcone, the acyltransferase activity was inhibited by sucralfate. The rate of inhibition of mucus glycoprotein acylation by sucralfate was of the competitive type and at 1.0 X 10(-4) M reached a value of 25%. The apparent KI value calculated from the double-reciprocal plots for sucralfate was 9.1 X 10(-7) M. As the acylation of mucin with fatty acids plays an important role in the maintenance of gastric mucosal integrity, the results suggest that stimulation of the fatty acyltransferase enzyme by sofalcone may be one of the beneficial effects of this drug towards ulcer healing.


Profile of Brazilian workers victims of occupational accidents with biological fluids.
To characterize the Brazilian workers victims of occupational accidents with biological fluids. Epidemiological and descriptive research, in which 284,877 notifications of the Notifiable Diseases Information System were analyzed between 2007 and 2014. We used Stata 13 for data analysis. The highest incidence density occurred in females with 0.8 cases per 1,000 workers/year (n = 222,042, 77.9%); in the age group of 20 to 24 years old, with 0.6 cases per 1,000 workers/year (n = 64,221, 23.3%); with some high school and some college, with 0.6 cases per 1,000 workers/year (n = 141,275, 49.6%). We found that these accidents occurred among 23 occupational subgroups. For the most part, the workers had an employment relationship and had issued the Occupational Accident Notification. It is necessary to rethink the measures of orientation to workers regarding the risks and relative prophylaxis for these accidents, with the aim of reducing them. Caracterizar os trabalhadores brasileiros vítimas de acidente de trabalho com fluidos biológicos. Pesquisa epidemiológica, descritiva, na qual foram analisadas 284.877 notificações do Sistema Nacional de Notificação de Agravos, entre 2007 e 2014. Utilizou-se Stata 13 para a análise dos dados. A maior densidade de incidência ocorreu no sexo feminino com 0,8 caso a cada 1.000 trabalhadores/ano (n = 222.042; 77,9%); na faixa etária de 20 a 24 anos com 0,6 caso a cada 1.000 trabalhadores/ano (n = 64.221; 23,3%); com Ensino Médio e Superior incompleto com 0,6 caso a cada 1.000 trabalhadores/ano (n = 141.275; 49,6%). Verificou-se que esses acidentes ocorreram entre 23 subgrupos ocupacionais. Em sua maioria, os trabalhadores possuíam vínculo empregatício e tiveram emitida a Comunicação de Acidente de Trabalho. Faz-se necessário repensar as medidas de orientação aos trabalhadores quanto aos riscos e profilaxia relativa para estes acidentes, visando reduzi-los ou diminui-los.


[Results of hemograms of a series of top-level cyclists: an example of a factor of biological variability].
We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 years, mean 25 +/- 4.5). Recruitment was by controlling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.


Hyperexcitability of motor and sensory neurons in neuromyotonia.
Two members of a family with a neuropathy resembling Charcot-Marie-Tooth disease were unable to relax their muscles after voluntary contraction. Muscle spasm often outlasted voluntary contraction by 30 seconds or more before subsiding into myokymia and fasciculations. The posture of the hand during muscle spasm resembled that of tetany, and Trousseau's and Chvostek's signs were present although no abnormality of calcium or magnesium metabolism could be demonstrated. Muscle spasms ceased during medication with carbamazepine, 600 mg daily. Nerve stimulation, electromyography, and regional neuromuscular blockade with curare indicated that the condition originated in peripheral nerve, while microneurographic recordings showed that sensory as well as motor fibers were hyperexcitable. Sural nerve biopsy revealed axonal degeneration involving myelinated and unmyelinated fibers. It was concluded that the neural hyperexcitability is caused by a membrane defect resulting in a low threshold for excitation throughout the length of the axon.


Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review.
Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeutic agents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiac imaging, and prevention strategies.


Photobiomodulation therapy in mood disorders: a systematic review.
Mood disorders are common, debilitating and impose a high-cost burden on society. Side effects and resistance to psychiatric drugs justify finding new treatment methods. Photobiomodulation therapy (PBMT) uses photons of light to repair, modulate and improve the function of target tissue. The purpose of this study is to systematically review the use of PBMT for the treatment of mood disorders and to identify the useful parameters of PBMT, the level of evidence of its effectiveness, and the degree of its practical recommendation. "Google scholar," "Pub Med," "Scopus," and "Science direct" online databases were searched based on Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) guidelines. The human or animal studies written in English and published from January 2009 to August 2021 were included. Sixteen studies, which included four randomized controlled trials (RCTs), met the inclusion criteria. Infrared wavelength ranges from 800 to 830 nm, power density of 250 mW/cm2 and energy density of 60 to 120 J/ cm2 were the most used PBMT parameters. Bias risk assessment was performed to evaluate the quality of RCTs in which 2 out of 4 RCTs were evaluated as high quality. Based on grade practice recommendations, PBMT can be classified as strongly recommended for moderate grade of major depressive disorder (MDD) and recommended for anxiety disorder. In bipolar disorder, further studies are needed to recommend this therapeutic method.


Rituximab exposure-response in triweekly R-CHOP treatment in DLBCL: A loading dose is recommended to improve clinical outcomes.
Previous exposure-response analyses for rituximab suggest that higher rituximab concentrations were associated with an improvement in efficacy, however, clinical studies investigating a higher rituximab dose had mixed results. To further explore the exposure-response relationship of rituximab, a prospective observational analysis was performed involving 121 newly diagnosed patients with diffuse large B-cell lymphoma treated with triweekly rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The trough concentration in the first cycle (C1-trough ) was significantly higher in patients achieving complete response (CR) compared with patients that did not achieve CR (22.00 μg/ml vs. 16.62 μg/ml, p = 0.0016), however, this difference between the two groups disappeared in later cycles. The relationship between rituximab C1-trough and achieving a CR was confirmed by matched-pair logistic regression analysis (odds ratio, 0.79; p = 0.0020). In addition, a higher C1-trough (≥18.40 μg/ml) was associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0038). The percentages of patients that did not achieve a CR and had recurrence after CR within 24 months were 35% and 22.50%, respectively, for patients with a C1-trough less than or equal to 18.40 μg/ml, compared with 12.35% and 6.17% for patients with C1-trough greater than 18.40 μg/ml. Disease stage was found to be the most significant influencing factor of C1-trough , with 51.02% of patients at stage IV with an observed C1-trough less than 18.40 μg/ml. For these advanced patients, population pharmacokinetic simulations using an established model suggest that a loading dose of 800 mg/m2 may help to improve clinical outcomes.


Chromosome Conformation Capture of Mitotic Chromosomes.
Despite more than a century of intensive study of mitotic chromosomes, their three-dimensional organization remains enigmatic. The last decade established Hi-C as a method of choice for study of spatial genome-wide interactions. Although its utilization has been focused mainly on studying genomic interactions in interphase nuclei, the method can be also successfully applied to study 3D architecture and genome folding in mitotic chromosomes. However, obtaining sufficient number of mitotic chromosomes as an input material and effective coupling with Hi-C method is challenging in plant species. An elegant way to overcome hindrances with obtaining a pure mitotic chromosome fraction is their isolation via flow cytometric sorting. This chapter presents a protocol describing plant sample preparation for chromosome conformation studies, for flow-sorting of plant mitotic metaphase chromosomes and for the Hi-C procedure.


Racial/Ethnic Representation in United States and Australian Obstetric Research.
To describe racial/ethnic representation in United States (US) and Australian obstetric research, represented by the Maternal-Fetal Medicine Units Network (MFMU) and Australian Research Centre for Health of Women and Babies (ARCH) trials. MFMU studies were identified through PubMed and ARCH studies through their online publication listing from 2011 to 2016. Observational and randomized cohorts and primary and secondary data analyses were included. Studies with race-based enrollment were excluded. Racial/ethnic representation was expressed as the mean racial/ethnic percentages of the studies (i.e.,: studies weighted equally regardless of sample size). Racial/ethnic percentages in MFMU studies were compared to US registered births and ARCH compared to Australian census ancestry data. 38 MFMU studies included 580,282 women. Racial/ethnic representation (% [SD]) included White 41.7 [12.3], Hispanic 28.1 [15.4], Black 26.2 [12.3], Asian 3.6 [2.3], and American Indian/Alaskan Native (AI/AN) 0.2 [0.02]. No studies reported Native Hawaiian/other Pacific Islanders (NHOPI) separately. Comparatively, registered US births (%) were White 75.7, Hispanic 28.1, Black 16.1, Asian/Pacific Islander 7.1, and AI/AN 1.1, which differed from the MFMU (P = 0.02). 20 ARCH studies included 51,873 women. The most reported groups were White 76.5 [17.4], Asian 15.2 [14.8], and Aboriginal/Torres Strait Islander 13.9 [30.5], compared to census numbers of White 88.7, Asian 9.4, and Aboriginal/Torres Strait Islander 2.8 (P < 0.01). Two ARCH studies reported African ethnicity. There is racial diversity in studies by MFMU and ARCH, with opportunities to increase enrollment and enhanced reporting of Asian, AI/AN, and NHOPI races in MFMU studies and Black race in ARCH studies.


Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes.
Andrographis paniculata has been employed as a folklore remedy. Andrographolide (Andro), 14-deoxy-11,12-didehydroandrographolide (DHA), andrographiside (AS), and neoandrographolide (Neo), are major diterpenoids isolated from this plant. In the present study, influence of the four diterpenoids on CYP1A1 mRNA expression was investigated in primary cultured mouse hepatocytes. Additionally, binding of these compounds to aryl hydrocarbon receptor (AhR) was examined using molecular docking analysis to clarify mechanism of CYP1A1 induction. Andro and DHA induced CYP1A1 expression by itself, and co-treatment with a CYP1A1 inducer (BNF, beta-naphthoflavone) showed a synergistic increase of CYP1A1 expression. Andro demonstrated higher enhancing activity than DHA at every similar concentration. On the other hand, Neo suppressed BNF-induced CYP1A1 expression, but AS did not modify the induction. Results from molecular docking analysis of BNF and four diterpenoids on ligand binding domain of AhR were consistent with levels of CYP1A1 mRNA expressions. Furthermore, difference of binding sites of BNF in the presence of diterpenoids might affect the synergism or inhibition of CYP1A1 expression. These results suggest that use of A. paniculata as a health supplement should be concerned in term of herb-drugs interactions or risk of carcinogenesis, according to its ability to influence CYP1A1 expression.


Enhanced performance and mechanisms of sulfamethoxazole removal in vertical subsurface flow constructed wetland by filling manganese ore as the substrate.
Sulfamethoxazole (SMX), a typical sulfonamide antibiotic, is ubiquitous in secondary effluent and may pose undesirable effects on the aquatic ecosystem and human health. Constructed wetland (CW) is more and more applied in advanced sewage treatment, and the substrate plays an important role in removing pollutants. Manganese (Mn) ore has been widely concerned as a new type of substrate to remove pollutants in CW due to its high adsorption and redox properties. However, the removal mechanism of antibiotics by Mn ore CW is still unclear. In this study, Mn ore was selected as the substrate of a vertical flow constructed wetland (VFCW) while gravel substrate was selected as a control group, and the removal efficiencies of SMX in two VFCWs were investigated and compared. Experimental devices were layered as different regions, including anaerobic (0-32 cm), anoxic (32-64 cm) and aerobic (64-80 cm) zones, to examine the removal characteristics of SMX in different regions. And the removal mechanism of SMX was also explored by examining the adsorption and oxidation of Mn ore and the microbial degradation performance. The results showed that the final removal efficiency of SMX in CW filled with Mn ore substrate (M-CW) (48.4%) increased by 39.6%, compared with CW filled with gravel substrate (G-CW) (8.8%). According to the calculation of mass balance, the total loss of SMX caused by the oxidation of Mn ore and biodegradation accounted for 33.0% of the total SMX input in M-CW, the SMX loss caused by the biodegradation in G-CW accounted for 13.0%, and the substrate adsorption in M-CW and G-CW occupied 15.0% and 7.0% of the total SMX input, respectively. Mn(II) was formed during the oxidation of SMX by Mn(III, IV) and dissimilated Mn(III, IV) reduction by microorganisms in anaerobic environment (0-32 cm). Whereafter, the produced Mn(II) entered into the aerobic zone (64-80 cm) with the water flow and was re-oxidized into biogenic Mn oxides (BioMnOx) which had high adsorption and oxidation performance for SMX. Therefore, Mn ore could enhance SMX removal efficiency in anaerobic and aerobic zones by Mn redox process.


[Intravascular measurements of the blood flow in rats].
The blood flow velocity in aorta was measured in rats with intravascular probes. Ultrasonic probes was fixed at the end of polyethylene tubing 0.6 mm in diameter. Miniature piezoelectric crystal worked on 33 MHz frequency. Simultaneously cardiac output were measured with cuff probes placed on ascending aorta. Correlative coefficient between them was 0.96 in static experiments. Dynamics of cardiac output process was caused by injection of vasoactive agents and asphyxia. The difference between intravascular probes and cuff probes blood flow parameters were 6-9%, strike volume 4-6%, cardiac output 5-7%. In ten cases intravascular probes was implanted in ascending aorta for hemodynamics study on conscious rats.


Prevalence of long-term right ventricular dysfunction after acute pulmonary embolism: a systematic review and meta-analysis.
Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term, full-spectrum right ventricular parameters on morphology, pressure and function at certain follow-up time points after PE onset. More exploration of right ventricular function would provide useful clues for long-term management of patients with PE. For this systematic review and meta-analysis, we completed a literature search in Pubmed, EMBASE and WebofScience (from Jan 1st, 1998 to April 20th, 2023). Studies of patients with acute PE followed-up longer than 3 months with right ventricle assessment and written in English-language were included. Right ventricular function was assessed by either echocardiography or computed tomographic pulmonary angiography (CTPA). The primary outcome was structural and functional parameters of the right ventricle, and the secondary outcomes were functional assessments [New York Heart Association (NYHA) functional classification and 6-min walk test distance (6 MWD)], at each follow-up time points. Random effect meta-analyses were performed using R software (PROSPERO: CRD42023433332). A total of 33 studies (3920 patients) were included in the final analysis. The 3-month, 6-month and 1-year prevalence of right ventricular dysfunction (RVD) was 0.34 [95% confidence interval (CI) 0.21-0.48, I2 = 96%], 0.26 (95% CI 0.17-0.36, I2 = 93%) and 0.34 (95% CI 0.19-0.48, I2 = 94%), respectively. Pooled tricuspid annulus plane systolic excursion (TAPSE), right ventricular to left ventricular diameter (RV/LV) ratio and pulmonary artery systolic pressure (PASP) at 1-year was 21.80 mm (95% CI 20.08-23.52, I2 = 93%), 0.64 (95% CI 0.48-0.81, I2 = 92%) and 27.33 mmHg (95% CI 18.88-35.78) (I2 = 96%), respectively. The proportion of NYHA III-IV was 0.06 (95% CI 0.0-0.12) and the pooled 6 MWD was 462.98 m (95% CI 447.55-478.41) over 1 year. Patients treated with thrombolysis had lower prevalence of RVD (1-year 0.17 and 0.07 in systemic thrombolysis and catheter-directed thrombolysis, respectively) than those treated with anticoagulation therapy alone (1-year 0.24) but the pooled risk ratio (RR) was not statistically significant. Although the conclusion of this study may be limited by its high heterogeneity from varied study designs, inclusion criteria and definition of RVD of each study, our findings suggested that persistent RVD and functional impairment were of considerable high prevalence during long-term follow-up after acute PE. Treatment strategy may influence the prevalence of long-term RVD. This study is supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061). The National Key Research and Development Program of China (2016YFC0905600). National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-02-03). CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8).


High esophageal stricture: a complication of "inlet patch" mucosa.
High esophageal stricture associated with a circumferential "inlet patch" of heterotopic gastric mucosa is reported in 2 patients. Biopsy specimens taken from the strictures demonstrated inflamed or ulcerated gastric fundal-type mucosa in both cases. Dilatation of the strictures followed by treatment with histamine H2-antagonists produced almost complete resolution of dysphagia in both patients.


Irritative contact dermatitis to scabicides as a sort of postscabies dermatitis.
In the years 1980-1981 we treated 112 cases of scabies with 20% sulphur ointment, or 1% lindane. In 18% irritative contact dermatitis occurred after the treatment.


Chemical forensic profiling and attribution signature determination of sarin nerve agent using GC-MS, LC-MS and NMR.
Sarin is a highly toxic nerve agent classified by the Chemical Weapon Convention as a Schedule 1 chemical with no use other than to kill or injure. Moreover, in recent times, chemical warfare agents have been deployed against both military and civilian populations. Chemical warfare agents always contain minor impurities that can provide important chemical attribution signatures (CAS) that can aid in forensic investigations. In order to understand the trace molecular composition of sarin, various analytical approaches including GC-MS, LC-MS and NMR were used to determine the chemical markers of a set of sarin samples. Precursor materials were studied and the full characterisation of a synthetic process was undertaken in order to provide new insights into potential chemical attribution signatures for this agent. Several compounds that were identified in the precursor were also found in the sarin samples linking it to its method of preparation. The identification of these CAS contributes critical information about a synthetic route to sarin, and has potential for translation to related nerve agents.


Delivering Coordinated Cardio-Obstetric Care from Preconception through Postpartum.
Coordinated preconception through postpartum cardio-obstetrics care is necessary to optimize both maternal and fetal health. Maternal mortality in the United States is increasing, largely driven by increasing cardiovascular (CV) disease burden during pregnancy and needs to be addressed emergently. Both for women with congenital and acquired heart disease, CV complications during pregnancy are associated with increased future risk of CV disease. Comprehensive cardio-obstetrics care is a powerful way of ensuring that women's CV risks before and during pregnancy are appropriately identified and treated and that they remain engaged in CV care long term to prevent future CV complications.


Comparison of 3-isobutyl-1-methylxanthine-induced accumulation of putrescine in rat pancreas and liver.
3-Isobutylmethylxanthine (IBMX), a potent phosphodiesterase inhibitor, causes accumulation of putrescine of same magnitude in rat pancreas and liver. IBMX produces increases of acetyl CoA: polyamine N'-acetyltransferase (PAT) and of ornithine decarboxylase (ODC) activities in both organs. However ODC activity is 300 times higher in liver than in pancreas. In the latter organ, there is a transient increase of N1-acetylspermidine, followed by a decrease of spermidine, alpha-Difluoromethylornithine (DFMO), a potent ODC inhibitor, impairs the accumulation of putrescine in liver but not in pancreas. These results suggest that in pancreas the accumulated putrescine is essentially formed from spermidine, via N1-acetylation and oxidation, while in liver it is formed from decarboxylation of ornithine. A possible involvement of cAMP in the stimulation of the polyamine interconversion pathway is discussed.


Light suppression of melatonin in unipolar depressed patients.
The effects of nocturnal light (500 lux) exposure on plasma melatonin were studied in seven men suffering from unipolar depression and in seven healthy men. Both groups showed significant declines in plasma melatonin concentrations during 1 hour's light exposure. Differential group declines were not detected.


Zoogeographic significance of Dmanisi large mammal assemblage.
We undertake a comparative mammalian zoogeographic analysis with the aim of revealing the extent to which the Dmanisi Early Pleistocene large mammal assemblage resembles, at the genus level, African, Arabian, and Eurasian localities of similar age. The inclusion of Old World Pliocene and Pleistocene mammalian faunas provides us with insights into the provincial origins of specific mammalian taxa and permits us to assess the relative affiliation of the Dmanisi mammalian faunas to other faunas in the Old World. Our analysis also allows us to consider hypotheses about the timing and direction of zoogeographic connections between western Eurasia and Africa during the Early Pleistocene. We utilize multiple zoogeographic analytical tools as a cross-comparison of Dmanisi with 42 other Eurasian and African mammalian-bearing localities between 2.7 and 0.7 Ma. Overall, we find that Dmanisi compares most closely with a subgroup of Greek, Italian, and Spanish localities that are slightly younger than Dmanisi itself. This could suggest a progressive dispersal from East to West of the large mammal communities during the late Early Pleistocene and the first occurrence at Dmanisi, and then later in Western Europe, of some taxa such as Stephanorhinus ex gr. etruscus-hundsheimensis, Equus altidens, Bison georgicus, Soergelia minor, Megantereon whitei, Canis borjgali, Canis (Xenocyon) lycaonoides. Dmanisi's habitats included drier areas, probably of open wooded savannah and grassland and by mountainous to semiarid rocky terrain. There is evidence that Dmanisi records short intervals of increased aridity in the middle part of the succession contemporaneous with the occurrence of Homo.


Biocompatible Magnetic Conjugated Polymer Nanoparticles for Optical and Lifetime Imaging Applications in the First Biological Window.
Conjugated polymers are organic semiconductors that can be used for fluorescence microscopy of living specimens. Here, we report the encapsulation of the bright-red-emitting conjugated polymer, poly[{9,9-dihexyl-2,7-bis(1-cyanovinylene)fluorenylene}-alt-co-{2,5-bis(N,N'-diphenylamino)-1,4-phenylene}] (CN-FO-DPD), and superparamagnetic iron oxide nanoparticles (SPIONs) within poly(styrene-co-maleic anhydride) (PSMA) micelles. The resulting particles exhibited an emission peak at 657 nm, a fluorescence quantum yield of 21%, an average diameter of 65 nm, and a ζ potential of -30 mV. They are taken up by cells, and we describe their use in fluorescence microscopy of living Hela cells and zebrafish embryos and their associated cytotoxicity in HEK, HeLa, and HCE cells.


Atypical valuation of monetary and cigarette rewards in substance dependent smokers.
Substance dependent (SD) relative to non-dependent (ND) individuals exhibit an attenuated reward positivity, an electrophysiological signal believed to index sensitivity of anterior cingulate cortex (ACC) to rewards. Here we asked whether this altered neural response reflects a specific devaluation of monetary rewards relative to drug-related rewards by ACC. We recorded the reward positivity from SD and ND individuals who currently smoke, following an overnight period of abstinence, while they engaged in two feedback tasks. In a money condition the feedback indicated either a monetary reward or no reward, and in a cigarette condition the feedback indicated either a drug-related reward or no reward. Overall, cigarette relative to monetary rewards elicited a larger reward positivity. Further, for the subjects who engaged in the money condition first, the reward positivity was smaller for the SD compared to the ND participants, but for the subjects who engaged in the cigarette condition first, the reward positivity was larger for the SD compared to the ND participants. Our results suggest that the initial category of feedback "primed" the response of the ACC to the alternative feedback type on subsequent trials, and that SD and ND individuals responded differently to this priming effect. We propose that for people who misuse addictive substances, the prospect of obtaining drug-related rewards engages the ACC to exert control over extended behaviors.


Meta-iodobenzylguanidine (MIBG), a novel high-affinity substrate for cholera toxin that interferes with cellular mono(ADP-ribosylation).
Meta-iodobenzylguanidine (MIBG) is a guanidine analogue of the neurotransmitter norepinephrine. Radioiodinated [131I]MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. Moreover, non-radiolabelled MIBG exerts several cell-biological effects, tentatively ascribed to interference with cellular mono(ADP-ribosyl) transferases (Smets, L.A., Bout, B. and Wisse, J. (1988) Cancer Chemother. Pharmacol. 21, 9-13; Smets, L.A., Metwally, E.A.G., Knol, E. and Martens, M. (1988) Leukemia Res. 12, 737-743). In the present study it was investigated whether MIBG could serve as an acceptor for the ribosyl transferase activity of cholera toxin and of erythrocyte membranes. MIBG appeared a substrate for the cholera toxin-catalyzed transfer of the ADP-ribose moiety of NAD to arginine-like residues with the highest affinity for this enzyme reported as yet (Km = 6.5 microM). MIBG was also ADP-ribosylated by the mono(ADP-ribosyl)transferase(s) of turkey erythrocyte membranes. Moreover, the drug appeared a potent affector of the ADP-ribose linkage to membrane proteins by these enzymes. Interference by MIBG was stronger than by related guanyltyramine, the monoamine precursors of MIBG, meta-iodobenzylamine had no effect at all. In contrast, the drug failed to affect endogenous, O-linked poly(ADP-ribose) polymerase, induced in nuclei of S49-leukemia cells by deoxyribonuclease. Since MIBG is the first described drug that specifically interferes with the cellular N-linked mono(ADP-ribosyl) transferase reactions, it may be an important tool to elucidate the physiological role of this posttranscriptional protein modification.


Lung, gastric, and soft tissue uptake of Tc-99m MDP and Ga-67 citrate associated with hypercalcemia.
Metastatic calcifications are associated with chronic renal failure, hyperparathyroidism, metastatic neoplasms, hypervitaminosis D, and hypercalcemia of other origins. Bone scanning agents accumulate within these extraskeletal metastatic calcifications. The authors describe two patients with hypercalcemia associated with Tc-99m MDP uptake in the lungs, stomach, and soft tissues. Ga-67 scintigraphy was also performed and showed increased uptake in the same locations as those of Tc-99m MDP, suggesting the existence of an inflammatory process. Despite adequate treatment, only partial resolution of extraskeletal uptake was observed.


Disparities in grant funding for Chronic rhinosinusitis.
The objective of this study was to identify the level of grant funding for chronic rhinosinusitis (CRS) with the purpose of elucidating if disparities exist compared to other common chronic diseases. Review of four major health research grant agencies from the United States (National Institutes of Health), Canada (Canadian Institute of Health Research), and United Kingdom (National Institute of Health Research and Medical Research Council). Research operating grants awarded in the fields of CRS, asthma, diabetes, and dementia were identified using database-specific search strategies. Searches were limited to the previous 10 years (2004-2014). Comparator chronic diseases were chosen to have similar prevalence rates and low mortality risk. Research efficiency was calculated as the monetary value of grants awarded per paper published. There is a large disparity in the number of grants awarded for research in CRS (n = 196; $74,774,384), asthma (n = 13,226; $8,358,861,941), diabetes (n = 54,902; $47,282,739,735), and dementia (n = 34,569; $16,709,900,125). In terms of research efficiency, CRS researchers received eight to 12 times less financial support per paper published compared to those in our comparator conditions. This study has demonstrated that over the last 10 years, CRS is disproportionately underfunded (∼$75 million) compared to other similarly prevalent chronic diseases such as asthma (∼$8.3 billion), diabetes (∼$47.2 billion), and dementia (∼$16.7 billion). We feel this justifies further research into identifying and reducing barriers to obtaining grant support for CRS. NA.


Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.
Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging.


Evaluation of a brushing machine for estimating density of spider mites on grape leaves.
Direct visual inspection and enumeration for estimating field population density of economically important arthropods, such as spider mites, provide more information than alternative methods, such as binomial sampling, but is laborious and time consuming. A brushing machine can reduce sampling time and perhaps improve accuracy. Although brushing technology has been investigated and recommended as a useful tool for researchers and integrated pest management practitioners, little work to demonstrate the validity of this technique has been performed since the 1950's. We investigated the brushing machine manufactured by Leedom Enterprises (Mi-Wuk Village, CA, USA) for studies on spider mites. We evaluated (1) the mite recovery efficiency relative to the number of passes of a leaf through the brushes, (2) mite counts as generated by the machine compared to visual counts under a microscope, (3) the lateral distribution of mites on the collection plate and (4) the accuracy and precision of a 10% sub-sample using a double-transect counting grid. We found that about 95% of mites on a leaf were recovered after five passes, and 99% after nine passes, and mite counts from brushing were consistently higher than those from visual inspection. Lateral distribution of mites was not uniform, being highest in concentration at the center and lowest at the periphery. The 10% double-transect pattern did not result in a significant correlation with the total plate count at low mite density, but accuracy and precision improved at medium and high density. We suggest that a more accurate and precise sample may be achieved using a modified pattern which concentrates on the center plus some of the adjacent area.


Novel compound heterozygous mutations in the SBP2 gene: characteristic clinical manifestations and the implications of GH and triiodothyronine in longitudinal bone growth and maturation.
Mutations in the selenocysteine insertion sequence binding protein 2 gene (SECISBP2 also known as SBP2) lead to a multisystemic disorder. Our objectives are to examine the clinical manifestations of the present patient and evaluate the effects of GH and triiodothyronine (T(3)) for longitudinal bone growth and maturation. A Japanese boy presented with unusual thyroid function tests (normal or slightly elevated TSH, low-normal or slightly decreased free T(3) (FT(3)), and elevated free thyroxine (FT(4))), short stature without GH deficiency, and delayed bone maturation. The entire coding region of the patient's SBP2 was analyzed. GH treatment was initiated when the patient was 4 years old, and combination therapy with GH plus T(3) was started when the patient was 10 years old. We monitored the patient's height and bone age until he was 11 years old. The patient showed typical symptoms of SBP2 deficiency, and novel compound heterozygous mutations were identified in SBP2 (p.M515fsX563/p.Q79X). Six years of GH monotherapy improved the patient's height s.d. from -3.4 to -1.7 without accelerating bone maturation, whereas 6 months of T(3) treatment combined with GH almost normalized the thyroid function tests and improved both longitudinal bone growth and maturation. In the growth plate, GH may compensate for decreased local T(3) effects on longitudinal bone growth; however, GH does not appear to compensate for the effects of T(3) on bone maturation. We believe that the present case has important implications for understanding the mechanism of thyroid hormone and GH on longitudinal bone growth and maturation.


Evolutionary plasticity of methionine biosynthesis.
Methionine is an essential cellular constituent, the initiator of protein synthesis and a precursor in many metabolic activities, such as methylation and formylation. Here we investigate the genomic distribution of the methionine biosynthetic pathway and analyze its evolutionary history by reconstructing the phylogeny of its enzymatic components. We demonstrate the evolutionary complexity of methionine synthesis and describe the various mechanisms that have shaped this biosynthetic pathway: gene duplication, functional reassignment, lateral acquisition and gene loss. Lateral gene transfer within and between domains and gene recruitment have played an important role in the evolution of this pathway, especially in its first and third enzymatic steps--homoserine activation and homocysteine methylation. These analyses are also the basis of predictions regarding methionine synthesis in Archaea, where the pathway is yet to be characterized. This study illustrates how diverse molecular solutions can fulfill a conserved function in living beings.


Rat testis LH/hCG recptors and testosterone production after treatment with GnRH.
Adults male rats were implanted subcutaneously for 1, 2 or 4 days with Alzet osmotic minipumps, infusing synthetic gonadotropin-releasing hormone (GnRH) at a rate of 0.1 microgram/h. Plasma LH increased significantly, reaching a maximum after 2 days treatment. Plasma and testicular testosterone levels increased to a maximum in 1 day, and decreased gradually thereafter, reaching the control level by day 4. Testicular specific [125I]hCG binding decreased gradually during the treatment, being 57% of the controls by day 4. It is concluded that changes of physiologic magnitude in circulatory LH are able to induce a significant loss of testicular LH/hCG binding capacity. Furthermore, after a short stimulatory phase there is a lack of response in testicular steroidogenesis to the elevated LH levels.


Higher serum aldosterone correlates with lower hearing thresholds: a possible protective hormone against presbycusis.
Aldosterone hormone is a mineralocorticoid secreted by adrenal gland cortex and controls serum sodium (Na(+)) and potassium (K(+)) levels. Aldosterone has a stimulatory effect on expression of sodium-potassium ATPase (Na, K-ATPase) and sodium-potassium-chloride cotransporter (NKCC) in cell membranes. In the present investigation, the relation between serum aldosterone levels and age-related hearing loss (presbycusis) and the correlation between these levels versus the degree of presbycusis in humans were examined. Serum aldosterone concentrations were compared between normal hearing and presbycusic groups. Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAE), hearing in noise test (HINT) and gap detection were tested for each subject and compared to the serum aldosterone levels. A highly significant difference between groups in serum aldosterone concentrations was found (p = 0.0003, t = 3.95, df = 45). Highly significant correlations between pure-tone thresholds in both right and left ears, and HINT scores versus serum aldosterone levels were also discovered. On the contrary, no significant correlations were seen in the case of TEOAEs and gap detection. We conclude that aldosterone hormone may have a protective effect on hearing in old age. This effect is more peripheral than central, appearing to affect inner hair cells more than outer hair cells.


Barriers to care and quality of primary care services in children with sickle cell disease.
The aims of this study were: to (1) identify barriers to care in children with sickle cell disease; (2) examine the quality of primary care services received by these children and (3) examine the relationship between barriers to care and quality of primary care services in children with sickle cell disease. Effective management in children with sickle cell disease requires early access to a comprehensive range of preventive screenings, urgent care treatments for vaso-occlusive pain crisis and ongoing prophylactic treatments. A cross-sectional survey of parents of children with sickle cell disease was conducted between April-September 2011. Parents of children with sickle cell disease completed the Barriers to Care Questionnaire and Parent's Perceptions of Primary Care. Parents of children with sickle cell disease (n = 38) reported health system barriers such as inability to contact doctors or clinics, extended wait times and inconvenient clinic hours. Some barriers were reported more frequently among children with concurrent sickle cell disease and asthma, compared with those children without a concurrent asthma condition. Parents who reported more barriers were least likely to perceive their care as accessible, comprehensive and coordinated. Minimizing healthcare barriers may improve the quality of primary care services received by children with sickle cell disease and consequently prevent complications associated with sickle cell disease. Nurses and other care providers need to identify healthcare barriers, so that access, coordination, comprehensiveness and overall quality of primary care services may be improved in children with sickle cell disease.


Local transport kinetics of glucose during acute and chronic nicotine infusion in rat brains.
Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (-10% to -20%) and in nearly all structures during chronic (-39% to -41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.


Positive reactions to gold sodium thiosulfate in patch test panels (TRUE Test) in Japan: A multicentre study.
The proportion of positive test results with gold sodium thiosulfate included in a patch test panel (P-GST) had been found to be greater than that with gold sodium thiosulfate 0.5% pet. by allergEAZE (A-GST). To compare positive reactions to P-GST and A-GST, and to evaluate late reactions after the day (D) 7 reading. A retrospective analysis was performed of 588 patients at participating departments (119 males; 469 females) who were patch tested with P-GST and A-GST in May 2015 to March 2016. Positive test reactions to P-GST and A-GST were observed in 15% and 6% of patients, respectively. Three patients reported a positive reaction occurring after the D7 reading. Gold sodium thiosulfate often gives a positive reaction after 2 to 3 weeks, and, in such cases, the positive reaction may be sustained, so it is recommended to assess the reaction for up to 1 month after application.


Gemcitabine plus vinorelbine as the second-line treatment and beyond in elderly patients with platinum-pretreated advanced non-small cell lung cancer.
The efficacy and tolerance of a gemcitabine and vinorelbine (GV) combination as salvage therapy have not been reported in elderly patients with advanced non-small cell lung cancer (NSCLC). We reviewed elderly patients with advanced NSCLC who had disease progression after one or more chemotherapy regimens, at least one including platinum, and then who were treated with GV as the salvage therapy. In total 40 patients were analyzed. GV was at least the third-line chemotherapy in 24 patients (60.0%). Only 2 patients (5.0%) experienced grade 3 febrile neutropenia. Nonhematologic toxicities were generally mild and there was no treatment-related mortality. Among 29 patients evaluable for treatment response, 10 (34.5%) and 9 (31.0%) achieved a partial response and stable disease, respectively. The median overall survival was 10.3 months and the median progression-free survival was 3.1 months. GV in combination is an effective and tolerable salvage regimen in elderly and heavily pretreated patients with advanced NSCLC.


Rapid evolution of avirulence genes in rice blast fungus Magnaporthe oryzae.
Rice blast fungus Magnaporthe oryzae is one of the most devastating pathogens in rice. Avirulence genes in this fungus share a gene-for-gene relationship with the resistance genes in its host rice. Although numerous studies have shown that rice blast R-genes are extremely diverse and evolve rapidly in their host populations, little is known about the evolutionary patterns of the Avr-genes in the pathogens. Here, six well-characterized Avr-genes and seven randomly selected non-Avr control genes were used to investigate the genetic variations in 62 rice blast strains from different parts of China. Frequent presence/absence polymorphisms, high levels of nucleotide variation (~10-fold higher than non-Avr genes), high non-synonymous to synonymous substitution ratios, and frequent shared non-synonymous substitution were observed in the Avr-genes of these diversified blast strains. In addition, most Avr-genes are closely associated with diverse repeated sequences, which may partially explain the frequent presence/absence polymorphisms in Avr-genes. The frequent deletion and gain of Avr-genes and rapid non-synonymous variations might be the primary mechanisms underlying rapid adaptive evolution of pathogens toward virulence to their host plants, and these features can be used as the indicators for identifying additional Avr-genes. The high number of nucleotide polymorphisms among Avr-gene alleles could also be used to distinguish genetic groups among different strains.


Prognostic stratification and healthcare approach in patients with multiple pathologies.
Polypathological patients constitute a prevalent, fairly homogeneous population, which is characterised by high clinical complexity, substantial vulnerability and significant resource consumption, in addition to high mortality and the need for comprehensive, coordinated care. It is particularly important to establish a reliable prognosis in these patients. It is also extremely useful for professionals involved in the decision-making process for patients and their families in vital planning and their preferences, for strategic health planning in management fields, and for clinical research, by facilitating their incorporation into clinical trials and other intervention studies. Two prognostic instruments stand out in terms of suitability for polypathological patients: PROFUND and PROFUNCTION. The former faithfully stratifies the risk of dying at 12 months and four years and the latter, the risk of suffering a significant functional deterioration at 12 months. In terms of the healthcare approach in patients with multiple pathologies, creating and executing a consensual, personalised action plan that is adapted to the patient's reality is encouraged. The plan will consider the prognosis, and the evidence and viability of interventions; its ultimate aim will be to ensure the synergy and alignment of the health team's goals and strategies with peoples' values and preferences, in order to achieve a more proactive health model focused on supporting patients in their ability to manage their illnesses. In the personalised action plan, the main areas of intervention are: health promotion and prevention; patient and caregiver activation and self-management; activation of a social support network and social support; optimisation of pharmacotherapy; rehabilitation, functional and cognitive preservation measures; and anticipated decision planning.


Vertebral fractures in patients with chronic obstructive pulmonary disease: the EOLO Study.
This study aimed to evaluate the prevalence of vertebral fractures to investigate the determinants of vertebral fracture risk in patients with COPD. The risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and the presence of low values of quantitative ultrasound (QUS) may represent additional risk factors. Chronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. Our study aimed to evaluate the prevalence of vertebral fractures and to investigate the main determinants of vertebral fracture risk in patients with COPD. In 3,030 ambulatory COPD patients (1,778 men and 1,262 women) aged 50 years or over, we evaluated: COPD severity, presence of vertebral fractures on lateral chest X-ray and bone status by using a quantitative ultrasound device. In men there was a strong association between COPD severity and fractures (p < 0.001), conversely in women the association between COPD severity and fractures was at limit (p = 0.049). In men, but not in women, glucocorticoid treatment was significantly associated with vertebral fractures. The patients with high or moderate risk of osteoporosis presented an increased risk of vertebral fracture (OR 2.71; 95% CI 2.04-3.60 and OR 1.54; 95% CI 1.26-1.88, respectively). Logistic regression analysis showed that COPD severity and glucocorticoid treatment, both inhaled and oral, were associated with increased risk of vertebral fractures. In COPD patients the risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and reduced QUS at calcaneous may represent additional risk factors.


Transport of 1-kestose across the tonoplast of Jerusalem artichoke tubers.
The capacity for 1-kestose uptake into the vacuole of fructan storing Jerusalem artichoke tubers was investigated. 1-kestose serves both as building block for fructan initiation and as a fructose donor for chain elongation. Tonoplast vesicles were isolated from actively storing tubers, and their vesicles were capable of transporting sucrose in a manner indicative of a sucrose/H(+) antiport. Under similar conditions, 1-kestose was not taken up by vesicles energized by either a pH jump or in the presence of ATP. When added together at 2 mM, sucrose uptake was not affected by the presence of 1-kestose. The data argues against the possible synthesis of 1-kestose in the cytosol and subsequent transport to the vacuole. The data also presents definite evidence for the existence a mechanism for sucrose accumulation in fructan storing vacuoles.


Contemporary endovascular management of splenic vascular pathologies.
The spleen is a commonly injured organ and the splenic vasculature is also susceptible to inflammation and trauma, often resulting in aneurysm formation. Splenic artery aneurysms carry a high risk of rupture and are associated with high mortality and morbidity. Due to the advances in endovascular techniques and devices, endovascular management of splenic vascular pathologies is now considered a first-line strategy. Endovascular embolisation and advance techniques including balloon- or stent-assisted coil embolisation enables minimally invasive management option while preserving splenic function.


Adenovirotherapy Delivering Cytokine and Checkpoint Inhibitor Augments CAR T Cells against Metastatic Head and Neck Cancer.
In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance the antitumor activity of HER2-specific CAR T cells, which alone are insufficient to cure solid tumors. We tested multiple cytokines in conjunction with PD-L1-blocking antibody and found that Ad-derived IL-12p70 prevents the loss of HER2.CAR-expressing T cells at the tumor site. Accordingly, we created a construct encoding the PD-L1-blocking antibody and IL-12p70 (CAd12_PDL1). In head and neck squamous cell carcinoma (HNSCC) xenograft models, combining local treatment with CAd12_PDL1 and systemic HER2.CAR T cell infusion improved survival to >100 days compared with approximately 25 days with either approach alone. This combination also controlled both primary and metastasized tumors in an orthotopic model of HNSCC. Overall, our data show that CAd12_PDL1 augments the anti-tumor effects of HER2.CAR T cells, thus controlling the growth of both primary and metastasized tumors.


Equivalence of fast flush and square wave testing of blood pressure monitoring systems.
The accurate recording of intraarterial pressure depends upon an appropriate dynamic response of the monitoring system. Generation of a square wave (SW) at the catheter tip is the engineering and in vitro laboratory gold standard. Fast flush (FF) testing is the clinical test of choice. Results from these two test methods have been assumed equal but have not been empirically confirmed. We studied three different 5.1 cm catheter sizes (16 G, 18 G, 20 G Becton Dickinson, Sandy, UT) attached to three different lengths of arterial pressure tubing (36 in, 91.4 cm; 72 in, 182.9 cm; 108 in, 274.3 cm). An arterial recording system was assembled in the standard fashion by attaching a catheter to arterial pressure tubing, which was attached to a transducer (TXX-R, Ohmeda, formerly Viggo-Spectramed, Oxnard, CA) whose signal was recorded by a strip chart recorder (Gould 2400, Rolling Meadows, IL). The system was attached to a pressurized saline flush. The catheter tip was inserted into one port of a pressure generator. With the other port of the pressure generator open to atmosphere, FF tests were performed by activating the flush device of the transducer. Subsequent step response signals from the FF tests were then recorded from which natural frequency (fn) and damping coefficient (zeta) were calculated. Next, square waves were generated by closing the port that was open to atmosphere and attaching a signal generator to a pressure generator. Square waves so generated were recorded as described above and natural frequency and damping coefficients calculated. These procedures were repeated after 0.05 cc of air was introduced in the transducer and repeated again in a system containing a damping device (R.O.S.E., Resonant OverShoot Eliminator, Viggo-Spectramed, Oxnard, CA). There was no significant difference between fn and zeta as calculated from the step response generated from the FF test versus fn and zeta as calculated from the square wave (SW) test in systems without air. However, in systems containing air, fn by FF testing was always less than fn by SW testing for all catheter sizes and extension tubing lengths (p < 0.05). Damping was also always greater by FF testing than by SW testing in systems with air for all catheter sizes and extension tubing lengths (p < 0.05). The R.O.S.E device created marked qualitative differences, although exact fn and zeta could not be quantified. For the characterization of dynamic response of invasive blood pressure monitoring systems, the FF test and SW test yield identical results. However, under certain conditions-air, R.O.S.E device-dynamic response as measured by FF testing was not equivalent to dynamic response as measured by the gold standard-the SW test. Specifically, small amounts of air in fluid-filled invasive blood pressure monitoring systems cause a slightly worse dynamic response as measured by FF testing versus the laboratory gold standard-the SW test.


Control strategies for microplastic pollution in groundwater.
Groundwater is the primary source of water that occurs below the earth's surface. However, the advancement in technology and the increasing population, which lead to the discharge of contaminants such as microplastics (MPs), have an adverse impact on the quality of groundwater. MPs are ubiquitous pollutants that are widely found throughout the world. The maximum abundance of MPs is 4 items/L and 15.2 items/L in groundwater at the specific location of China and USA. Various factors can affect the migration of MPs from soil to groundwater. The occurrence of MPs in water causes serious health issues. Therefore, taking appropriate strategies to control MP contamination in groundwater is urgent and important. This review summarizes the current literature on the migration process of MPs from soil to groundwater along with possible methods for the remediation of MP-polluted groundwater. The main objective of the review is to summarize the technical parameters, process, mechanism, and characteristics of various remediation methods and to analyze strategies for controlling MP pollution in groundwater, providing a reference for future research. Possible control strategies for MP pollution in groundwater include two aspects: i) prevention of MPs from entering groundwater; ii) remediation of polluted groundwater with MPs (ectopic remediation and in-situ remediation). Formulating legislative measures, strengthening public awareness and producing more environment-friendly alternatives can be helpful to reduce the production of MPs from the source. Manage plastic waste reasonably is also a good strategy and the most important part of the management is recycling. The shortcomings of the current study and the direction of future research are also highlighted in the review.


In vivo and in vitro evidences of dehydroepiandrosterone protective role on the cardiovascular system.
Dehydroepiandrosterone (DHEA) and its sulfate ester, Dehydroepiandrosterone Sulfate (DHEA-S) have been considered as putative anti-aging hormones for many years. Indeed, while DHEAS is the most abundant circulating hormone, its concentration is markedly decreased upon aging and early epidemiologic trials have revealed a strong inverse correlation between the hormone concentrations and the occurrence of several dysfunctions frequently encountered in the elderly. Naturally, hormonal supplementation has been rapidly suggested to prevent DHEA (S) deficiency and therefore, age-related development of these pathologies, using the same strategy as estrogen replacement therapy proposed in postmenopausal women. All references were searched using PubMed and the following strategy: our initial selection included all articles in English and we sorted them with the following keywords: "DHEA or DHEA-S" and "heart or vascular or endothelium or cardiovascular disease". The search was limited to neither the publication date nor specific journals. The final selection was made according to the relevance of the article content with the aims of the review. According to these criteria, fewer than 10% of the articles retrieved at the first step were discarded. In this short review, we have focused on the cardiovascular action of DHEA. We started by analyzing evidences in favor of a strong inverse association between DHEA (S) levels and the cardiovascular risk as demonstrated in multiple observational epidemiologic studies for several decades. Then we discussed the different trials aimed at supplementing DHEA (S), both in animals and human, for preventing cardiovascular diseases and we analyzed the possible reasons for the discrepancy observed among the results of some studies. Finally, we presented putative molecular mechanisms of action for DHEA (S), demonstrated in vitro in different models of vascular and cardiac cells, highlighting the complexity of the involved signaling pathways. The identification of the beneficial cardiovascular effects of DHEA (S) and a better understanding of the involved mechanisms should be helpful to develop new strategies or pharmacologic approaches for many lethal diseases in Western countries.


Malignant transformation of intra-cranial epithelial cysts: systematic article review.
Epidermoid and dermoid cysts are among the most benign intra cranial tumors. Their malignant transformation into squamous cell carcinoma is rare. The authors reviewed the literature. MEDLINE and SCIENCE DIRECT searches, and examination of the references in the selected articles yielded 74 patients, 52 of whom fulfilled Garcia's criteria and were selected for the study. Survival analyses were performed to determine whether survival differences were of statistical significance, and P < 0.05 was considered as significant. Malignant transformation is characterized by a rapid onset of symptoms, recurrence, leptomeningeal carcinomatosis (LC), and tumor enhancement at Computed Tomography Scan or Magnetic Resonance Imaging (87.8 showed this radiological feature). In this review, the SCCs were classified in five groups: (1) Initial malignant transformation of a benign cyst; (2) malignant transformation from a remnant cyst; (3) malignant transformation of a dermoid and epithelial cyst; (4) malignant transformation with leptomeningeal carcinomatosis; (5) other malignancies arising from benign cysts. The median survival was 9 months. Statistics show that LC was of poor prognosis and radiotherapy, although not statistically significant, seems effective against such lesions, with a median survival of 26 months as opposed to 3 months (P=0.077). Although rare, malignant transformation of intracranial epithelial cysts has a poor prognosis and surgery followed by radiotherapy seems to be the best therapeutic modality.


Management of endoscopic retrograde cholangiopancreatography-related perforation.
Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation occurs in 0.1-1.8% of patients after therapeutic ERCP. It is a serious complication with a high mortality. However, little evidence exists in the medical literature and the optimal management remains unclear. This review aims to critically evaluate the optimal management of therapeutic ERCP-related perforation.


The role of spatial switching in the attentional blink.
The attentional blink (AB) is a well-established paradigm in which identification of a target T2 is reduced shortly after presentation of an earlier target T1. An important question concerns the importance of backward masking during the AB. While task switching has been found to be a strong modulator mediating the AB without any masking of T2, the present study investigated whether spatial switching could similarly produce an AB without masking. Using a spatial AB paradigm in which items appeared at different locations; we found (a) a significant AB without backward masking of T2 but no AB when no distractors followed T2, (b) no evidence for Lag 1 sparing. These findings show that when there is a spatial switch between the targets, presenting the distractor following T2 at the same location than T2 (backward masking) is not a necessary condition for the AB to occur, but T2 has to be followed by surrounding distractors (appearing at different locations than T2). This pattern of data confirms that spatial switching is a robust modulator of the AB, but to a less extent than task switching.


The star plot: an alternative display method for multivariate data in the analysis of food and drugs.
The star plot (SP) is a method of displaying multivariate data. It can be used to display data with more than two variables. Combined with principal component analysis (PCA), more than two PCs can be displayed in one plane. Different variants of this method are applied to an atomic absorption spectrometry (AAS) data set and to three near infra-red (NIR) spectral data sets. The results show that SP offers an easy way of visualising the multivariate data for food and drugs in a plane, and it is able to help the analyst to identify and to detect different qualities of food and drug composition. Moreover, when an object is added or removed, the PC's must be computed all over again, which is not the case for the SP-plot. The application of SP to the examples presented in the text suggests that the SP approach can be applied as an alternative method for displaying multivariate chemometric data in place of PCA or, to improve visualisation of the results already obtained with PCA.


Delay prior to expedited carotid endarterectomy: a prospective audit of practice.
To identify reasons for delay before carotid endarterectomy (CEA) in a reconfigured "fast-track" system where patients were admitted from the TIA (transient ischaemic attack) Clinic for urgent CEA. Prospective audit in 89 recently symptomatic patients. Ten patients (11%) suffered recurrent symptoms between admission and surgery. Two strokes were sufficiently severe that CEA was cancelled. The median delay from index symptom to CEA was 8 days. 74/87 (85%) underwent CEA <14 days from the index symptom; 39/87 (45%) within 7 days. Forty-five (51%) were ready for CEA <24 hours of admission; 74 (83%) <72 hours. The most common reasons for delay to CEA were logistical, especially a failure to plan for access to weekend operating. Two-thirds of the Tuesday/Friday theatre lists that were reserved for urgent CEAs were actually used for CEA; 27 (33%) were not used for CEA but were utilized for another vascular procedure, and five (4%) were cancelled the day before and went unused. The vast majority of patients (85%) underwent CEA <14 days from the index symptom, but 11% still suffered recurrent symptoms prior to surgery. Transferring patients directly from the TIA Clinic reduced overall delays, but Vascular Units adopting such an approach might then be vulnerable to criticisms regarding prolonged lengths of pre-operative in-patient stay while patients were worked up for theatre. Protected theatre lists both optimized (and delayed) access to CEA, but the most important cause of delay was that we had not planned for weekend operating using specialist anaesthetic and theatre staff.


Vortex dynamics in the two-dimensional BCS-BEC crossover.
The Bardeen-Cooper-Schrieffer (BCS) condensation and Bose-Einstein condensation (BEC) are the two limiting ground states of paired Fermion systems, and the crossover between these two limits has been a source of excitement for both fields of high temperature superconductivity and cold atom superfluidity. For superconductors, ultra-low doping systems like graphene and LixZrNCl successfully approached the crossover starting from the BCS-side. These superconductors offer new opportunities to clarify the nature of charged-particles transport towards the BEC regime. Here we report the study of vortex dynamics within the crossover using their Hall effect as a probe in LixZrNCl. We observed a systematic enhancement of the Hall angle towards the BCS-BEC crossover, which was qualitatively reproduced by the phenomenological time-dependent Ginzburg-Landau (TDGL) theory. LixZrNCl exhibits a band structure free from various electronic instabilities, allowing us to achieve a comprehensive understanding of the vortex Hall effect and thereby propose a global picture of vortex dynamics within the crossover. These results demonstrate that gate-controlled superconductors are ideal platforms towards investigations of unexplored properties in BEC superconductors.


Identification and functional studies of Akirin, a potential positive nuclear factor of NF-κB signaling pathways in the Pacific white shrimp, Litopenaeus vannamei.
As conserved nuclear factors, Akirins play critical roles in regulating antimicrobial peptides (AMPs) transcription downstream of NF-κB dependent signaling pathways in insects and mammals. However, no any functional studies was reported in penaeid shrimp. The identification and functional analysis of Akirin in the Pacific white shrimp, Litopenaeus vannamei were made in this research. The 833 nucleotides cDNA of Litopenaeus vannamei Akirin (LvAkirin) was obtained with an open reading frame of 639 bp, which encodes a putative protein of 212 amino acids. The molecular weight of LvAkirin is about 23.7 kDa with theoretical pI of 9.05. Two predicted nuclear localization signals (NLSs) were found and amino acid sequence alignments showed that Akirins are highly conserved between insects and mammals. The constitutive expression of LvAkirin mRNA was confirmed in all the examined tissues and high level appeared in testis followed by hemocytes and gill. LvAkirin mRNA was strongly induced in response to Vibrio parahaemolyticus infection. Silencing LvAkirin by dsRNA significantly reduced the expression of NF-κB dependent anti-lipopolysaccharide factor, crustin and penaeidin3a as well as transcription factors, Dorsal and Relish post Vibrio anguillarum (V. anguillarum) and Micrococcus lysodeikticus (M. lysodeikticus) challenge. Antibacterial activities of shrimp plasma was analyzed and high cumulative mortality was found in LvAkirin-silenced shrimps post bacteria challenge. Hence, we proposed LvAkirin might function as a positive nuclear factor of NF-κB dependent signaling pathways in shrimp innate immunity.


Intra-amniotic inflammation in human gastroschisis: possible aetiology of postnatal bowel dysfunction.
To assess amniotic fluid for evidence of an inflammatory exudate in association with fetal gastroschisis. University College Hospital, London and Institute of Child Health, London. Samples of amniotic fluid in the third trimester from pregnant women with a diagnosis of fetal gastroschisis (n = 10) and from a control group (n = 10) with a normal fetus. Cytological analysis of the fluid was performed. Flow cytometry was performed on the amniotic fluid using antibodies for the myeloid cell antigen CD15, the leucocyte beta integrin CD11b/CD18 and CD3, CD19, CD56 and CD25. Tumour necrosis factor alpha and interleukin-8 levels were assayed in the amniotic fluid. An acute inflammatory exudate, composed predominantly of neutrophil polymorphs and mononuclear cells, was found in the amniotic fluid in fetal gastroschisis but not in control cases. When amniotic fluid samples from cases of fetal gastroschisis were stained with CD15, analysis by flow cytometry showed a clear positive population. This CD15 population showed markedly elevated levels of CD11b. No distinct population of CD15 positive cells was seen in amniotic fluid samples examined from the control group. No staining was seen with antibodies to CD3, CD19, CD56 or CD25 in amniotic fluid obtained from either group. There was no significant difference between tumour necrosis factor alpha levels measured in the amniotic fluid of cases of fetal gastroschisis (median 102 pg/mL; range 20-340) and those of the control group (140 pg/mL; range 20-548) (P = 0.1). The levels of interleukin-8 were markedly elevated in the amniotic fluid of cases of fetal gastroschisis (median 6320 pg/mL; range 4732-13,800) compared with the control group (median 1738 pg/mL; range 623 2861;) (P < 0.01). Human fetal gastroschisis is associated with an inflammatory exudate in the amniotic fluid which may have implications for postnatal bowel function.


Fragment-specific internal fixation of distal radius fractures.
The treatment of complex, intra-articular distal radius fractures can be challenging. Goals of treatment include the restoration of articular congruity and maintenance of a stable reduction to allow for early range-of-motion, prevention of arthrosis, and ultimately return of upper extremity function. Proper understanding of individual fracture patterns is paramount in achieving these goals and avoiding complications. Through the use of limited surgical incisions and low-profile,anatomically contoured implants, fragment-specific internal fixation provides a rational approach to the treatment of these complex injuries.


Microbial fingerprinting detects unique bacterial communities in the faecal microbiota of rats with experimentally-induced colitis.
An abnormal composition of the gut microbiota is believed to be associated with the pathogenesis of inflammatory bowel disease (IBD). We utilized terminal restriction fragment length polymorphism (T-RFLP) analysis to quantify faecal bacterial communities from rats with experimental colitis. Male Sprague Dawley rats (n=10/group) ingested 2% dextran sulfate sodium (DSS) or water for up to 7 days. Rats were killed and colonic tissues collected for histological analysis. Damage severity score in the distal colon was significantly greater (P<0.001) following DSS consumption compared to controls. T-RFLP faecal bacterial profiles generated with either MspI or CfoI revealed a significant difference (P<0.001) in community composition between healthy and colitic rats, with bacterial composition in healthy rats more variable than in rats with colitis. Operational taxonomic units (OTU: taxonomically related groups of bacteria) associated with either the healthy or colitic state were identified. OTU (116, 226, 360, and 948; CfoI) and (118 and 188; MspI) were strongly associated with untreated healthy rats, while OTU (94, 98, 174, and 384; CfoI) and (94 and 914; MspI) were predominantly associated with DSS-treated colitic rats. Phylogenetic OTU assignment suggested that Bacteroidales and Lactobacillus sp. were predominantly associated with the colitic and healthy rats, respectively. These results show that faecal bacterial profiling is a rapid, sensitive and non-invasive tool for detecting and identifying changes in gut microbiota associated with colitis. Restoring microbial homeostasis by targeting colitis-associated OTU through specific microbiological interventions could form the basis of novel therapeutic strategies for IBD.


Brain imaging in research on anesthetic mechanisms: studies with propofol.
Brain imaging helps to refine our understanding of the anesthetic effect and is providing novel information that result in the formulation of hypotheses. They have shown that anesthetics act on specific structures that have been known to be important for consciousness at large. They have also helped to show that anesthetics act on specific structures regionally, rather than being non-specific, general depressant of the central nervous system (CNS). A constant finding is that the drugs that we use seem to exert their action on specific sites within the CNS. This is true for a wide variety of drugs like midazolam, anesthetic vapors and opiates. The thalamus has consistently shown marked deactivation coincident with the anesthesia-induced loss of consciousness, appearing to be a very important target of anesthetic effect. Additionally, when vibro-tactile or pain stimulation is given, anesthetics significantly effect cortical structures even before loss of consciousness while loss of transmission at the thalamic level seems to coincide with loss of consciousness. Finally, the use of radioligands allow in vivo characterization of anesthetic effects on neurotransmitter systems.


Cancer Immunotherapy: A Simple Guide for Interventional Radiologists of New Therapeutic Approaches.
The therapeutic options in the treatment of cancer therapy have been recently significantly increased with systemic immune-targeted therapies. Novel immunotherapy approaches based on immune checkpoint blockade or engineered cytotoxic T lymphocytes have reached late-stage clinical development, with highly encouraging results. The success of cancer immunotherapy has generated a tremendous interest in further developing and exploring these strategies in combination with other approaches such as radiotherapy and local ablative therapies in oncology. The goal of this review is to discuss current approaches in immunotherapy and provide simple and constructive explanations on their mechanisms of action as well as certain more common and serious toxicities.


[Diagnostic image (279). A man with swelling and crusts on his lower legs and feet].
A 68-year-old man presented with painful swollen legs due to elephantiasis nostras verrucosa.


Elevated neutrophil - to - monocyte ratio as a prognostic marker for poor outcomes in neonatal sepsis.
Neonatal sepsis is one of the leading causes of neonatal death. The aim of this study was to evaluate the value of neutrophil - to - monocyte ratio (NMR) in predicting mortality in neonatal sepsis. In this present retrospective study, a total of 134 neonates with sepsis were included. Baseline laboratory parameters were collected. The best cutoff value of NMR was determined by receiver operating characteristic (ROC) curve. Univariate and multivariate analysis were carried out to survey the predict value of NMR. The results showed that NMR in non-survival group was significantly higher than that in survival group. Results from multivariate analysis showed that high NMR was an independent risk factor for neonatal sepsis (Hazard ratio (HR): 7.519, p = 0.001). ROC displayed that the area under curve (AUC) of NMR was 0.740, sensitivity and specificity of NMR were 80% and 65.8% when 7.65 was selected. NMR could be a promising prognostic factor for neonatal sepsis.


Increasing interhemispheric connectivity between human visual motion areas uncovers asymmetric sensitivity to horizontal motion.
Our conscious perceptual experience relies on a hierarchical process involving integration of low-level sensory encoding and higher-order sensory selection.1 This hierarchical process may scale at different levels of brain functioning, including integration of information between the hemispheres.2-5 Here, we test this hypothesis for the perception of visual motion stimuli. Across 3 experiments, we manipulated the connectivity between the left and right visual motion complexes (V5/MT+) responsible for horizontal motion perception2,3 by means of transcranial magnetic stimulation (TMS).4,5 We found that enhancing the strength of connections from the left to the right V5/MT+, by inducing spike-timing-dependent plasticity6 in this pathway, increased sensitivity to horizontal motion. These changes were present immediately and lasted at least 90 min after intervention. Notably, little perceptual changes were observed when strengthening connections from the right to the left V5/MT+. Furthermore, we found that this asymmetric modulation was mirrored by an asymmetric perceptual bias in the direction of the horizontal motion. Overall, observers were biased toward leftward relative to rightward motion direction. Crucially, following the strengthening of the connections from right to left V5/MT+, this bias could be momentarily reversed. These results suggest that the projections connecting left and right V5/MT+ in the human visual cortex are asymmetrical, subtending a hierarchical role of hemispheric specialization7-10 favoring left-to-right hemisphere processing for integrating local sensory input into coherent global motion perception.


Slow potential-guided radiofrequency catheter ablation in atrioventricular nodal reentrant tachycardia: characteristics of the potential associated with successful ablation.
To examine the characteristics of Haïssaguerre's slow potential (SP) specific to effective catheter ablation of the slow pathway in AV nodal reentrant tachycardia, the properties of SP and its recording site were analyzed in 52 patients who underwent successful SP-guided ablation. The properties of SP included the ratio of the amplitude of SP to that of atrial potential (A)(SP/A), the SP duration, the interval between His-bundle potential (HP) and SP (HP-SP), the interval between A and SP (A-SP), the interval between SP and ventricular potential (V) (SP-V), and the ratio of A-SP to the interval between A and the V (A-SP/A-V). The SP recording site was determined by the ratio of the amplitude of A to that of V (A/V) and by the relative position of the ablation catheter on X ray (right anterior oblique projection), expressed as the ratio of the distance between the coronary sinus ostium and SP site to that between the coronary sinus ostium and HP recording site (relative SP position). Twenty-eight slow pathways were ablated with a single energy application, while the other 24 required applications > or = 2. In all successful applications, SP/A, SP duration, HP-SP, A-SP, SP-V, A-SP/A-V, A/V, and relative SP position were 51% +/- 25%, 28 +/- 5 ms, -11 +/- 9 ms, 57 +/- 25 ms, 68 +/- 13 ms, 46% +/- 9%, 15% +/- 13%, and 51% +/- 13%, respectively. A significant correlation was observed between the relative SP position and A-SP, and between the relative SP position and A-SP/A-V (r = 0.60 and 0.37, respectively), while it was not between the relative SP position and HP-SP, nor between the relative SP position and SP-V. When the characteristics of SP were comparatively analyzed between the effective and ineffective applications in 24 patients in whom applications > or = 2 were required, there was no difference observed in HP-SP, A-SP, SP-V, A-SP/A-V, and A/V. However, SP/A, SP duration, and the relative SP position in the effective applications were all greater than those in the ineffective ones (56% +/- 20% vs 35% +/- 18%, P < 0.001; 29 +/- 4 vs 26 +/- 5 ms, P < 0.01; and 52% +/- 15% vs 33% +/- 11%, P < 0.001, respectively). These results indicate that SP with an amplitude over a half of A amplitude and recorded at the mid-septum of the tricuspid annulus can be a marker for successful slow pathway ablation. Although the local atrial electrogram appears late as the SP recording site shifts to the lower position, the timing of SP relative to HP and V remained unchanged, suggesting that SP is independent of the local atrial activation.


The effect of polyclonal antibody on intracellular calcium increase induced by Mycoplasma hyopneumoniae in porcine tracheal cells.
An investigation was undertaken to assess whether polyclonal convalescent and hyperimmune sera obtained from pigs inhibit Mycoplasma hyopneumoniae induced increases in intracellular calcium [Ca2+](i) in ciliated porcine tracheal cells. Basal [Ca2+](i) in the tracheal cells was 97+/-13 nM (n=22 cells in four experiments) and after exposure to M. hyopneumoniae (300 micro g/mL or 10(11) CCU/mL), [Ca2+](i) increased by 246+/-56 nM within 100 s. After pre-treatment with hyperimmune or convalescent serum, M. hyopneumoniae increased [Ca2+](i) by 196+/-43 and 223+/-65 nM, respectively. It was found that neither hyperimmune nor convalescent serum significantly prevented the increase in [Ca2+](i) compared with M. hyopneumoniae alone. It was concluded that polyclonal antibodies produced by mycoplasma vaccination or exposure to the pathogen do not prevent M. hyopneumoniae-induced increase in [Ca2+](i).


Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.
Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.


A routine method for cytogenetic analysis of small urinary bladder tumor biopsies.
A method that allows routine cytogenetic analysis of small cystoscopic biopsies from urothelial tumors is described. This method is based on prolonged mild collagenase disaggregation, a 12-16 hour culture, and harvesting procedures adapted to give maximal metaphase recovery. In addition to providing a means for cytogenetic studies of small biopsies from urinary bladder tumors, this method provides the advantages of direct preparations, with chromosome morphology and banding sufficient for karyotypic analysis. Conventional cell synchronization techniques, applied to this system, should enable high-resolution banding and optimize analysis.