A complicated way of boiling water: nuclear safety in water history.
Water and nuclear reactors are much closer intertwined than usually perceived. First, water is the source of the steam that drives the turbines of most nuclear power plants around the world. Next to generating electricity, water is the key to preventing accidents in nuclear plants. As uranium keeps on generating heat when the power plant is turned off, its core needs to be cooled continuously. This crucial connection between water and nuclear is focus of the paper. Nuclear safety will appear as relying heavily on earlier knowledge, institutions, and regulatory frameworks, which were related to water. The three parts of this article discuss technologies, actors and risks of nuclear power. Studying water as a resource in a much broader sense than being boiled for steam shows how determining water is to make nuclear power function. As this paper is part of a special issue, Water History in the time of COVID-19, it has undergone modified peer review.


Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives.
Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes.


Early life risk factors of being overweight at 10 years of age: results of the German birth cohorts GINIplus and LISAplus.
To develop a prediction model that quantifies the risk of being overweight at 10 years of age. In total, 3121 participants from the GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISAplus (Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics) German birth cohorts were recruited. We predicted standardized body mass index (BMI) at 10 years of age using standardized BMIs from birth to 5 years. Parental education, family income and maternal smoking during pregnancy were considered as covariates. Linear and logistic regression models were used to evaluate the impact of risk factors on BMI and on being overweight at 10 years of age, respectively. Birth weight, standardized BMI at 5 years (60-64 months) (β=0.77; 95% confidence interval (CI): 0.73-0.81) and maternal smoking during pregnancy were positively associated with standardized BMI at 10 years of age. Standardized BMI and overweight at 5 years were strongest predictors of being overweight at 10 years. Conversely, high parental education conferred a protective effect (β=-0.15; 95% CI: -0.29 to -0.01). Being overweight at 5 years (60-64 months) increased the risk of being overweight at 10 years of age with odds ratios above 10. Among children who were predicted to be overweight at 10 years, cross-validation results showed that 76.8% of female subjects and 68.1% of male subjects would be overweight at 10 years of age. BMI and being overweight at 5 years of age are strong predictors of being overweight at 10 years of age. The effectiveness of targeted interventions in children who are overweight at 5 years of age should be explored.


Rate and predictors of disengagement in an early psychosis program with time limited intensification of treatment.
Service disengagement is a frequent problem in early intervention in psychosis. The goal of this study was to evaluate the rate and variables associated with service disengagement in a three year specialized program that allows treatment intensification on a case to case basis. 328 early psychosis patients were assessed at baseline on a large set of socio-demographic and clinical variables and were followed-up over 36 months. Patients who left the program for reasons related to engagement with care were compared to patients who completed the program. Rates of disengagement were low (6.3%). Patients with lower socio-economic status, who committed offences during the program or with a diagnosis of Schizophreniform/brief psychotic disorder were more likely to disengage from the program. The engagement strategies implemented in the context of our early intervention programs have allowed to keep disengagements to a relatively low level. In this context, only 3 variables emerged to guide adaptation of the intervention in order to improve this already good engagement rate.


The identification of ulcerative plaque with high resolution duplex carotid scanning.
A retrospective study evaluated 50 patients who had pathologically proven intraplaque hemorrhage. The patients were pathologically divided into two groups by the presence or absence of intimal ulcerations. These two groups were then sonographically compared with regard to surface characteristics of the plaque, plaque size, size of the sonolucent area within the plaque, and location of the sonolucent area relative to the intimal surface. No defined sonographic characteristics could be used to separate these two groups of patients with heterogeneous plaques into those who had or did not have ulcerations. Most importantly, merely sonographically evaluating the surface of the plaque to determine if it was smooth or irregular could not be used as a successful means to identify which patients were at risk for ulceration.


Platelet-mimicking nanoparticles co-loaded with W18O49 and metformin alleviate tumor hypoxia for enhanced photodynamic therapy and photothermal therapy.
W18O49-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles (NPs) and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49 from oxidation and immune evasion, and increase the accumulation of W18O49 in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption. As a result, ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced tumor cell apoptosis. Therefore, our work provides a novel strategy for simultaneous enhanced PDT and PTT, which is promising in bioapplication. STATEMENTE OF SIGNIFICANCE: W18O49-mediated photodynamic therapy and photothermal therapy are limited by the poor delivery of nanoparticles to tumors, the easily oxidized property, and tumor hypoxia environment, which will induce tumor treatment failure. Herein, we report the development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49 from oxidation and immune evasion, and increase the accumulation of W18O49 in tumor sites via the passive EPR effect and active adhesion. Metformin can alleviate the tumor hypoxia through reducing oxygen consumption. Hence, ROS and heat generation are both greatly increased. PM-W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced apoptosis. Therefore, our work provides a novel strategy in bioapplication.


Beware Weakening the Ivory Tower of MDT Diagnosis in Interstitial Lung Disease.
Accurate diagnosis of interstitial lung disease (ILD) has always been the cornerstone of ensuring appropriate treatment planning and prognostic discussions with patients [...].


[Haemorrhage and haemostasis in face, visceral cranium, neck and middle ear region (author's transl)].
Head and neck surgery is accompanied by more or less heavy tendency to bleed. Spontaneous bleeding will occur, because of general and local peculiarities depending on the vascularisation of this region. The general part of the paper deals with normal haemostasis and the diagnosis of haemorrhagic diathesis. This part also shows simple surgical measures in order to stop bleeding. The special section of the paper explains bleeding problems by case history. Here mainly complications are shown exceedingly imporant to the ENT Doctor, because of their more common frequency i.e. nose-bleeding, adenotonsillextomy as well as alarming haemorrhage from great vessels of the neck (arrosion bleeding of the carotid artery, lesion due to accidents and following necksurgery).


Salmonella in healthy pigs: prevalence, serotype diversity and antimicrobial resistance observed during 1998-1999 and 2004-2005 in Japan.
To determine prevalence, serotype diversity and antimicrobial resistance of Salmonella in healthy pigs, faecal samples from 6771 pigs on 73 farms collected during 1998-1999 and 2004-2005 were examined. Salmonella isolates were serotyped and tested for susceptibility to 22 antimicrobials: benzylpenicillin, ampicillin, amoxicillin, cefazolin, cephaloridine, gentamicin, kanamycin, streptomycin, fradiomycin, colistin, tetracycline, chlortetracycline, oxytetracycline, chloramphenicol, thiamphenicol, sulfadimethoxine, sulfamethoxazole, sulfamethoxypyridazine, trimethoprim, sulfamethoxazole/trimethoprim, norfloxacin and ofloxacin. Farm-level and pig-level Salmonella prevalences were 35.5% and 2.2% in 1998-1999, and 35.7% and 3.3% in 2004-2005. Prevalence by growth stage was 2.4% for sows, 3.3% for weaned pigs, 2.7% for fattening pigs and 3.8% for finishing pigs. The predominant serotypes identified were Agona (28.4%), Typhimurium (17.9%) and Infantis (16.4%) in 1998-1999, and Typhimurium (32.5%), Anatum (24.6%) and Infantis (13.5%) in 2004-2005. Compared with the 1998-1999 isolates, the 2004-2005 isolates showed significantly higher rates of resistance to all the antimicrobials except tetracyclines (P<0.01 to P<0.05) and resistance to 2 antimicrobials [19.4% (13/67) vs. 39.7% (50/126), P<0.01]. This study provides national estimates of Salmonella prevalence in healthy pigs of different growth stages in Japan.


Pathogen sensing by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is mediated by direct binding to muramyl dipeptide and ATP.
Nucleotide binding and oligomerization domain-containing protein 2 (NOD2/Card15) is an intracellular protein that is involved in the recognition of bacterial cell wall-derived muramyl dipeptide. Mutations in the gene encoding NOD2 are associated with inherited inflammatory disorders, including Crohn disease and Blau syndrome. NOD2 is a member of the nucleotide-binding domain and leucine-rich repeat-containing protein gene (NLR) family. Nucleotide binding is thought to play a critical role in signaling by NLR family members. However, the molecular mechanisms underlying signal transduction by these proteins remain largely unknown. Mutations in the nucleotide-binding domain of NOD2 have been shown to alter its signal transduction properties in response to muramyl dipeptide in cellular assays. Using purified recombinant protein, we now demonstrate that NOD2 binds and hydrolyzes ATP. Additionally, we have found that the purified recombinant protein is able to bind directly to muramyl dipeptide and can associate with known NOD2-interacting proteins in vitro. Binding of NOD2 to muramyl dipeptide and homo-oligomerization of NOD2 are enhanced by ATP binding, suggesting a model of the molecular mechanism for signal transduction that involves binding of nucleotide followed by binding of muramyl dipeptide and oligomerization of NOD2 into a signaling complex. These findings set the stage for further studies into the molecular mechanisms that underlie detection of muramyl dipeptide and assembly of NOD2-containing signaling complexes.


COVID-19 vaccine hesitancy: A narrative review of four South Asian countries.
Vaccine hesitancy remains a global issue, especially within poverty-stricken countries where there's an interplay of financial and non-financial barriers. This narrative review aims to understand attitudes and behaviors toward COVID-19 vaccination in four South Asian countries and make context-specific recommendations to vaccine program drivers and decision-makers. A search was conducted using PubMed and Science Direct, and CINHAL from January 2020 up to May 2022 restricted to the English language for terms: "Afghanistan" OR "Pakistan" OR "India" OR "Bangladesh" in combination with "COVID-19 vaccine" and other related terms. All articles were initially included, and those with relevance were included in the synthesis of this paper. A narrative review was performed for this study. Our narrative review included a total of eighteen studies with a sample size (n = 223-5,237) averaging about 1,325 participants per study conducted. The studies included revealed public hesitancy to receive the COVID-19 vaccine ranging from 6.3 to 56.2% with an average of 31.63% across all eighteen studies. Several reasons were linked to this observation in these four South Asian countries, and the predominant ones included: Insufficient information provided to the general public about the side effects of the vaccines, concerns regarding vaccine safety, and skepticism of vaccine efficacy. Vaccine hesitancy is a global problem within the context of COVID-19, and issues regarding equity, misinformation, and poverty in South Asian countries makes it difficult to meet goals for herd immunity. Policymakers and governments should aim toward financial and non-financial incentives to drive the public toward vaccination.


Translational research: A patient-centered approach to bridge the valley of death.
Animal models have evolved to be a key component of translational research of cancer, and they are now extensively used to test drug candidates, predict drug responses, and essentially drive discovery of cancer biology. However, the model-centric approach has not yielded the expected abundance of treatment advances. We propose that the focus of translational research needs to shift from animal models to human patients, and the goal should be to understand why tumor responses and outcomes are so variable between patients and how it can be predicted at the individual level and thus to generate hypotheses that are more relevant to people than to atypically sensitive animal models.


Protein ubiquitination is regulated by phosphorylation. An in vitro study.
Protein ubiquitination has been implicated in ATP-dependent protein turnover and in a number of biological processes in eukaryotic cells. The ubiquitination activating enzyme, E1, and ubiquitin carrier protein, E2, are two essential enzymes in the protein ubiquitination machinery. Using purified E1 and E2 from rabbit reticulocytes and various protein kinases, which include cAMP-dependent protein kinase, protein kinase C, and protein tyrosine kinase, we demonstrated that E1 is phosphorylated by protein kinase C, with a stoichiometry of 0.65 mol of phosphate/mol of E1, and one of the E2 isoforms, E2(32kDa), is phosphorylated by protein tyrosine kinase to 2 eq of phosphate/mol of protein. Phosphorylation of E1 causes a 2-fold enhancement of its activity as monitored by ubiquitin-dependent ATP in equilibrium PPi exchange. When 1 eq of phosphate was incorporated into E2(32kDa), a 2.4-fold activation was also observed for its activity to catalyze the ubiquitination of histone H2A. The regulatory significance of this finding is discussed.


Lehualides A-D, metabolites from a Hawaiian sponge of the genus Plakortis.
A collection of an undescribed marine sponge of the genus Plakortis yielded four new "polyketide-derived" metabolites, lehualides A-D (1-4). The structures of compounds 1-4 were elucidated by interpretation of spectral data. Compound 2 demonstrated cytotoxicity against an ovarian cancer cell line, while compound 4 was active against both ovarian cancer and leukemia cell lines.


Brain metabolism and specific transport at the blood-brain barrier after portocaval anastomosis in the rat.
The rapid metabolism of [1-14C]butyrate and [2-14C]pyruvate in the brain was studied after intracarotid injection in control rats and rats given an end-to-side portocaval anastomosis (PCA). At 10 or 50 sec after injection there was a 40-50% lowering of the total amount of radioactivity in the brain of operated rats for both compounds. The percentage distribution of label in various metabolic fractions, e.g. amino acids, was unaltered by PCA. The results from the metabolic studies focused on an impaired transport of short chain monocarboxylic acids between blood and brain in rats with a PCA. The brain uptake index (BUI) of acetate, butyrate, pyruvate and glucose was determined by rapid intracarotid injection of the 14C test compound plus 3H2O as a reference marker. At 3 weeks after PCA, transport of all 3 monocarboxylic acids into brain was reduced by 40-50%. The reduction in [2-14C]pyruvate uptake was absent at one week, but thereafter, up to 50 weeks after operation, was consistently present. Eadie-Hofstee analysis of influx at varying substrate concentrations indicated a reduction in Vmax values of pyruvate and butyrate uptake without changes in Km. The calculated influx rate of glucose in operated rats was reduced in direct proportion to the lowering of plasma glucose. Portocaval anastomosis in the rat induces selective changes on substrates that are transported across the blood-brain barrier via a facilitated transport process.


Diversity of the surface properties of Lactococci and consequences on adhesion to food components.
Bacteria possess surface properties, related to their charge, hydrophobicity and Lewis acid/base characteristics, that are involved in the attachment processes of microorganisms to surfaces. Fermentation bulks and food matrixes are complex heterogeneous media containing various components with different physicochemical characteristics. The aim of the present study was to investigate whether (i) bacteria present in a food matrix, interacted physicochemically at their surface level with the other constituents and (ii) the diversity of bacterial surface properties could result in a diversity of microbial adhesion to components and thus in a diversity of tolerance to toxic compounds. The surface properties of 20 lactic acid bacteria were characterized by the MATS method showing their relatively hydrophilic and various basic characteristics. The results obtained from a set of representative strains showed that (i) the strains with higher affinity for apolar solvents adsorbed more to lipids and hydrophobic compounds, (ii) the more the strains adsorbed to a toxic solvent, the less they were tolerant to this solvent. A diversity of bacterial surface properties was observed for the strains in the same species showing the importance of choosing bacteria according to their surface properties in function of technological objectives.


Lack of nitric oxide synthase type 2 (NOS2) results in reduced neuronal apoptosis and mortality following mouse hepatitis virus infection of the central nervous system.
The role of nitric oxide synthase type-2 (NOS2)-derived nitric oxide (NO) in the pathogenesis of mouse hepatitis virus (MHV)-induced central nervous system disease was examined. Infection of NOS2 knockout ((-/-)) and NOS2(+/+) mice with MHV resulted in similar kinetics of viral clearance from the brain and comparable levels of demyelination. MHV-infected NOS2(-/-) mice displayed a marked decrease in mortality as compared to infected NOS2(+/+) mice that correlated with a significant decrease (P < or = 0.001) in the number of apoptotic cells (determined by TUNEL staining) present in the brain. Confocal microscopy revealed that the majority of cells (>70%) undergoing apoptosis were neurons. These studies indicate that NOS2-generated NO contributes to apoptosis of neurons but not demyelination following MHV infection.


A model for mechano-electrical feedback effects on atrial flutter interval variability.
Atrial flutter is a supraventricular arrhythmia, based on a reentrant mechanism mainly confined to the right atrium. Although atrial flutter is considered a regular rhythm, the atrial flutter interval (i.e., the time interval between consecutive atrial activation times) presents a spontaneous beat-to-beat variability, which has been suggested to be related to ventricular contraction and respiration by mechano-electrical feedback. This paper introduces a model to predict atrial activity during atrial flutter, based on the assumption that atrial flutter variability is related to the phase of the reentrant activity in the ventricular and respiratory cycles. Thus, atrial intervals are given as a superimposition of phase-dependent ventricular and respiratory modulations. The model includes a simplified atrioventricular (AV) branch with constant refractoriness and conduction times, which allows the prediction of ventricular activations in a closed-loop with atrial activations. Model predictions are quantitatively compared with real activation series recorded in 12 patients with atrial flutter. The model predicts the time course of both atrial and ventricular time series with a high beat-to-beat agreement, reproducing 96+/-8% and 86+/-21% of atrial and ventricular variability, respectively. The model also predicts the existence of phase-locking of atrial flutter intervals during periodic ventricular pacing and such results are observed in patients. These results constitute evidence in favor of mechano-electrical feedback as a major source of cycle length variability during atrial flutter.


Quality control in aminoacyl-tRNA synthesis its role in translational fidelity.
Accurate translation of mRNA into protein is vital for maintenance of cellular integrity. Translational fidelity is achieved by two key events: synthesis of correctly paired aminoacyl-tRNAs by aminoacyl-tRNA synthetases (aaRSs) and stringent selection of aminoacyl-tRNAs (aa-tRNAs) by the ribosome. AaRSs define the genetic code by catalyzing the formation of precise aminoacyl ester-linked tRNAs via a two-step reaction. AaRSs ensure faithful aa-tRNA synthesis via high substrate selectivity and/or by proofreading (editing) of noncognate products. About half of the aaRSs rely on proofreading mechanisms to achieve high levels of accuracy in aminoacylation. Editing functions in aaRSs contribute to the overall low error rate in protein synthesis. Over 40 years of research on aaRSs using structural, biochemical, and kinetic approaches has expanded our knowledge of their cellular roles and quality control mechanisms. Here, we review aaRS editing with an emphasis on the mechanistic and kinetic details of the process.


Applicability of the UK DCD risk score in the modern era of liver transplantation: A U.S. update.
Careful graft and recipient selection have resulted in improved outcomes in liver transplantation (LT) using donation after cardiac death (DCD) organs. The UK DCD Risk Score was established as a risk stratification tool to guide selection. We evaluated the applicability of the UK DCD Risk Score in a contemporary US cohort of adult DCD LT recipients using the United Network for Organ Sharing registry (2011-2020). A total of 3,899 DCD LTs were included in our study (UK DCD Risk Score 0-5 points: 1,438 [36.9%], 6-10 points: 2,034 [52.2%]; 11-20 points: 427 [11.0%]). Compared to a score of 6-10 points, a score of 0-5 points was associated with decreased risk of graft loss (HR = .79, 95%CI: .68-.93, p = .004), while a score of 11-20 points was associated with increased risk of graft loss (HR = 1.26, 95%CI: 1.01-1.56, p = .04). The 5-year graft survival for patients with risk scores of 0-5, 6-10, and 11-20 were 75.9%, 71.8%, and 66.5%, respectively. The C-statistic for the UK DCD Risk Score in our contemporary cohort was .611. The UK DCD Risk Score demonstrates a more limited ability to differentiate recipient outcomes in the modern era of DCD LT in the US. Acceptable long-term outcomes are achievable for patients stratified to the highest-risk group.


[Effect Of Polyelectrolytes on Catalytic Activity of Alcohol Dehydrogenase].
Fluorescent and optical spectroscopy were used to study the interaction of alcohol dehydrogenase (ADH) with negatively charged polystyrene sulfonate (PSS) and dextran sulfate (DS), as well as positively charged poly(diallyldimethylammonium) (PDADMA). As found, DS and PDADMA did not affect the structural and catalytic enzyme properties. In contrast, PSS slightly decreased the protein self-fluorescence over 1 h of incubation, which is associated with partial destruction of its quaternary (globular) structure. Investigation of the ADH activity with and without PSS showed its dependency on the incubation time and the PSS presence. Sodium chloride (2.0 M and 0.2 M) or ammonium sulfate (0.1 M) added to the reaction mixture did not completely protect the enzyme quaternary structure from the PSS action. However ammonium sulfate or 0.2 M sodium chloride stabilized the enzyme and partially inhibited the negative PSS effect.


Immunosuppressive and monoclonal antibody treatment for myasthenia gravis: A network meta-analysis.
We intended to compare and rank all the immunotherapies including immunosuppressant agents or monoclonal antibodies for myasthenia gravis (MG). A network meta-analysis was performed to synthesize the direct evidence and indirect evidence. Quantitative MG score (QMGS) was defined as the primary outcome. The secondary outcomes included the glucocorticoid reduction and hazard ratios (HR) from the counts of adverse events (AEs). We identified 14 studies including 808 MG patients. For the primary outcome, cyclosporine A (CsA) was hierarchically the best with statistical significances of -1.18 (-1.81, -0.59) vs placebo (PLA), -0.98 (-1.72, -0.23) vs mycophenolate mofetil, and -0.77 (-1.57, -0.032) vs tacrolimus (TAC). When the intervention periods were controlled, both eculizumab (ECZ) of -1.50 (-2.81, -0.18) and CsA of -1.23 (-1.81, -0.64) vs PLA reached a statistical significance. Belimumab and ECZ ranked the most tolerable therapies while CsA of 2.41 (0.58, 10.01) ranked the last vs PLA. These findings demonstrated that ECZ represented the most effective and tolerable therapeutic alternative to be recommended for refractory MG. TAC may be a beneficial therapy to treat MG extensively while the efficacy of CsA and cyclophosphamide may be limited by their multiple or severe AEs.


The impact of cigar pack size and pricing policies on youth and adult cigar use in the US.
Over 250 US localities have adopted cigar pack quantity and price policies. No empirical studies exist on their impact on tobacco use. A quasi-experimental design was used to assess the impact of cigar policies on cigar and cigarette use among (1) Minnesota youth (n=569,528, triennially 2007-2019); (2) New York youth (n=111,236, annually 2000-2020), (3) New York adults (n=62,295, annually 2003-2019), and (4) District of Columbia (DC) adults (n=5027, annually 2015-2019). We estimated the county-level policy coverage for 15 local policies in Minnesota. Differences-in-differences approach was used to compare the policy in NYC with the rest of the state (no policy). We examined changes in DC use before and after policy implementation. Analyses adjust for sociodemographic characteristics. In Minnesota, youth in counties with a greater proportion of the population covered by a policy had lower odds of cigar use (AOR: 0.51; 95% CI: 0.38-0.69). Similarly, adult cigar use in DC declined following policy enactment (AOR: 0.65; 95% CI: 0.46-0.93). Cigarette use also decreased in both Minnesota and DC following policy enactment. However, in New York, the NYC policy did not have a significant impact on cigar use among youth (AOR: 0.95; 95% CI: 0.47-1.93) or adults (AOR: 1.98; 95% CI: 0.85-1.37) in NYC compared to the rest of the state. The only significant effect in NYC was reduced odds for adult cigarette use (AOR: 0.79; 95% CI: 0.68-0.92). Findings suggest regulating cigar packaging could decrease cigar consumption without increasing cigarette consumption, but effects may differ across jurisdictions.


[Semiautomatic sharpener for microtome knives].
An electromechanical drive of the knife frame turning the machine of the model of C1310 into semiautomatic is proposed. A reversive electric motor RD-09 is used as the drive. The modified machine gives a high quality of the cutting edge of knives and excluded the constant presence of a laboratory technician.


Midline Extraperitoneal Approach to Retroperitoneal Lymph Node Dissection in Testicular Cancer: Minimizing Surgical Morbidity.
Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity. To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. Open midline EP-RPLND was performed using a standardized technique. Perioperative and long-term outcomes were analyzed. Complications were graded using the Clavien-Dindo classification. A descriptive analysis using SAS software was performed. A total of 68 patients underwent midline EP-RPLND successfully (98.6%). The median age was 28 yr (range 17-55). On preoperative imaging the size of the retroperitoneal mass or lymphadenopathy was <2cm in 29 patients, 2-4.9cm in 15 patients, and >5cm in 24 patients, of which 19 were >10cm. The median estimated blood loss was 325ml (interquartile range [IQR] 200-612.5). The median number of lymph nodes resected was 36 (IQR 24.5-49); the median number of positive nodes was one (IQR 0-4). The median time for return of bowel function was 2 d (IQR 1-2) and hospital stay 3 d (IQR 3-4). There were no cases of ileus. Eleven patients had 12 (17.6%) 90-d complications. Of these, six (55%) were Clavien grade 1, five (45%) were grade 2, and one was grade 3b (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the post-chemotherapy group. Midline EP-RPLND can be performed safely without compromising the completeness of the resection. This approach is associated with rapid return of bowel function, minimal rates of ileus, and short hospital stay. A midline extraperitoneal approach for retroperitoneal lymph node dissection in testicular cancer is safe and effective and leads to faster return of bowel function and earlier discharge.


Specific mRNAs accumulate in long-wavelength UV-irradiated mouse epidermis.
Total RNA from hairless mice epidermis was analysed by RNA-DNA hybridization on slot blots at various times following irradiation with long-wavelength UV light (UV-B or UV-B plus UV-A). Densitometric scanning of the autoradiographies indicates that the amount of RNA which hybridizes with an Ha-ras DNA probe remains constant for up to 72 h after irradiation. The amount of the transcript which hybridizes to a c-fos DNA probe increases dose dependently from 15 min to 2 h after irradiation. RNA which hybridizes to a tubulin DNA probe accumulates in parallel with the increase in mitotic index associated with the radiation-induced hyperplasia.


Developmental Biology: miRs and Steroids and Growth Control.
The Drosophila miRNA-encoding gene bantam controls cell and tissue growth. A new study now reveals that a large part of its effects on growth could come from its inhibition of the production of the molting hormone ecdysone.


Primary Lymphoepithelial Carcinoma of the Submandibular Gland in A Young Patient: A Case Report.
Lymphoepithelial carcinoma (LEC) is a rare entity of malignancy. It has been associated with Epstein-Barr virus (EBV), and in regions where it is endemic, such as Southeast Asia, EBV is typically associated with nasopharyngeal carcinoma. The incidence of such malignancies in the young population is unusual. Here we report a 17-year-old with a 5-year history of a painless right submandibular mass presenting with a sudden increase in size for one month before surgery. Neck examination revealed a firm right submandibular gland measuring five by five cm, with an irregular surface, non-tender with normal overlying skin. We performed a fine needle aspiration cytology (FNAC), and he underwent computed tomography (CT) scan of the neck. He underwent a right submandibulectomy. Lymph nodes from levels I and II were also removed. The final histopathology was reported as LEC. Following this tissue diagnosis, another follow-up surgery, a modified radical neck dissection, was carried out for locoregional clearance. Postoperatively, he completed chemoradiotherapy treatment and is now on regular follow-up.


Local mobility of nucleic acids as determined from crystallographic data. I. RNA and B form DNA.
The local mobility of DNA and RNA can be described well by a segmented rigid body model in which the phosphates, riboses and bases are treated as independent groups. We have developed a computer program for extracting information about the translational and rotational mobility of these groups from X-ray diffraction data of single crystals of DNA and RNA fragments. We plan to extend our studies from the B DNA helix studied here to A and Z form helices for which diffraction data are available. The mobilities described here may be important in allowing the flexibility necessary for interaction of nucleic acids with proteins, ligands or other nucleic acids, and are crucial to our understanding of the factors governing both structural stability and motion of nucleic acids on a larger scale.


Coacervation with surfactants: From single-chain surfactants to gemini surfactants.
Coacervation is a spontaneous process during which a colloidal dispersion separates into two immiscible liquid phases: a colloid-rich liquid phase in equilibrium with a diluted phase. Coacervation is usually divided into simple coacervation and complex coacervation according to the number of components. Surfactant-based coacervation normally contains traditional single-chain surfactants. With the development of surfactants, gemini surfactants with two amphiphilic moieties have been applied to form coacervation. This review summarizes the development of simple coacervation and complex coacervation in the systems of single-chain surfactants and gemini surfactants. Simple coacervation in surfactant solutions with additives or at elevated temperature and complex coacervation in surfactant/polymer mixtures by changing charge densities, molecular weight, ionic strength, pH, or temperature are reviewed. The comparison between gemini surfactants and corresponding monomeric single-chain surfactants reveals that the unique structures of gemini surfactants endow them with higher propensity to generate coacervation.


Pupillary function in early multiple sclerosis.
Autonomic pupillary function was assessed with pupillometry in 95 mildly or moderately disabled patients with multiple sclerosis (MS) and 81 healthy subjects. The parasympathetic pupillary function was measured as initial diameter (mm), time to minimum diameter (seconds), reflex amplitude (mm), relative reflex amplitude (%), and maximal constriction velocity (mm/seconds). To reflect the sympathetic pupillary function maximal redilatation velocity (mm/seconds), and time of 75% of redilatation (seconds) were measured. Of MS patients 85-99% were within the reference values of healthy subjects. In MS patients the effect of age was observed in the initial diameter, reflex amplitude, and time of 75% redilatation. There were no such age related effects in healthy subjects. In age adjusted analysis the initial diameter and time of 75% redilatation differed significantly from healthy controls. Autonomic pupillary functions were not associated with fatigue, visual defect, or bladder disturbance, as measured by Fatigue Severity Scale, Kurtzke's Functional System Scales, Expanded Disability Status Scale, or the Multiple Sclerosis Functional Composite. Our results suggest that both parasympathetic and sympathetic pupillary functions are disturbed already early in the course of MS. However, the disturbance is not severe at this stage of the disease. The dysfunction is age-dependent and thus possibly related to the dimished remyelination capacity of the central nervous system.


Paralytic poliomyelitis in Italy (1981-85).
Fifteen cases of presumptive poliomyelitis occurring in Italy between 1981-85 were studied in order to differentiate between paralysis caused by poliovirus and that of different etiology. Out of seven confirmed cases three were "temporally associated with vaccination". Three aspects are discussed: the need for a careful differential diagnosis of paralytic cases; the over concern about the problem of vaccine-associated cases: the risk connected with re-importation of wild poliovirus strains.


Effects on mortality of changing trends in the management of burned children in Turkey: eight years' experience.
This retrospective review of data from a single burn centre revealed a sharp decrease in the mortality associated with childhood burn. Between January 1998 and January 2006, 1035 children were admitted to our burn unit in Ankara. The overall mortality was 5.8%, falling from 23% between 1998 and 2000 to 5.6% between 2001 and 2005. Scalds were commonest among the younger and flame and electrical burns among the older children. Flame burns were associated with the largest burned body surface areas and highest mortality rates. Electrical burns remained a major health problem with significant amputation rates and lengths of hospital stay. Candidaemia was a mortal consequence of burn. Renovation of the unit with changes in the management of burn victims from conservative treatment to more up-to-date approaches were associated with improved outcomes.


[Condition of the visual system and school achievements in 6 to 10 years old children from Wielkopolska region as detected by visual screening and questionnaire studies].
The study aimed at comparing results of the visual screening with school achievements and results of questionnaire studies. Basic optometric tests, including visual acuity, phoria, stereo near vision, colour vision, near point of convergence and plus lens test were examined in 1138 children, 6 to 10 years of age, 88 pupils were examined in their glasses. Also questionnaire studies were conducted among parents and teachers, related to visual condition of studied children. For every of the children data were obtained on his/her school achievements. A relationship was demonstrated between visual complaints and results of the visual screening and also between school achievements and vision screening results. The results corroborate the assumption that school achievements require efficient visual system in near and distant vision. Proper condition of the visual system exerts significant effects on educational and perceptive functions of a child.


Isoproterenol-induced mortality and cardiac lipids of aspirin-pretreated rats with various fat intakes.
The effect of altering cardiac concentrations of precursors and inhibitors of prostaglandin synthesis by varying fat intake was determined in rats injected with the cardiotoxic drug isoproterenol, following pretreatment with aspirin or potassium phosphate buffer solution. Prior to injection, four groups of rats were fed either a low-fat diet (3.7 energy percent coconut oil or 3.7 energy percent safflower oil) or a high-fat diet (3.7 energy percent safflower oil-36.4 energy percent coconut oil mixture or 40.1 energy percent safflower oil.) Mortality as well as fatty acid composition of cardiac lipids changed in response to altered kinds and amounts of fats. Mortality and cardiac C20:4/C22:6 ratio were lowered by feeding 3.7 energy percent coconut oil, and increased by feeding 40.1 energy percent safflower oil. Aspirin reduced mortality in rats fed 40.1 energy percent safflower oil, but not in rats fed other diets. Results suggest that dietary manipulations which increase tissue content of polyunsaturated fatty acids of the n-6 type relative to those of n-3 type may increase sensitivity to isoproterenol, and that effectiveness of aspirin in reducing isoproterenol-induced mortality depends upon the n-6/n-3 ratio of cardiac fatty acids.


Complete Second Branchial Cleft Fistulas: A Clinicosurgical Experience.
A complete second branchial fistula is very rare and has an internal opening at the tonsillar fossa and an external opening at the lower third of the sternocleidomastoid (SCM). Patients commonly present with persistent or intermittent mucoid or mucopurulent discharge from an external opening. The diagnosis is most often clinical and radiological investigations are rarely needed. Treatment of choice is complete surgical excision. The aim of this article is to aware young ENT surgeons of the various clinical and intraoperative surgical findings that can be encountered while dealing with these cases. This observational study was done for a period of 10 years. A total of 20 cases of fistula were included which intraoperatively had a complete track from tonsillar fossa to neck. Excision of the tract was carried out via combined transcervical and transoral approach under general anaesthesia using two incisions in stepladder pattern. Each patient was seen after one year of surgery to assess for any recurrence. Different findings of patients including age/sex at surgery, initial presentation, family history, laterality of the fistula tract, Intraoperative surgical findings, complications, and recurrences. were noted. Of the 20 patients, 13 (65%) were females and 7 (35%) were Females. Most common complaint was fistulous opening with intermittent discharge(15patients; 75%).Branchial cleft fistulae more commonly affected the right neck (14 patients, 78%) among unilateral cases and 2 patients (10%) had bilateral fistulae. No patient had associated congenital anomaly/syndrome, family history or and visible opening in tonsillar area. Glossopharyngeal nerve was identified in 12 cases and track was seen passing lateral to it except in one case. The internal opening of track was seen over posterior tonsillar pillar in 15 cases (75%) while in 5 patient the track was seen entering tonsillar tissue or bed. Tonsillectomy was done in 5 cases while not done in 15 cases where track was seen entering posterior pillar. All patients were seen at one year follow up. No recurrence was seen at one year of follow up. Complete second branchial cleft fistulae are rare. They are usually right sided and unilateral. The track passes between carotid bifurcation and invariably passes lateral to both glossopharyngeal and hypoglossal nerves. Track usually ends at the posterior tonsillar pillar. Tonsillectomy is not routinely indicated. Recurrences are not typically seen.


Identifying and tracking mobile elements in evolving compost communities yields insights into the nanobiome.
Microbial evolution is driven by rapid changes in gene content mediated by horizontal gene transfer (HGT). While mobile genetic elements (MGEs) are important drivers of gene flux, the nanobiome-the zoo of Darwinian replicators that depend on microbial hosts-remains poorly characterised. New approaches are necessary to increase our understanding beyond MGEs shaping individual populations, towards their impacts on complex microbial communities. A bioinformatic pipeline (xenoseq) was developed to cross-compare metagenomic samples from microbial consortia evolving in parallel, aimed at identifying MGE dissemination, which was applied to compost communities which underwent periodic mixing of MGEs. We show that xenoseq can distinguish movement of MGEs from demographic changes in community composition that otherwise confounds identification, and furthermore demonstrate the discovery of various unexpected entities. Of particular interest was a nanobacterium of the candidate phylum radiation (CPR) which is closely related to a species identified in groundwater ecosystems (Candidatus Saccharibacterium), and appears to have a parasitic lifestyle. We also highlight another prolific mobile element, a 313 kb plasmid hosted by a Cellvibrio lineage. The host was predicted to be capable of nitrogen fixation, and acquisition of the plasmid coincides with increased ammonia production. Taken together, our data show that new experimental strategies combined with bioinformatic analyses of metagenomic data stand to provide insight into the nanobiome as a driver of microbial community evolution.


Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity.
The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC50) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells.


Fatal visceral larva migrans from Toxocara catis infection of the heart and liver in a child.
We discuss the pathophysiology and epidemiology of Toxocara catis infection complicated by visceral larval migrans . We describe a previously healthy 19-month-old white male child found dead in bed by his mother. He had what was thought to be an upper respiratory infection for several days.The child had eosinophilic hepatitis and myocarditis complicating visceral larval migrans due to Toxocara catis infection from the family cat. We discuss the pathologic and clinical aspects of visceral larval migrans due to of Toxocara catis infection.


Parameter optimization in a finite element mandibular fracture fixation model using the design of experiments approach.
Only a few mandibular bone finite element (FE) models have been validated in literature, making it difficult to assess the credibility of the models. In a comparative study between FE models and biomechanical experiments using a synthetic polyamide 12 (PA12) mandible model, we investigate how material properties and boundary conditions affect the FE model's accuracy using the design of experiments approach. Multiple FE parameters, such as contact definitions and the materials' elastic and plastic deformation characteristics, were systematically analyzed for an intact mandibular model and transferred to the fracture fixation model. In a second step, the contact definitions for the titanium screw and implant (S-I), implant and PA12 mandible (I-M), and interfragmentary (IF) PA12 segments were optimized. Comparing simulated deformations (from 0 to -5 mm) and reaction forces (from 10 to 1'415 N) with experimental results showed a strong sensitivity to FE mechanical properties and contact definitions. The results suggest that using the bonded definition for the screw-implant contact of the fracture plate is ineffective. The contact friction parameter set with the highest agreement was identified: titanium screw and implant μ = 0.2, implant and PA12 mandible μ = 0.2, interfragmentary PA12 mandible μ = 0.1. The simulated reaction force (RMSE = 26.60 N) and surface displacement data (RMSE = 0.19 mm) of the FE analysis showed a strong agreement with the experimental biomechanical data. The results were generated through parameter optimization which means that our findings need to be validated in the event of a new dataset with deviating anatomy. Conclusively, the predictive capability of the FE model can be improved by FE model calibration through experimental testing. Validated preoperative quasi-static FE analysis could allow engineers and surgeons to accurately estimate how the implant's choice and placement suit the patient's biomechanical needs.


High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis.
To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p < 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p = 0.002). P4HA2 expression was significantly higher in female cases than in male cases (p = 0.049) and was related to lymph node metastasis (p = 0.019) and a higher TNM stage (p = 0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4. P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target.


Structural and ultrastructural characteristics of interrenal gland and chromaffin cell of matrinxã, Brycon cephalus Gunther 1869 (Teleostei-Characidae).
This work presents the structure and ultrastructure of the interrenal gland and chromaffin cells, as well as the morphology of the head kidney of Brycon cephalus. The head kidney is composed of fused bilateral lobes located anterior to the swim bladder and ventrolateral to the spinal column. The parenchyma revealed lympho-haematopoietic tissue, melano-macrophage centres, interrenal gland and chromaffin cells. The interrenal gland consisted of cords or strands of cells grouped around the posterior cardinal vein and their branches. Chromaffin cells are found in small groups, closely associated with the interrenal gland and/or under the endothelium of the posterior cardinal vein. So far, the ultrastructural analysis has revealed only one interrenal cell type which contained abundant smooth endoplasmic reticulum and numerous mitochondria with tubulo-vesicular cristae, characteristic of steroid-producing cells. Two types of chromaffin cells were observed. The first type was characterized by the presence of vesicles with round, strongly electron-dense granules, which were eccentrically located. Such cells were interpreted as noradrenaline cells. Meanwhile, cells which contained smaller vesicles and electron-lucent granules, with a small halo separating the granule from the vesicular limiting membrane, were identified as adrenaline cells.


Quinpirole-induced behavioral sensitization is enhanced by prior scheduled exposure to sucrose: A multi-variable examination of locomotor activity.
Sensitization of dopaminergic neural reward circuits has been hypothesized to be involved in the development of drug addiction. Highly palatable foods activate these same brain areas, specifically the nucleus accumbens. In this study, the effects of a highly palatable food (sucrose) on these circuits were investigated using the dopamine D(2)/D(3) receptor agonist quinpirole. Male Long-Evans rats received 30 min daily access to 0.3 M sucrose solution or water over nine consecutive days, followed by nine daily injections of quinpirole (0.5 mg/kg, s.c.) or saline. Locomotor activity was assessed using an automated open-field system. Locomotor sensitization developed, as quinpirole-treated rats traveled significantly more, and exhibited a greater number of movements than saline controls. A characteristic pattern of an initial suppression of locomotor activity, followed by excitation of activity was observed in quinpirole-treated rats. Pre-exposure to sucrose attenuated the initial suppression of activity, and facilitated excitation of activity. Rats that were pre-exposed to sucrose exhibited a reduced suppression of activity as compared to rats pre-exposed to water. Rats receiving sucrose and quinpirole also displayed a significantly greater enhancement of locomotor activity as compared to rats receiving water and quinpirole. These results support the hypothesis that highly palatable foods can alter the same neural reward circuits as drugs of abuse, and may facilitate sensitization-related addiction. This may aid in further understanding the neural basis of eating disorders.


On the use of nonrigid-molecular symmetry in nuclear motion computations employing a discrete variable representation: A case study of the bending energy levels of CH5.
A discrete-variable-representation-based symmetry adaptation algorithm is presented and implemented in the fourth-age quantum-chemical rotational-vibrational code GENIUSH. The utility of the symmetry-adapted version of GENIUSH is demonstrated by the computation of seven-dimensional bend-only vibrational and rovibrational eigenstates of the highly fluxionally symmetric CH5+ molecular ion, a prototypical astructural system. While the numerical results obtained and the symmetry labels of the computed rovibrational states of CH5+ are of considerable utility by themselves, it must also be noted that the present study confirms that the nearly unconstrained motion of the five hydrogen atoms orbiting around the central carbon atom results in highly complex rotational-vibrational quantum dynamics and renders the understanding of the high-resolution spectra of CH5+ extremely challenging.


Warfarin-induced skin necrosis: an entity occasionally requiring burn wound expertise.
We describe a severe case of warfarin-induced skin necrosis with extensive full-thickness tissue loss involving approximately 12 per cent of the body surface area. The early management was conservative, with wound observation only, and no aggressive débridement was attempted. Wound and associated systemic sepsis followed, and the patient was transferred to our burn unit. The wounds were then managed with aggressive therapy including surgical excision, temporary coverage with allograft, and final closure with split-thickness autograft. This case illustrates important principles of appropriate surgical management of extensive skin lesions of this type.


Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K(+) channel activation and decrease in cytosolic calcium concentration.
Flavonoid galetin 3,6-dimethyl ether (FGAL) has been isolated from the aerial parts of Piptadenia stipulaceae and has shown a spasmolytic effect in guinea pig ileum. Thus, we aimed to characterize its relaxant mechanism of action. FGAL exhibited a higher relaxant effect on ileum pre-contracted by histamine (EC50=1.9±0.4×10(-7) M) than by KCl (EC50=2.6±0.5×10(-6) M) or carbachol (EC50=1.8±0.4×10(-6) M). The flavonoid inhibited the cumulative contractions to histamine, as well as to CaCl2 in depolarizing medium nominally Ca(2+)-free. The flavonoid relaxed the ileum pre-contracted by S-(-)-Bay K8644 (EC50=9.5±1.9×10(-6) M) but less potently pre-contracted by KCl or histamine. CsCl attenuated the relaxant effect of FGAL (EC50=1.1±0.3×10(-6) M), but apamin or tetraethylammonium (1mM) had no effect (EC50=2.6±0.2×10(-7) and 1.6±0.3×10(-7) M, respectively), ruling out the involvement of small and big conductance Ca(2+)-activated K(+) channels (SKCa and BKCa, respectively). Either 4-aminopyridine or glibenclamide attenuated the relaxant effect of FGAL (EC50=1.8±0.2×10(-6) and 1.5±0.5×10(-6) M, respectively), indicating the involvement of voltage- and ATP-sensitive K(+) channels (KV and KATP, respectively). FGAL did not alter the viability of intestinal myocytes in the MTT assay and decreased (88%) Fluo-4 fluorescence, indicating a decrease in cytosolic Ca(2+) concentration. Therefore, the relaxant mechanism of FGAL involves pseudo-irreversible noncompetitive antagonism of histaminergic receptors, KV and KATP activation and blockade of CaV1, thus leading to a reduction in cytosolic Ca(2+) levels.


Spinal injuries in belt-wearing car occupants killed by head-on collisions.
In 34 post-mortem examinations of car occupants wearing seat belts and killed in straight or oblique head-on collisions, a thorough investigation of the spine was performed. The autopsy results were correlated with the findings in the cars in order to reconstruct the events when the occupant's body struck the interior of the car. In 2 cases the victims had worn lap belts, in 15 cases shoulder belts and in 17 cases combined shoulder-lap belts (three-point belts). In victims involved in head-on collisions while wearing lap belts, fractures of the neural arch of the axis were found which were probably due to flexion of the neck pivoting round the lower part of the impacting face and simultaneous stretching of the neck. Severe injuries to the cervical spine in those victims wearing shoulder belts were mainly due to the occupant sliding under the belt which then caught the neck and mandible. Such injuries were also caused by the impact of the head against forward parts of the car. In those wearing shoulder-lap belts injuries to the upper part of the cervical spine resulted from the impact of the head against internal parts of the car. When a slight impact of the head occurred minor injuries to the lower cervical spine were seen. Injuries to the thoracolumbar spine in the cases examined were the consequence of a violent extension between the upper part of the trunk held back by the shoulder belt and the pelvis restrained by the lap belt or by the knees striking the fascia panel. In front seat occupants this extension can be increased if either rear seat occupants without belts or heavy objects on the rear seat are projected forwards against their backs.


Isolation of actinobacterial endophytes from wheat sprouts as biocontrol agents to control seed pathogenic fungi.
Seed-borne Streptomyces can transmit vertically from generation to generation and be a mutualism between the endosymbionts and hosts. The aim of this study was to isolate and characterize endophytic Streptomyces strains from wheat sprouts, and to investigate their protection against wheat seed pathogenic fungi Penicillium. Endophytic Streptomyces sp. F6 and Streptomyces sp. F39 were isolated from wheat sprouts germinated under sterile conditions. Both Streptomyces strains could produce siderophores, and showed antagonistic activities against the seed pathogenic fungi Penicillium sp. Z17. The inoculation of Streptomyces sp. F39 and F6 could protect wheat seed germination and promote seedling growth under Penicillium sp. Z17 infection. However, the protection efficiency was impacted by the Streptomyces spore concentrations, the concentration ratios of Streptomyces spores to pathogen spores, and inoculation methods. The results suggested that wheat sprouts harbored diverse endophytic Streptomyces species which derived from wheat seeds, these strains should be more likely transmitted to the next generation, and confer competitive ability to pathogens on the offspring. Owing to the more intimate correlation between sprout endophytic flora with host plants, these strains are more suitable for mature plant interiors compared with those from rhizosphere soils and root interiors.


Investigating intra-individual variability of face scanning in autistic children.
Atypical face scanning is suggested to be related to social interactions and communicative deficits in autistic children. We systematically examined whether autistic and non-autistic children used consistent scanning patterns when performing different tasks and scanning different types of faces. We found that autistic children scanned faces more variably than non-autistic children: While non-autistic children used more consistent scanning patterns, autistic children's scanning patterns changed frequently when watching different faces. Autistic children's variable face scanning patterns might delay and impair face processing, resulting in a social interaction deficit. What's more, variable scanning patterns may create an unstable and unpredictable perception of the environment for autistic children. Developing in such an unstable environment might motivate autistic children to retract from the environment, avoid social interaction, and focus instead on the performance of repetitive behavior. Therefore, studying face scanning variability might represent a new avenue for understanding core symptoms in autistic people.


Primary pulmonary hyalinizing clear cell carcinoma with vocal-cord squamous cell carcinoma: a case report with systematic review.
Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland-type carcinoma. Until now, 23 cases of pulmonary HCCC have been reported. Here, we present a patient with primary pulmonary HCCC along with vocal-cord squamous cell carcinoma (SCC) revealed by biopsy examination. The patient underwent radiotherapy for vocal-cord SCC, followed by right upper lobectomy and lymph node dissection 10 months later. Histology revealed polygonal cells with eosinophilic or clear cytoplasm in the myxoid matrix together with hyaline degeneration. The tumor involved the whole layer of the segmental bronchus and regionally involved the alveolar tissue along with one intrapulmonary lymph node. Targeted RNA sequencing revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1)- activating transcription factor 1 (ATF1) fusion. We analyzed the data on pulmonary malignant tumors between 2000 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database and reviewed all cases of pulmonary HCCC with EWSR1 fusion by searching PubMed. The results showed that head and neck (HN) adenoid cystic carcinoma (ACC) (47.89%) and HNSCC (22.54%) were the most common carcinomas occurring with pulmonary salivary gland-type malignant tumors. Screening of 24 cases of pulmonary HCCC with EWSR1 fusion revealed that five cases demonstrated lymph node metastases and only two had documented tumor recurrences. HCCC is rare and easily misdiagnosed as SCC, but the treatment regimen differs between pulmonary HCCC and SCC. Hence, pulmonary tumors with clear cells must be diagnosed with caution. Next-generation sequencing (NGS) may be useful for diagnosis, especially in cases with a history of squamous cell carcinoma (SCC).


Advances in musculoskeletal tumor imaging.
In the last 2 decades, there has been a dramatic change in the clinical approach to the tumors of the musculoskeletal system. The role of medical imaging in diagnosis, staging,and eventual follow-up of patients who have musculoskeletal neoplasia has expanded. This article presents an overview of the role of imaging, recent advances in technology,and state-of-the-art techniques for evaluating musculoskeletal neoplasms. Conventional imaging modalities, ultrasound, CT, MRI, positron emission tomography, and image-guided interventions are discussed.


The Five-Year Effect of a Single Zoledronate Infusion on Bone Mineral Density Following Denosumab Discontinuation in Women with Postmenopausal Osteoporosis.
The long-term effects of zoledronate treatment in women with postmenopausal osteoporosis who stop denosumab therapy when they become osteopenic are not known. In a prospective, randomized, controlled clinical trial we previously reported that a single intravenous infusion of zoledronate 5 mg given to such patients 6 months after the last denosumab injection effectively prevents bone loss in the majority of them for up to 3 years. The study was extended for an additional 2 years and included all 19 patients from one Trial Site of the total 27 patients originally randomized in the zoledronate arm. Baseline characteristics of this cohort treated with denosumab for 2.4 ± 0.2 years were not different from those of the whole initial cohort or from the patients who did not participate in this extension. At the end of 5 years 7 patients had become again osteoporotic requiring additional treatment, 9 remained osteopenic while 3 did not complete the study extension. Thus, more than half of the osteoporotic women who became osteopenic with denosumab treatment and stopped it, maintained the BMD gains 5 years after a single zoledronate infusion with no additional treatment. Whether these results are also applicable to patients treated with denosumab for longer periods remains to be established.


On Ramanujan's definition of mock theta function.
In his famous "deathbed" letter, Ramanujan "defined" the notion of a mock theta function and offered some examples of functions he believed satisfied his definition. Very recently, Griffin et al. established for the first time that Ramanujan's mock theta functions actually satisfy his own definition. On the other hand, Zwegers' 2002 doctoral thesis [Zwegers S (2002) Mock theta functions. PhD thesis (Univ Utrecht, Utrecht, The Netherlands)] showed that all of Ramanujan's examples are holomorphic parts of harmonic Maass forms. This has led to an alternate definition of a mock theta function. This paper shows that Ramanujan's definition of mock theta function is not equivalent to the modern definition.


Laser-flash photolysis indicates that internal electron transfer is triggered by proton uptake by Alcaligenes xylosoxidans copper-dependent nitrite reductase.
Enzyme-catalysed electron transfer reactions are often controlled by protein motions and coupled to chemical change such as proton transfer. We have investigated the nature of this control in the blue copper-dependent nitrite reductase from Alcaligenes xylosoxidans (AxNiR). Inter-Cu electron transfer from the T1Cu site to the T2Cu catalytic site in AxNiR occurs via a proton-coupled electron transfer mechanism. Here we have studied the kinetics of both electron and proton transfer independently using laser-flash photolysis for native AxNiR and its proton-channel mutant N90S. In native AxNiR, both inter-Cu electron transfer and proton transfer exhibit similar rates, and show an unusual dependence on the nitrite concentration. An initial decrease in the observed rates at low nitrite concentrations is followed by an increase in the observed rates at high nitrite concentrations (> 5 mm). In N90S, in which the T1Cu reduction potential is elevated by 60 mV, no inter-Cu electron transfer or proton transfer was observed in the absence of nitrite. Only in the presence of nitrite were both processes detected, with similar [nitrite] dependence, but the nitrite dependence was different compared with native enzyme. The substrate dependence in N90S was similar to that observed in steady-state assays, suggesting that this substitution resulted in proton-coupled electron transfer becoming rate-limiting. A pH perturbation experiment with native AxNiR revealed that protonation triggers inter-Cu electron transfer and generation of NO. Our results show a strong coupling of inter-Cu electron transfer and proton transfer for both native AxNiR and N90S, and provide novel insights into the controlled delivery of electrons and protons to the substrate-utilization T2Cu active site of AxNiR.


The use of insulin in diabetes mellitus.
1. The DNA structure of human insulin is very similar to animal insulin. 2. Many insulin preparations are available in order to achieve the best possible control. 3. Care needs to be taken with regard to insulin administration in order to avoid complications.


Matrix metalloproteinases in cardiovascular disease.
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are regulated by inflammatory signals to mediate changes in extracellular matrix. Members of the MMP family share sequence homology, act on interstitial protein substrates, acutely participate in inflammatory processes and chronically mediate tissue remodelling. MMPs are important in vascular remodelling, not only in the overall vasculature architecture but also, more importantly, in the advancing atherosclerotic plaque. MMP activation modifies the architecture of the plaque and may directly participate in the process of plaque rupture. MMPs also participate in cardiac remodelling following myocardial infarction and development of dilated cardiomyopathy. Soluble MMPs are now potential biomarkers in delineating cardiovascular risk for plaque rupture and coronary risk. They also constitute innovative direct or indirect targets to modify cardiovascular tissue remodelling in atherosclerosis and heart failure.


Contemporary performance of U.S. teaching and nonteaching hospitals.
To compare the performance of U.S. teaching and nonteaching hospitals using a portfolio of contemporary, publicly reported metrics. The authors classified acute care general hospitals filing a Medicare Institutional Cost Report according to teaching intensity: nonteaching, teaching, or Council of Teaching Hospitals member. They compared aggregate results across categories for Hospital Compare process compliance, mortality, and readmission rates (acute myocardial infarction [AMI], heart failure, pneumonia); Surgical Care Improvement Project (SCIP) performance; compliance with Leapfrog standards; patient experience; patient services and key technologies; safety (computerized physician order entry, intensive care unit staffing, National Quality Forum safe practices, hospital-acquired conditions); and cost/resource utilization (Medicare-adjusted expense per case; Leapfrog efficiency and resource use standards). Availability of patient services and advanced technologies were associated with teaching intensity (P < .0001), as were most hospital safety metrics. Teaching intensity was favorably associated with SCIP performance, AMI and heart failure process scores, and mortality (P < .0001). It was unfavorably associated with higher AMI and pneumonia readmission rates (P < .0001) and lower scores for individual patient satisfaction measures. Costs per case were similar (P = .4194) across hospital categories after correction for federally allowed adjustments (case mix, wages, and low-income patient care). Teaching hospitals offer advanced clinical capabilities, educate the next generation of providers, care for disadvantaged urban populations, and are leaders in health care research and innovation. However, many stakeholders may be unaware of an additional value-relatively higher quality and safety in many areas, with similar adjusted costs.


Gender Distribution and Trends of Ophthalmology Subspecialties, 1992-2020.
To describe the gender trends in ophthalmology primary practice areas using the American Board of Ophthalmology (ABO) diplomates. A trend study plus a cross-sectional study of the ABO's database. The de-identified records of all (N = 12,844) ABO-certified ophthalmologists between 1992 and 2020 were obtained. The year of certification, gender, and self-reported primary practice for each ophthalmologist was recorded. Subspecialty was defined as the self-reported primary practice emphasis. Practice trends of the entire population and the subpopulation of subspecialists were explored based on gender and were then visualized using tables and graphs and analyzed using the χ2 or Fisher exact test. A total of 12,844 board-certified ophthalmologists were included. Nearly half (47%) reported a subspecialty as their primary practice area (n = 6042), of whom the majority were male (65%, n = 3940). In the first decade, men outnumbered women reporting subspecialty practices by more than 2:1. Over time, the number of women subspecialists increased whereas the number of men remained stable, such that by 2020 women comprised almost half of new ABO diplomates reporting subspecialty practice. When all subspecialists were compared within gender, there was not a significant difference (P = .15) between the percentage of male (46%) and female (48%) ophthalmologist reporting a subspecialty practice. However, a significantly greater proportion of women than men reported primary practice in pediatrics (20.1% vs 7.9%, P < .001) and glaucoma (21.8% vs 16.0%, P < .0001). Alternatively, a significantly greater proportion of men reported primary practice in vitreoretinal surgery (47.2% vs 22.0%, P < .0001). There was no significant difference between the proportion of men and women reporting cornea (P = .15) or oculoplastics (P = .31). The number of women in ophthalmology subspecialty practice has increased steadily over the past 30 years. Men and women subspecialize at the same rate, but significant differences exist between the types of ophthalmology practiced by each gender.


ATP-evoked increase in intracellular calcium via the P2Y receptor in proliferating bovine trophoblast cells.
Bovine trophoblasts actively proliferate to elongate blastocysts before implantation. The trophoblast at this stage secretes cytokines and starts to differentiate into an endocrine cell (binucleate cell) for successful pregnancy. Intracellular calcium ([Ca2+]i) may act as a second messenger in the trophoblast response. In this study, we investigated [Ca2+]i signals in a bovine trophoblast cell line (BT-1) using fura-2 fluorescence. We found that an application of ATP (> or =1 microM) induced a transient increase in [Ca2+]i in BT-1 cells. The ATP-induced increase was not affected by the removal of extracellular Ca2+, but was suppressed by suramin (100 microM), an antagonist of P2 receptors. Pretreatment with pertussis toxin (0.1 or 1 microg/ml) partially inhibited the response to ATP. The order of potency to increase [Ca2+]i was ATP=UTP>ADP. ATP-induced [Ca2+]i responses preferentially occurred in cells at the periphery of the colony. The reduced responses at the center of the colony were associated with an increase in cell density and decrease in bromodeoxyuridine incorporation. These results indicated that ATP stimulated P2Y receptors coupled to pertussis toxin-sensitive and -insensitive G proteins, leading to an increase in [Ca2+]i as a result of release of Ca2+ from intracellular stores in BT-1 cells. The occurrence of ATP-induced [Ca2+]i signals depended on the cell confluence and reflected the high proliferative activity of the trophoblast cell population.


Beyond the biomedical, towards the agentic: A paradigm shift for population health science.
Life expectancy in the United States is decreasing. Health disparities are widening. Growing evidence for and integration of social and structural determinants into theory and practice has not yet improved outcomes. The COVID-19 pandemic reinforced the fact. In this paper, we argue that the biomedical model and its underlying scientific paradigm of causal determinism, which currently dominate population health, cannot meet population health needs. While criticism of the biomedical model is not new, this paper advances the field by going beyond criticism to recognize the need for a paradigm shift. In the first half of the paper, we present a critical analysis of the biomedical model and the paradigm of causal determinism. In the second half, we outline the agentic paradigm and present a structural model of health based on generalizable, group-level processes. We use the experience of the COVID-19 pandemic to illustrate the practical applications of our model. It will be important for future work to investigate the empirical and pragmatic applications of our structural model of population health.


Effectiveness of a Lifestyle Intervention for People With a Severe Mental Illness in Dutch Outpatient Mental Health Care: A Randomized Clinical Trial.
People with a severe mental illness (SMI) have a life expectancy reduced by 10 to 20 years compared with the general population, primarily attributable to cardiometabolic disorders. Lifestyle interventions for people with SMI can improve health and reduce cardiometabolic risk. To evaluate the effectiveness of a group-based lifestyle intervention among people with SMI in outpatient treatment settings compared with treatment as usual (TAU). The Severe Mental Illness Lifestyle Evaluation (SMILE) study is a pragmatic cluster randomized clinical trial performed in 8 mental health care centers with 21 flexible assertive community treatment teams in the Netherlands. Inclusion criteria were SMI, age of 18 years or older, and body mass index (calculated as weight in kilograms divided by height in meters squared) of 27 or greater. Data were collected from January 2018 to February 2020, and data were analyzed from September 2020 to February 2023. Weekly 2-hour group sessions for 6 months followed by monthly 2-hour group sessions for another 6 months, delivered by trained mental health care workers. The intervention targeted overall lifestyle changes, emphasizing establishing a healthy diet and promoting physical activity. TAU (control) did not include structured interventions or advice on lifestyle. Crude and adjusted linear mixed models and multivariable logistic regression analyses were performed. The main outcome was body weight change. Secondary outcomes included changes in body mass index, blood pressure, lipid profiles, fasting glucose level, quality of life, self-management ability, and lifestyle behaviors (physical activity and health, mental health, nutrition, and sleep). The study population included 11 lifestyle intervention teams (126 participants) and 10 TAU teams (98 participants). Of 224 included patients, 137 (61.2%) were female, and the mean (SD) age was 47.6 (11.1) years. From baseline to 12 months, participants in the lifestyle intervention group lost 3.3 kg (95% CI, -6.2 to -0.4) more than those in the control group. In the lifestyle intervention group, people with high attendance rates lost more weight than participants with medium and low rates (mean [SD] weight loss: high, -4.9 [8.1] kg; medium, -0.2 [7.8] kg; low, 0.8 [8.3] kg). Only small or no changes were found for secondary outcomes. In this trial, the lifestyle intervention significantly reduced weight from baseline to 12 months in overweight and obese adults with SMI. Tailoring lifestyle interventions and increasing attendance rates might be beneficial for people with SMI. Netherlands Trial Register Identifier: NTR6837.


Changes in the levels of prostaglandins and thromboxane and their roles in the accumulation of exudate in rat carrageenin-induced pleurisy--a profile analysis using gas chromatography-mass spectrometry.
Injection of lambda-carrageenin into the pleural cavity of rats caused the accumulation of the pleural exudate. When levels of prostaglandins (PGs) and thromboxane (TX) B2 were quantified by gas chromatography-mass spectrometry as their methyl ester (ME)-dimethylisopropylsilyl (DMiPS) ether or ME-methoxime-DMiPS ether derivatives, 6-keto-PGF1 alpha reached the maximum at 1 hr after carrageenin, then PGE2 and TXB2 showed peaks at 3 hr and waned off before 9 hr. The PGF/ alpha level was kept low, but PGD2, PGE1 and PGF1 alpha were not detected. Aspirin (100 mg/kg, i.p.) significantly decreased the PG and TXB2 levels and suppressed the rate of plasma exudation until 5 hr, but did not at 7 hr, when it was measured by the amount of exuded pontamine sky blue injected intravenously. OKY-025 (300 mg/kg, i.p.), a selective TXA synthetase inhibitor, and tranylcypromine (20 mg/kg, i.p.), a PGI synthetase inhibitor, could not extensively inhibit the accumulation of the exudate. These results suggest that the cyclooxygenase products of arachidonic acid, particularly PGE2, definitely play an important role in the exudation during the first 5 hr.


Stochastic gradient descent algorithm for the predictive modelling of grate combustion and boiler dynamics.
Pressure and water level control are quite challenging in grate-fired boilers due to higher combustion lag. Fluctuation in the pressure and the water level is more evident in the coal-fired grate boilers due to the presence of lower volatile and higher char. This results in suboptimal operation and poor performance of the boiler. This paper presents a novel predictive and dynamic simulation model for the drum dynamics analysis of a grate-fired boiler by combining a data-driven model and a thermodynamic model. A data-driven methodology is employed for the estimation of combustion, heat transfers, and circulation performance of the boiler. A novel thermodynamic model is proposed for the boiler dynamics of a hybrid boiler. The proposed data-driven model has been integrated with the thermodynamic model to reduce the randomness and improve consistency. Pressure and water level errors are estimated by comparing the predicted value and experimental result and the multi-objective optimisation technique is employed for the minimisation of errors. The Stochastic Gradient Descent algorithm is proposed for its ability to quick learning and adaptation to variations in fuel and combustion characteristics. The model demonstrates good accuracy in predicting the combustion and boiler dynamics of a grate-fired boiler. The proposed model has good potential to be used for the reciprocating grate solid-fuel boiler control in fluctuating load conditions.


NMR-Based Metabolomics to Evaluate Individual Response to Treatments.
The aim of this chapter is to highlight the various aspects of metabolomics in relation to health and diseases, starting from the definition of metabolic space and of how individuals tend to maintain their own position in this space. Physio-pathological stimuli may cause individuals to lose their position and then regain it, or move irreversibly to other positions. By way of examples, mostly selected from our own work using 1H NMR on biological fluids, we describe the effects on the individual metabolomic fingerprint of mild external interventions, such as diet or probiotic administration. Then we move to pathologies (such as celiac disease, various types of cancer, viral infections, and other diseases), each characterized by a well-defined metabolomic fingerprint. We describe the effects of drugs on the disease fingerprint and on its reversal to a healthy metabolomic status. Drug toxicity can be also monitored by metabolomics. We also show how the individual metabolomic fingerprint at the onset of a disease may discriminate responders from non-responders to a given drug, or how it may be prognostic of e.g., cancer recurrence after many years. In parallel with fingerprinting, profiling (i.e., the identification and quantification of many metabolites and, in the case of selected biofluids, of the lipoprotein components that contribute to the 1H NMR spectral features) can provide hints on the metabolic pathways that are altered by a disease and assess their restoration after treatment.


Impact of prostate radiotherapy on survival outcomes in clinically node-positive prostate cancer: A multicentre retrospective analysis.
To evaluate clinical outcomes for cN1M0 prostate cancer treated with varied modalities. Men with radiological stage cN1M0 prostate cancer on conventional imaging, treated from 2011-2019 with various modalities across four centres in the UK were included. Demographics, tumour grade and stage, and treatment details were collected. Biochemical and radiological progression-free survival (bPFS, rPFS) and overall survival (OS) were estimated using Kaplan Meier analyses. Potential factors impacting survival were tested with univariable log-rank test and multivariable Cox-proportional hazards model. Total 337 men with cN1M0 prostate cancer were included, 47% having Gleason grade group 5 disease. Treatment modalities included androgen deprivation therapy (ADT) in 98.9% men, either alone (19%) or in combinations including prostate radiotherapy (70%), pelvic nodal radiotherapy (38%), docetaxel (22%), or surgery (7%). At median follow up of 50 months, 5-year bPFS, rPFS, and OS were 62.7%, 71.0%, and 75.8% respectively. Prostate radiotherapy was associated with significantly higher bPFS (74.1% vs 34.2%), rPFS (80.7% vs 44.3%) and OS (86.7% vs 56.2%) at five years (log rank p < 0.001 each). On multivariable analysis including age, Gleason grade group, tumour stage, ADT duration, docetaxel, and nodal radiotherapy, benefit of prostate radiotherapy persisted for bPFS [HR 0.33 (95% CI 0.18-0.62)], rPFS [HR 0.25 (0.12-0.51)], and OS [HR 0.27 (0.13-0.58)] (p < 0.001 each). Impact of nodal radiotherapy or docetaxel was not established due to small subgroups. Addition of prostate radiotherapy to ADT in cN1M0 prostate cancer yielded improved disease control and overall survival independent of other tumour and treatment factors.


Quantitative outcomes of endoscopic strip craniectomy for metopic craniosynostosis in children with severe trigonocephaly.
To assess intermediate-term (> 3 years) outcomes of endoscopic strip craniectomy with postoperative helmet therapy (ESC + HT) for the treatment of infants with severe trigonocephaly. This retrospective study examined cranial morphology of consecutive patients with severe trigonocephaly treated with minimally invasive ESC + HT. Preoperative and follow-up clinical parameters were collected from patient charts. Interfrontal divergence angle (IFDA), a validated and accurate measure of forehead narrowing, was measured on preoperative CT scans and on preoperative and postoperative 2D photographs. Seven patients (4 male, 3 female) were included with a mean age at surgery of 2.76 months (range 1.8 to 4.1 months) and mean clinical follow-up of 3.71 years (photographic follow-up 2.73 years). The mean operative time was 91.4 min, with a mean estimated blood loss (EBL) of 57.1 ml and mean hospital length of stay of 1.14 days. IFDA improved from 118.8° to 135.9° (p < 0.01), with the mean final measurement falling within normal limits. The head circumference percentile was not significantly changed in follow-up. There was a statistically significant improvement in the inner-to-outer canthal distance ratio (p = 0.01) in follow-up, showing an improvement in hypotelorism. There were no dural tears, CSF leaks, infections, or other significant surgical morbidities, and there were no serious complications related to the use of helmet therapy. All patients achieved excellent aesthetic results judged by photographic comparison. This study demonstrated that patients treated with ESC + HT for metopic craniosynostosis showed measurable and significant improvement in forehead shape. This technique is a safe and effective alternative to more invasive surgical interventions.


A method for MR quantification of flow velocities in blood and CSF using interleaved gradient-echo pulse sequences.
The aim of this study was to establish a rapid method for in vivo quantification of a large range of flow velocities using phase information. A basic gradient-echo sequence was constructed, in which flow was encoded along the slice selection direction by variation of the amplitude of a bipolar gradient without changes in sequence timings. The influence of field inhomogeneities and eddy currents was studied in a 1.5 T interleaved sequences for calibration and in vivo flow determination were constructed, and flow information was obtained by pairwise subtraction of velocity-encoded from velocity non-encoded phase images. Calibration was performed in a nongated mode using flow phantoms, and the results were compared with theoretically calculated encoding efficiencies. In vivo flow was studied in healthy volunteers in three different areas using cardiac gating; central blood flow in the great thoracic vessels, peripheral blood flow in the popliteal vessels, and flow of cerebrospinal fluid (CSF) in the cerebral aqueduct. The results show good agreement with results obtained with other techniques. The proposed method for flow determination was shown to be rapid and flexible, and we thus conclude that it seems well suited for routine clinical MR examinations.


Discontinuation of metformin to prevent metformin-induced high colonic FDG uptake: is 48 h sufficient?
In this retrospective, single-center observational study, we investigated whether discontinuing metformin for at least 48 h prevents metformin-induced [18F]fluorodeoxyglucose (FDG) uptake in all segments of the colon. Patients with type 2 diabetes who were using metformin before undergoing an FDG PET/CT scan were included. Two groups were created: patients who discontinued metformin for less than 48 h (< 48 h group) and patients who discontinued metformin for between 48 and 72 h (≥ 48 h group). A control group comprised non-diabetic patients who were not using metformin before undergoing an FDG PET/CT. We visually scored the uptake of FDG in four segments of the colon-the ascendens, transversum, descendens, and rectosigmoid-using a four-point scale (1-4) and considered scores of 3 or 4 to be clinically significant. Colonic FDG uptake in the ≥ 48 h group (n = 23) was higher than uptake in the control group (n = 96) in the colon descendens [odds ratio (OR) 14.0; 95% confidence interval (CI) 4.8-40.9; p value: 0.001] and rectosigmoid (OR 11.3; 95% CI 4.0-31.9; p value: 0.001), and there was no difference in the colon ascendens and transversum. Colonic FDG uptake in the < 48 h group (n = 25) was higher than uptake in the ≥ 48 h group (n = 23) in the colon transversum (OR 4.8; 95% CI 1.3-18.5; p value: 0.022) and rectosigmoid (p value: 0.023), and there was no difference in the colon ascendens and descendens. Discontinuing metformin for 48 h before undergoing an FDG PET/CT still gives a high uptake in the distal parts of the colon when compared with non-diabetic patients who are not using metformin. Discontinuing metformin for 48 h seems to be useful for scanning the more proximal segments of the colon.


Use of Western Neuropsychological Test Battery in Detecting HIV-Associated Neurocognitive Disorders (HAND) in Zambia.
This is a study of neuroAIDS in sub-Saharan Africa, involving 266 Zambian adults infected with the human immunodeficiency virus (HIV), clade C. All HIV+ participants were receiving combination antiretroviral therapy (CART), and were administered a comprehensive neuropsychological (NP) test battery covering seven ability domains that are frequently affected by neuroAIDS. The battery was developed in the U.S. but has been validated in other international settings and has demographically-corrected normative standards based upon 324 healthy Zambian adults. Compared to the healthy Zambian controls, the HIV+ sample performed worse on the NP battery with a medium effect size (Cohen's d = 0.64). 34.6 % of the HIV+ individuals had global NP impairment and met criteria for HIV associated neurocognitive disorder (HAND). The results indicate that the Western-developed NP test battery is appropriate for use in Zambia and can serve as a viable HIV and AIDS management tool.


The Development and Psychometric Evaluation of the HIV Stigmatizing Attitudes Scale (HSAS) in Tanzania.
HIV stigmatizing attitudes are embedded in social context, making it important to develop culturally specific tools for accurate measurement. The goal of this study was to develop and evaluate the psychometric properties of the HIV Stigmatizing Attitudes Scale (HSAS) in Moshi, Tanzania. Items were adapted based on a scale developed by Visser et al. which was one of the first to measure HIV stigmatizing attitudes in the general population (i.e., people not living with HIV). Items were translated into Swahili and modified with iterative feedback. The HSAS was administered to participants (N = 1494) in an HIV stigma reduction intervention study at two antenatal care clinics in Moshi, Tanzania. The HSAS was found to have strong domain coherence and high reliability based on Cronbach's alpha, Omega 6 coefficient values, and the composite reliability coefficient, and high validity based on content-oriented evidence, relations to other variables, and response process. Factor analysis revealed a two-factor structure (Moral Judgment and Interpersonal Distancing), consistent with the original Visser scale. The HSAS provides a robust way to measure HIV stigma in the Tanzanian context and can be culturally adapted to other settings.


Villous motility: relationship to lymph flow and blood flow in the dog jejunum.
Villous contraction frequency, lymph flow, blood flow, and arteriovenous oxygen difference were measured in dog jejunum. Venous pressure elevation and plasma dilution were used to increase capillary fluid filtration. Both perturbations produced concomitant increases in villous contraction frequency and lymph flow. A highly significant correlation (r = 0.83, p less than 0.001) was obtained between villous contraction frequency and lymph flow. This finding, coupled with the observation that stimulation of net fluid absorption increases villous contraction frequency, suggests that villous motility is increased by a myogenic response elicited by increments in interstitial fluid pressure. In another series of experiments local arterial pressure was reduced in 20-mmHg steps from 120 to 20 mmHg. Although blood flow fell proportionately to arterial pressure, villous contraction frequency and oxygen uptake were maintained at a normal level when arterial pressure was between 120 and 60 mmHg. Villous motility and oxygen consumption fell progressively as arterial pressure was reduced below 60 mmHg. This observation indicates that ischemia does not alter villous contraction frequency unless blood flow is reduced below the level necessary to maintain normal tissue oxygenation.


Assessment of human parvovirus B19 infection in Egyptian hemodialysis patients.
Parvovirus B19V has been shown to be associated with end-stage renal disease (ESRD) with increased risk of post-infection anemia, especially in hemodialysis (HD) patients. This effect may be due to immunosuppression, insufficient erythropoietin, or short lifespan of red blood cells. Therefore, parvovirus infection should be investigated in this group of patients suffering from anemia or pancytopenia. We assessed the frequency of parvovirus B19 in HD patients attending Suez Canal University Hospital and analyzed the correlation of this infection with hematological parameters in those patients compared with normal individuals. We recruited 80 ESRD patients on hemodialysis and 70 healthy controls. History-taking, full examination, and complete blood count (CBC) were performed for all study subjects. Parvovirus B19 detection was performed through polymerase chain reaction (PCR), which included the QIAamp DNA Mini Kit for extracting DNA, which was amplified using TaqMan Universal Master Mix and detected using TaqMan MGB probes by real-time PCR using Rotor Gene Analyzer (6000). HD patients had a significantly higher frequency of B19V infection than the control group (p = .02). We also found that parvovirus B19-infected HD patients had significantly lower CBC values than uninfected patients. The frequency of parvovirus B19 was significantly higher in HD patients and was associated with lower hematological parameters than in uninfected patients, suggesting a significant role of this virus in the pathogenesis of anemia and/or pancytopenia in ESRD.


Generation of high-sensitivity antisense cDNA probes by asymmetric PCR.
Monitoring changing levels of mRNA by hybridization analysis relies on the use of labeled probes. The development of antisense single-stranded cDNA probe methodologies (unidirectional polymerase chain reaction [PCR] amplification or asymmetric PCR amplification) allows the production of probes of high sensitivity and low background with excellent linearity of detection. Because the methods are PCR-based, templates do not need extensive modification: selection of oligonucleotide sequences determines the target amplified. Thus such methods are flexible, being successfully achieved on a variety of templates including recombinant plasmids or dsDNA from reverse-transcription PCR (RT-PCR). In addition these probes are relatively easily stripped from hybridization membranes, so allowing repeated probing in Northern analysis.