The assignment of carbonyl resonances in 13C-n.m.r. spectra of peracetylated mono- and oligo-saccharides containing D-glucose and D-mannose: an alternative method for structural determination of complex carbohydrates.
In the present study, proton homonuclear (COSY) and 13C-1H heteronuclear shift-correlation, n.m.r. spectroscopies have been used to assign the carbonyl carbon resonances of peracetylated D-gluco- and D-mannopyranose monosaccharides and oligosaccharides containing residues of parent D-glucopyranose monomers. Chemical shifts of these assigned resonances, particularly those arising from acetyl groups near to aglycon substitution sites, were found to be sensitive to the position and configuration of glycosidic linkages present. In addition, evidence is presented that indicates that the shifts of these carbonyl carbon resonances depend on long-range interactions with other peracetylated pyranose monomers resulting from folding of the oligosaccharide chain. These results suggest that carbonyl carbon resonances of peracetylated carbohydrates may be useful probes of oligosaccharide structure.


Full-view LED-based optoacoustic tomography.
Optoacoustic tomography is commonly performed with bulky and expensive short-pulsed solid-state lasers providing high per-pulse energies in the millijoule range. Light emitting diodes (LEDs) represent a cost-effective and portable alternative for optoacoustic signal excitation that can additionally provide excellent pulse-to-pulse stability. Herein, we introduce a full-view LED-based optoacoustic tomography (FLOAT) system for deep tissue in vivo imaging. It is based on a custom-made electronic unit driving a stacked array of LEDs, which attains 100 ns pulse width and highly stable (0.62 % standard deviation) total per-pulse energy of 0.48 mJ. The illumination source is integrated into a circular array of cylindrically-focused ultrasound detection elements to result in a full-view tomographic configuration, which plays a critical role in circumventing limited-view effects, enhancing the effective field-of-view and image quality for cross-sectional (2D) imaging. We characterized the FLOAT performance in terms of pulse width, power stability, excitation light distribution, signal-to-noise and penetration depth. FLOAT of the human finger revealed a comparable imaging performance to that achieved with the standard pulsed Nd:YAG laser. It is anticipated that this compact, affordable and versatile illumination technology will facilitate optoacoustic imaging developments in resource-limited settings for biological and clinical applications.


Amyloid imaging in clinical trials.
The possibility to map amyloid-beta, the Alzheimer's disease hallmark protein, in vivo opens the application for amyloid imaging in clinical trials with disease-modifying agents. Monitoring change in amyloid burden, particularly when potential amyloid-lowering drugs are at play, requires accurate analytical methods. Studies to date have used suboptimal methods that do not account for heterogeneous changes in flow associated with disease progression and potentially with anti-amyloid drugs. In this commentary, we discuss practical and methodological issues regarding longitudinal amyloid imaging and propose several quantitative, yet feasible, alternatives for reliable assessment of changes over time in amyloid burden.


The rectosigmoid problem.
The lack of consensus over the transition point for the end of the sigmoid and beginning of the rectum is a problem for the colorectal multidisciplinary team. In this review, we survey the wide number of landmarks for the rectosigmoid junction, and describe the theoretical and evidence-based strengths and weaknesses of each one. Without a reliable definition of the rectum, sigmoid and rectal cancers will be classified inconsistently. As the treatment strategies for sigmoid and rectal cancers are radically different, incorrect tumour localisation has a substantial impact on patient management, leading to under or over treatment. Inconsistent classification will confound investigation of metastatic patterns and treatment outcomes. Now that the rectosigmoid junction has been recognised as a distinct segment of colon by the International Classification of Diseases, further heterogeneity in management and outcomes could result to the detriment of patients and research. We describe a bespoke, anatomical and reliable landmark for the rectosigmoid junction; the sigmoid take-off.


Endometriosis in adolescents--analysis of 6 cases.
To study the characteristics, diagnosis and treatment of endometriosis in adolescent patients. Six cases of adolescent endometriosis in our hospital were reviewed retrospectively. Endometriosis is the most common cause of chronic pelvic pain in adolescents. There may be a natural progression of endometriosis from atypical lesions in adolescents to classic lesions in adults. Congenital abnormalities of the reproductive tract are the main reasons for the adolescent endometriosis. Endometriosis should be strongly suspected in adolescent girls with chronic pelvic pain, especially unresponsive to oral contraceptives and nonsteroidal anti-inflammatory drugs. The treatment involves the operations and medicines.


Miniaturized dynamic liquid-liquid extraction of organophosphate triesters from blood plasma using the hollow fibre-based XT-tube extractor.
A miniaturized liquid-liquid extractor for bioanalytical sample preparation is described. The extractor consists of a polypropylene hollow fibre mounted inside polytetrafluoroethylene (PTFE) tubing by means of a cross (X) connector and a tee (T) connector. All parts are commercially available, inexpensive, and easily assembled. The aqueous sample, injected into a carrier flow, is pumped along the outside of the fibre and the organic phase, which also wets the pores of the hollow fibre wall, is pumped inside. Eight organophosphate triester (OPE) plasticisers/flame retardants were extracted from 50 microL spiked blood plasma that had been mixed with 50 microL formic acid to denature plasma proteins. The organic phase was a mixture of hexane and methyl tert-butyl ether (MTBE). A high concentration of formic acid in the sample and of MTBE in the organic phase had positive effects on the recovery of some OPE. When investigating the recovery as a function of extraction time it was found that the extraction reached a maximum after 10 min, at a flow-rate of 15 microL min(-1). Recoveries varied between 40 and 80% with RSD around 4% for most compounds. The whole 150- microL extract was injected into a GC-MS system equipped with a programmed-temperature vaporization (PTV) injector. With the MS in selected-ion monitoring (SIM) mode, the LOD for triphenyl phosphate and 2-ethylhexyl diphenyl phosphate were 0.3 and 0.2 ng mL(-1), respectively. More than 40 plasma extractions were performed with the same fibre without any detectable change in extraction efficiency.


Crystal structure of tris-(4,7-diphenyl-1,10-phenanthroline-κ2 N,N')cobalt(III) tris-(hexa-fluoro-phosphate) monohydrate.
The title compound, [Co(C72H48N6)](PF6)3·H2O, crystallizes with one tripositive complex mol-ecule, three hexa-fluoro-phosphate anions and one solvent mol-ecule of water in the asymmetric unit. The N6 coordination set around the central CoIII atom defines a distorted octa-hedral environment. Four fluorine atoms of one hexa-fluoro-phosphate anion are disordered over two sets of positions with site-occupancy factors of 0.697 (5) and 0.303 (5). In the crystal, inter-molecular π-π stacking inter-actions, C-H⋯π, C-H⋯F and O-H⋯F and inter-actions are present.


Management of periorbital cellulitis at the Pediatric Emergency Department: A ten years study.
Periorbital cellulitis is a diagnostic and therapeutic emergency, jeopardizing the prognosis for vision and survival. The goal of this study was to analyze the epidemiological and therapeutic features and outcomes of periorbital cellulitis cases treated in the pediatric emergency department. A retrospective study including all the children aged between 1 month and 15 years treated for periorbital cellulitis in the Pediatric Emergency Department of the Mohamed VI University Teaching Hospital in Marrakech over a period of 10 years (January 1, 2010-December 31, 2019). In all, 168 cases of periorbital cellulitis were recorded, with an increasing of the number of cases, from 2 in 2010 to 39 in 2019. The most affected age bracket was the group under 5 years of age (62.5%). The most frequent mode of entry was sinusitis (22%). Preseptal cellulitis was most common (76.7%). The main clinical signs found in orbital cellulitis were proptosis (64%) and chemosis (35.8%), versus conjunctival hyperemia (78%) in preseptal cellulitis. Ophthalmoplegia was present in two cases of orbital cellulitis. The right side was most affected (44%). An orbital CT scan was performed in all cases in our study, showing preseptal cellulitis in 129 patients (76.7%), orbital cellulitis in 14 cases (8.3%), subperiosteal abscess in 20 cases (12%) and orbital abscess in 5 cases (3%). Prior treatment with non-steroidal anti-inflammatory medication was noted in 6%. The most commonly used antibiotic was amoxicillin-clavulanic acid. Steroid treatment was prescribed in 6% of cases. Surgical treatment was indicated in 12 patients (7.1%). The mean hospital length of stay was 3 days for the preseptal cases and 8 days for the orbital cases. All patients had good outcomes with medical and/or surgical treatment. With follow-up of over one year, no complications were noted. The majority of our cases had positive outcomes, highlighting the advantage of early diagnosis, adapted antibiotic treatment and multidisciplinary care, rendering surgery rarely necessary.


Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk.
Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-β (transforming growth factor-β) (highest in the Veillonella cluster) and Wnt/β-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.


Integration of single-layer skin hollow fibers and scaffolds develops a three-dimensional hybrid bioreactor for bioartificial livers.
Bioartificial liver support systems are expected to be an effective therapy as a "bridge" for liver transplantation or reversible acute liver disease. A major roadblock in the application of bioartificial livers is the need for a bioreactor that fully meets the requirements of hepatocyte culture, mass transfer and immunobarriers. In this study, we developed a three-dimensional hybrid bioreactor (3DHB) on a base of single-layer skin polyethersulfone hollow fibers by integrating with polyurethane scaffolds. The mass transfer of bilirubin and albumin from the intracapillary space to the extracapillary space of the hollow fibers was not significantly different between 3DHBs and hollow fiber bioreactors (HFBs). Cell viability staining showed that high-density hepatocytes were uniformly found in different regions of the 3DHB after 7 days of culture. Liver-specific functions of human mature hepatocytes cultured in the 3DHB, such as albumin secretion, urea production, ammonia removal rate and cytochrome P450 activity, were maintained stably and were significantly higher compared with the HFB. These results indicated that the 3DHB has good mass transfer and improves cell distribution and liver-specific functions. Meanwhile, the ammonia and unconjugated bilirubin concentrations in plasma from patients with liver failure were significantly decreased during 6 h of circulation by hepatocytes cultured in the 3DHB. Most hepatocytes in the 3DHB were viable after 6 h exposure to the patient plasma. We further demonstrated that bioartificial liver systems with 3DHB can remove toxins from and endure the deleterious effects of the patient plasma. Therefore, the 3DHB has the potential to accomplish different actions for the clinical application of bioartificial livers.


Apoptosis in the failing heart.
Apoptosis is a tightly regulated, energy-requiring process of programmed cell death. While necrosis is a form of cell death that results from acute cellular injury, apoptosis is controlled autodigestion of the cell that occurs through activation of endogenous proteases. This process results in the cleavage of chromatin into oligonucleosome-length DNA fragments and its multiples. This DNA fragmentation demonstrates a characteristic laddering pattern on DNA agarose gel electrophoresis. The heart undergoes extensive remodeling during embryogenesis wherein apoptosis significantly contributes to the development of the cardiac chambers and correct routing of the great vessels. Pathologic stimuli can also result in apoptosis and include ischemia, hypoxia, inflammation, cytokines, growth factors, and toxic agents. Better understanding of the molecular mechanisms responsible for regulating apoptosis in the failing myocardium may soon lead to strategies aimed at preventing further myocyte loss and enhancing myocyte replacement through regulated cell growth.


Nurse leadership: Sustaining a culture of safety.
Nurse leaders are essential to manage nursing practices that affect patient safety; therefore, they must create and sustain a sound safety culture in a diverse cultural environment. To describe the specific actions required by nurse leadership to enhance the sustainability of a safety culture in hospitals and among a diverse nursing team, ultimately improving patient outcomes. Two hospitals in the United Arab Emirates (UAE) were selected purposively, based on the diversity of the nursing team. A quantitative design, using Reason's safety culture framework and Ekenedo's behavioural safety model, formed the theoretical background of this study to identify the safety culture and positive work environment that exist among culturally diverse nurses. Thirty-four nurse managers and 417 nurses were conveniently selected to participate. Various instruments were used to gather hospital outcomes and other data from respondents pertaining to their demographics, patient safety, positive work environments and safety culture. Findings received from the nursing team describe the correlation between patient safety, a diverse nursing workforce and positive work environment affecting a safety culture and promoting positive patient outcomes. Nurse leaders' integration of specific actions to address the system, as well as diverse nursing teams' behavioural practices, create a patient care environment that adequately contributes to safety culture practices and enhances positive patient outcomes, which are essential for a culture of safety. The study contributes by providing a structured integration of specific actions for nurse leaders to sustain practices ensuring positive patient outcomes.


Polymorphisms of the interleukin-6 (IL-6) gene contribute to cervical cancer susceptibility in Bangladeshi women: A case-control study.
Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer-related deaths among females in Bangladesh. Interleukin-6 (IL-6) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single-nucleotide polymorphisms (SNPs) of IL-6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women. DNA was extracted from venous blood samples from cervical cancer patients (n = 126) and healthy controls (n = 120). Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR) with 95% confidence interval (CI) and p values. We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55-5.07, p = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29-9.51, p = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76-12.81, p < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12-13.51, p = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer. Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL-6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women.


Psychophysics of reading--V. The role of contrast in normal vision.
How does contrast affect reading rate? What is the role of contrast sensitivity? We measured reading rate as a function of the contrast and character size of text for subjects with normal vision. Reading rates were highest (about 350 words/min) for letters ranging in size from 0.25 degree to 2 degrees. Within this range, reading was very tolerant to contrast reduction--for 1 degree letters, reading rate decreased by less than a factor of two for a tenfold reduction in contrast. The results were very similar for white-on-black and black-on-white text. Reading rate declined more rapidly for very small (less than 0.25 degree) and very large (greater than 2 degrees) letters. People with low vision usually require large characters to read, so high contrast is particularly important for them. Taking 35 words/min to be a threshold for reading, we constructed a contrast-sensitivity function (CSF) for reading. We were able to relate the shape of this CSF to the shape of sine-wave grating CSFs.


Complete genome sequence of Mannheimia bovis isolated from a healthy feedlot calf in Saskatchewan, Canada.
A lack of whole genome sequences for Mannheimia spp. other than Mannheimia haemolytica complicates their identification. Here, we present the genome sequence of Mannheimia bovis 39324.S-11, isolated from a healthy calf on a feedlot in Saskatchewan, Canada, and compare it to ZY190616T, which is currently the only other isolate of M. bovis for which sequence is publicly available.


Engineering properties, microplastics and emissions assessment of recycled plastic modified asphalt mixtures.
The use of recycled plastic in asphalt is raising interest since contributing to increase the sustainability of roads pavements. The engineering performance of such roads are commonly assessed but scarcely correlated to the environmental impacts of incorporating recycled plastic in asphalt. This research encompasses an evaluation of the mechanical behaviour and environmental impact of introducing low melting point recycled plastics, low density polyethylene and commingled polyethylene/polypropylene, to conventional hot mix asphalt. While this investigation reveals a reduction in moisture resistance between 5 and 22 % contingent on the plastic content, the benefits include a significant 150 % enhancement in fatigue resistance and 85 % improvement in rutting resistance when compared with conventional hot mix asphalt (HMA). From an environmental perspective, high-temperature asphalt production with higher plastic content resulted in decreased gaseous emissions for both types of recycled plastics up to 21 %. Further comparison studies indicate that microplastic generation from recycled plastic-modified asphalt is comparable to that from commercial polymer-modified asphalt products, long employed by the industry. Overall, the use of low melting point recycled plastics as an asphalt modifier is promising since offering both engineering and environmental benefits when compared to conventional asphalt.


Is interleukin-6 receptor blockade (tocilizumab) beneficial or detrimental to pig-to-baboon organ xenotransplantation?
The interleukin (IL)-6/IL-6 receptor-α (IL-6Rα)/signal transduction and activation of the transcription 3 (STAT3) pathway plays an important role in inflammation. Anti-human IL-6Rα blockade by tocilizumab (TCZ) has been used in pig-to-baboon organ xenotransplant models, but whether it is beneficial remains uncertain. After xenotransplant, there were significant increases in both baboon and pig IL-6 in the baboon serum, especially in baboons that received TCZ before xenotransplant. In vitro observations demonstrated that human, baboon, and pig IL-6 can activate the IL-6/IL-6Rα/STAT3 pathway in human, baboon, and pig cells, respectively. Activation of the IL-6/IL-6Rα/STAT3 pathway was blocked by TCZ in human and baboon cells but not in pig cells (ie, pig IL-6R). Siltuximab (human IL-6 inhibitor) bound to both human and baboon, but not pig, IL-6 and suppressed activation of the IL-6/IL-6Rα/STAT3 pathway. These results indicate that TCZ and siltuximab do not cross-react with pig IL-6R and pig IL-6, respectively. Rapamycin partially inhibited human, baboon, and pig IL-6/IL-6Rα/STAT3 pathways and suppressed inflammatory gene expression. TCZ treatment increased serum IL-6 because it could no longer bind to baboon IL-6Rα. We suggest that increased serum IL-6 may be detrimental to the pig xenograft because it is likely to bind to pig IL-6R, resulting in activation of pig cells.


Massive Thrombosis of the Transplanted Heart in the Early Postoperative Period.
We experienced a case with the left atrium almost completely filled with a thrombus after orthotopic heart transplantation while the patient was supported on extracorporeal membrane oxygenation for primary graft failure. The patient had recurrent thrombosis even after successful surgical thrombectomy and appropriate anticoagulation. The cardiac thrombosis resolved only after starting plasmapheresis.


A general method for analyzing arbitrary planar negative-refractive-index multilayer slab optical waveguide structures.
In this paper, a general method for analyzing arbitrary planar negative-refractive-index (NRI) multilayer slab optical waveguide structures was proposed. Some degenerated examples were introduced to prove the accuracy of the proposed method. The analytical and numerical results show excellent agreement. The method can also be degenerated to analyze arbitrary planar conventional optical waveguide structures. Based on this general method, the analysis and calculation of any kinds of planar NRI slab optical waveguide structures and planar conventional optical waveguide structures can be achieved easily.


Patient-controlled analgesia.
This overview has addressed some of the key principles relating to patient-controlled analgesia. It is important to remember that PCA will continue to develop in the future and new techniques are being devised. PCA can provide an effective method of analgesia for many patients. However, it is not the only form of analgesia available, therefore a thorough assessment must be made before starting to use this analgesic technique.


The social support, psychological resilience and quality of life of nurses in infectious disease departments in China: A mediated model.
This paper aimed to investigate the relationship between social support and quality of life for nurses in infectious disease departments in China, as well as the function of psychological resilience in mediating this relationship. Nurses in infectious disease departments play a critical role in the prevention and control of infectious diseases and in public health care services in general, and their quality of life can affect the quality of clinical nursing work they do. However, there are few studies on the relationship between nurses' social support networks and their quality of life. A cross-sectional study was conducted using a sample of 866 clinical nurses from the infectious disease departments of 10 general hospitals in China. Data were collected using a questionnaire survey from January to May 2021. The mediating influence of psychological resilience on social support and quality of life was investigated using structural equation modelling. The score of quality of life was (36.36 ± 7.64). Quality of life was positively correlated with social support and psychological resilience (r1 = 0.521, r2 = 0.583; p < .01), and psychological resilience was positively correlated with social support (r = 0.426; p < .01) as well. The mediating effect of psychological resilience between social support and quality of life was 0.233, accounting for 37% of the total effect. The quality of life of nurses working in infectious disease departments is in the middle level. Psychological resilience is a mediating variable between social support and quality of life. Managers can improve the quality of life of nurses by both increasing social support and strengthening psychological resilience. Managers should pay attention to the degree of social support provided to nurses and take proactive measures to build psychological resilience so that nurses can effectively manage stress and negative emotions from work and life in order improve their quality of life.


Helicoverpa armigera GATAe transcriptional factor regulates the expression of Bacillus thuringiensis Cry1Ac receptor gene ABCC2 by its interplay with additional transcription factors.
Helicoverpa armigera is a worldwide pest that has been efficiently controlled by transgenic plants expressing Bt Cry toxins. To exert toxicity, Cry toxins bind to different receptors located in larval midgut cells. Previously, we reported that GATA transcription factor GATAe activates the expression of multiple H. armigera Cry1Ac receptors in different insect cell lines. Here, the mechanism involved in GATAe regulation of HaABCC2 gene expression, a key receptor of Cry1Ac, was analyzed. HaGATAe gene silencing by RNAi in H. armigera larvae confirmed the activation role of HaGATAe on the expression of HaABCC2 in the midgut. The contribution of all potential GATAe-binding sites was analyzed by site-directed mutagenesis using Hi5 cells expressing a reporter gene under regulation of different modified HaABCC2 promoters. DNA pull-down assays revealed that GATAe bound to different predicted GATA-binding sites and mutations of the different GATAe-binding sites identified two binding sites responsible for the promoter activity. The binding site B9, which is located near the transcription initiator site, has a major contribution on HaABCC2 expression. Also, DNA pull-down assays revealed that all other members of GATA TF family in H. armigera, besides GATAe, HaGATAa, HaGATAb, HaGATAc and HaGATAd also bound to the HaABCC2 promoter and decreased the GATAe dependent promoter activity. Finally, the potential participation in the regulation of HaABCC2 promoter of several TFs other than GATA TFs expressed in the midgut cells was analyzed. HaHR3 inhibited the GATAe dependent activity of the HaABCC2 promoter, while two other midgut-related TFs, HaCDX and HaSox21, also bound to the HaABCC2 promoter region and increased the GATAe dependent promoter activity. All these data showed that GATAe induces HaABCC2 expression by binding to HaGATAe binding sites in the promoter region and that additional TFs participate in modulating the HaGATAe-driven expression of HaABCC2.


Localization of the raf-1 protooncogene on chromosome 6 of the mouse.
The murine c-raf-1 gene was localized by in situ hybridization to 6C3, proximal to c-ki-ras-2 and distal to the Igk locus. The localization of this protooncogene may be relevant to the correlation of chromosome breakpoints in neoplastic disease.


Reemergence of thyroidectomy as treatment for Graves' disease.
Hyperthyroidism of Graves' disease may be treated very effectively by antithyroid pills, such as PTU and Tapazole, by radioactive iodine therapy, and by subtotal thyroidectomy. Each form of therapy has advantages and disadvantages, and thus treatment should be individualized. While therapy with radioactive iodine would appear to be ideal since it does not require an operation and is less expensive than surgical management, it suffers from a high rate of progressive hypothyroidism and from the fact that the time until a euthyroid state is obtained is often prolonged. In addition, the long-term carcinogenic risk of the therapy for thyroid neoplasia has never been completely defined since the data most often quoted have a mean follow-up time of only eight years. Furthermore, new "low-dose" radioiodine regimens may be more dangerous in this regard. Subtotal thyroidectomy, while not totally without complications, remains a rapid, safe, and effective treatment for Graves' disease. The careful use of propranolol has facilitated the preparation of some patients and has lessened the risk of operation. Thyroidectomy should remain the treatment of choice for young adults with this disease.


[Masked hypertension: myth or reality?].
Masked hypertension is also referred as reverse white coat hypertension. Masked hypertension is diagnosed in subjects who have normal clinic blood pressure (BP) <140/90 mmHg and elevated ambulatory BP or home BP, with daytime systolic BP> or = 135 mmHg or daytime diastolic BP > or = 85 mmHg. Its prevalence varies between 10 to at least 47% and differs substantially according to the reference population and the specific criteria.Subjects with masked hypertension have been shown to have more extensive target organ damage, specifically, a higher prevalence of carotid atherosclerosis and of left ventricular cardiac hypertrophy. Longitudinal studies of patients with masked hypertension show higher levels of cardiovascular morbidity and mortality than in reference populations. These studies show that ambulatory or home BP measurements predict risk much better than the usual clinical measurements and that those who are found to be hypertensive by ambulatory or home measurements have greater risks than those who are not. Who should be tested for masked hypertension? Our reference study shows that 3 characteristics are most likely to predict masked hypertension: male sex, age over 60 years, and office systolic BP of more than 130 mmHg. Masked hypertension is indeed a reality. Individual patients should be tested and treated, based on the physician's clinical judgment.


Direct detection of acetylcholinesterase inhibitor binding with an enzyme-based surface plasmon resonance sensor.
Acetylcholinesterase (AChE) inhibitors are potentially lethal but also have applications as therapeutic drugs for neurodegenerative diseases such as Alzheimer's. Enzyme inhibitor binding are difficult to be detected directly by surface plasmon resonance (SPR) due to their small molecular weight. In this article, we describe the detection of AChE inhibitor binding by SPR without the use of competitive binding or antibodies. AChE was immobilized on the gold surface of an SPR sensor through covalent attachment to a self-assembled monolayer (SAM) of a COOH-terminated alkanethiol. The activity of the immobilized protein and the surface density were determined by using a standard photometric assay. Binding of two reversible inhibitors, which are used as therapeutic drugs, was detectable by SPR without the need to further modify the surface or the use of other reagents. The binding affinities (K(A)) obtained from the fits were 3.8 × 10(3)M(-1) for neostigmine and 1.7 × 10(3)M(-1) for eserine, showing a higher affinity of the sensor for neostigmine. We believe that the SPR sensor's ability to detect these inhibitors is due to conformational changes of the enzyme structure on inhibitor binding.


Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1).
Familial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both, is observed in about 20% of individuals with premature coronary heart disease. We previously identified a locus linked to FCHL on 1q21-q23 in Finnish families with the disease. This region has also been linked to FCHL in families from other populations as well as to type 2 diabetes mellitus. These clinical entities have several overlapping phenotypic features, raising the possibility that the same gene may underlie the obtained linkage results. Here, we show that the human gene encoding thioredoxin interacting protein (TXNIP) on 1q, which underlies combined hyperlipidemia in mice, is not associated with FCHL. We show that FCHL is linked and associated with the gene encoding upstream transcription factor 1 (USF1) in 60 extended families with FCHL, including 721 genotyped individuals (P = 0.00002), especially in males with high triglycerides (P = 0.0000009). Expression profiles in fat biopsy samples from individuals with FCHL seemed to differ depending on their carrier status for the associated USF1 haplotype. USF1 encodes a transcription factor known to regulate several genes of glucose and lipid metabolism.


Further insight into how pharmacists ascribe value to technician certification and how that value might be further enhanced.
National pharmacy technician certification in the U.S. is believed to hold a valuable place in promoting technician competence, but the views of pharmacists from varying settings and positions could help further clarify how certification could be optimized. The aims of this study were to determine differences among pharmacists in how they view certification, the level of value they ascribe to certification, and how they might make further improvements in the certification process. A self-administered survey was constructed and delivered in QualitricsXM in spring of 2019 to a random sample of pharmacists in 4 U S. states chosen for high proportions of both certified and non-certified pharmacy technicians and for their differences in technician regulation and scope of practice. Analysis employed a host of bivariate tests then summative backward elimination regression analyses in consideration of Type I error and in that the approach taken was to acquire a "gestalt" of events rather than test individual hypotheses. Pharmacists' opinions on the impact of certification varied by their job position, their practice setting, and sometimes their sex and work status. Pharmacists in clinical and in supervisory positions saw the positive impact of certification in different ways than did staff pharmacists. Certain groups would like to see more support for certification from their employers, while others aim for more support from certification vendors, and some pharmacists would like to see more content on "soft skills" in the certification process. Certification is seen as most beneficial to technicians in the hospital setting. The results of this study suggest differences among pharmacists in their perceptions of the value of certification and what might be done to further enhance that value. The results of this study will hopefully provide some clarification and direction for certification vendors, policymakers, educators, and pharmacy leaders.


Genetic control of sensitivity to Moloney-virus-induced leukemias in mice. I. Demonstration of multigenic control.
The appearance of hematopoietic malignancies and the level of viremia were studied in mice of different inbred strains and their F1 or F2 hybrids inoculated with the Moloney leukemia virus (MLV). The viremia was regularly measured in individual mice by radioimmunoassay of the major internal virion component p30. A complex genetic control was found. (1) The level of circulating virus was controlled by at least two genes. An H-2 linked gene, tentatively called Rmv-1, displayed a dominant sensitivity. Alleles for resistance existed in H2b and H-2r haplotypes and alleles for sensitivity in H-2a, H-2d and H-2f. Another gene with dominant resistance mapped outside the H-2 complex and probably interacted with Rmv-1. (2) A good correlation existed between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. (3) Nevertheless, additional genes which were not involved in the viremia control could be determinant in the induction of malignancies. One of them with a resistant allele in DBA/2 mice seemed to inhibit the appearance of leukemia despite a high level of viremia. Another gene controlled the spleen involvement resulting in generalized leukemias in sensitive lines contrasting with mainly thymus-localized tumors in resistant animals.


The impact of cold spells on schizophrenia admissions and the synergistic effect with the air quality index.
Under current global climate conditions, there are insufficient studies on the health influences of cold spells, especially on mental health. This study aimed to examine the effect of cold spells on schizophrenia admissions and to analyze the potential interaction effect with the air quality index (AQI). Daily data on schizophrenia admissions and climatic variables in Hefei were collected from 2013 to 2019. Based on 20 definitions, the impacts of cold spells were quantified separately to find the most appropriate definition for the region, and meta-regression was used to explore the different effect sizes of the different days in a cold spell event. In addition, the potential interaction effect was tested by introducing a categorical variable, CSH, reflecting the cold spell and AQI level. The cold spell defined by temperature below the 6th centile while lasting for at least three days produced the optimum model fit performance. In general, the risk of schizophrenia admissions increased on cold spell days. The largest single-day effect occurred on the 12th day with RR = 1.081 (95% CI: 1.044, 1.118). In a single cold spell event, the effect of the 3rd and subsequent days of a cold spell (RR = 1.082, 95% CI: 1.036, 1.130) was higher than that on the 2nd day (RR = 1.054, 95% CI: 1.024, 1.085). Similarly, the effect of the 2nd day was also higher than that of the 1st day (RR = 1.027, 95% CI: 1.012, 1.042). We found a synergistic effect between cold spells and high AQI in the male group, and the relative excess risk due to interaction (RERI) was 0.018 (95% CI: 0.005-0.030). This study suggested that the impacts of cold spells should be considered based on the definition of the most appropriate for the region when formulating targeted measures of schizophrenia. The discovery of the synergistic effect was referred to help the selection of the timing of precautions for susceptible people.


Impairment of long-term graft function after kidney transplantation by intraoperative vascular complications.
Surgical complications in kidney transplantation often demand reoperation and therefore may severely affect graft survival. Major complications can be divided into ureteral and vascular related. Reoperation for ureteral complications is supposed to worsen graft survival, but vascular complications or anastomosis technique has not been evaluated for this issue. Between 1994 and 2004 260 patients underwent kidney transplantation. All ureterovesical junctions were performed in extravesical technique with ureteral stenting in 132/260 (50.7%) patients. Arterial end-to-side anastomosis was performed routinely except for 13/260 (5%) with end-to-end anastomosis. Mean follow-up was 43 months (0-121) including serum creatinine and ultrasound inter alia. Graft failure rate was 8.1% 12 months and 12.7% 60 months postoperatively. Of the patients, 29/260 (11.5%) underwent reoperation within 30 days after transplantation (stenosis or leakage of the ureterovesical junction: n = 8; vascular complications: n = 10; thrombectomy for graft vein thrombosis: n = 1; evacuation of hematoma: n = 6; nephrectomy for complete graft ischemia: n = 4). Reoperation for vascular-related complications significantly enhances the risk of graft failure (P < 0.05, Cox proportional hazard) compared to urological complications. Arterial end-to-end anastomosis was also found to have a negative impact on graft survival. No correlation between routine ureteral stenting and ureteral stenosis or leakage was found. Our data emphasize the importance of vascular complications compared to ureteral ones in kidney transplantation. Resolving 'non-urological' problems successfully, kidney transplantation is a safe procedure in urological hands.


Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis.
Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.


Candida tropicalis as a novel dietary additive to reduce methane emissions and nitrogen excretion in sheep.
The goal of this study was to investigate Candida tropicalis as a kind of environmentally friendly dietary additive to manipulate ruminal fermentation patterns, reduce methane emissions and nitrogen excretion, and to screen the appropriate dose for sheep. Twenty-four Dorper × thin-tailed Han crossbred ewes (51.12 kg ± 2.23 kg BW) were selected and randomly divided into four groups which were fed Candida tropicalis at dose of 0 (control), 4 × 108 (low dose), 4 × 109 (medium dose), and 4 × 1010 (high dose) colony-forming units (CFU)/d per head, respectively. The experiment lasted 33 days with 21 days for adaptation and 12 days for nutrient digestibility trial and respiratory gases sampling. The results showed that nutrients intake was not affected by Candida tropicalis supplementation (P > 0.05), whereas apparent digestibility of nutrients significantly increased compared with the control group (P < 0.05). Nitrogen and energy utilization increased with Candida tropicalis supplementation (P < 0.05). Compared with the ewes of the control group, rumen fluid pH and NH3-N concentration were not affected (P > 0.05), whereas total volatile fatty acid concentration and molar proportion of propionate were greater (P < 0.05), and molar proportion of acetate and the ratio of acetate to propionate were less (P < 0.05) when the ewes were fed Candida tropicalis. Daily total CH4 production (L/d) and CH4 emissions yield (L/d of CH4 per kg of dry matter intake, metabolic weight, or digestibility dry matter intake) were decreased at the low dose group (P < 0.05). The abundance of total bacteria, methanogen, and protozoa in rumen fluid was significantly higher at medium dose and high dose of Candida tropicalis supplementation (P < 0.05) compared with low dose and the control group. In summary, Candida tropicalis supplementation has a potential to reduce CH4 emissions and nitrogen excretion, and the optimal dose should be 4 × 108 CFU/d per head.


The effect of NOD2 activation on TLR2-mediated cytokine responses is dependent on activation dose and NOD2 genotype.
The mechanism by which mutations in NOD2 predispose to Crohn's disease (CD) is incompletely understood. In mice, NOD2 has been found to function as a negative regulator of Toll-like receptor 2 (TLR2) signaling. In contrast, studies in humans so far showed no negative regulatory interaction between NOD2 and TLR2, and in fact suggest a synergistic effect between the two. Here, we show that this interaction is dose dependent. Adding low doses of muramyl dipeptide (MDP) to TLR2 primed monocytes results in a significant increase in cytokine production, whereas adding higher doses of MDP led to a striking downregulation of the responses. This downregulation by high-dose MDP does not occur in monocytes from NOD2-deficient patients. The inhibitory role of NOD2 at high concentrations of MDP implicates a safety mechanism to prevent exaggerated antibacterial immune responses in the gut to high or perpetuating bacterial load. This regulatory mechanism is lost in NOD2-deficient CD patients.


Experimental training in molecular pharmacology education based on drug-target interactions.
Drug development has been challenged by the dual drawbacks involving unpredictable disease outcomes and drug resistance, which has placed greater demands on pharmacology education. Molecular pharmacology, as a frontier crossover field of pharmacology, focuses on the research of new drugs and targets. However, due to the lack of a systematic experimental training system, molecular pharmacology has not made a corresponding contribution in promoting the training of innovative talent in pharmacology. We aim to establish an experimental training program suitable for molecular pharmacology to improve students' ability to engage in drug development in future. Based on the feasibility of drug-target projects, a comprehensive training program containing molecular docking, target stability experiment, and fluorescent probe detection of protein expression in living cells and mice was conducted among 20 pharmacy graduate students. The experimental training was assessed by the experimental training report and the student recognition questionnaires. All 20 students mastered the experimental principles and operations required for the training program. The experimental reports proved that the students were in good command of the experimental principles, operations and applications. The results of the Likert questionnaire indicated that the training program promoted the understanding of the drug research process and increased motivation to learn. The designed experimental training program has a positive effect on the training of pharmacology talents, and can be implemented as a part of molecular pharmacology education.


Decreased expression of HLA class II antigens on human uveal melanoma cells after in vivo X-ray irradiation.
In order to determine the presence of HLA antigens on human uveal melanomas, we tested anti-HLA monoclonal antibodies on tissue sections of these tumors. A great variety in expression of HLA class I and II antigens was present. A significantly lower expression of HLA class II antigens was present on uveal melanomas that had been irradiated before enucleation. These tumors lacked a lymphocytic infiltrate in comparison with nonirradiated tumors. These data suggest that radiotherapy affects expression of histocompatibility antigens on tumors.


Proteomic analysis of phosphoproteins regulated by abscisic acid in rice leaves.
Abscisic acid (ABA) is a hormone that regulates plant development and adaptation to environmental stresses. Protein phosphorylation has been recognized as an important mechanism for ABA signaling. However, the target phosphoproteins regulated by ABA are still largely unknown. Here, we report the identification of ABA-regulated phosphoproteins in rice using proteomic approaches. Six ABA-regulated phosphoproteins were identified as G protein beta subunit-like protein, ascorbate peroxidase, manganese superoxide dismutase, triosephosphate isomerase, putative Ca(2+)/H(+) antiporter regulator protein, and glyoxysomal malate dehydrogenase. These results provide new insight into the regulatory mechanism for some ABA signaling proteins and implicate several previously unrecognized proteins in ABA action.


Activation of human eosinophils in vitro by respiratory syncytial virus.
To determine the nature of the interaction between viruses and eosinophils, normodense eosinophils were separated from the blood of healthy volunteers and incubated in vitro with respiratory syncytial virus (RSV). After incubation for 2 h with the virus, 29.5 +/- 15.8% of the eosinophils demonstrated specific binding of the virus to the cell membrane, as detected by fluorescent staining with an anti-RSV MAb. Superoxide production and leukotriene C4 release were measured as determinants of cell activation. Using a cytochrome c reduction assay, superoxide could be detected in the supernatant 30 min after exposure to RSV. Maximal release was reached at 3 h postexposure (5.88 +/- 2.19 nmol cytochrome c reduction/5 x 10(5) cells). The virus-induced superoxide generation varied in magnitude among different subjects and ranged from 0.6 to 11.5 nmol cytochrome c reduction/5 x 10(5) cells. RSV also appeared to prime eosinophils to the effects of other known cell activators, as demonstrated by an increase in superoxide production upon subsequent stimulation of RSV-primed cells with phorbol-12-myristate-13-acetate (21.4 +/- 5.8 versus 9.4 +/- 2.7 nmol cytochrome c reduction/5 x 10(5) cells for primed and unprimed cells, respectively) (p less than 0.04). RSV did not directly induce leukotriene C4 release from the eosinophils but primed the cells to exhibit a more vigorous response on subsequent challenge with the calcium ionophore A23187 (9.16 +/- 1.04 versus 4.2 +/- 1.3 ng leukotriene C4/1 x 10(6) cells) (p less than 0.005). These findings indicate that RSV can activate or prime eosinophils to release various inflammatory mediators.(ABSTRACT TRUNCATED AT 250 WORDS)


Questioning questions - the perception of f0 scaling in German questions between categorical function and continuous attitude.
In previous studies comparing the intonation of questions and statements in German, greater f0 excursions of phrase-final rises have been associated with questions in both read speech and spontaneous speech. This holds for production studies as well as perception studies. However, a major question remains whether these differences are perceived categorically or continuously. Furthermore, we ask whether the differences in f0 scaling correspond to categorical linguistic functions or rather an attitudinal continuum. We conducted three different perception experiments: a classical categorical perception task, an imitation task, and a semantic evaluation task. The results suggest that f0 scaling in phrase-final rises is perceived as a phonetic continuum rather than in phonological categories. Furthermore, the gradual increase of the final rise is associated with a gradual increase in perceived questioning. Lastly, the phonetic cues to this degree of questioning are distinct from those to the other investigated meanings surprise and uncertainty. Accordingly, this study supports the assumption that questioning constitutes an attitudinal meaning in its own right.


Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1 year later: evaluation of prognostic value.
Primary sclerosing cholangitis (PSC) is a slowly progressive liver disease. Reliable biomarkers to predict outcome are urgently needed to serve as surrogate endpoints and/or stratifiers in clinical trials. Reduction in serum alkaline phosphatase (ALP) has been proposed as prognostic surrogate marker in PSC. The aim of this study was to asses if ALP at diagnosis (T0), 1 year later (T1), and percentage change between both time points hold prognostic value, and to determine the optimal threshold. We retrospectively collected ALP levels at T0 and T1 for patients included in a large PSC cohort. The association of ALP at T0, T1, and percentage change with the combined endpoint (PSC-related death, liver transplantation) was analysed. Predictive value was determined using C-statistics. A total of 366 patients were included, of whom 66 (18%) reached an endpoint: 26 (7%) PSC-related death, 40 (11%) liver transplantation. At T0 and T1, 84% used ursodeoxycholic acid. A positive association was observed between level of ALP at T0 and T1 and the hazard of reaching an endpoint, up to values around 2.5 times upper limit of normal (xULN). A larger decrease in ALP between T0 and T1 decreased the event rate. A range of thresholds (0.5-3×ULN) with about similar C-statistics was found. In this cohort, the optimal threshold was 1.3×ULN at T1. ALP can be used to discriminate between PSC patients with a good and a poor prognosis. These findings indicate that ALP can serve as stratifier, and potentially as surrogate endpoint for clinical trials in PSC.


Changes of Th17 cells, regulatory T cells, Treg/Th17, IL-17 and IL-10 in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
The aim of this study was to investigate the changes of Helper T cells 17 (Th17 cells), Regulatory T cells (Treg cells), Treg/Th17, Interleukin-17 (IL-17) and Interleukin-10 (IL-10) in patients with type 2 diabetes mellitus (T2DM). Four electronic resource databases were searched from their inception to 1 August 2021. Case-control studies about changes of Th17 cells, Treg cells, Treg/Th17, IL-17 and IL-10 in patients with T2DM were retrieved. We performed this meta-analysis via RevMan V.5.3 and Stata14. 20 studies with 1242 individuals were included in the meta-analysis. Compared with the controls, the patients with T2DM had significantly increased levels of percentage of Th17 cells (SMD, 1.74; 95% CI, 0.47-3.01; p < 0.001), IL-17 (SMD, 2.17; 95% CI, 0.06-4.28; p < 0.001), IL-10 (SMD, 1.20; 95% CI, 0.81-1.59; p = 0.003), but decreased levels of percentage of Treg cells (SMD, -1.17; 95% CI, -2.22 to -0.13; p < 0.001) and Treg/Th17 ratio (SMD, -4.43; 95% CI, -7.07 to -1.78; p < 0.001). Subgroup analysis showed that percentage of CD4+CD25+FOXP3+ Tregs (SMD, -2.36; 95% CI, -3.19 to -1.52; p = 0.003) in patients was notably lower than controls. While not significant changes were found in the percentage of CD4+CD25+Tregs (SMD, 0.03; 95% CI, -0.34-0.40; p = 0.63) between patients and controls. For plasma or serum IL-10, a higher plasma IL-10 level (SMD,1.37; 95% CI, 0.92-1.82; p = 0.01) was observed in T2DM. While serum IL-10 (SMD, 0.73; 95% CI, 0.35-1.12; p = 0.79) had no obvious difference between patients and controls. For ELISA or flow cytometry, IL-10 (SMD, 1.2; 95% CI, 0.71-1.70; p = 0.001) was higher in T2DM patients by using detection method of ELISA. Yet IL-10 using flow cytometry and subgroup analysis of IL-17 had no significant differences. Adaptive immune system indeed plays an essential role in the process of T2DM. Imbalance between Th17 and Treg triggers pro-inflammatory environment in patients with T2DM.


Inactivation of superoxide dismutase by several thiocarbamic acid derivatives.
4 thiocarbamic acid derivatives inhibited superoxide dismutase (SOD) activity in vitro. Dimethyldithiocarbamate also inhibited tissue SOD in mice in vivo. These data extend previously published results on the inhibitory action of diethyldithiocarbamate on SOD activity.


Uterine transarterial embolization as nonsurgical management for uterine rupture following vaginal delivery: A report of two cases.
Uterine rupture (UR) is an unexpected, rare, and serious obstetrical condition, occurring in less than 0.1% of pregnancies. Complete UR is defined as a direct communication between the uterine cavity and the peritoneum due to a complete rupture of the myometrium. Here, we present 2 cases of non-surgical management of UR following vaginal delivery, which were both treated by uterine transarterial embolization (UAE). A 26-year-old woman (G0P0) was referred to the emergency ward at 35 weeks of amenorrhea to treat the rupture of membranes, in the context of twin pregnancy. A vaginal delivery was performed and blood loss exceeded 2 liters. Gelatin sponge was injected in an attempt to occlude the right uterine artery. The injection was unsuccessful. After the medical team's discussion, it was decided to definitively occlude the right uterine artery. A 37-year-old woman (G3P3) was referred for a vaginal delivery for a medical termination at 38 weeks of amenorrhea. The ultrasound revealed a left latero-uterine pelvic hematoma, suggestive of UR. Four fibered coils were used to definitively occlude the left uterine artery. Computed tomography scan showed a progressive resorption of hematoma and satisfactory enhancement of the uterine wall in the 2 cases. Transarterial embolization may allow for bleeding to stop without resorting to exploratory laparotomy, with ad-integrum restitution of the uterine wall, and thus prevent a potential hysterectomy. The findings in these 2 cases suggest that UAE should be considered if pregnant women develop UR after delivery.


Role of nitric oxide in the prevention of severe adverse events associated with blood products.
The reduction in vitro of nitric oxide binding to the globin portion of hemoglobin (SNOHb) in fresh and liquid preserved red blood cells has been reported to be responsible for the severe adverse events (SAEs) associated with red blood cell transfusion. No in vivo data were reported that the reduction in SNOHb in red blood cells following transfusion was irreversible. In addition, no clinical data were reported that the reduction in SNOHb in red blood cells produced severe adverse events (SAEs) in recipients.


Radiographic evidence of metaphyseal sclerosis secondary to canine distemper virus: 4 cases in juvenile dogs.
Metaphyseal sclerosis secondary to canine distemper virus has been described histopathologically, but its radiographic appearance has not been described. Describe the radiographic appearance of metaphyseal sclerosis secondary to canine distemper virus in juvenile dogs as distinct from metaphyseal osteopathy (formerly called hypertrophic osteodystrophy). Four dogs (2 intact females and 2 intact males) between 2.5 and 4 months of age presented to 2 different veterinary teaching hospitals. Retrospective case series in which definitive diagnosis of canine distemper virus based on antemortem positive reverse transcription-polymerase chain reaction (RT-PCR) result or necropsy was required. All 4 dogs were presented for evaluation of neurologic abnormalities, respiratory signs, and lethargy; 2 dogs had gastrointestinal signs and ocular abnormalities. Radiographs on all patients featured multifocal, symmetric, metaphyseal sclerosis, with no evidence of lysis or changes to the adjacent growth plate. The metaphyseal sclerosis was most apparent at the proximal humeral diaphyses and other included long bones. Diagnosis of distemper was confirmed by necropsy (2 of 4 dogs) or positive RT-PCR results (2 of 4 dogs). Three dogs were euthanized because of progressive illness, and 1 dog was lost to follow-up. Identification of metaphyseal sclerosis on radiographs during diagnostic evaluation of young dogs should lead to a clinical suspicion of canine distemper virus infection. Sclerosis identified secondary to canine distemper virus is distinct from the necrosis and inflammation of metaphyseal osteopathy.


Development of a capillary electrophoresis-mass spectrometry method for the analysis of metformin and its transformation product guanylurea in biota.
A method with capillary electrophoresis coupled to mass spectrometry was optimized to determine the uptake of metformin and its metabolite guanylurea by zebrafish (Danio rerio) embryos and brown trout (Salmo trutta f. fario) exposed under laboratory conditions. Metformin was extracted from fish tissues by sonication in methanol, resulting in an absolute recovery of almost 90%. For the extraction of guanylurea from brown trout, solid-phase extraction was implemented with a recovery of 84%. The use of a mixture of methanol and glacial acetic acid as a non-aqueous background electrolyte was vital to achieve robust analysis using a bare fused-silica capillary with an applied voltage of +30 kV. Problems with adsorption associated with an aqueous background electrolyte were eliminated using a non-aqueous background electrolyte made of methanol/acetic acid (97:3) with 25 mM ammonium acetate (for zebrafish embryos) or 100 mM ammonium acetate (for brown trouts), depending on the sample complexity and matrix influences. High resolution and high separation selectivity from matrix components were achieved by optimization of the ammonium acetate concentration in the background electrolyte. An extensive evaluation of matrix effects was conducted with regard to the complex matrices present in the fish samples. They required adapting the background electrolyte to higher concentrations. Applying this method to extracts of zebrafish embryos and brown trout tissue samples, limits of detection for both metformin and guanylurea in zebrafish embryos (12.2 μg/l and 15 μg/l) and brown trout tissues (15 ng/g and 34 ng/g) were in the low μg/l or ng/g range. Finally, metformin and guanylurea could be both quantified for the first time in biota samples from exposure experiments.


Comparative studies in two cases of testicular feminization syndrome, one with and the other without the fluorescent distal band q12 of the Y.
In two patients with testicular feminization syndrome, one Yq12-positive and the other Yq12-negative, we compared phenotype, gonadal histology and ultrastructure, in vivo steroid response of the testes to the administration of exogenous gonadotropin during adrenal suppression, and of the adrenal gland to ACTH. The assumption that the constitutive Y heterochromatin could function as a regulator of steroid biosynthesis and metabolism, with or without effect at other levels, was not firmly supported by the observations reported here. However, further studies along this line may help elucidate the biologic role of this portion of the Y chromosome in humans.


Autosuturing device in intestinal urinary conduits.
The autosuturing device has been used to close the base of 41 urinary intestinal conduits: 12 colonic, 25 ileal, and 4 jejunal. The techniques are described. There were no urine or bowel leaks, although in one postoperative gastrointestinal bleeding occurred in association with a partial small-bowel obstruction probably related to the stapled enteroanastomosis. Use of the instruments reduced peritoneal contamination and facilitated conduit manipulation. Operating time was reduced. Four patients have passed stones composed of struvite and apatite with staples embedded within. The autosuturing device should be considered an alternative rather than a substitute for conventional proximal conduit closure and bowel anastomoses.


Adaptive narratives and fantastical falsehoods?
Johnson et al. make a strong case for Conviction Narrative Theory, but it remains unclear why so many adaptive narratives include supernatural causes and other falsehoods. Focusing on religions, I argue that an adaptive decision-making system might include supernatural falsehoods because they simplify complex problems, they are sensitive to long-term incentives, and they evoke strong emotions in a communicative context.


Mechanisms of disease: the evolving understanding of liver allograft rejection.
Liver transplantation is a successful treatment for select forms of liver disease and is unrivalled amongst other forms of solid organ transplantation in the ability of the recipient to develop long-term tolerance to the allograft. Much of this success can be attributed to the inherently tolerogenic manner in which antigens are presented in the liver and the presence of specialized regulatory lymphocyte populations. These observations are not universal, however, and a proportion of recipients develop problematic allograft rejection. Anti-allograft responses lead to an influx of effector cells that target hepatic parenchymal cells and induce apoptosis through members of the tumor necrosis factor superfamily. Anti-rejection therapies have traditionally targeted the entire lymphocyte response against the allograft and, whilst these therapies have been efficacious at limiting effector cell responses, they have also had deleterious effects on the regulatory cell populations that are required to promote long-term tolerance. The emergence of newer anti-rejection drugs that have the potential to target the effector response selectively, whilst preserving the much needed tolerogenic responses, has afforded us the opportunity to refine our future immunosuppressant strategies.


Computerized Analysis of Digital Photographs for Evaluation of Tooth Movement.
Various methods have been introduced for evaluation of tooth movement in orthodontics. The challenge is to adopt the most accurate and most beneficial method for patients. This study was designed to introduce analysis of digital photographs with AutoCAD software as a method to evaluate tooth movement and assess the reliability of this method. Eighteen patients were evaluated in this study. Three intraoral digital images from the buccal view were captured from each patient in half an hour interval. All the photos were sent to AutoCAD software 2011, calibrated and the distance between canine and molar hooks were measured. The data was analyzed using intraclass correlation coefficient. Photographs were found to have high reliability coefficient (P > 0.05). The introduced method is an accurate, efficient and reliable method for evaluation of tooth movement.


Effects of dredging at Aratu port in All Saints Bay, Brazil: monitoring the metal content in water and sediments.
This work reports the chemical monitoring of saline water and sediments at Aratu port, All Saints Bay, Brazil, when subjected to a deep dragging process (DDP) over a 2-year period (2010-2012). The aim of this work was to detect which metals had possible deleterious effects on the biota. It analyzed percentage of silt + clay and TOC and metal concentrations (As, Cd, Cu, Cr, Ni, Pb, and Zn) before, during, and after the DDP. The determination of metal concentration in sediments used the following techniques: atomic absorption spectrometer with flame, also with hydrate generation, and cold vapor spectrophotometry. The DDP disturbed the concentrations of metals in sediments and water, but 15 months after the DDP, only Cu and Zn were detectable on the bottom saline water, and 20 months after the DDP, only Zn was detectable in water. This fact indicates that these metals were longer available for absorption by the marine biota with probable deleterious effect. Indeed, studies by others during the DDP in Aratu port, indicated the decrease from 50 to 40 of the number of microalgae species identified. On the other hand, in the sediments, 20 months after the DDP, the concentrations of As, Cr, Cu, Pb, and Hg, returned to the original values, but Ni and Zn did not return to their original values. Comparison with studies by others indicated that the sediments from dredging were inappropriate for disposal at sea. This work indicated that the metals Cu, Ni, and Zn are the most deleterious elements to the marine environment.


Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells.
We evaluated gene expression profiles after inducing differentiation in cultured interstitial cystitis and control urothelial cells. Bladder biopsies were taken from patients with interstitial cystitis and controls, that is women undergoing surgery for stress incontinence. Primary cultures were grown in keratinocyte growth medium with supplements. To induce differentiation in some plates the medium was changed to Dulbecco's modified Eagle's minimal essential medium-F12 (Media Tech, Herndon, Virginia) with supplements. RNA was analyzed with Affymetrix(R) chips. Three patients with nonulcerative interstitial cystitis were compared with 3 controls. After inducing differentiation 302 genes with a described function were altered at least 3-fold in interstitial cystitis and control cells (p <0.01). Functions of the 162 up-regulated genes included cell adhesion (eg claudins, occludin and cingulin), urothelial differentiation, the retinoic acid pathway and keratinocyte differentiation (eg skin cornified envelope components). The 140 down-regulated transcripts included genes associated with basal urothelium (eg p63, integrins beta4, alpha5 and alpha6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins, and members of the Wnt and Notch pathways. When comparing interstitial cystitis control cells after differentiation, only 7 genes with a described function were altered at least 3-fold (p <0.01). PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased, and AKR1C2 and MKNK1 were increased in interstitial cystitis cases. Differentiation associated changes occurred in interstitial cystitis and control cells. Comparing interstitial cystitis vs control cases revealed few differences. This study may have included patients with interstitial cystitis and minimal urothelial deficiency, and/or we may have selected cells that were most robust in culture. Also, the abnormal urothelium in interstitial cystitis cases may be due to post-translational changes and/or to the bladder environment.


Closed retrograde nailing of pathological humeral fractures.
We treated 19 patients with 21 pathological humeral fractures secondary to metastatic disease. All patients were stabilized using retrograde Ender's nails. Open reduction was required in one patient and mean operative time was 40 min (range 30-65 min). All patients retained satisfactory elbow and shoulder function while 16 patients reported good pain relief. Functional recovery was rated as good in 15 patients, fair in three, and poor in one. In our experience the retrograde technique using Ender's nails provides secure stabilization with minimal morbidity, minimal blood loss, and short operative time, and is well suited for this category of patients.


Delayed retropubic urethroplasty of completely transected female membranous urethra.
Injuries to the female urethra, especially in childhood, are rarely seen with pelvic trauma. Complete transection of the membranous urethra was sustained by a ten-year-old girl in a car accident. A delayed retropubic urethroplasty after suprapubic cystostomy drainage was accomplished. The technique of the repair is described. Delayed repair in a female child is an excellent alternative to primary realignment if a primary repair cannot be accomplished.


Evolutionary origin and functioning of pregenital abdominal outgrowths in a viviparous insect, Arixenia esau.
Although pregenital abdominal outgrowths occur only rarely in pterygote insects, they are interesting from the evolutionary viewpoint because of their potential homology to wings. Our previous studies of early development of an epizoic dermapteran, Arixenia esau revealed that abdominal segments of the advanced embryos and larvae, growing inside a mother's uterus, are equipped with paired serial outgrowths. Here, we focus on the origin and functioning of these outgrowths. We demonstrate that they bud from the lateral parts of the abdominal nota, persist till the end of intrauterine development, and remain in contact with the uterus wall. We also show that the bundles of muscle fibers associated with the abdominal outgrowths may facilitate flow of the haemolymph from the outgrowths' lumen to the larval body cavity. Following completion of the intrauterine development, abdominal outgrowths are shed together with the larval cuticle during the first molt after the larva birth. Using immunohistochemical and biochemical approaches, we demonstrate that the Arixenia abdominal outgrowths represent an evolutionary novelty, presumably related to intrauterine development, and suggest that they are not related to serial wing homologs.


Advancing positive social determinants of health through collective impact and the 100% New Mexico Model.
Communities across the U.S. and globally confront the challenge of transforming negative social determinants of health (SDOH) into positive ones. To address this complex social problem, the collective impact (CI) approach has promise but has been critiqued for insufficiently challenging structural inequities. Research applying CI to SDOH is limited. This mixed-methods study examined early adoption of CI in the 100% New Mexico initiative that aims to address SDOH population-wide in a state with strong cultural identity and assets but also persistent socio-economic inequality. A web-based survey, interviews and focus groups were conducted with initiative participants in June and July 2021. Survey participants rated agreement on a 4-point scale with six items assessing CI foundation adapted from the Collective Impact Community Assessment Scale. Interviews and focus groups centered on motivation to engage, progress achieved in model components, CI core conditions, and contextual factors influencing experiences. Surveys were analyzed using descriptive means and proportions. Qualitative data were analyzed using thematic analysis and an inductive approach followed by stratified analyses and co-interpretation of emergent findings with model developers. Fifty-eight participants completed the survey, and 21 individuals participated in interviews (n = 12) and two focus groups (n = 9). Survey mean scores were highest related to initiative buy-in and commitment, and lower related to shared ownership, having multiple perspectives and voices involved, and adequate resources. Qualitative results showed that the framework's cross-sector emphasis helped motivate participation. Participants embraced the focus on leveraging existing community assets that is characteristic of CI and the current framework. Counties implemented effective engagement and visibility strategies including mural projects and book clubs. Participants expressed communication challenges across county sector teams which influenced feelings of accountability and ownership. Participants did not report challenges lacking relevant, available, and timely data or tension between funder-driven and community-driven desired outcomes, in contrast with previous CI research. Multiple foundational conditions of CI were supported in 100% New Mexico, including evidence for support of the common agenda addressing SDOH, shared measurement framework, and mutually reinforcing activities. Study results suggest that efforts to launch CI to address SDOH, which is by nature multi-sector, should include robust strategies to address communication needs of local teams. The use of community-administered surveys to identify gaps in SDOH resource access contributed to ownership and a sense of collective efficacy that may portend sustainability; however, relying on volunteers in the absence of other resources extensively also threatens sustainability.


Acute sodium valproate intoxication: occurrence of renal failure and treatment with haemoperfusion-haemodialysis.
In a child who probably received an overdose of sodium valproate, progressive coma, intermittent tonic-clonic seizures and anuria developed. Laboratory investigations revealed coagulopathy, and anaemia and mildly disturbed liver function. Progressive renal insufficiency, probably due to rhabdomyolysis and myoglobulinuria, occurred later. Treatment consisted of supportive measures, combined haemoperfusion and haemodialysis and IV thiopentone. Clinical and biochemical normalisation was observed after 11 days.


Live birth following IVF/ICSI using oocytes from donor who was conceived via IVF: a case report.
The purpose of the study was to report a case of live birth following donor oocyte in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in which the oocyte donor herself was conceived via IVF. To our knowledge, such a case has not been previously reported. Retrospective chart review; this case is reported after chart review of a successful outcome. A 42 year-old woman, with diminished ovarian reserve, and her husband desired to conceive. She underwent a fresh IVF/ICSI cycle with her own oocytes, which unfortunately was not fruitful in terms of pregnancy or cryopreserved embryos. The couple was counseled regarding the option of donor oocytes, and they elected to proceed with a fresh cycle of donor oocyte IVF/ICSI. The couple selected an anonymous oocyte donor from a donor agency who was a first-time oocyte donor and, interestingly, was conceived via IVF herself. The fresh donor oocyte/IVF/ICSI cycle did not result in pregnancy; however, two supernumerary blastocysts were cryopreserved for future cycles. The recipient's subsequent frozen-thawed embryo transfer (FET) resulted in a singleton gestation and live birth. An oocyte donor who was conceived via IVF had good ovarian response to stimulation, a good number of oocytes retrieved, and the formation and cryopreservation of blastocysts which, in a subsequent FET cycle, resulted in pregnancy and live birth for a recipient couple. To our knowledge, this is the first case reported of live birth with the use of donor oocytes from an oocyte donor who herself was conceived via IVF.


Organizing principles underlying microorganism's growth-robustness trade-off.
Growth Robustness Reciprocity (GRR) is an intriguing microbial manifestation: the impairment of microorganism's growth enhances their ability to resist acute stresses, and vice-versa. This is caused by regulatory interactions that determine higher expression of protection mechanisms in response to low growth rates. But because such regulatory mechanisms are species-specific, GRR must result from convergent evolution. Why does natural selection favor such an outcome? We used mathematical models of optimal cellular resource allocation to identify the general principles underlying GRR. Non-linear optimization allowed to predict allocation patterns of biosynthetic resources (ribosomes devoted to the synthesis of each cell component) that maximize growth. These models predict the down-regulation of stress defenses under high substrate availabilities and low stress levels. Under these conditions, stress tolerance ensues from growth-related damage dilution: the higher the substrate availability, the fastest the dilution of damaged proteins by newly synthesized proteins, the lower the accumulation of damaged components into the cell. In turn, under low substrate availability growth is too slow for effective damage dilution, and the expression of the defenses up to some optimal level then increases growth. As a consequence, slow-growing cells are pre-adapted to withstand acute stresses. Therefore, the observed negative correlation between growth and stress tolerance can be explained as a consequence of optimal resource allocation for maximal growth. We acknowledge fellowship SFRH/BPD/90065/2012 and grants PEst-C/SAU/LA0001/2013-2014 and FCOMP-01-0124-FEDER-020978 financed by FEDER through the "Programa Operacional Factores de Competitividade, COMPETE" and by national funds through "FCT, Fundação para a Ciência e a Tecnologia" (project PTDC/QUI-BIQ/119657/2010).


Erratum: Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.
[This corrects the article on p. 386 in vol. 10, PMID: 27478544.].


Comparative Study on Pyrolysis Kinetics Behavior and High-Temperature Fast Pyrolysis Product Analysis of Coastal Zone and Land Biomasses.
The pyrolysis characteristics of land biomass (corn stalks (Cs), pine sawdust (Ps)) and coastal zone biomass (Jerusalem artichoke stalks (JAs) and reed (Re)) were investigated based on thermogravimetric analysis (TGA) and products' analysis. The kinetic parameters were obtained by three isoconversional methods (Friedman, KAS, and FWO) and one model-fitting method (DAEM). The simultaneous effect of high temperature (700-900 °C) and high heating rate (1000 °C/s) on the pyrolysis product simulating the typical conditions of a fluidized bed gasifier was studied. TGA showed that high heating rates deepen the thermal cracking process of biomass. Compared with the land biomass, the initial decomposition temperature (T i ) of the coastal biomass is reduced significantly owing to its higher proportion of hemicellulose. These methods agree with the trends shown by the activation energy (E a) distribution calculated, with fluctuations between 160 and 350 kJ/mol. The mean value activation energies of Re and JAs were higher than those of Cs and Ps between 10% and 90% conversion. The DAEM model showed that Cs and JAs have a good linear relationship between ln A and E α during the main pyrolysis stage, while Ps and Re are relatively weaker. The kinetic compensation effect was evident for Cs and JAs during the main thermal cracking stage. Py-GC-MS results confirmed that phenols, hydrocarbons, PAHs, and oxygen heterocycle compounds were strongly present in the released volatile products. High-temperature fast pyrolysis of JAs produced a larger amount of PAH compounds than from Cs, Ps, and Re. A larger amount of hydrocarbons and phenols was generated from high-temperature fast pyrolysis of Ps. Some oxygen-containing volatiles are easily converted into aromatic products with higher stability under high temperature.


Systemic Arterial Hypertension in the Emergency Service: medication adherence and understanding of this disease.
To identify the epidemiological profile of hypertension patients, how much they understand about the disease and the rate of adherence to treatment by these patients who had been hospitalized in the Brazilian emergency service. This cross-sectional study was performed with 116 patients, both male and female and aged over 18 years, who had been hospitalized in the Emergency Service of a University Hospital between March and June, 2013. The studied variables were data referring to socio-demographics, comorbidities, physical activity and knowledge regarding the disease. Patient adherence to treatment and the identification of the barriers were respectively evaluated using the Morisky test and the Brief Medication Questionnaire. Most of the patients involved in this study were women (55%), with white skin color (55%), married (51%), retirees or pensioners (64%) and with a low educational level (58%). Adherence to treatment, in most cases (55%), was moderate and the most prevalent adherence barrier was recall (67%). When medication was acquired at no cost to the patient, there was greater adherence to treatment. This study's patients had a moderate understanding about the disease. The high correlation between the number of drugs used and the recall barrier suggests that monotherapy is an option that can facilitate treatment adherence and reduce how often the patients forget to take their medication.


Exogenous humanin and MOTS-c function as protective agents against gentamicin-induced hair cell damage.
Loss of hair cells can lead to irreversible sensorineural hearing loss. Therefore, hair cell preservation is critical for hearing. Mitochondrial derived peptides (MDPs) are bioactive peptides and prominent members of this family are humanin (HN) and the mitochondrial-open-reading frame of the twelve S c (MOTS-c). The protective roles of HN and MOTS-c in age-related diseases and in various tissues exposed to cellular stresses have been demonstrated. The involvement of MDPs in the inner ear remains to be investigated. Therefore, we determined the expression of rattin, the homolog of humanin, in inner ear tissues. Then, we found that HN and MOTS-c showed a significant protective effect on hair cells in organ of Corti explants exposed to gentamicin. Treatment with HN decreased gentamicin-induced phosphorylation of AKT, whereas treatment with MOTS-c increased phosphorylation of AMPKα in explants. Our data indicate that MDPs exert a protective function in gentamicin-induced hair cell damage. Therefore, MDPs may contribute to design new preventive strategies against hearing loss.


Exploring the release of hazardous volatile organic compounds from face masks and their potential health risk.
Hazardous chemicals released from the petroleum-derived face mask can be inhaled by wearers and cause adverse health effects. Here, we first used headspace solid-phase microextraction coupled with GC-MS to comprehensively analyze the volatile organic compounds (VOCs) released from 26 types of face masks. The results showed that total concentrations and peak numbers ranged from 3.28 to 197 μg/mask and 81 to 162, respectively, for different types of mask. Also, light exposure could affect the chemical composition of VOCs, particularly increasing the concentrations of aldehydes, ketones, organic acids and esters. Of these detected VOCs, 142 substances were matched to a reported database of chemicals associated with plastic packaging; 30 substances were identified by the International Agency for Research on Cancer (IARC) as potential carcinogenic to humans; 6 substances were classified in the European Union as persistent, bioaccumulative, and toxic, or very persistent, very bioaccumulative substance. Reactive carbonyls were ubiquitous in masks, especially after exposure to light. The potential risk of VOCs released from the face masks were then accessed by assuming the extreme scenario that all the VOC residues were released into the breathing air within 3 h. The result showed that the average total concentration of VOCs (17 μg/m3) was below the criterion for hygienic air, but seven substances, 2-ethylhexan-1-ol, benzene, isophorone, heptanal, naphthalene, benzyl chloride, and 1,2-dichloropropane exceeded the non-cancer health guidelines for lifetime exposure. This finding suggested that specific regulations should be adopted to improve the chemical safety of face masks.


Dynamics of melanin-concentrating hormone (MCH) serum levels in major depressive disorder during antidepressant treatment.
In preclinical studies, the hypothalamic polypeptide melanin-concentrating hormone (MCH) has been shown to be involved in depression-like behavior and modulations of MCH and MCH-receptors were proposed as potential new antidepressant drug targets. For the first time, MCH serum levels were explored in 30 patients with major depressive disorder (MDD) prior to (T1) and after 2 (T2) and 4 weeks (T3) of antidepressant treatment and in 30 age- and sex-matched healthy controls by applying a fluorescence immunoassay. Levels of MCH did not differ significantly between un-medicated patients (444.11±174.63pg/mL SD) and controls (450.68±210.03pg/mL SD). In MDD patients, MCH levels significantly decreased from T1 to T3 (F=4.663; p=0.013). Post-hoc analyses showed that these changes were limited to patients treated with mirtazapine but not escitalopram and female but not male patients. MCH-levels showed high correlations from T1 to T3 (r≥0.964, p<0.001) and were found to correlate significantly with parameters of sleep within the controls. Small sample size. No follow-up measures were performed within the control group. Our findings suggest peripheral MCH-levels not to be altered in depression but possibly reflecting depression-related state properties that can be modulated by sleep, medication and sex.


Effect of pulse parameters on ablation efficiency in dual-frequency HIFU therapy.
High-intensity focused ultrasound (HIFU) has now been widely used to ablate various benign and malignant tumors. But it is still critical to increase the ablation efficiency in many clinical applications. Dual-frequency HIFU has been proven to be more efficient in ablation, but the principle on selecting the pulse parameters in this method remains to be explored. In this study, the in vitro lesion areas under different pulse repetition frequencies (PRFs), duty ratios, and frequency differences were compared, cavitation activity was also monitored during HIFU exposure. The results showed that different pulse parameters caused different types of lesions. In HIFU therapy, those pulse parameters that maximize the thermal effect, reduce heat dissipation and generate sufficient cavitation activities should be considered. But the method of evaluating or predicting the damage by using the cavitation dose is only applicable to mechanical damage.


Measurement of hydrostatic intraperitoneal pressure: a useful tool for the improvement of dialysis dose prescription.
The prescription of peritoneal dialysis should be individualized based on parameters of tolerance and adequacy. Determination of the intraperitoneal fill volume is essential for optimal patient care. Fill volume enhancement is a factor of exchange surface area recruitment: the wetted, contact peritoneal dialysis membrane. Nevertheless, fill volume enhancement can also lead to patient discomfort, with the potential risk of too high an intraperitoneal pressure (hernia, gastro-esophageal reflux). The perception of the individual patient is also a subjective parameter of fill volume tolerance assessment. In contrast, measurement of the hydrostatic intraperitoneal pressure (IPP, cmH(2)O) allows an objective approach to fill volume tolerance. From our clinical experience of more than 10 years of IPP measurements in child care, we can give a recommendation for normal values in children: less than 18 cm of water, usually between 5 and 15 cm, correlated to the intraperitoneal fill volume (naturally), but individually taking into account age, gender, "accustomization" and overall body mass index.


Wrong-site surgery: can we prevent it?
Wrong-site surgery happens frequently enough that it is a significant risk for many surgeons during their professional careers. But it is an event that should never happen. Most wrong-site surgery is wrong-side surgery, followed by wrong-digit and wrong-vertebral-level surgery. Wrong-site surgery results from misinformation or misperception of the patient's orientation. The key to preventing wrong-site surgery is to have multiple independent checks of critical information. Discrepancies among the operative record, consent, and the surgeon's record of the history and physical examination should ideally be resolved prior to the day of surgery to avoid time-consuming reconciliations. We noted that the preoperative verification was the most effective of the three steps of the Universal Protocol and that the patient was a more reliable source of accurate information than the documents. Marking the operative site gives patients a voice after they are sedated or anesthesia is induced. Wrong-site surgery has involved local or regional anesthesia at the wrong site when anesthesiologists did not adhere to formal time-outs for their procedures. Surgeons need to have access to all relevant information and to be engaged in the processes to prevent wrong-site surgery, particularly in the final time-out. Junior members of the operating room team must be made comfortable about speaking up if concerned. During spinal surgery, the vertebral level needs to be confirmed radiographically. Wrong-site surgical problems can occur after an operation if accurate information is not provided to accompany the specimen or if leftover labels from a previous patient are used to identify the specimen.


Voltage-induced inhibition of antigen-antibody binding at conducting optical waveguides.
Optical waveguides coated with electrically conducting indium-tin oxide (ITO) are demonstrated here as a new class of substrate for fluorescent immunosensors. These waveguides combine electrochemical control with evanescent excitation and image-based detection. Presented here are preliminary results utilizing these waveguides that demonstrate influence of waveguide voltage on antigen binding. Specifically, waveguide surfaces were bisected into electrically addressable halves, anti-ovalbumin immobilized in patterns on their surfaces, and a 1.3 V bias applied between waveguide halves in the presence of Cy5-labeled ovalbumin in 10 mM phosphate buffer (pH 7.4) containing 150 mM NaCl and 0.05% Tween-20. Fluorescence imaging indicated that binding of the antigen to positively biased waveguide halves was inhibited nearly 10-fold compared with negatively biased waveguide halves and unbiased controls. Furthermore, it is shown that ovalbumin binding to positively biased waveguide regions is regenerated after removal of applied voltage. These results suggest that electrochemical control of immunosensor substrates can be used as a possible strategy toward minimizing cross-reactive binding and/or nonspecific adsorption, immunosensor regeneration, and controlled binding.


Vegetative incompatibility among monoconidial isolates of Bipolaris sorokiniana.
Bipolaris sorokiniana is a phytopathogenic fungus that causes diseases of cereal crops, such as leaf-spot disease, common root rot, and black point of grain. Because of its great morphological, physiological, and genetic variability, this fungus is difficult to control. The aim of this investigation was to study the variability of isolates of B. sorokiniana by means of vegetative incompatibility. Thirty-five isolates of B. sorokiniana from different geographical regions in Brazil and other countries were used. The vegetative incompatibility between the isolates and the influences of different culture media on these reactions were evaluated. The total protein profile of the isolates was analyzed when the isolates were cultured separately, and in cultures of compatibility and incompatibility reactions. Eighteen of 31 confrontations showed vegetative incompatibility. The results obtained with different culture media for the vegetative compatibility/incompatibility genotypes suggested that the type of substratum influences these reactions. No differences in protein profiles among the isolates were observed. This result suggests that there is no induction of expression of different proteins in vegetative incompatibility reactions.


Survival and soluble immune mediators of immune checkpoint inhibitor-induced interstitial lung disease in patients with non-small cell lung cancer.
Immune checkpoint inhibitor-related interstitial lung disease (ICI-ILD) is a serious adverse event frequently observed in patients with non-small cell lung cancer (NSCLC). We investigated the clinical effects and mechanism of action of ICI-ILD in NSCLC patients treated with ICI. We retrospectively screened patients with advanced or recurrent NSCLC who received PD-1/PD-L1 inhibitor monotherapy and examined the prognostic impact of ICI-ILD. In addition, we analyzed the levels of 72 different soluble immune mediators in pre-treatment plasma to explore possible mechanisms associated with the development of ICI-ILD. Furthermore, the relationships between soluble immune mediators associated with ICI-ILD development and survival were analyzed. Of 141 patients with NSCLC, 25 (17.7%) developed ICI-ILD. Logistic regression analysis revealed that pre-treatment CXCL9, MMP-1, IL-6, and IL-19 levels were associated with ICI-ILD development. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between patients with or without ICI-ILD. In patients with ICI-ILD, patients with lower grade ICI-ILD had better OS than those with higher-grade ICI-ILD. In ICI-ILD patients, there was a trend for patients with lower-grade ICI-ILD to have better PFS and OS than those with higher-grade ICI-ILD. Among four soluble immune mediators associated with ICI-ILD, a high level of IL-19 was significantly correlated with worse OS and PFS. The identified soluble immune mediators, including CXCL9, MMP-1, IL-6, and IL-19, may be useful as biomarkers to associate with ICI-ILD development. Although we did not detect significant differences in PFS and OS between patients with and without ICI-ILD, PFS and OS were longer in those with lower-grade ICI-ILD than in patients with higher-grade ICI-ILD. Among biomarkers, IL-19 may be a causal and prognostic factor for ICI-ILD.


Seeing racial avoidance on New York City streets.
Here, using publicly available traffic camera feeds in combination with a real-world field experiment, we examine how pedestrians of different races behave in the presence of racial out-group members. Across two different New York City neighbourhoods and 3,552 pedestrians, we generate an unobtrusive, large-scale measure of inter-group racial avoidance by measuring the distance individuals maintain between themselves and other racial groups. We find that, on average, pedestrians in our sample (93% of whom were phenotypically non-Black) give a wider berth to Black confederates, as compared with white non-Hispanic confederates.


What's new in the localization of sex steroids in the human ovary and its tumors?
It is important to understand the distribution of steroidogenesis in steroid producing tissues in order to obtain a better understanding of steroid metabolism. Recent advances in purification and subsequent generation of antibodies against cytochromes P-450 specific for steroid hormone biosynthesis have made it possible to localize the sites of steroidogenesis immunohistochemically. This review provides the localization of sex-steroid hormone biosynthesis in normal and pathological human ovaries including sex-cord stromal tumors, hyperthecosis and Brenner tumor, as determined by the tissue distribution of immunoreactivity of individual enzymes specific for different stages of the biosynthetic process.