Effects of Exercise on Physical Function and Quality of Life in Prostate Cancer Patients Receiving Androgen Deprivation Therapy: High-Intensity Interval Training versus Moderate-Intensity Continuous Training.
We assessed the effects of exercise on the physical function and health quality of life (hQoL) in prostate cancer patients underwent androgen deprivation therapy (ADT). Additionally, the effects of high-intensity interval training (HIIT) on the physical function and hQoL in these patients were compared with those of moderate-intensity continuous training (MICT). Seventeen prostate cancer patients who underwent ADT were prospectively allocated to either HIIT (n = 9) or MICT (n = 8). In these patients, physical function and hQoL were measured before and after 12 weeks of exercise and 3-6 months after the exercise program, respectively. Although the whole-body total mass significantly increased after the exercise program, it was equivalent regardless of the exercise methods. After the exercise program, muscle strength and endurance improved and tended to be maintained until 3-6 months later. Improvement in muscle endurance was more prominent after HIIT, and that in muscle strength was more prominent after MICT. Performance in the senior fitness test improved after the exercise program, and HIIT was more effective for lower and upper muscle endurance and flexibility, although MICT was more effective for the others. The hQoL significantly improved 3-6 months after the exercise program. The 12-week exercise program has a positive effect on the physical function and hQoL in prostate cancer patients who underwent ADT. In these patients, compared with MICT, HIIT may be a better option for improving muscle endurance, which is thought to be significant for preventing falls and fractures in elderly patients.


Infants' developing sensitivity to native language phonotactics: A meta-analysis.
We used Bayesian modeling to aggregate experiments investigating infants' sensitivity to native language phonotactics. Our findings were based on data from 83 experiments on about 2000 infants learning 8 languages, tested using 4 different methods. Our results showed that, unlike with artificial languages, infants do exhibit sensitivity to native language phonotactic patterns in a lab setting. However, the exact developmental trajectory depends on the phonotactic pattern being tested. Before 8 months, infants tuned into non-local dependencies between vowels: specifically, vowel harmony. Between 8- and 10-months, infants demonstrated a consistent sensitivity to both local dependencies and non-local consonant dependencies. Sensitivity to non-local vowel dependencies that are not based on harmony emerged only after 10-months. These findings provide a benchmark for future experimental and computational research on the acquisition of phonotactics.


Rhodopsin, Zn(2+), and retinitis pigmentosa: a short tale requiring continuation.
Understanding the relationship between the visual pigment rhodopsin and Zn2+ under normal conditions and in case of deficiency of the latter, as well as the realization of the role of Zn2+ in the development of the hereditary disease retinitis pigmentosa, have great theoretical and practical importance. In this mini-review, we briefly examine the basic experimental data on the role of Zn2+ in the retina and photoreceptors, binding of endogenous Zn2+ by zinc-binding sites of differing affinities in rhodopsin, the influence of the exogenous Zn2+ on various properties of rhodopsin, including its ability for phosphorylation and activation of transducin, as well as its thermal stability and regeneration. Conflicting results on the correlation between Zn2+ content in the blood serum and the development of retinitis pigmentosa in patients are demonstrated. The review also shows the success of the application of animal models of induced or hereditary retinal degeneration and discusses some of the methodological approaches and therapeutic techniques to relieve the manifestations of this disease.


Alpha-fetoprotein (AFP) as tumor marker in a patient with urothelial cancer with exceptional response to anti-PD-1 therapy and an escape lesion mimic.
The development of a new lesion in a patient with a complete remission to anti-PD-1 therapy is highly concerning for a drug resistant escape lesion. Here, we present a case of a 62-year-old patient with chemotherapy-resistant metastatic urothelial cancer who had a complete remission to pembrolizumab. The patient's disease burden tracked closely to serum levels of alpha-fetoprotein (AFP) expressed by the tumor and served as an accurate tumor marker. Surveillance imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion in the absence of an increase in AFP levels. Biopsy of this lesion revealed a benign intraparenchymal lymph node with no evidence of metastatic carcinoma. This case indicates that in some patients, biomarkers aberrantly expressed by their tumors, such as AFP in this patient, may be used as a tumor marker for response to anti-PD-1 therapy and emphasizes the importance of confirming potential escape lesions by pathologic examination.


Improvement in PET myocardial perfusion image quality and quantification with flurpiridaz F 18.
Rubidium-82 ((82)Rb), the currently commercially available radiotracer for positron emission tomography (PET) myocardial perfusion imaging (MPI), has led to wide availability of PET-MPI for stress-rest imaging. Compared to SPECT MPI, myocardial perfusion PET images have higher spatial and contrast resolution, are less affected by radiotracer scatter, benefit from more precise attenuation correction, and allow dynamic first pass imaging. In addition, PET imaging allows assessment of myocardial function at peak stress and measurement of absolute myocardial blood flow, thus providing critical data not available with SPECT imaging. Further enhancements of the high quality of PET perfusion images may be realized by technologies under development such as respiratory gating, combined respiratory, and ECG gating to generate "motion-frozen" cardiac images, automated patient motion correction software, and high-definition PET, which reduces distortions introduced by the circular geometry of the scanner. Early studies indicate that the experimental PET radiopharmaceutical flurpiridaz F 18 provides high-quality, high-resolution myocardial perfusion images that may enable improved clinical MPI, and has properties well suited to optimized performance by application of these quantitative analytic technologies.


Cubital tunnel syndrome due to old lateral humeral condyle fractures with gouty stone: A case report.
Cubital tunnel syndrome is a peripheral nerve compression disease, which is caused by the reduction of cubital tunnel space and the compression of ulnar nerve in the cubital tunnel. The main clinical symptoms were numbness and hypoesthesia in the distribution area of ulnar nerve. We report a case of complex cubital tunnel syndrome caused by an old lateral humeral condyle fracture combined with gouty stone compression. Before surgery, the patient's left hypothenar, ring finger and little finger were numb, decreased grip strength, positive paper clamp test. And finger numbness and finger weakness were significantly improved after ulnar nerve release combined with Gout stone resection. In this case report, the elbow joint deformity caused by old lateral humeral condyle fracture was not treated surgically. Only ulnar nerve release combined with Gout stone resection was performed, and the patient's symptoms were significantly relieved. In this case report, for the treatment of cubital tunnel syndrome caused by multiple causes, we only need to find out the main causes of clinical symptoms and targeted treatment, which can not only reduce surgical trauma, but also achieve good treatment results. Its treatment method and treatment result, hoping to provide reference experience forthe diagnosis and treatment of similar diseases.


Could termites be hiding a goldmine of obscure yet promising yeasts for energy crisis solutions based on aromatic wastes? A critical state-of-the-art review.
Biodiesel is a renewable fuel that can be produced from a range of organic and renewable feedstock including fresh or vegetable oils, animal fats, and oilseed plants. In recent years, the lignin-based aromatic wastes, such as various aromatic waste polymers from agriculture, or organic dye wastewater from textile industry, have attracted much attention in academia, which can be uniquely selected as a potential renewable feedstock for biodiesel product converted by yeast cell factory technology. This current investigation indicated that the highest percentage of lipid accumulation can be achieved as high as 47.25% by an oleaginous yeast strain, Meyerozyma caribbica SSA1654, isolated from a wood-feeding termite gut system, where its synthetic oil conversion ability can reach up to 0.08 (g/l/h) and the fatty acid composition in yeast cells represents over 95% of total fatty acids that are similar to that of vegetable oils. Clearly, the use of oleaginous yeasts, isolated from wood-feeding termites, for synthesizing lipids from aromatics is a clean, efficient, and competitive path to achieve "a sustainable development" towards biodiesel production. However, the lacking of potent oleaginous yeasts to transform lipids from various aromatics, and an unknown metabolic regulation mechanism presented in the natural oleaginous yeast cells are the fundamental challenge we have to face for a potential cell factory development. Under this scope, this review has proposed a novel concept and approach strategy in utilization of oleaginous yeasts as the cell factory to convert aromatic wastes to lipids as the substrate for biodiesel transformation. Therefore, screening robust oleaginous yeast strain(s) from wood-feeding termite gut system with a set of the desirable specific tolerance characteristics is essential. In addition, to reconstruct a desirable metabolic pathway/network to maximize the lipid transformation and accumulation rate from the aromatic wastes with the applications of various "omics" technologies or a synthetic biology approach, where the work agenda will also include to analyze the genome characteristics, to develop a new base mutation gene editing technology, as well as to clarify the influence of the insertion position of aromatic compounds and other biosynthetic pathways in the industrial chassis genome on the expressional level and genome stability. With these unique designs running with a set of the advanced biotech approaches, a novel metabolic pathway using robust oleaginous yeast developed as a cell factory concept can be potentially constructed, integrated and optimized, suggesting that the hypothesis we proposed in utilizing aromatic wastes as a feedstock towards biodiesel product is technically promising and potentially applicable in the near future.


Electric footshocks differentially affect plasma and spinal cord vasopressin and oxytocin levels.
Rats exposed for three minutes to repeated electric footshocks showed an approximate 10-fold increase of basal plasma vasopressin (AVP) and oxytocin (OXT) levels. In contrast, spinal AVP and OXT contents measured in the same rats remained unchanged when compared to undisturbed controls. This observation suggests that spinal AVP and OXT do not play a major role in the short-term adaptation of the organism to stress.


Klp10A, a microtubule-depolymerizing kinesin-13, cooperates with CP110 to control Drosophila centriole length.
Klp10A is a kinesin-13 of Drosophila melanogaster that depolymerizes cytoplasmic microtubules. In interphase, it promotes microtubule catastrophe; in mitosis, it contributes to anaphase chromosome movement by enabling tubulin flux. Here we show that Klp10A also acts as a microtubule depolymerase on centriolar microtubules to regulate centriole length. Thus, in both cultured cell lines and the testes, absence of Klp10A leads to longer centrioles that show incomplete 9-fold symmetry at their ends. These structures and associated pericentriolar material undergo fragmentation. We also show that in contrast to mammalian cells where depletion of CP110 leads to centriole elongation, in Drosophila cells it results in centriole length diminution that is overcome by codepletion of Klp10A to give longer centrioles than usual. We discuss how loss of centriole capping by CP110 might have different consequences for centriole length in mammalian and insect cells and also relate these findings to the functional interactions between mammalian CP110 and another kinesin-13, Kif24, that in mammalian cells regulates cilium formation.


Reorganization of seagrass communities in a changing climate.
Although climate change projections indicate significant threats to terrestrial biodiversity, the effects are much more profound and striking in the marine environment. Here we explore how different facets of locally distinctive α- and β-diversity (changes in spatial composition) of seagrasses will respond to future climate change scenarios across the globe and compare their coverage with the existing network of marine protected areas. By using species distribution modelling and a dated phylogeny, we predict widespread reductions in species' range sizes that will result in increases in seagrass weighted and phylogenetic endemism. These projected increases of endemism will result in divergent shifts in the spatial composition of β-diversity leading to differentiation in some areas and the homogenization of seagrass communities in other regions. Regardless of the climate scenario, the potential hotspots of these projected shifts in seagrass α- and β-diversity are predicted to occur outside the current network of marine protected areas, providing new priority areas for future conservation planning that incorporate seagrasses. Our findings report responses of species to future climate for a group that is currently under represented in climate change assessments yet crucial in maintaining marine food chains and providing habitat for a wide range of marine biodiversity.


The role of biofilm formation in the pathogenesis and antimicrobial susceptibility of Cutibacterium acnes.
Cutibacterium acnes (previously known as Propionibacterium acnes) is frequently found on lipid-rich parts of the human skin. While C. acnes is most known for its role in the development and progression of the skin disease acne, it is also involved in many other types of infections, often involving implanted medical devices. C. acnes readily forms biofilms in vitro and there is growing evidence that biofilm formation by this Gram-positive, facultative anaerobic micro-organism plays an important role in vivo and is also involved in treatment failure. In this brief review we present an overview on what is known about C. acnes biofilms (including their role in pathogenesis and reduced susceptibility to antibiotics), discuss model systems that can be used to study these biofilms in vitro and in vivo and give an overview of interspecies interactions occurring in polymicrobial communities containing C. acnes.


Meta analysis of robot-assisted versus conventional laparoscopic fundoplication in children.
Minimally invasive fundoplication may be performed using either a robot-assisted (RF) or conventional laparoscopic (LF) technique. Evidence comparing RF and LF in children remains unclear. This study aims to elucidate the comparative safety and efficacy of RF versus LF by systematic review and meta-analysis. Comparative studies investigating RF versus LF in children were identified from multiple electronic literature databases. Meta-analysis was performed using random effects modeling. Safety parameters investigated were post-operative morbidity and intra-operative conversions. Efficacy outcomes of interest were operative success, re-operation, post-operative complications, length of hospital stay (LOS), total operating time (OT), analgesia requirement, and cost. Six observational studies met inclusion criteria, reporting outcomes of 297 children. No randomized controlled trials were identified. Pooled analysis determined no statistically significant differences between RF and LF for conversions, OT, LOS, and post-operative complications. There was no standardized follow up beyond the early post-operative period to enable data synthesis for remaining outcomes of interest. Limited evidence indicates higher costs with RF. Safety and short-term efficacy seem comparable between RF and LF in children. There is insufficient evidence to assess comparative effectiveness for many important procedure specific outcome measures. Higher quality and longer follow-up studies are required.


Finding citations for PubMed: a large-scale comparison between five freely available bibliographic data sources.
As an important biomedical database, PubMed provides users with free access to abstracts of its documents. However, citations between these documents need to be collected from external data sources. Although previous studies have investigated the coverage of various data sources, the quality of citations is underexplored. In response, this study compares the coverage and citation quality of five freely available data sources on 30 million PubMed documents, including OpenCitations Index of CrossRef open DOI-to-DOI citations (COCI), Dimensions, Microsoft Academic Graph (MAG), National Institutes of Health's Open Citation Collection (NIH-OCC), and Semantic Scholar Open Research Corpus (S2ORC). Three gold standards and five metrics are introduced to evaluate the correctness and completeness of citations. Our results indicate that Dimensions is the most comprehensive data source that provides references for 62.4% of PubMed documents, outperforming the official NIH-OCC dataset (56.7%). Over 90% of citation links in other data sources can also be found in Dimensions. The coverage of MAG, COCI, and S2ORC is 59.6%, 34.7%, and 23.5%, respectively. Regarding the citation quality, Dimensions and NIH-OCC achieve the best overall results. Almost all data sources have a precision higher than 90%, but their recall is much lower. All databases have better performances on recent publications than earlier ones. Meanwhile, the gaps between different data sources have diminished for the documents published in recent years. This study provides evidence for researchers to choose suitable PubMed citation sources, which is also helpful for evaluating the citation quality of free bibliographic databases.


Course of viral hepatitis B and combined B and C hepatitis in children treated for neoplastic diseases.
Viral hepatitis C in children is milder than in adults. Patients with tumors, because of immune deficits, seem to be at risk of rapid liver disease progression. Little is known about the course of HCV and dual HBV-HCV infections in such patients. The study assessed clinical courses of HCV and dual HBV-HCV infections in 249 children with tumors aged 1-18 years, divided into four groups: with HCV infection - 53, HBV-HCV infection - 53, HBV only - 33 and infection-free - 110. Hepatitis C was often chronic - in 83.3% of patients with HCV and 77.3% of those with dual infection. Over 80% had no jaundice. Mean AlAT activity was the highest in the HCV group (149.2I202.7 IU/l), lower in the dual infection group (123.3I148.1 IU/l; p<0.02), and the lowest in HBV (92.7I152.9 IU/l). Transaminasemia course in patients with HCV and dual HBV-HCV infections was most frequently fluctuating (50.9% and 45.3%, respectively). 52.8% of children with HCV demonstrated no advanced inflammatory lesions with invasion of the lamina limitans, no marked fibrosis, and minimum changes in descriptive classification. In 92.3% of children with dual infections, inflammatory activity was mild or mean, with no fibrosis in 61.5%, and persistent chronic inflammation predominant in descriptive classification (46.1%). HCV and HBV-HCV infections in children with neoplastic diseases tend to take chronic forms, but their clinical course is mild with signs of severe inflammatory activity or hepatic stroma remodeling observed on histopathology.


Brain tissue accumulates 67copper by two ligand-dependent saturable processes. A high affinity, low capacity and a low affinity, high capacity process.
We characterized the mechanism of copper accumulation by the brain, using rat hypothalamic tissue slices incubated with 67Cu as a model system. Two ligand-dependent saturable processes were discerned: a high affinity, low capacity process and a low affinity, high capacity process. Vo versus [S] for the high affinity process was a hyperbolic function having an apparent Km and Vmax of 6 microM copper and 23 pmol/min/mg protein, respectively. Vo versus [S] for the low affinity process was a sigmoidal function having an "apparent Km" (So5) and maximal velocity at saturating [S] of 40 microM copper and 425 pmol/min/mg protein, respectively. The two processes were similar in that each exhibited: (a) a requirement for complexing of copper for optimal 67Cu accumulation; (b) a broad ligand specificity with respect to amino acids (histidine, cysteine, threonine, glycine) and peptides (Gly-His-Lys, glutathione) and ineffectiveness of albumin in serving as a facilitatory ligand; (c) a requirement for thermic but not metabolic energy. In spite of these similarities, a 50- or 1000-fold molar excess of ligand (histidine) inhibited 67Cu accumulation by the low affinity process by 60 and 85%, respectively, whereas excess histidine facilitated 67Cu accumulation by the high affinity process by 1.6-4-fold. These results are consistent with 1) a carrier-mediated facilitated diffusion, analogous to that of neutral amino acids, as a means of transporting complexed copper into brain tissue, and 2) the existence of two distinct carrier sites interacting in a positive cooperative manner: a high and a low affinity site.


Theoretical study of mechano-chemical couplings in a compartmental enzyme system. I. Analytical treatment.
This paper deals with theoretical aspects of the volume changes of a system in which diffusion, convection and reaction processes are coupled. This study involves a material able to swell in the presence of a chemical effector produced by an enzyme reaction. Three limiting factors of volume change rate were considered: fluid flow, diffusion or reaction limitations. Dimensionless diffusion-reaction and diffusion-convection parameters were introduced to allow quantitative predictions in limit cases. The steady states appear to be independent of convection processes; however, the transient states depend on diffusion, convection and reaction processes.


Seasonal changes in infaunal community structure in a hypertrophic brackish canal: Effects of hypoxia, sulfide, and predator-prey interaction.
We conducted a one-year survey of macrozoobenthic community structure at 5 stations in a eutrophic canal in inner Tokyo Bay, focusing on the impacts of hypoxia, sediment H2S, and species interaction in the littoral soft-bottom habitats. Complete defaunation or decreasing density of less-tolerant taxa occurred under hypoxia during warmer months, especially at subtidal or sulfidic stations; this was followed by rapid recolonization by opportunistic polychaetes in fall-winter. Sedimentary H2S increased the mortality of macroinvertebrates under hypoxia or delayed population recovery during recolonization. The density of several polychaetes (e.g., Pseudopolydora reticulata) declined in winter, coincident with immigration of the predator Armandia lanceolata. This suggests that absence of A. lanceolata under moderate hypoxia enabled the proliferation of prey taxa. We conclude that oxygen concentration, sediment H2S, and hypoxia-induced changes in species interactions are potential drivers for spatiotemporal changes in macrozoobenthic assemblage structure in hypoxia-prone soft-bottom communities.


Predictors of the multiwire technique use in carotid artery stenting.
The multiwire technique (MWT) in carotid artery stenting (CAS), characterized by the use of more than one guidewire to support guiding catheter in patients with hostile neck anatomy, increases procedural time, enhancing the risk of periprocedural stroke. The aim of the present study was to identify which factors are predictors of the MWT use in CAS, in order to stratify patients with longer procedure at potential higher risk of periprocedural stroke. The study retrospectively included patients who underwent CAS for stenotic plaque between January 2015 and December 2019. Exclusion criteria was incomplete clinical data. For each patients were registered clinical data, main aortic arch and supra-aortic vessel anatomical features, carotid plaque characteristics, and procedural details. The sample was divided in two group on the basis of the number of guides used during the stenting procedure: one guide (standard technique, ST) or more than one guidewire (MWT) to support the guiding catheter. Differences between groups were tested by Chi-square text or Fisher's exact test and Mann-Whitney U test. Logistic regression analysis was used to identify predictors for the use of the MWT. The area under the ROC (AUC) curve was used to assess performance of the model to predict the use of the multiwire technique. The final sample included 146 of the 204 (71%) patients who underwent CAS during the study period. The median age of the patients was 79 years (IQR 71-83 years) with 47/146 (32%) females. CAS was performed with MWT in 17/146 (12%) of the cases. MWT was used more likely in patients with aortic arch type II or III as compared to ST (71% vs 37%, P = 0.02) while plaques with heavy concentric calcifications were more frequent in ST as compared to MWT (38% vs 12%, P = 0.03). At multivariable analysis aortic arch type II or III (OR 5.08, 95% CI 1.48-17.93, P < 0.01), plaque stenosis > 79% (OR 4.13, 95% CI 1.03-16.61, P = 0.04), and plaque heavy concentric calcifications (OR 0.19, 95% CI 0.04-0.94, P = 0.04) were independent predictors of MWT use. The model showed an AUC of 0.827 (95% CI 0.756-0.884) for the prediction of the MWT use during CAS. Aortic arch type II or III, carotid plaque with stenosis higher than 79% of the lumen or without heavy concentric calcifications were predictors for the use of the MWT during CAS. These features should be considered during planning of CAS as hallmark of vascular stiffness and therefore of higher procedure complexity.


Effect of non-steroidal anti-inflammatory drugs on post-surgical complications against the backdrop of the opioid crisis.
The USA is currently going through an opioid crisis, associated with tremendous economic and societal impacts. In response to this crisis, healthcare professionals are looking for alternative pain management methods, and non-steroidal anti-inflammatory drugs (NSAIDs) are a sensible choice because of their effectiveness after surgical procedures. However, before surgeons start prescribing NSAIDs in place of opioids, it is crucial to first understand their potential post-surgical complications. The goal of this review is to summarize the data obtained through both animal and human studies, which suggest how a dramatic increase in NSAID use may affect these post-surgical complications. We first provide a short review outlining the mechanisms of action of NSAIDs, followed by a summary of animal studies, which show a trend towards the negative effects of NSAIDs on wound healing and an association between NSAID use and wound infections. Lastly, we present evidence from human studies on the association of NSAIDs with the following complications: anastomotic leaks, necrotizing soft tissue infections, bleeding complications, orthopedic injuries, wound healing, and cancer care. The human studies are much more variable in their conclusions as to whether NSAIDs are beneficial or not, with the only strong evidence showing that NSAIDs inhibit bone healing. This may partially be explained by male and female differences in response to NSAIDs as many animal studies showing the inhibitory effects of NSAIDs were performed on females, while all the human studies were performed with both sexes. We conclude that strong caution should be used in the prescription of NSAIDs, especially in female patients, but larger scale studies are warranted before solid recommendations can be made.


[Application of the trigemino-facial reflex in acquired peripheral facial paralysis in childhood].
The AA report the results of the blink reflex and facial nerve stimulation in 16 children with acquired facial paralysis. Generally these verifications permitted the localization of the most impaired nerve segment and thereafter to give a recovery prognosis.


Recurrence of renal cell carcinoma more than 5 years after nephrectomy.
We evaluated clinical features and predictive factors for the recurrence of renal cell carcinoma (RCC) developing more than 5 years after nephrectomy. We retrospectively reviewed 239 patients with RCC who underwent surgery for the primary lesion. To identify factors that affected recurrence more than 5 years after nephrectomy (delayed recurrence) and its clinical outcomes, we performed a multivariate analysis using Cox's proportional hazards model and a survival study. Recurrence developing within 5 years after nephrectomy (early recurrence) was found in 57 patients and delayed recurrence in 11 patients. The multivariate analysis revealed no clinical and pathologic features influencing delayed recurrence in 114 patients who survived more than 5 years after nephrectomy without having early recurrence. The patients with delayed recurrence showed better clinical outcomes than those with early recurrence when the rate was determined from the time of recurrence. Although delayed recurrence is not a rare event for patients with RCC, no clinical and pathologic factors at the time of the initial treatment can predict the recurrence. Patients who are free of recurrence for more than 5 years after surgery for a primary lesion should be carefully followed up for delayed recurrence.


[Metabolism of bone in culture (author's transl)].
A method for studying in vitro bone matrix resorption by the use of 35S injection was investigated. Various hormones were tested and their effects on 35S and 45Ca metabolism were compared.


Machine learning versus logistic regression for the prediction of complications after pancreatoduodenectomy.
Machine learning is increasingly advocated to develop prediction models for postoperative complications. It is, however, unclear if machine learning is superior to logistic regression when using structured clinical data. Postoperative pancreatic fistula and delayed gastric emptying are the two most common complications with the biggest impact on patient condition and length of hospital stay after pancreatoduodenectomy. This study aimed to compare the performance of machine learning and logistic regression in predicting pancreatic fistula and delayed gastric emptying after pancreatoduodenectomy. This retrospective observational study used nationwide data from 16 centers in the Dutch Pancreatic Cancer Audit between January 2014 and January 2021. The area under the curve of a machine learning and logistic regression model for clinically relevant postoperative pancreatic fistula and delayed gastric emptying were compared. Overall, 799 (16.3%) patients developed a postoperative pancreatic fistula, and 943 developed (19.2%) delayed gastric emptying. For postoperative pancreatic fistula, the area under the curve of the machine learning model was 0.74, and the area under the curve of the logistic regression model was 0.73. For delayed gastric emptying, the area under the curve of the machine learning model and logistic regression was 0.59. Machine learning did not outperform logistic regression modeling in predicting postoperative complications after pancreatoduodenectomy.


Systems biology approaches in cell signaling research.
The use of methods for global and quantitative analysis of cells is providing new systems-level insights into signal transduction processes. Recent studies reveal important information about the rates of signal transmission and propagation, help establish some general regulatory characteristics of multi-tiered signaling cascades, and illuminate the combinatorial nature of signaling specificity in cell differentiation.


The influence of perceived stress on the human microbiome.
Microbial dysbiosis, a shift from commensal to pathogenic microbiota, is often associated with mental health and the gut-brain axis, where dysbiosis in the gut may be linked to dysfunction in the brain. Many studies focus on dysbiosis induced by clinical events or traumatic incidents; however, many professions in austere or demanding environments may encounter continuously compounded stressors. This study seeks to explore the relationship between microbial populations and stress, both perceived and biochemical. Eight individuals enrolled in the study to provide a longitudinal assessment of the impact of stress on gut health, with four individuals providing enough samples for analysis. Eleven core microbial genera were identified, although the relative abundance of these genera and other members of the microbial population shifted over time. Although our results indicate a potential relationship between perceived stress and microbial composition of the gut, no association with biochemical stress was observed. Increases in perceived stress seem to elucidate a change in potentially beneficial Bacteroides, with a loss in Firmicutes phyla. This shift occurred in multiple individuals, whereas using cortisol as a stress biomarker showed contradictory responses. These preliminary data provide a potential mechanism for gut monitoring, while identifying targets for downstream modulation.


Mitogenic stimulation of mouse lymphoid cells by Aleuria aurantia agglutinin.
An investigation was undertaken to determine if an agglutinin isolated from Aleuria aurantia possesses a mitogenic activity. Proliferation response of mouse lymphoid cell cultures was measured by 3H-thymidine uptake. The results revealed that Aleuria aurantia agglutinin at the concentration of 1 microgram/ml is mitogenic for Thy-1+ splenocytes and cortisone-resistant thymocytes.


Electromotive drug administration of lidocaine to anesthetize the bladder before botulinum-A toxin injections into the detrusor.
Prospective, open label, cross-over-designed clinical study. To evaluate the effectiveness of an instillation of lidocaine into the bladder with versus without electromotive drug administration (EMDA) to anesthetize the bladder before botulinum-A toxin injections. Neurourology, Swiss Paraplegic Center, Balgrist University Hospital, Zurich, Switzerland. In all, 28 patients with severe neurogenic detrusor overactivity but preserved bladder sensibility were treated with botulinum-A toxin injections into the detrusor muscle. A measure of 300 u of botulinum-A toxin (Botox) was injected at 30 sites sparing the trigone. Prior to the injection, the bladder was anesthesized with conventional lidocaine instillation in a group of 10 patients and with lidocaine instillation enhanced by EMDA in 28 patients. The patients scored the injection pain on a 10-point rating scale. Pain rating scores with versus without EMDA enhancement of the lidocaine instillation were analyzed and the costs of the EMDA procedure were compared to general/spinal anesthesia. The mean pain score of the 10 patients who underwent the injections of Botox after conventional lidocaine instillation was 4.0 (SD 1.6). Following EMDA enhanced lidocaine instillation slight even or no pain occurred during the injections of Botox, and the mean pain score was 0.5 (SD 0.2). Compared to spinal or general anesthesia, the local anesthesia saved around 15% of the costs. EMDA enhanced instillation of lidocaine enables a sufficient anesthesia of the bladder wall that ensures a painless application of the botulinum-A toxin injections into the detrusor muscle. This method may avoid general or spinal anesthesia in patients with preserved bladder sensibility. It ensures considerable cost reduction, avoids anesthesia-related risks and complications and enables the procedure on an outpatient basis.


Vasectomy: benefits versus risks.
The benefits and risks of modern vasectomy are presented, including a discussion of precautions and contraindications, the incidence of specific complications and suggestions for minimizing them, and the incidence of and reasons for procedure failures. Long-term side effects, including psychological sequelae, are also discussed.


How to teach the fundamentals of meta-analyses.
Conducting meta-analyses is an exciting and rewarding way of summarizing and quantifying the current knowledge, which is also becoming increasingly important in clinical research. There are many articles published on interpreting meta-analysis and specific statistical methods, which makes it challenging to obtain an overview, also for teachers and supervisors. The aim of this article is to provide a guide for teaching the fundamentals of meta-analysis, with as goal to improve the quality of published meta-analyses. This article provides tips and key references on how to conduct meta-analyses, based on own research, supervising and teaching experience, mainly working with junior clinical researchers. This article contains up-to-date guidelines, practical examples and recommendations to improve the identification and selection of relevant articles, data-extraction, quality assessment, statistical analyses and presentation and publication of results. Time-saving tips and commonly encountered problems such as heterogeneity and publication bias are also discussed. This article is based on recommendations from world renowned organizations and authors, and covers practical examples and pitfalls. Although conducting meta-analysis may seem complex and difficult, it is also achievable for junior researchers and clinicians. Expert guidance is however recommended to achieve high-quality research.


Implications of phenomenological grounding in the "microscopic": an experiential relativity from the microcosmos.
The implications of phenomenological grounding in the microscopic (atomic) level of reality are discussed. In such a state the body is experienced as process within an environment organized by "infinite" time. The world-self phenomenon is experienced as coconstituted, and the feeling of individuality is replaced by the experience of intimate integration.


Synthesis and spectroscopic study on photochromism of a new thiosemicarbazone compound containing pyrazolone.
A new photochromic compound 1,3-diphenyl-4-(4'-fluro)benzal-5-pyrazolone-4-ethyl thiosemicarbazone (DP4FBP-ETSC) was synthesized by direct condensation of 1,3-diphenyl-5-pyrazolone with N4-ethyl thiosemicarbazide. The product was characterized by elemental analysis, IR and 1H NMR spectra. The photochromic properties of the compound were studied using time-dependent fluorescence emission spectra, the UV-vis reflection spectra in the solid state and the UV-vis absorption spectroscopy in liquid. The reaction rate constant of compound was also analyzed. The results show that DP4FBP-ETSC can perform photochromism.


Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor.
We have investigated the effect of oxidants on ligand recognition and internalization by the macrophage mannose receptor. Rat bone marrow macrophages were treated with increasing concentrations of H2O2 for 30 min at 37 degrees C. Fifty percent inhibition of ligand uptake was observed at 250 microM, with only 10% of control uptake remaining following exposure to 1 mM H2O2 for 30 min. Electron micrographic analysis of macrophages following H2O2 treatment showed no morphological alterations compared to untreated cells. Ligand uptake was also inhibited by the following H2O2 generating systems: menadione, xanthine/xanthine oxidase, glucose/glucose oxidase, and phorbol 12-myristate 13-acetate-stimulated polymorphonuclear leukocytes. Inhibition could be blocked by catalase plus or minus superoxide dismutase. Treatment of macrophages at 4 degrees C with H2O2 had no effect on ligand binding, whereas treatment with H2O2 at 37 degrees C reduced binding to 15% of control levels and decreased the number of surface receptors to one-third of control cells. H2O2 treatment inhibited ligand degradation by macrophages, but did not prevent ligand movement from the surface to the interior of the cell. In addition, ligand delivery to lysosomes was blocked by oxidant treatment. These results suggest that treatment of macrophages with reagent H2O2 or H2O2-generating systems inhibits the normal ligand delivery and receptor recycling process involving the mannose receptor. Potential mechanisms might include receptor oxidation, alterations in ATP levels, or membrane lipid peroxidation.


The Effect of Intravenous Infiltration Management Program for Hospitalized Children.
This study aimed to identify the effect of IV infiltration management program among hospitalized children. This was a quasi-experimental study with history comparison group design with 2,894 catheters inserted during 3 months comparison phase and 3,651 catheters inserted during 4 months experimental phase. The intervention was composed of seven activities including applying poster, documentation of catheter insertion, parents education, making infiltration report, assessment of vein condition before inserting catheter, appropriate site selection, and documentation of catheter insertion, and assessment of peripheral catheter insertion site every shift. Data were analyzed using of X2-test, Fisher's exact test. The infiltration incidence rate was 0.9% for experimental group and 4.4% for comparison group, which was significantly different (x2=80.42, p<.001). The catheter maintenance period (p=.035) and infiltration state (p=.039) were significantly different among participants with infiltration between comparison and experimental groups. IV Infiltration management program was founded to be effective in reducing the IV infiltration incidence rate and increasing early detection of IV infiltration. Considering the effect of IV Infiltration management program, we recommend that this infiltration management program would be widely used in the clinical settings.


Potential Treatment of COVID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARS-CoV-2?
Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.


Therapy of endodermal sinus tumor of the ovary.
Endodermal sinus tumor of the ovary can be differentiated histologically and immunohistochemically from ovarian embryonal cell carcinoma. A case report of a patient with endodermal sinus tumor is presented in which a long-term remission was achieved by unilateral adnexectomy and combination chemotherapy. Review of the current literature indicates that tumor removal followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide is the most effective method of therapy for this highly malignant ovarian neoplasm. The addition of hysterectomy with contralateral ovariectomy or radiation therapy does not appear to significantly improve the survival of patients with this tumor. Serial plasma determinations of alpha fetoprotein provide biochemical monitoring of response to therapy and may be useful in predicting occult tumor recurrence.


Interaction of KRSR Peptide with Titanium Dioxide Anatase (100) Surface: A Molecular Dynamics Simulation Study.
Due to its tensile strength and excellent biocompatibility, titanium (Ti) is commonly used as an implant material in medicine and dentistry. The success of dental implants depends on the formation of a contact between the oxidized surface of Ti implant and the surrounding bone tissue. The adsorption of proteins and peptides to the implant surface allows the bone-forming osteoblast cells to adhere to such modified surfaces. Recently, it has been observed that tetrapeptide KRSR (Lys-Arg-Ser-Arg) functionalization could promote osteoblast adhesion to implant surfaces. This may facilitate the establishment of an efficient bone-to implant contact and improve implant stability during the healing process. GROMACS, a molecular dynamics software package was used to perform a 200 ns simulation of adsorption of the KRSR peptide to the TiO2 (anatase) surface in an aqueous environment. The molecule conformations were mapped with Replica Exchange Molecular Dynamics (REMD) simulations to assess the possible peptide conformations on the anatase surface, and the umbrella sampling method was used to calculate the binding energy of the most common conformation. The simulations have shown that the KRSR peptide migrates and attaches to the surface in a stable position. The dominant amino acid residue interacting with the TiO2 surface was the N-terminal charged lysine (K) residue. REMD indicated that there is a distinct conformation that is taken by the KRSR peptide. In this conformation the surface interacts only with the lysine residue while the ser (S) and arg (R) residues interact with water molecules farther from the surface. The binding free energy of the most common conformation of KRSR peptide to the anatase (100) surface was ΔG = -8.817 kcal/mol. Our result suggests that the N-terminal lysine residue plays an important role in the adhesion of KRSR to the TiO2 surface and may influence the osseointegration of dental implants.


Co-culture of endothelial cells and smooth muscle cells affects gene expression of angiogenic factors.
Endothelial cells (EC) are in contact with the underlying smooth muscle cells (SMC). The interactions between EC and SMC in the vessel wall are considered to be involved in the control of growth and function of blood vessels. A co-culture system of EC and SMC and a method for separation of these cells was developed in order to investigate whether the presence of physical contact between EC and SMC affected the gene expression of angiogenic factors. Human EC and SMC were prepared from the great saphenous veins. Autologous EC were added on top of the confluent layer of SMC. After 72 h in co-culture, the EC were magnetically separated from SMC with the use of superparamagnetic beads. RT-PCR products for bFGF, bFGFR, VEGF, PDGF-AA, PDGF-BB, TGF-beta, and beta-actin were analyzed to study the mRNA expressions. The protein level of selected factors was studied by ELISA technique. In co-cultured SMC there was a statistically significant higher gene expression of VEGF, PDGF-AA, PDGF-BB, and TGF-beta and significant lower gene expression of bFGF and its receptor than in single cultured SMC. The protein level of PDGF-BB and TGF-beta was also significantly higher in co-cultured SMC. In co-cultured EC there were no significant differences in gene expression of PDGF-AA, PDGF-BB, and TGF-beta compared with single cultured EC. The gene expression and protein synthesis of VEGF was significantly higher in co-cultured EC. The findings from the present study suggest that cell-cell interactions of EC and SMC affect the gene and protein expression of angiogenic factors.


Neuropathic pain in dogs and cats: if only they could tell us if they hurt.
Neuropathic pain is difficult to diagnose in veterinary patients because they are unable to verbalize their pain. By assuming that neuropathic pain may exist based on the history of events that each patient has experienced, a focused client history and neurologic examination may identify a lesion resulting in persistent or spontaneous pain. Once neuropathic pain is diagnosed, a trial analgesic or acupuncture session(s) should be prescribed with instructions for owners to observe behavior. Dosing of the analgesic can be titrated to the patient's needs while avoiding adverse effects. When a particular analgesic may be ineffectual, an alternate class should be tried. As research into the neurobiologic mechanisms of neuropathic pain continues, specific therapies for its management should eventually appear in the human clinical setting and subsequently be investigated for veterinary clinical use.


Formalin fumigation and steaming of various composts differentially influence the nutrient release, growth and yield of muskmelon (Cucumis melo L.).
Nutrient disorder and presence of disease-causing agents in soilless media negatively influence the growth of muskmelon. To combat these issues, use of environmentally-friendly sanitation techniques is crucial for increased crop productivity. The study was conducted under greenhouse and field conditions to investigate the effect of two different sanitation techniques: steaming and formalin fumigation on various media's characteristics and their impact on muskmelon yield. Media: jantar, guar, wheat straw and rice hull and peat moss of 10% air-filled porosity and sanitized with formalin and steaming. Steaming of guar, jantar, and wheat straw increased the phosphorus (P) and potassium (K) concentrations by 13.80-14.86% and 6.22-8.45% over formalin fumigation. Likewise, P and K concentrations in muskmelon were higher under steaming. Steaming significantly inhibited the survival of Fusarium wilt sp. melonis, root knot nematode sp. meloidogyne and nitrifying bacteria in media than formalin fumigation. In conclusion, steaming decreased the prevalence of nitrifying bacteria and pathogens which thus improved the NO3--N:NH4+-N ratios, P and K nutritional balance both in the media and muskmelon transplants. Hence, steaming as an environment-friendly approach is recommended for soilless media. Further, optimization of steaming for various composts with different crops needs to be investigated with steaming teachnique.


Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway.
Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.


Transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule.
The characteristics of renal transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule were studied. It was found that the uptake of pyruvate in these vesicle preparations occurred by means of multiple transport systems. An electrogenic and Na+-requiring system confined to pars convoluta, exists for transport of pyruvate with an intermediate affinity, KA = 0.71 +/- 0.08 mM. In vesicles from pars recta, the uptake of pyruvate was mediated by a dual transport system with a high (KA1 = 0.30 +/- 0.05 mM) and low affinity (KA2 = 5.75 +/- 0.82 mM). The relation of these three pyruvate transport systems to the transport of other monocarboxylates and dicarboxylates was determined by examination of the inhibitory effect of L-lactate, beta-hydroxybutyrate and L-malate on the renal uptake of pyruvate. It was found that L-malate efficiently reduced the uptake of pyruvate by vesicles from pars convoluta, while addition of monocarboxylates (L-lactate, beta-hydroxybutyrate) has no effect on the transport of pyruvate in this region of proximal tubule. Furthermore, it was observed that Na+-dependent uptake of L-malate was specifically inhibited to about the same extent by 1 mM pyruvate. These findings strongly suggest that pyruvate and L-malate are taken up by the same transport system in vesicles from pars convoluta, which is different from that of L-lactate and beta-hydroxybutyrate. Experiments designed to investigate the substrate specificity for the high and low affinity system for pyruvate in pars recta, revealed that monocarboxylates (L-lactate, beta-hydroxybutyrate) substantially inhibit pyruvate transport at the low, but not the high substrate concentration, indicating that all monocarboxylates compete for the same high-affinity transport system. By contrast, L-malate at low concentrations preferentially inhibited the low-affinity system for pyruvate. This observation led us to suggest that L-malate and pyruvate share a common transport system in pars recta with low affinity for pyruvate and high affinity for L-malate.


Rapid growth of MXene-based membranes for sustainable environmental pollution remediation.
Water consumption has grown in recent years due to rising urbanization and industry. As a result, global water stocks are steadily depleting. As a result, it is critical to seek strategies for removing harmful elements from wastewater once it has been cleaned. In recent years, many studies have been conducted to develop new materials and innovative pathways for water purification and environmental remediation. Due to low energy consumption, low operating cost, and integrated facilities, membrane separation has gained significant attention as a potential technique for water treatment. In these directions, MXene which is the advanced 2D material has been explored and many applications were reported. However, research on MXene-based membranes is still in its early stages and reported applications are scatter. This review provides a broad overview of MXenes and their perspectives, including their synthesis, surface chemistry, interlayer tuning, membrane construction, and uses for water purification. Application of MXene based membrane for extracting pollutants such as heavy metals, organic contaminants, and radionuclides from the aqueous water bodies were briefly discussed. Furthermore, the performance of MXene-based separation membranes is compared to that of other nano-based membranes, and outcomes are very promising. In order to shed more light on the advancement of MXene-based membranes and their operational separation applications, significant advances in the fabrication of MXene-based membranes is also encapsulated. Finally, future prospects of MXene-based materials for diverse applications were discussed.


Deadly Encounter: Endosomes Meet Mitochondria to Initiate Apoptosis.
Mitochondrial outer membrane permeabilization (MOMP) is a crucial event enabling apoptotic cell death. In this issue of Developmental Cell, Wang et al. reveal an interaction contributing to full MOMP execution, which depends on endosomes accumulating on apoptotic mitochondria. This causes mitochondrial lipid alterations that may contribute to functional pore assembly.


Sleep in Children with Autism Spectrum Disorder: A Narrative Review and Systematic Update.
Sleep problems are a common comorbidity for children with autism spectrum disorder (ASD), and research in this area has a relatively long history. Within this review, we first outline historic patterns in the field of sleep and ASD. Second, we conducted a systematic update and coded these studies based on their alignment with historic patterns. Research on ASD and sleep over the past two decades has primarily focused on four principal areas: (1) documenting the prevalence and types of sleep problems; (2) sleep problem treatment options and efficacy; (3) how sleep problems are associated with other behavioral, contextual, or biological elements; and (4) the impact of child sleep problems on families and care providers. The systematic update in this paper includes empirical studies published between 2018 and 2021 with terms for sleep and ASD within the title, keywords, or abstract. In sum, 60 studies fit the inclusion/exclusion criteria and most fit within the historic patterns noted above. Notable differences included more global representation in study samples, studies on the impacts of COVID-19, and a growing body of work on sleep problems as an early marker of ASD. The majority of studies focus on correlates of sleep problems noting less optimal behavioral, contextual, and biological elements are associated with sleep problems across development for children with ASD. Recommendations for future directions include continued expansion of global and age representation across samples, a shift toward more treatment and implementation science, and studies that inform our mechanistic understanding of how sleep and ASD are connected. The online version contains supplementary material available at 10.1007/s40675-022-00234-5.


Biodegradable products by lipase biocatalysis.
The interest in the applications of biocatalysis in organic syntheses has rapidly increased. In this context, lipases have recently become one of the most studied groups of enzymes. We have demonstrated that lipases can be used as biocatalyst in the production of useful biodegradable compounds. A number of examples are given. 1-Butyl oleate was produced by direct esterification of butanol and oleic acid to decrease the viscosity of biodiesel in winter use. Enzymic alcoholysis of vegetable oils without additional organic solvent has been little investigated. We have shown that a mixture of 2-ethyl-1-hexyl esters can be obtained in a good yield by enzymic transesterification from rapeseed oil fatty acids for use as a solvent. Trimethylolpropane esters were also similarly synthesized as lubricants. Finally, the discovery that lipases can also catalyze ester syntheses and transesterification reactions in organic solvent systems has opened up the possibility of enzyme catalyzed production of biodegradable polyesters. In direct polyesterification of 1,4-butanediol and sebacic acid, polyesters with a mass average molar mass of the order of 56,000 g mol-1 or higher, and a maximum molar mass of about 130,000 g mol-1 were also obtained by using lipase as biocatalyst. Finally, we have demonstrated that also aromatic polyesters can be synthesized by lipase biocatalysis, a higher than 50,000 g mol-1 mass average molar mass of poly(1,6-hexanediyl isophthalate) as an example.


Galactokinase deficiency: lessons from the GalNet registry.
Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.


Comparison of induced astigmatism with phacoemulsification and extracapsular cataract extraction.
This paper presents an evaluation of the astigmatism induced in two groups of consecutive surgeries for cataract. At risk is the hypothesis that phacoemulsification (Group 2) induces less astigmatism than extracapsular cataract extraction (Group 1) in a series.


Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride.
We examined a 56-year-old man with keratoconjunctivitis sicca and marked ocular surface disease in whom the prolonged frequent use of topical medications containing the preservative benzalkonium chloride was associated with corneal endothelial damage requiring corneal transplantation in one eye. The histopathologic findings on examination of the excised button were consistent with toxic endothelial disease. Postoperatively, the patient's symptoms continued until the preservative-containing medications were substituted with nonpreserved saline eyedrops.


Medial epicondylar fissure fracture as a complication of transcondylar screw placement for the treatment of humeral intracondylar fissure.
To report the incidence of medial epicondylar fissure fracture (MEFF) after medial-to-lateral transcondylar screw placement in dogs with humeral intracondylar fissure (HIF) and to identify risk factors for MEFF. Retrospective study. Seventy-four client-owned dogs (88 elbows). Medical records of dogs surgically treated for HIF, and postoperative imaging studies were reviewed for demographics, fracture characteristics, and repair techniques. The width of the transcondylar screw was expressed relative to the height of the condyle. Screw angle and degree of countersinking were recorded. Information from case records and follow-up radiographs were used to identify complications. Medial epicondylar fissure fracture was identified in 10 elbows (11.4%) following medial-to-lateral transcondylar screw placement: 4 cases were detected intraoperatively, 2 on immediate postoperative radiographs, 1 during routine radiographic follow up, and 3 when radiographs were reviewed for this study. A larger relative screw size was found to increase the risk of MEFF (P = .004, OR = 1.5). Fifteen additional complications were identified in 13/80 elbows at a median of 6 weeks postoperatively (range 1-56 weeks). Screw loosening was the most frequent complication (n = 9) and was the only complication in dogs with MEFF (n = 3); MEFF tended to increase the risk of perioperative screw loosening (P = .06). Medial epicondylar fissure fracture occurred in 10/88 elbows treated for HIF and was more common in elbows treated with a larger screw size relative to the height of the condyle. Placing transcondylar screws with a diameter inferior to 41% of the height of the condyle is recommended to avoid MEFF. Medial epicondylar fissure fracture appears to have a low clinical significance in the perioperative period, although its effect on long-term outcome remains unknown.


The effect of COVID-19 vaccination on anticoagulation stability in adolescents and young adults using vitamin K antagonists.
The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users. A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events. 101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe. the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.


Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.
The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6-7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, β=-0.12) and follow-up (P=0.002, β=-0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=-0.94%/year and -0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis.


Primary Angioplasty Is the Optimal Approach to Early Reperfusion in Patients with Acute Myocardial Infarction.
Primary angioplasty offers several advantages to thrombolysis for the treatment of acute myocardial infarction. First, most patients are candidates for primary angioplasty. In contrast, only 20--30% meet eligibility criteria for thrombolysis. Second, angioplasty is superior to thrombolysis in achieving infarct artery patency, restoring normal coronary blood flow, and preventing temporary or permanent reocclusion. Third, angioplasty results in lower rates of mortality, recurrent ischemia, or stroke than thrombolysis. Finally, the cost of an angioplasty strategy is lower than the thrombolysis strategy due to earlier hospital discharge, fewer expensive complications, and fewer subsequent procedures and hospitalizations.


Bioactive and UV protective silk materials containing baicalin - The multifunctional plant extract from Scutellaria baicalensis Georgi.
There has been a phenomenal increase in the research and development of new health and hygiene-related textile products. This work reports a novel approach to develop antibacterial, antioxidant and UV-protective silk using an adsorption technique of baicalin (a bioactive ingredient from the root of Scutellaria baicalensis Georgi). Baicalin displayed high adsorption capability at pH2.75, contributing to the sufficient functionalities on silk. The equilibrium adsorption research showed that the Langmuir isotherm was able to describe the behavior of baicalin, indicating the electrostatic interactions between the ionized carboxyl groups in baicalin and the positively charged amino groups in silk. The treated silk with 2% owf (on the weight of fiber) baicalin exhibited excellent antioxidant activity, high antibacterial activities against Escherichia coli and Staphylococcus aureus, and very good ultraviolet protection ability comparable to that of the commercial benzotriazole ultraviolet absorber. The baicalin treatment had no obvious impact on the functional groups, crystal structure and surface morphology of silk. The functionalities of the treated silk obviously declined after first laundering cycle and slowly decreased in the following washing cycles. Encouraging results demonstrate that the baicalin-functionalized silk is a promising material for protective clothing and medical textiles.


Clinical assessment of the Hitachi 736-30 chemistry analyzer.
We assessed the Hitachi 736-30 as a possible replacement for the SMAC I and as a laboratory cost-saving measure. For 24 analytes, both intra- and interassay precisions were acceptable; they also had good measuring ranges. Essentially no interference from lipemia was observed, while minimal interference from bilirubin was demonstrated. Hemoglobin interfered in the measurement of 12 of the analytes. Correlation with the SMAC I, Demand, Astra-8, ACA, and Varian Atomic Absorption Spectrophotometer was found to be acceptable, except for chloride which showed poor correlation with SMAC I and Astra-8 (Hitachi = 0.888 [SMAC] + 11.102, r = 0.9652; Hitachi = 0.885 [Astra] + 10.264, r = 0.9136). The Hitachi 736-30 offers reagent and method flexibility, high volume capability, and "walk-away" operation.


Amelioration of the behavioral phenotype in weaver mutant mice through bilateral intrastriatal grafting of fetal dopamine cells.
Weaver mutant mice lose more than two-thirds of their nigral dopamine neurons. Behaviorally, weaver homozygotes display tremor, gait instability, and toppling over to the sides after a few steps. The recovery of functional responses was determined in a battery of behavioral tests in weaver mutants after bilateral transplantation of mesencephalic cell suspensions (prepared from wild-type mice) to the striatum. Equilibrium was tested by the time mice were able to stay on a suspended balance rod before falling off. Locomotor coordination was measured by the number of times mice toppled over to the sides as they moved about in an open-field matrix. Locomotor activity was quantified by the number of square crossings in an open-field matrix. Grafted weaver mutants performed significantly better than non-grafted mutant mice in all of these three tasks. The findings clearly demonstrate that bilateral transplants of foetal DA cells enhance motor performance in the weaver model of chronic nigrostriatal DA deficiency.


9,10-Phenanthrenequinone induces DNA deletions and forward mutations via oxidative mechanisms in the yeast Saccharomyces cerevisiae.
The estimated cancer risk from diesel exhaust particles (DEP) in the air is approximately 70% of the cancer risk from all air pollutants. DEP is comprised of a complex mixture of chemicals whose carcinogenic potential has not been adequately assessed. The polycyclic aromatic hydrocarbon quinone 9,10-phenanthrenequinone (9,10 PQ) is a major component of DEP and a suspect genotoxic agent for DEP induced DNA damage. 9,10 PQ undergoes redox cycling to produce reactive oxygen species that can lead to oxidative DNA damage. We used two systems in the yeast Saccharomyces cerevisiae to examine possible differential genotoxicity of 9,10 PQ. The DEL assay measures intra-chromosomal homologous recombination leading to DNA deletions and the CAN assay measures forward mutations leading to canavanine resistance. Cells were exposed to 9,10 PQ aerobically and anaerobically followed by DNA damage assessment. The results indicate that 9,10 PQ induces DNA deletions and point mutations in the presence of oxygen while exhibiting negligible effects anaerobically. In contrast to the cytotoxicity observed aerobically, the anaerobic effects of 9,10 PQ seem to be cytostatic in nature, reducing growth without affecting cell viability. Thus, 9,10 PQ requires oxygen for genotoxicity while different toxicities exhibited aerobically and anaerobically suggest multiple mechanisms of action.


Hole traps and Cu-related shallow donors in ZnO nanorods revealed by temperature-dependent photoluminescence.
This work presents positive experimental evidence for the hole traps in ZnO nanorods, which take part in recombination and change the thermal quenching of Cu-related green emission. The evolution of Cu impurity upon annealing, as well as the formation of Cu-related shallow donors with an energy level of ∼0.11 eV are also indicated by temperature-dependent photoluminescence.


Recombinant expression, refolding, purification and characterization of Pseudomonas aeruginosa protease IV in Escherichia coli.
Several protease IV enzymes are widely used in proteomic research. Specifically, protease IV from Pseudomonas aeruginosa has lysyl endopeptidase activity. Here, we report the recombinant expression, refolding, activation, and purification of this protease in Escherichia coli. Proteolytic instability of the activated intermediate, a major obstacle for efficient production, is controlled through ammonium sulfate precipitation. The purified protease IV exhibits superior lysyl endopeptidase activity compared to a commercial product.


Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.
To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population. Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses. We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations. These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.


Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients with metabolic dysfunction-associated fatty liver disease: a population-based cohort study with 9.7 million Korean subjects.
Although an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all- and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single-etiology MAFLD (S-MAFLD) or MAFLD of pure metabolic origin; (2) mixed-etiology MAFLD (M-MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non-MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. Among the 9,718,182 participants, the prevalence of S-MAFLD and M-MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow-up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer-related deaths occurred among the entire cohort. Compared with the non-MAFLD group, the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.04; mortality, aHR = 1.06; 95% CI: 1.04-1.08) and highest among patients with M-MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29-1.32; mortality, aHR = 1.45; 95% CI: 1.42-1.48, respectively). The M-MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all-cancer incidence (aHR = 1.38, 95% CI = 1.36-1.39), followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06-1.11). Similar trends were observed for cancer-related mortality. MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer-related outcomes.


Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy-linked E40K mutation.
Canine degenerative myelopathy (DM), a fatal neurodegenerative disease in dogs, shares clinical and genetic features with amyotrophic lateral sclerosis, a human motor neuron disease. Mutations in the SOD1 gene encoding Cu/Zn superoxide dismutase (SOD1) cause canine DM and a subset of inherited human amyotrophic lateral sclerosis. The most frequent DM causative mutation is homozygous E40K mutation, which induces the aggregation of canine SOD1 but not of human SOD1. However, the mechanism through which canine E40K mutation induces species-specific aggregation of SOD1 remains unknown. By screening human/canine chimeric SOD1s, we identified that the humanized mutation of the 117th residue (M117L), encoded by exon 4, significantly reduced aggregation propensity of canine SOD1E40K. Conversely, introducing a mutation of leucine 117 to methionine, a residue homologous to canine, promoted E40K-dependent aggregation in human SOD1. M117L mutation improved protein stability and reduced cytotoxicity of canine SOD1E40K. Furthermore, crystal structural analysis of canine SOD1 proteins revealed that M117L increased the packing within the hydrophobic core of the β-barrel structure, contributing to the increased protein stability. Our findings indicate that the structural vulnerability derived intrinsically from Met 117 in the hydrophobic core of the β-barrel structure induces E40K-dependent species-specific aggregation in canine SOD1.


Characterization of a quaternary liquid system improving the bioavailability of poorly water soluble drugs.
The aim of this work is the characterization of the quaternary system composed of water, triacetin (oil), ethanol (alcohol), and Tween 80 (surfactant), as its results enable the enhancement of the bioavailability of nimesulide, a poorly water soluble nonsteroidal antiinflammatory drug widely employed in the pharmaceutical field. Particular attention is devoted to the surfactant-free ternary system, as it proved able to solubilize nimesulide as well, and the absence of a surfactant is desirable in order to keep the preparation as tolerable as possible. Both bulk and interfacial properties of this system are investigated, and a mathematical model to calculate the interface composition of a three-component two-phase system is developed. This model is based on Gibbs' theory on interfaces, which considers an arbitrary mathematical dividing surface so that the two phases continue uniformly up to it, although interface regions have no sharply defined boundaries. We find that both the quaternary and the ternary systems investigated show a miscibility lacuna and that, in the surfactant-free ternary system, an increase of the ethanol weight fraction is reflected as an impoverishment of the ethanol interfacial molar fraction.


ivis Dimensionality Reduction Framework for Biomacromolecular Simulations.
Molecular dynamics (MD) simulations have been widely applied to study macromolecules including proteins. However, the high dimensionality of the data sets produced by simulations makes thorough analysis difficult and further hinders a deeper understanding of biomacromolecules. To gain more insights into the protein structure-function relations, appropriate dimensionality reduction methods are needed to project simulations onto low-dimensional spaces. Linear dimensionality reduction methods, such as principal component analysis (PCA) and time-structure-based independent component analysis (t-ICA), could not preserve sufficient structural information. Though better than linear methods, nonlinear methods, such as t-distributed stochastic neighbor embedding (t-SNE), still suffer from the limitations in avoiding system noise and keeping inter-cluster relations. ivis is a novel deep learning-based dimensionality reduction method originally developed for single-cell data sets. Here, we applied this framework for the study of light, oxygen, and voltage (LOV) domains of diatom Phaeodactylum tricornutum aureochrome 1a (PtAu1a). Compared with other methods, ivis is shown to be superior in constructing a Markov state model (MSM), preserving information of both local and global distances, and maintaining similarity between high and low dimensions with the least information loss. Moreover, the ivis framework is capable of providing new perspectives for deciphering residue-level protein allostery through the feature weights in the neural network. Overall, ivis is a promising member of the analysis toolbox for proteins.


Interocular transfer of preoperatively trained visual discriminations in goldfish (Carassius auratus) following selective commissure transections.
Goldfish were monocularly trained on either a red/green or circle/square discrimination task to show a differential classically conditioned cardiac deceleration. Combined section of the minor and horizontal commissure was then performed in animals trained on the colour problem, and transection of the posterior commissure in fish which had acquired the shape task. Both groups were then examined for retention and transfer. The results indicate that the engram for colour is fully represented bilaterally whilst that for shape is only established weakly in the naive side.


A 13C NMR study of poly(adenosine diphosphate ribose) and its monomers: evidence of alpha-(1'' leads to 2') ribofuranosy1 ribofuranoside risidue.
The 13C NMR spectra of poly(adenosine diphosphate ribose), ribosyl adenosine 5', 5''-bis(phosphate) and related compounds were analyzed. The structure of the ribose-ribose linkage was determined as alpha-(1'' leads to 2')ribofuranosyl ribofuranoside, from the 13C chemical shifts of methyl-alpha- and methyl-beta-D-ribofuranosides, and from the downfield displacements of 13C NMR signals by glycosidic bond formation.


Preconcentration and SERS-based determination of infliximab in blood by using a TNF-α-modified gold-coated copper oxide nanomaterial.
Infliximab (INF) is a chimeric monoclonal immunoglobulin acting against tumor necrosis factor-alpha (TNF-α). The drug is used for the treatment of chronic autoimmune and inflammatory diseases. A target-specific nanomaterial is presented for the extraction of INF from human plasma along with a label-free surface enhanced Raman spectroscopy (SERS) method for its determination using a handheld device. A gold-coated copper oxide chip was functionalized with TNF-α and used to extract the drug from plasma. INF was recovered from the extractor by lowering the pH value to 2.5. The disulfide bond structure of the drug was then reduced and used for its oriented chemisorption onto a gold-coated copper oxide substrate for SERS measurements using the INF-specific band at 936 cm-1. The working range of the SERS method was between 10-7 and 10-14 M of reduced INF. The relative standard deviation (RSD), between three different measurements was 4.2% (intra-day) and 7.1% (inter-day). The quantification and detection limits of the assay (LOQ, LOD) were 0.01 pM and 1.4 fM respectively. The SERS detection was cross-validated against ELISA where 99% agreement was found between the two methods. Graphical abstractSchematic representation of the determination of Infliximab (INF) in blood. A gold coated copper oxide chip was functionalised with tumor necrosis factor (TNF-α) and used to extract INF from blood plasma. The captured INF was released, reduced, chemisorbed onto a second gold-coated copper oxide substrate and screened by surface-enhanced Raman spectroscopy (SERS) using a handheld device.


Evaluation of Electrocardiographic T-peak to T-end Interval in Subjects with Increased Epicardial Fat Tissue Thickness.
The association between periatrial adiposity and atrial arrhythmias has been shown in previous studies. However, there are not enough available data on the association between epicardial fat tissue (EFT) thickness and parameters of ventricular repolarization. Thus, we aimed to evaluate the association of EFT thickness with indices of ventricular repolarization by using T-peak to T-end (Tp-e) interval and Tp-e/QT ratio. The present study included 50 patients whose EFT thickness ≥ 9 mm (group 1) and 40 control subjects with EFT thickness < 9 mm (group 2). Transthoracic echocardiographic examination was performed in all participants. QT parameters, Tp-e intervals and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. QTd (41.1 ± 2.5 vs 38.6 ± 3.2, p < 0.001) and corrected QTd (46.7 ± 4.7 vs 43.7 ± 4, p = 0.002) were significantly higher in group 1 when compared to group 2. The Tp-e interval (76.5 ± 6.3, 70.3 ± 6.8, p < 0.001), cTp-e interval (83.1 ± 4.3 vs. 76±4.9, p < 0.001), Tp-e/QT (0.20 ± 0.02 vs. 0.2 ± 0.02, p < 0.001) and Tp-e/QTc ratios (0.2 ± 0.01 vs. 0.18 ± 0.01, p < 0.001) were increased in group 1 in comparison to group 2. Significant positive correlations were found between EFT thickness and Tp-e interval (r = 0.548, p < 0.001), cTp-e interval (r = 0.259, p = 0.01), and Tp-e/QT (r = 0.662, p < 0.001) and Tp-e/QTc ratios (r = 0.560, p < 0.001). The present study shows that Tp-e and cTp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in subjects with increased EFT, which may suggest an increased risk of ventricular arrhythmia.


Increasing the portion size of a sandwich increases energy intake.
This study investigated the effect on energy intake of increasing the portion size of a food served as a discrete unit. A within-subject design with repeated measures was used. The sample comprised 75 young adults (37 females and 38 males) from a university community. Individuals ate lunch in the lab once a week for 4 weeks. Each week, they were served one of four sizes of a deli-style sandwich (6, 8, 10, or 12 inches), of which they could eat as much as they wanted. Energy intakes were determined for each meal, as were ratings of hunger and satiety before and after each meal. A linear mixed model with repeated measures was used. The influence of subject characteristics was examined using analysis of covariance. The portion size of the sandwich significantly influenced lunch intake for both males and females (P<.0001). The majority of individuals consumed the entire 6-inch sandwich. When served the 12-inch sandwich, compared with the 8-inch sandwich, females consumed 12% more energy (74 kcal) and males consumed 23% more energy (186 kcal). Despite these differences, ratings of hunger and fullness were not significantly different after eating the 12-inch and 8-inch sandwiches. These results suggest that increasing the portion size of a food served as a discrete unit leads to increased energy intake at a single meal without differentially influencing ratings of hunger and satiety. Dietitians should educate their clients about strategies to moderate the effect on intake of increased portions of high-calorie foods.


Impaired defense mechanisms in bay mussels, Mytilus edulis, with hemic neoplasia.
Immunocompetence of bay mussels, Mytilus edulis, with hemic neoplasia was investigated with an in vitro yeast phagocytosis assay and by in vivo clearance from the blood of injected Cytophaga sp. bacteria. The yeast phagocytosis assay was conducted with hemocytes maintained in 90% plasma. Neoplastic hemocytes, characterized by enlarged nuclei and scant cytoplasm, failed to phagocytose yeast cells. In contrast, greater than 90% of hemocytes from unaffected animals and morphologically normal hemocytes from mussels with the disease phagocytosed yeast. Substitution of normal plasma with that from a mussel with advanced disease (essentially 100% neoplastic hemocytes) did not affect the phagocytic capability of normal hemocytes. Conversely, normal plasma did not enhance the phagocytic capabilities of neoplastic cells. Mussels with advanced disease showed reduced bacterial clearance; control or lightly affected mussels (less than 11% neoplastic hemocytes) cleared greater than 90% of injected bacteria in 4 hr, while mussels with advanced disease cleared 44-83%. These experiments indicate that mussels with advanced hemic neoplasia have compromised defense systems. This may account for the reported mortality in mussels and other bivalve molluscs with hemic neoplasia.


Stenosis and Pseudostenosis of the Upper Extremity Arteries in Large-Vessel Vasculitis.
Pseudostenosis is a magnetic resonance angiography (MRA) artifact that mimics arterial stenosis. The study objective was to compare imaging and clinical aspects of stenosis and pseudostenosis in a cohort of large-vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu's arteritis (TAK). Patients with LVV and comparator conditions (healthy or vasculopathies) underwent MRA of the aortic arch vessels. The subclavian and axillary arteries were systematically assessed for presence of stenosis and pseudostenosis by two independent readers. Serial and delayed imaging and clinical assessments were used to confirm suspected pseudostenoses. Multivariable regression analyses were used to identify associations between angiographic pathology and clinical findings. 184 MRA scans were analyzed from patients with GCA (n=36), TAK (n=47), and comparators (n=25). Pseudostenoses were frequently observed (48/184 scans, 26%) in the distal subclavian artery only on the side of injection and were shorter in length compared to true stenoses (25 mm vs 78 mm, p<0.01). There was no difference in prevalence of pseudostenosis by diagnosis (GCA=33%, TAK=23%, comparator=20%, p=0.44), disease activity status (p=0.31), or treatment status (p=1.00). Percent and length of true stenosis was independently associated with pulse and blood pressure abnormalities in the upper extremity. Adjusting for length and stenosis degree, absence of collateral arteries was associated with arm claudication (odds ratio=2.37, p=0.03). While a pseudostenosis could be falsely interpreted an arterial stenosis, radiographic and associated clinical features can help distinguish true disease from arterial susceptibility artifacts. In addition, the peripheral vascular examination can help to confirm a suspected true stenosis, as specific aspects of angiographic pathology are associated with vascular examination abnormalities in large-vessel vasculitis.


Gram-negative osteomyelitis: clinical and microbiological profile.
Despite the growing interest in the study of Gram-negative bacilli (GNB) infections, very little information on osteomyelitis caused by GNB is available in the medical literature. To assess clinical and microbiological features of 101 cases of osteomyelitis caused by GNB alone, between January 2007 and January 2009, in a reference center for the treatment of high complexity traumas in the city of São Paulo. Most patients were men (63%), with median age of 42 years, affected by chronic osteomyelitis (43%) or acute osteomyelitis associated to open fractures (32%), the majority on the lower limbs (71%). The patients were treated with antibiotics as inpatients for 40 days (median) and for 99 days (median) in outpatient settings. After 6 months follow-up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was isolated from 101 clinical samples. The most frequently isolated pathogens were Enterobacter sp. (25%), Acinetobacter baumannii (21%) e Pseudomonas aeruginosa (20%). Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for Pseudomonas aeruginosa and 60% for Acinetobacter baumannii. Osteomyelitis caused by GNB remains a serious therapeutic challenge, especially when associated to nonfermenting bacteria. We emphasize the need to consider these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial treatment can be administered since the very beginning of the therapy.


Changes in ovine hepatic circulation and oxygen consumption at birth.
The umbilical vein provides the majority of hepatic blood flow during fetal life. After birth, liver blood flow is derived from the hepatic artery and portal vein, but ductus venosus patency can alter portal venous blood flow to the liver. To characterize changes in hepatic blood flow and oxygen metabolism in the immediate perinatal period, we studied liver and ductus venosus blood flow in seven fetal sheep before and after birth using the radionuclide-labeled microsphere method. Hepatic blood flow fell from 423 +/- 117 (mean +/- SD) mL/min/100 g liver in the fetus to 144 +/- 73 by 2 h after delivery. Although portal venous blood flow increased progressively from 2 to 10 h (137 +/- 48 to 305 +/- 140 mL/min/100 g), because of increasing ductus venosus shunt flow, total hepatic blood flow did not change. Hepatic arterial flow was 46 +/- 24 mL/min/100 g at 2 h, providing 35% of total hepatic blood flow, and did not change over the next 8 h. Hepatic oxygen delivery fell after birth from 58 +/- 25 mL/min/100 g liver in the fetus to 21 +/- 11 at 2 h and then remained constant. Hepatic oxygen consumption was 7.3 +/- 2.6 mL/min/100 g liver in the fetus and ranged from 3.2 +/- 1.5 to 4.1 +/- 1.8 mL/min/100 g liver during the 10 h after birth. Loss of the umbilical-placental circulation at birth substantially reduces hepatic blood flow. Hepatic arterial flow does not increase to compensate for decreases in total hepatic blood flow. The persistent ductus venosus shunt compromises portal venous supply to the liver.(ABSTRACT TRUNCATED AT 250 WORDS)


Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation.
The capacity of dendritic cells (DC) to initiate immune responses is dependent on their specialized migratory and tissue homing properties. Chemotaxis and transendothelial migration (TEM) of DC were studied in vitro. Immature DC were generated by culture of human monocytes in granulocyte-macrophage colony-stimulating factor and IL-4. These cells exhibited potent chemotaxis and TEM responses to the CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and monocyte chemotactic protein-3, and weak responses to the CC chemokine MIP-3beta and the CXC chemokine stromal cell-derived factor (SDF)-1alpha. Maturation of DC induced by culture in lipopolysaccharide, TNF-alpha or IL-1beta reduced or abolished responses to the former CC chemokines but markedly enhanced responses to MIP-3beta and SDF-1alpha. This correlated with changes in chemokine receptor expression: CCR5 expression was reduced while CXCR4 expression was enhanced. These findings suggest two stages for regulation of DC migration in which one set of chemokines may regulate recruitment into or within tissues, and another egress from the tissues.