Effects of captopril on hemodynamic and metabolic parameters in awake endotoxemic Yucatan minipigs.
Angiotensin II (AII), a potent vasoconstrictor, contributes to ischemic and decompensatory phases of shock. Captopril may benefit vital organ and tissue perfusion by inhibiting AII formation. We fitted 13 approximately 50-kg pigs with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate portosystemic and transhepatic kinetics. We placed them in slings 72 hr later and following a 3-hr control period, they were infused with E. coli endotoxin at 15 micrograms/kg/hr for 6 hr. We kept eight as controls and five received a primed (2 mg/kg) continuous infusion (2 mg/kg/hr) of captopril 1 hr after initiation of endotoxin. Arterial hypotension developed by 60 min and hypoglycemia by 100 min in both groups; captopril had no effect on these parameters. Blood lactate increased from 7.8-32.1 mg/dl 80 min postendotoxin, and for the third to fifth hours of endotoxin infusion was significantly higher than those of the control group. 6-3H-glucose-derived appearance (Ra) values remained at 1.88-2.35 mg/kg/min throughout the experiment. Glucose disappearance (Rd) values were elevated from 60-120 min of endotoxin, increasing to 2.68-3.13 mg/kg/min versus 1.86 mg/kg/min preendotoxin. These changes corresponded to those in lactate, and incurred only a brief significant net glucose deficit (%Rd-%Ra) that peaked at 61.1% at 100 min. For 140-360 min postendotoxin, glucose balance was at most 8.3% in deficit (200 min) and 13.6% in positive balance (280 min) versus a net deficit of up to 25.4% (220 min) for the untreated group for much of the experiment. Portal and hepatic venous blood flow in captopril-treated pigs was lower than that in untreated pigs before endotoxin (8.2 and 10.0 ml/kg/min versus 12.9 and 17.9 ml/kg/min, respectively), but was not depressed following endotoxin infusion, versus 50% reductions in the untreated pigs, postendotoxin. Captopril maintained hepatosplanchnic blood flow and effected modest improvements in glucose kinetics.


Shared Concerns and Opportunity for Joint Action in Creating a Food Environment That Supports Health.
The food industry is a for-profit industry with high relevance to universal eating disorders prevention. To date, policy which targets the food industry and food environment has been underutilized in efforts to decrease the incidence of eating disorders and associated risk factors. In contrast, food policy has been extensively leveraged with the aim of reducing the incidence of obesity. While philosophical misalignments with these later efforts may have constituted an obstacle to identifying the food environment as a key target for eating disorders prevention, food policy is an area where shared interests can be found. Specifically, a shared goal of obesity and eating disorders prevention efforts is creating a food environment that supports health, while minimizing the influence of the food industry that profits from the sale of highly palatable, processed foods and "diet" foods and from increasing portions of foods served and eaten.


Evaluation of Ovarian Reserve Tests and Age in the Prediction of Poor Ovarian Response to Controlled Ovarian Stimulation-A Real-World Data Analysis of 89,002 Patients.
This study aimed to explore the value of ovarian reserve tests (ORTs) for predicting poor ovary response (POR) and whether an age cutoff could improve this forecasting, so as to facilitate clinical decision-making for women undergoing in vitro fertilization (IVF). A retrospective cohort study was conducted on poor ovary response (POR) patients using real-world data from five reproductive centers of university-affiliated hospitals or large academic hospitals in China. A total of 89,002 women with infertility undergoing their first traditional ovarian stimulation cycle for in vitro fertilization from January 2013 to December 2019 were included. The receiver operating characteristic (ROC) curve was performed to estimate the prediction value of POR by the following ORTs: anti-Mullerian hormone (AMH), antral follicle count (AFC), basal FSH (bFSH), as well as patient age. In this retrospective cohort, the frequency of POR in the first IVF cycle was 14.8%. Age, AFC, AMH, and bFSH were used as predicting factors for POR, of which AMH and AFC were the best indicators when using a single factor for prediction (AUC 0.862 and 0.842, respectively). The predictive values of the multivariate model included age and AMH (AUC 0.865), age and AFC (AUC 0.850), age and all three ORTs (AUC 0.873). Compared with using a single factor alone, the combinations of ORTs and female age can increase the predictive value of POR. Adding age to single AMH model improved the prediction accuracy compared with AMH alone (AUC 0.865 vs. 0.862), but the improvement was not significant. The AFC with age model significantly improved the prediction accuracy of the single AFC model (AUC 0.846 vs. 0.837). To reach 90% specificity for POR prediction, the cutoff point for age was 38 years old with a sensitivity of 40.7%, 5 for AFC with a sensitivity of 55.9%, and 1.18 ng/ml for AMH with a sensitivity of 63.3%. AFC and AMH demonstrated a high accuracy when using ROC regression to predict POR. When testing is reliable, AMH can be used alone to forecast POR. When AFC is used as a prediction parameter, age is suggested to be considered as well. Based on the results of the cutoff threshold analysis, AFC ≤ 5 and AMH ≤ 1.18 ng/ml should be recommended to predict POR more accurately in IVF/ICSI patients.


Higher Flow on Cardiopulmonary Bypass in Pediatrics Is Associated With a Lower Incidence of Acute Kidney Injury.
Adequate perfusion is of paramount concern during cardiopulmonary bypass (CPB) and different methodologies are employed to optimize oxygen delivery. Temperature, hematocrit, and cardiac index (CI) are all modulated during CPB to ensure appropriate support. This study examines 2 different perfusion strategies and their impact on various outcome measures including acute kidney injury (AKI), urine output on CPB, ICU length of stay, time to extubation, and mortality. Predicated upon surgeon preference, the study institution employs 2 different perfusion strategies (PS) during congenital cardiac surgery requiring CPB. One method utilizes a targeted 2.4 L/min/m2 CI and nadir hematocrit of 28% (PS1), the other a 3.0 L/min/m2 CI with a nadir hematocrit of 25% (PS2). This study retrospectively examines CPB cases during which the 2 perfusion strategies were applied to determine potential differences in packed red blood cell administration, urine output during CPB, AKI post-CPB as defined by the KDIGO criteria, and operative survival as defined by the Society of Thoracic Surgeons. Significant differences were found in urine output while on CPB (P < 0.01) and all combined stages of postoperative AKI (P = 0.01) with the PS2 group faring better in both measures. No significant difference was found between the 2 groups for packed red blood cell administration, mortality, time to extubation, or ICU length of stay. Avoiding a nadir hematocrit less than 25% has been well established but maintaining anything greater than that may not be necessary to achieve adequate oxygen delivery on CPB. Our results indicate that higher CI and oxygen delivery on CPB are associated with a lower rate of AKI and this may be achieved with increased flow rather than increasing the hematocrit thus avoiding unnecessary transfusion.


Postmortem abdominal radiographic findings in feline cadavers.
Postmortem radiographic examinations of animals are commonly performed in judicial investigations to rule out gunshot and fractures. However, there was no available data on radiographic postmortem changes of animals. Forty-one sets of abdominal radiographs of feline cadavers made within 12 h of death were evaluated for postmortem changes. Intravascular gas was detected in 11 of 41 (27%) cadavers. The most common site of intravascular gas was the liver. Intravascular gas was also present in the aorta, femoral artery, celiac and cranial mesenteric arteries, and caudal superficial epigastric artery. Intrasplenic gas was detected in two cadavers. Only two cadavers had distended small intestine. One cadaver had pneumatosis coli. The changes detected were most likely due to putrefaction.


The Use of Virtual Reality in Back Pain Rehabilitation: A Systematic Review and Meta-Analysis.
This systematic review aimed to synthesize the existing evidence of extended reality (XR) on pain and motor function outcomes in patients with back pain. Following the Cochrane guidelines, relevant articles of any language were selected by 2 independent reviewers from CINAHL, Cochrane, Embase, Medline and Web of Knowledge databases. Of 2,050 unique citations, 24 articles were included in our review. These studies included a total of 900 back pain patients. Despite broader XR search, all interventions were virtual reality (VR) based and involved physical exercises (n = 17, 71%), hippotherapy (n = 4, 17%), motor imagery (n = 1, 4%), distraction (n = 1, 4%), and cognitive-behavior therapy (n = 1, 4%). Sixteen controlled studies were included in a meta-analysis which suggested that VR provides a significant improvement in terms of back pain intensity over control interventions (Mean Difference: -0.67; 95% CI: -1.12 to -0.23; I2 = 85%). Almost all included studies presented high risk of bias, highlighting the need to improve methodology in the examination of VR interventions. While the specific set of studies showed high heterogeneity across several methodological factors, a tentative conclusion could be drawn that VR was effective improving back pain intensity and tends to have a positive effect on improving other pain outcomes and motion function. PERSPECTIVE: Extended reality technologies have appeared as interesting nonpharmacological options for the treatment of back pain, with the potential to minimise the need for opioid medications. Our systematic review summarised existing applications of extended reality for back pain and proposed a few recommendations to direct further studies in the field.


Male size, sperm transfer, and colony fitness in the western harvester ant, Pogonomyrmex occidentalis.
Mating success in the western harvester ant, Pogonomyrmex occidentalis, increases with male size. We tested the hypothesis that increased mating success increases male fitness and the fitness of colonies that make large males by comparing the sperm content of males prior to and at the conclusion of the mating swarm. The number of sperm a male initially possesses is a function of male size, and large males transfer a greater proportion of their sperm than do small males. For colonies, the payoff per unit of investment is an increasing function of male size, and investment in large males is not equivalent to investing in a larger number of small males. Allocation ratios in species that show size variation in reproductives may need to be modified by the individual fitness functions.


A cases series of endovascular and microsurgical combined treatment of intracranial aneurysms.
Our scientific paper is aimed at describing multimodal treatment of intracranial aneurysms represented by microsurgery and endovascular therapy. We report four cases of intracranial aneurysms treated in our Department of Neurosurgery by microsurgery (clipping) and endovascular treatment (coiling), through the joint efforts of a team of highly skilled neurosurgeons. Mixed treatment has been imposed by the complications we were presented with, resulting from either of the two surgical methods employed. Although endovascular surgery is considered a newer treatment method, favored by many practitioners, and preferred by patients, there are situations where open surgery is still required. There are certain situations were using one of the surgical methods fails and a complementary procedure is required for a secure and successful treatment. The cases reported here will demonstrate the utility of combining the two procedures.


Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study.
Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with "elevated" PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14-15.6), and the median follow-up PSA was 5.08 (IQR: 3.18-8.4). At a median follow-up of 53 months (range: 6-77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.


Gender differences in views about cognitive health and healthy lifestyle behaviors among rural older adults.
Research suggests that men and women often differ in knowledge and beliefs about causes and treatments of a variety of diseases. This study examines gender differences in views about cognitive health and behaviors that have been associated with its maintenance, focusing on older adults living in rural areas. We conducted 6 focus groups in rural West Virginia. Participants included 37 women and 30 men, aged 55 years and older. Men and women held similar views of cognitive decline, as well as largely similar views about causes of Alzheimer's disease (AD). However, women were more concerned about developing AD than were men. Gender differences were also noted with respect to healthy lifestyle beliefs, including diet, leisure-time physical activity, and strategies to maintain cognitive health. Findings illustrate the importance of considering gender with respect to health beliefs, health behaviors, and health promotion, and emphasize the need to develop interventions designed for specific populations. Results highlight a critical need to translate research findings to the community.


Automatic Identification of Information Quality Metrics in Health News Stories.
Objective: Many online and printed media publish health news of questionable trustworthiness and it may be difficult for laypersons to determine the information quality of such articles. The purpose of this work was to propose a methodology for the automatic assessment of the quality of health-related news stories using natural language processing and machine learning. Materials and Methods: We used a database from the website HealthNewsReview.org that aims to improve the public dialogue about health care. HealthNewsReview.org developed a set of criteria to critically analyze health care interventions' claims. In this work, we attempt to automate the evaluation process by identifying the indicators of those criteria using natural language processing-based machine learning on a corpus of more than 1,300 news stories. We explored features ranging from simple n-grams to more advanced linguistic features and optimized the feature selection for each task. Additionally, we experimented with the use of pre-trained natural language model BERT. Results: For some criteria, such as mention of costs, benefits, harms, and "disease-mongering," the evaluation results were promising with an F1 measure reaching 81.94%, while for others the results were less satisfactory due to the dataset size, the need of external knowledge, or the subjectivity in the evaluation process. Conclusion: These used criteria are more challenging than those addressed by previous work, and our aim was to investigate how much more difficult the machine learning task was, and how and why it varied between criteria. For some criteria, the obtained results were promising; however, automated evaluation of the other criteria may not yet replace the manual evaluation process where human experts interpret text senses and make use of external knowledge in their assessment.


Biomedical imaging ontologies: A survey and proposal for future work.
Ontology is one strategy for promoting interoperability of heterogeneous data through consistent tagging. An ontology is a controlled structured vocabulary consisting of general terms (such as "cell" or "image" or "tissue" or "microscope") that form the basis for such tagging. These terms are designed to represent the types of entities in the domain of reality that the ontology has been devised to capture; the terms are provided with logical definitions thereby also supporting reasoning over the tagged data. This paper provides a survey of the biomedical imaging ontologies that have been developed thus far. It outlines the challenges, particularly faced by ontologies in the fields of histopathological imaging and image analysis, and suggests a strategy for addressing these challenges in the example domain of quantitative histopathology imaging. The ultimate goal is to support the multiscale understanding of disease that comes from using interoperable ontologies to integrate imaging data with clinical and genomics data.


The morphology, ultrastructure, and distribution of synapses on an intersegmental interneuron of the locust.
The structure and synaptic relationships of an intersegmental interneurone in the mesothoracic ganglion of the locust were studied by intracellular labelling for light and electron microscopy. Before labelling, the interneurone was characterized physiologically. It is depolarized and produces spikes when either of the two forewings are elevated, and by sensory inputs from the tarsi of the middle legs. The gross morphology of the interneurone is quite distinctive. Its cell body is on the ventral surface of the ganglion near the midline and its primary neurite lies in the T-tract. Its axon performs a characteristic lateral loop around the lateral dorsal tract before entering an anterior connective and ascending at least as far as the prothoracic ganglion. Within the mesothoracic ganglion, the interneurone gives rise to a profusion of branches. Ultrastructural examination and reconstruction of three regions of the interneurone from serial sections shows that input and output synapses are present in approximately equal numbers, and often are close to each other. There is no evidence for separate input and output regions. Output synapses are characterized by the presence of a presynaptic bar and a population of 500-2,000 round, electron-lucent vesicles. Most of the estimated 10(5)-10(6) synapses occur on the smaller diameter processes or on spines. The spines are of uniform diameter along their lengths, and are pre- or postsynaptic or both, but the postsynaptic spines are of smaller diameter than the others.


Assessing the robustness of positive vascular surgery randomized controlled trials using their fragility index.
The fragility index (FI) measures the robustness of statistically significant findings in randomized controlled trials (RCTs) by quantifying the minimum number of event conversions required to reverse a dichotomous outcome's statistical significance. In vascular surgery, many clinical guidelines and critical decision-making points are informed by a handful of key RCTs, especially regarding open surgical versus endovascular treatment. The objective of this study is to evaluate the FI of RCTs with statistically significant primary outcomes that compared open vs endovascular surgery in vascular surgery. In this meta-epidemiological study and systematic review, MEDLINE, Embase, and CENTRAL were searched for RCTs comparing open versus endovascular treatments for abdominal aortic aneurysms, carotid artery stenosis, and peripheral arterial disease to December 2022. RCTs with statistically significant primary outcomes were included. Data screening and extraction were conducted in duplicate. The FI was calculated by adding an event to the group with the smaller number of events while subtracting a nonevent to the same group until Fisher's exact test produced a nonstatistically significant result. The primary outcome was the FI and proportion of outcomes where the loss to follow-up was greater than the FI. The secondary outcomes assessed the relationship of the FI to disease state, presence of commercial funding, and study design. Overall, 5133 articles were captured in the initial search with 21 RCTs reporting 23 different primary outcomes being included in the final analysis. The median FI (first quartile, third quartile) was 3 (3, 20) with 16 outcomes (70%) reporting a loss to follow-up greater than its FI. Mann-Whitney U test revealed that commercially funded RCTs and composite outcomes had greater FIs (median, 20.0 [5.5, 24.5] vs median, 3.0 [2.0, 5.5], P = .035; median, 21 [8, 38] vs median, 3.0 [2.0, 8.5], P = .01, respectively). The FI did not vary between disease states (P = .285) or between index and follow-up trials (P = .147). There were significant correlations between the FI and P values (Pearson r = 0.90; 95% confidence interval, 0.77-0.96), and the number of events (r = 0.82; 95% confidence interval, 0.48-0.97). A small number of event conversions (median, 3) are needed to alter the statistical significance of primary outcomes in vascular surgery RCTs evaluating open surgical and endovascular treatments. Most studies had loss to follow-up greater than its FI, which can call into question trial results, and commercially funded studies had a greater FI. The FI and these findings should be considered in future trial design in vascular surgery.


Localization of metabotropic GABA receptor subunits GABAB1 and GABAB2 relative to synaptic sites in the rat developing cerebellum.
The highest densities of the two metabotropic GABA subunits, GABAB1 and GABAB2, have been reported as occurring around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. In order to determine how this distribution is achieved during development, we investigated the expression pattern and the cellular and subcellular localization of the GABAB1 and GABAB2 subunits in the rat cerebellum during postnatal development. At the light microscopic level, immunoreactivity for the GABAB1 and GABAB2 subunits was very prominent in the developing molecular layer, especially in Purkinje cells. Using double immunofluorescence, we demonstrated that GABAB1 was transiently expressed in glial cells. At the electron microscopic level, immunoreactivity for GABAB receptors was always detected both pre- and postsynaptically. Presynaptically, GABAB1 and GABAB2 were localized in the extrasynaptic membrane of parallel fibres at all ages, and only rarely in GABAergic axons. Postsynaptically, GABAB receptors were localized to the extrasynaptic and perisynaptic plasma membrane of Purkinje cell dendrites and spines throughout development. Quantitative analysis and three-dimensional reconstructions further revealed a progressive developmental movement of the GABAB1 subunit on the surface of Purkinje cells from dendritic shafts to its final destination, the dendritic spines. Together, these results indicate that GABAB receptors undergo dynamic regulation during cerebellar development in association with the establishment and maturation of glutamatergic synapses to Purkinje cells.


Some clinico-pathologic and prognostic data in malignant lymphomas seen at Kenyatta National Hospital over a 13 year period.
Records were available for 197 patients with malignant lymphomas (MLs) aged 13 years and above seen at Kenyatta National Hospital (KNH) between the years 1973 and 1986. There were 110 cases of Hodgkin's disease (HD) and 87 cases of non-Hodgkin's lymphomas (NHLs). The distribution of the two groups according to sex and histologic sub-types was not significantly different. HD patients were on average significantly younger than NHL patients (28.8 years versus 41.1 years). Over 70% of both HD and NHL cases presented in stages III and IV and the distribution of the groups according to stage of disease was not statistically significant. There was no significant correlation between stage of disease at diagnosis and histologic subtypes for either group. Losses to follow-up were high in both groups. Female sex was associated with longer periods of follow-up in both groups, being statistically significant for HD and not so for NHLs. Age was not correlated with duration of follow-up for NHLS whereas for HD cases, older age (above 53 years) was associated with shortened follow-up periods. The mortality rate was higher in NHLs than in HD cases.


Post-thoracotomy intercostal block: comparison of its effects on pulmonary function with those of intramuscular meperidine.
Study of 34 patients who had undergone thoracotomy revealed that the group given intercostal nerve block analgesia had a significantly smaller decline in vital capacity after operation than did the group given narcotic analgesia only. The postoperative increase in arterial CO2 tension of the nerve block group also was significantly smaller than that of the narcotic group. The study suggests that intercostal nerve block for post-thoracotomy analgesia offers some advantage in preserving effort-dependent pulmonary function when compared with postoperative narcotic analgesia.


Cloning and genomic organization of the TTL gene on mouse chromosome 2 and human chromosome 2q13.
Tubulin tyrosine ligase (TTL) is a cytosolic enzyme involved in the posttranslational modification of tubulin. In the assembled form microtubules are detyrosinated over time at the C-terminus of alpha-tubulin. After microtubular disassembly TTL restores tyrosine residues back to the detyrosinated tubulin leading to a cycle of detyrosination/tyrosination. Here we report the isolation of the human and mouse TTL cDNA. In comparison with other known TTL sequences, namely bovine, rat and porcine, we found that only porcine TTL deviates in length by having an insertion of two glutamate residues. In mouse and human TTL the genomic coding sequence is composed of seven exons with normal intron/exon boundaries. Using fluorescence in situ hybridization (FISH), we mapped the murine TTL gene to mouse chromosome 2 (MMU2). Human TTL has been located to chromosome 2q13 (HSA2q13). In addition, we found frequently truncated PCR products of hTTL transcripts with aberrant splicing in tumors.


Complete Genome Sequencing of a Multidrug-Resistant and Human-Invasive Salmonella enterica Serovar Typhimurium Strain of the Emerging Sequence Type 213 Genotype.
Salmonella enterica subsp. enterica serovar Typhimurium strain YU39 was isolated in 2005 in the state of Yucatán, Mexico, from a human systemic infection. The YU39 strain is representative of the multidrug-resistant emergent sequence type 213 (ST213) genotype. The YU39 complete genome is composed of a chromosome and seven plasmids.


Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis.
Myelin basic protein (MBP) or helper T cells reactive against MBP induce an autoimmune disease, experimental allergic encephalomyelitis, in B10.PL and PL/J inbred mice. In both strains, virtually the entire repertoire of MBP-specific T cells recognize an N-terminal peptide fragment in the context of the I-Au molecule encoded by the major histocompatibility complex (MHC) and utilize a very limited set of T-cell receptor genes. To delineate the nature of the trimolecular complex, consisting of the T-cell receptor, MBP-peptide fragment, and MHC molecule (I-Au), we have synthesized 13 variants of the 9-mer N-terminal immunodominant peptide differing at residue 4 and studied their immune recognition in vitro and in vivo. These substitutions have a striking range of effects on T-cell activation, ability to bind to the MHC molecule, and initiation of immune responses in vivo. An understanding of the autoimmune peptide/MHC/T-cell receptor interactions allowed us to design variant 9-mer peptides that have high affinity for an MHC molecule and are effective in blocking experimental allergic encephalomyelitis, possibly through two distinct mechanisms, peripheral T-cell tolerance and the inhibition of binding of the encephalitogenic peptide to the MHC molecules.


Isolation of the cytoskeleton from Giardia. Tubulin and a low-molecular-weight protein associated with microribbon structures.
The sucking disk of Giardia is supported by a large, plate-like organelle: the ventral disk cytoskeleton. Extraction by Triton-X 100 of Giardia trophozoites from the mouse gut, or of G. duodenalis or G. lamblia grown from cultures, yields cell-free disk cytoskeletons. Up to 8 flagellar axonemes may be attached to an isolated disk. Disks are seen in the electron microscope to be composed of concentrically coiled microtubules bonded to microribbons. Microribbons are large, laminated structures, linked by dense networks of crossbridges. They are made up of regularly arranged subunits. Microtubules and microribbons are preserved in Triton for long periods, but crossbridges are slowly dissolved. Whereas the addition of ATP causes axonemes to resume bending, active movements were not detected in disks. It seems more likely that a disk is a passive effector, which may be acted upon by other contractile structures of the cytoplasm. It is highly specialized and quintessential cytoskeleton. Disks and axonemes will dissolve in sodium dodecyl sulphate (SDS), and after SDS-gel electrophoresis 2 prominent bands are apparent. One, corresponding to tubulin, migrates in low ionic strength, high pH buffers as 2 closely spaced bands of equal staining density. The other, a smaller protein, is a complex polypeptide band of molecular weight 30 000 Daltons. Allowing for staining differences, the 2 proteins are probably present in cytoskeletons in roughly equal amounts. Because of their size microribbons account for at least 75% of the structured material stained by electron stains in pellets of cytoskeletons. Disk and axoneme microtubules comprise the minority fraction. This result suggests that, like microtubules, microribbons are a source of structural tubulin and probably also contain the 30 000 mol. wt protein.


Finite Element Analysis of Implant-Assisted Removable Partial Denture Attachment with Different Matrix Designs During Bilateral Loading.
The aim of this study was to investigate the effect of different matrix designs on resilient attachment on an implant-assisted removable partial denture (IARPD) using finite element analysis (FEA). A laser scanner was used to extract the geometrical data of a human partially edentulous mandible. A 12-mm-long and 4.8-mm-diameter-wide implant was modeled, and two types of intradental attachment of snap fastener principle (elliptical) and resilient attachment (titanium) matrices were modeled along with tooth roots and periodontal ligaments. The modeling was performed with a combination of reverse engineering and solid modeling. The model incorporated a removable partial denture and was loaded with realistic bilateral forces. The FEA was used to analyze the stress and strain distributions in the IARPD and in the metal framework. Stresses and deformations in the metal framework and resin denture base surfaces were analyzed for the elliptical and titanium matrix designs. The maximum von Mises stresses were 605.85 and 614.96 MPa in the metal framework surface and 10.35 and 10.63 MPa in the resin denture base surface, respectively, for the elliptical and titanium matrix designs. The maximum deformations (displacements) were 418.5 and 428.3 μm in the metal framework surface for the elliptical and titanium matrix designs, respectively. The corresponding values of displacements for the resin denture base surface were 325.52 and 249.22 μm for the elliptical and titanium matrix designs, respectively. The maximum displacements in the matrixes were, however, nearly the same (229.51 and 229.47 μm) for both the elliptical and titanium matrixes. The titanium matrix design was a more favorable design compared with the elliptical design, because it had lower lateral deformation as indicated by the maximum displacement.


Sleep in adolescents and young adults.
Sleep has an important role in maintaining health and wellbeing; this relationship is becoming increasingly recognised for adolescents and young adults. Many physicians will encounter young people who present with complaints or conditions that have some relation to poor sleep. This review article looks at why sleep matters within this population group, how it can impact on longer term health consequences and discusses some tools to help enable the clinician to evaluate and address sleep within clinical practice.


An overview of current advancements in pancreatic islet transplantation into the omentum.
Pancreatic islet transplantation to restore insulin production in Type 1 Diabetes Mellitus patients is commonly performed by infusion of islets into the hepatic portal system. However, the risk of portal vein thrombosis or elevation of portal pressure after transplantation introduces challenges to this procedure. Thus, alternative sites have been investigated, among which the omentum represents an ideal candidate. The surgical site is easily accessible, and the tissue is highly vascularized with a large surface area for metabolic exchange. Furthermore, the ability of the omentum to host large volumes of islets represents an intriguing if not ideal site for encapsulated islet transplantation. Research on the safety and efficacy of the omentum as a transplant site focuses on the utilization of biologic scaffolds or encapsulation of islets in a biocompatible semi-permeable membrane. Currently, more clinical trials are required to better characterize the safety and efficacy of islet transplantation into the omentum.


Cell growth inhibition in HPV 18 positive uveal melanoma cells by E6/E7 siRNA.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, the molecular development of UM is not fully understood and current therapeutic modalities result in poor outcomes. Increasingly, data have shown that human papillomaviruses (HPVs) contribute to the development of cervical cancer and other malignancies, and the key viral oncoprotein E6/E7 has become the target of gene therapy in HPV-related cancers. In this study, we identified HPV 18 infection in the UM cell line, VUP, for the first time and silenced HPV 18 E6/E7 expression using siRNA. Our results demonstrated that down regulation of HPV 18E6/E7 led to growth inhibition and cell cycle block in VUP cells by activation of the p53 and Rb pathways. We propose that HPV is possibly involved in the development of UM, and provide a novel target for the development of therapeutic strategies for UM.


Pediatric tuina for the treatment of attention deficit hyperactivity disorder (ADHD) symptoms in preschool children: study protocol for a pilot randomized controlled trial.
Medication and behavior therapy are the conventional treatments for attention deficit hyperactivity disorder (ADHD), but they have limitations for preschool children. Evidence suggests that pediatric tuina, which is a modality of traditional Chinese medicine, might have beneficial effects on this condition. To assess the feasibility of conducting an RCT in terms of recruitment, use, and acceptability of the parent-administered pediatric tuina for ADHD symptoms in preschoolers. It is a single-center, two-arm, parallel, open-label, pilot randomized controlled trial (RCT). Sixty children with pre-specified ADHD symptoms (hyperactivity, anxiety, and sleep disturbance) together with one of their parents will be recruited and randomized into two groups at a 1:1 ratio. Parents in the parent-administered tuina group (intervention group, n = 30) will attend an online training program to learn pediatric tuina skills for ADHD symptoms and conduct this treatment on their children at home. Parents in the parent-child interaction group (comparison group, n = 30) will attend an online training about progressive muscle relaxation exercise and do this exercise with their children at home. Additional teaching materials will be provided to the participants in both groups. Both interventions should be carried out every other day during a 2-month treatment period, with each time around 20 min. Assessment will be performed at baseline, week 4, and week 8. The primary outcome measure is the Swanson, Nolan, and Pelham parent scale; the secondary outcomes include preschool anxiety scale, children's sleep habits questionnaire, and parental stress scale. A process evaluation embedded within the outcome evaluation will be performed. Differences in the scale scores and test parameters between groups will be examined using a linear mixed-effects model. Qualitative data will be analyzed using thematic content analysis, facilitated by QSR NVivo. This study will provide evidence on the acceptability and feasibility of pediatric tuina for ADHD in preschool children. The process evaluation will help to better understand the facilitators and barriers of the intervention functioning. The study was registered at ClinicalTrials.gov (Identifier: NCT04237259 ) on 14 February 2020. Protocol version: 2; date, 23 June 2020.


Global transitions of proteins explored by a multiscale hybrid methodology: application to adenylate kinase.
Efficient and accurate mapping of transition pathways is a challenging problem in allosteric proteins. We propose here a to our knowledge new methodology called collective molecular dynamics (coMD). coMD takes advantage of the collective modes of motions encoded by the fold, simultaneously evaluating the interactions and energetics via a full-atomic MD simulation protocol. The basic approach is to deform the structure collectively along the modes predicted by the anisotropic network model, upon selecting them via a Monte Carlo/Metropolis algorithm from among the complete pool of all accessible modes. Application to adenylate kinase, an allosteric enzyme composed of three domains, CORE, LID, and NMP, shows that both open-to-closed and closed-to-open transitions are readily sampled by coMD, with large-scale motions of the LID dominating. An energy-barrier crossing occurs during the NMP movements. The energy barrier originates from a switch between the salt bridges K136-D118 at the LID-CORE interface and K57-E170 and D33-R156 at the CORE-NMP and LID-NMP interfaces, respectively. Despite its simplicity and computing efficiency, coMD yields ensembles of transition pathways in close accord with detailed full atomic simulations, lending support to its utility as a multiscale hybrid method for efficiently exploring the allosteric transitions of multidomain or multimeric proteins.


USP22 promotes proliferation in renal cell carcinoma by stabilizing survivin.
Renal cell carcinoma (RCC) is one of the commonest urological tumors. The incidence of RCC ranks third among urological tumors, after prostate cancer and bladder tumors. However, the etiology of RCC remains unclear. Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, is associated with the occurrence and progression of numerous tumors. However, the roles of USP22 in RCC have not yet been investigated. Survivin is a member of the inhibitor of apoptotic protein family involved in RCC progression. The present study first detected the expression of USP22 and survivin in RCC tissues using immunohistochemistry and western blotting. It was revealed that the protein levels of USP22 and survivin in RCC tissues were higher than those in adjacent normal renal tissue. Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved-caspase-3. By contrast, overexpression of USP22 promoted the growth of ACHN cells, upregulated the expression of survivin and decreased the level of cleaved-caspase-3. Notably, the changes in USP22 expression did not affect the SURVIVIN mRNA level. Finally, it was confirmed that USP22 interacted with survivin and stabilized it by downregulating its ubiquitination. The present results indicate that USP22 may regulate survivin via deubiquitination, thereby promoting the proliferation of RCC cells. The results of the current study suggest that USP22 may represent a novel therapeutic target for patients with RCC.


Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis in myelodysplastic syndrome-derived cell line P39.
In most cases, apoptosis is considered to involve mitochondrial dysfunction with sequential release of cytochrome c from mitochondria, resulting in activation of caspase-3. However, we found that etoposide induced apoptosis in P39 cells, a myelodysplastic syndrome-derived cell line, without the release of cytochrome c. Furthermore, in etoposide-treated P39 cells, no changes in mitochondrial membrane potential (delta psi m) were detected by flow cytometry. Flow cytometry using a pH-sensitive probe demonstrated that lysosomal pH increased during early apoptosis in P39 cells treated with etoposide. A reduction in the ATP level preceded the elevation of lysosomal pH. In addition, specific inhibitors of vacuolar H+-ATPase induced apoptosis in P39 cells but not in HL60 cells. Although etoposide-induced activation of caspase-3 was followed by DNA ladder formation in P39 cells, E-64d, an inhibitor of lysosomal thiol proteases, specifically suppressed etoposide-induced activation of caspase-3. Western blotting analysis provided direct evidence for the involvement of a lysosomal enzyme, cathepsin L. These findings indicate that lysosomal dysfunction induced by a reduction in ATP results in leakage of lysosomal enzymes into the cytosolic compartment and that lysosomal enzyme(s) may be involved in activation of caspase-3 during apoptosis in P39 cells treated with etoposide.


Left heart bypass using the oscillated blood flow with totally implantable vibrating flow pump.
Aiming at a totally implantable ventricular assist device (VAD), a vibrating flow pump (VFP) was developed in Tohoku University. A transcutaneous energy transmission system (TETS) using an amorphous fiber was developed for the totally implantable VAD system. The VFP works with a higher frequency than the natural heart of a biological system, a frequency of 10-50 Hz. In this research, animal experiments on left heart bypass were performed with healthy goats. Blood from the apex of the left ventricle was received and was sent to the aorta so that an adequate supporting effect of the left heart was provided. In particular, the depression effect of the left ventricle was obvious. As a result, sufficient artificial heart flow was provided. For a totally implantable type VAD, left heart bypass of almost 100% may become necessary in some situations. Therefore, apex approaches of left heart bypass may be desirable. From an anatomical consideration, an apex of the heart is suitable for the VFP of this totally implantable type. In the left heart bypass for which the apex of the heart was used, an almost 100% bypass was possible. This is a requirement that is important when waiting for recovery of sufficient cardiac function. It is also important that left heart circulation is maintained fully by an artificial heart of the complete implantation type. The VFP was considered to be useful as a totally implantable type artificial heart from the results.


Effective teamwork and productivity conferences.
The popularity of various types of team building has grown dramatically in recent years, but many organizations have invested large amounts of time and money for little practical benefit. The growth of team-building activities has been characterized as "management by best-seller." This article examines the long-term impact of a number of team-building activities in terms of their positive effects on both employees and the work situation. Assessments are made of outward bound activities, empowerment programs, discussions of best-selling business books, motivational speakers, and group retreats to examine working relationships. A case study is then presented of a well-planned and structured retreat for a hospital. A group of about 75 supervisors and managers identified the strengths and problems of the hospital, analyzed the causes of the effectiveness and ineffectiveness of each department and the entire hospital, and proposed specific changes to improve teamwork and productivity. Conditions needed for the success of this approach were discussed.


Fucoidans as Potential Therapeutics for Age-Related Macular Degeneration-Current Evidence from In Vitro Research.
Age-related macular degeneration (AMD) is the major reason for blindness in the industrialized world with limited treatment options. Important pathogenic pathways in AMD include oxidative stress and vascular endothelial growth factor (VEGF) secretion. Due to their bioactivities, fucoidans have recently been suggested as potential therapeutics. This review gives an overview of the recent developments in this field. Recent studies have characterized several fucoidans from different species, with different molecular characteristics and different extraction methods, in regard to their ability to reduce oxidative stress and inhibit VEGF in AMD-relevant in vitro systems. As shown in these studies, fucoidans exhibit a species dependency in their bioactivity. Additionally, molecular properties such as molecular weight and fucose content are important issues. Fucoidans from Saccharina latissima and Laminaria hyperborea were identified as the most promising candidates for further development. Further research is warranted to establish fucoidans as potential therapeutics for AMD.


Divergent responses of soil buffering capacity to long-term N deposition in three typical tropical forests with different land-use history.
Elevated anthropogenic nitrogen (N) deposition has become an important driver of soil acidification at both regional and global scales. It remains unclear, however, how long-term N deposition affects soil buffering capacity in tropical forest ecosystems and in ecosystems of contrasting land-use history. Here, we expand on a long-term N deposition experiment in three tropical forests that vary in land-use history (primary, secondary, and planted forests) in Southern China, with N addition as NH4NO3 of 0, 50, 100, and 150 kg N ha(-1) yr(-1), respectively. Results showed that all three forests were acid-sensitive ecosystems with poor soil buffering capacity, while the primary forest had higher base saturation and cation exchange capacity than others. However, long-term N addition significantly accelerated soil acidification and decreased soil buffering capacity in the primary forest, but not in the degraded secondary and planted forests. We suggest that ecosystem N status, influenced by different land-use history, is primarily responsible for these divergent responses. N-rich primary forests may be more sensitive to external N inputs than others with low N status, and should be given more attention under global changes in the future, because lack of nutrient cations is irreversible.


Helicobacter pylori VacA, a paradigm for toxin multifunctionality.
Bacterial protein toxins alter eukaryotic cellular processes and enable bacteria to successfully colonize their hosts. In recent years, there has been increased recognition that many bacterial toxins are multifunctional proteins that can have pleiotropic effects on mammalian cells and tissues. In this review, we examine a multifunctional toxin (VacA) that is produced by the bacterium Helicobacter pylori. The actions of H. pylori VacA represent a paradigm for how bacterial secreted toxins contribute to colonization and virulence in multiple ways.


Massive autogenous bone grafts.
Autogenous bone graft is the best biologic material available to repair a skeletal defect. These necrotic grafts are revascularized and repaired through creeping substitution to provide an almost identical structure for the one it replaced. There is a limited supply of autogenous bone, but it is the standard against which other methods should be measured.


The contribution of oxytocin and vasopressin to mammalian social behavior: potential role in autism spectrum disorder.
Oxytocin (OT) and arginine-vasopressin (AVP) are 2 peptides that are produced in the brain and released via the pituitary gland to the peripheral blood, where they have diverse physiological functions. In the last 2 decades it has become clear that these peptides also play a central role in the modulation of mammalian social behavior by their actions within the brain. Several lines of evidence suggest their involvement in autism spectrum disorder (ASD), which is known to be associated with impaired social cognition and behavior. Recent clinical trials using OT administration to autistic patients have reported promising results. Here, we aim to describe the main data that suggest a connection between these peptides and ASD. Following a short illustration of several major topics in ASD biology we will (a) briefly describe the oxytocinergic and vasopressinergic systems in the brain, (b) discuss a few compelling cases manifesting the involvement of OT and AVP in mammalian social behavior, (c) describe data supporting the role of these peptides in human social cognition and behavior, and (d) discuss the possibility of the involvement of OT and AVP in ASD etiology, as well as the prospect of using these peptides as a treatment for ASD patients.


Perioperative Amino Acid Infusion for Preventing Hypothermia and Improving Clinical Outcomes During Surgery Under General Anesthesia: A Systematic Review and Meta-analysis.
Amino acid (AA) infusion is sometimes selected to avoid hypothermia during general anesthesia. However, the widespread clinical use of AA infusion therapy has not been established. This study aimed to clarify the evidence that AA infusion can increase patient body temperature and improve clinical outcomes using the Grading of Recommendations Assessment, Development, and Evaluation system. We searched MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Japana Centra Revuo Medicina) in November 2015. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) involving AA infusion compared with placebos during surgery under general or combined general/epidural anesthesia. Study quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system and the Cochrane methodology. The primary outcome was difference in body temperature before and after perioperative AA infusion. Shivering frequency, blood loss volume, postoperative intubation time, and hospitalization period were also assessed as clinical outcomes. We analyzed the outcome data using a random effect model. From 298 screened titles, 14 RCTs met our inclusion criteria, including 626 patients (327 in AA and 299 in placebo groups). In 626 participants from 14 RCTs, AA infusion increased body temperature by a mean difference (MD) of 0.46°C (95% confidence interval [CI], 0.31-0.62, low-quality evidence). Regarding other outcomes, AA infusion decreased shivering frequency by a risk ratio of 0.34 (95% CI, 0.12-0.94; 7 RCTs, 248 participants, very low-quality evidence), shortened postoperative intubation time by MD of -125 minutes (95% CI, -210 to -38.8; 2 RCTs, 158 participants, moderate-quality evidence), and shortened the hospitalization period by MD of -1.81 days (95% CI, -2.07 to -1.55; 3 RCTs, 230 participants, low-quality evidence) compared with placebo. There was no significant difference in the volume of blood loss between the 2 groups (standardized MD, -0.20, 95% CI, -0.44 to 0.04; low-quality evidence). There was no publication bias. AA infusion in the perioperative period increased patient body temperature and improved clinical outcomes compared with placebo. However, the evidence to support the use of AA infusion is limited, and further large-scale RCTs are required.


Entrapment of enzyme aggregates in chitosan beads for aroma release in white wines.
Glycosidases are enzymes involved in the cascade reactions leading to the release of aromatic compounds in white wines. However, the use of commercial soluble glycosidases is facing difficulties due to their fast inactivation, poor reaction control, low efficiency of enzyme use, and the presence of catalyst residues in the product. Co-immobilization as cross-linked enzyme aggregates (combi-CLEAs) is a sound alternative allowing the immobilization of enzymes in their own protein matrix, yielding highly stable and active biocatalysts. Notwithstanding, their micrometer sized particles limit their application in industrial processes. To overcome this, combi-CLEAs of β-D-glucosidase (βG) and α-L-arabinofuranosidase (ARA) were entrapped in polymeric chitosan beads. The effect of crosslinking reagents and crosslinking time on the specific activity and stability of combi-CLEAs was studied, and the best conditions for the entrapment of the combi-CLEAs in polymeric chitosan beads were determined varying the concentration of the chitosan solution and the pH of the gelation agent solution. The resulting biocatalyst beads (average diameter 1.24 mm), retained full activity after 91 days of incubation under winemaking conditions, having specific activities of 0.91 and 0.88 international units of activity per gram for βG and ARA, respectively. Such characteristics make them suitable for aroma enhancement in wines.


Microextraction and Determination of Poly- and Perfluoroalkyl Substances, Challenges, and Future Trends.
Per- and polyfluoroalkyl substances (PFAS) are fluorocarbon compounds in which hydrogen atoms have been partly or entirely replaced by fluorine. They have a very wide range of applications, while they are persistent in the environment and exhibit bioaccumulative and toxic properties. Neither chemical nor biological mechanisms can decompose PFAS due to their strong C-F bonds. PFAS have shown adverse effects on various organisms, even at trace levels. Accordingly, highly sensitive and selective analytical methods are required for their tracing in biological and environmental matrices. The physicochemical properties of PFAS like surfactant characteristics and high-water solubility are unique and different from other known pollutants. Accordingly, the number of articles on the analysis of PFAS is less than the other well-known contaminants. The routine PFAS sample preparation methods (like solvent extraction) coupled with chromatographic systems, face challenges such as high limits of detection, need for laborious derivatization, limited selectivity, and expensive instrumentation. Recent efforts to address these limitations have aroused considerable attention to the development of microextraction techniques, which are consistent with the principles of green chemistry and can be made easily portable and automated. Moreover, these methods have shown enough sensitivity and selectivity for the analysis of different analytes (including PFAS) in a wide range of samples with different matrices. This research aims to review the microextraction methods and detection techniques, applied for the sample pretreatment of PFAS in various matrices, along with a critical discussion of the challenges and potential future trends.


Biomaterials and controlled release strategy for epithelial wound healing.
The skin and cornea are tissues that provide protective functions. Trauma and other environmental threats often cause injuries, infections and damage to these tissues, where the degree of injury is directly correlated to the recovery time. For example, a superficial skin or corneal wound may recover within days; however, more severe injuries can last up to several months and may leave scarring. Thus, therapeutic strategies have been introduced to enhance the wound healing efficiency and quality. Although the skin and cornea share similar anatomic structures and wound healing process, therapeutic agents and formulations for skin and cornea wound healing differ in accordance with the tissue and wound type. In this review, we describe the anatomy and epithelial wound healing processes of the skin and cornea, and summarize the therapeutic molecules that are beneficial to the respective regeneration process. In addition, biomaterial scaffolds that inherently possess bioactive properties or modified with therapeutic molecules for topical controlled release and enhanced wound healing efficiency are also discussed.


How Low Nucleation Density of Graphene on CuNi Alloy is Achieved.
CuNi alloy foils are demonstrated to be one of the best substrates for synthesizing large area single-crystalline graphene because a very fast growth rate and low nucleation density can be simultaneously achieved. The fast growth rate is understood to be due the abundance of carbon precursor supply, as a result of the high catalytic activity of Ni atoms. However, a theoretical understanding of the low nucleation density remains controversial because it is known that a high carbon precursor concentration on the surface normally leads to a high nucleation density. Here, the graphene nucleation on the CuNi alloy surfaces is systematically explored and it is revealed that: i) carbon atom dissolution into the CuNi alloy passivates the alloy surface, thereby drastically increasing the graphene nucleation barrier; ii) carbon atom diffusion on the CuNi alloy surface is greatly suppressed by the inhomogeneous atomic structure of the surface; and iii) a prominent increase in the rate of carbon diffusion into the bulk occurs when the Ni composition is higher than the percolation threshold. This study reveals the key mechanism for graphene nucleation on CuNi alloy surfaces and provides a guideline for the catalyst design for the synthesis of graphene and other 2D materials.


The phenotypic predisposition of the parent in F1 hybrid is correlated with transcriptome preference of the positive general combining ability parent.
Sprague and Tatum (1942) introduced the concepts of general combining ability (GCA) and specific combining ability (SCA) to evaluate the breeding parents and F1 hybrid performance, respectively. Since then, the GCA was widely used in cross breeding for elite parent selection. However, the molecular basis of GCA remains to unknown. We studied the transcriptomes of three varieties and three F1 hybrids using RNA-Sequencing. Transcriptome sequence analysis revealed that the transcriptome profiles of the F1s were similar to the positive GCA-effect parent. Moreover, the expression levels of most differentially expressed genes (DEGs) were equal to the parent with a positive GCA effect. Analysis of the gene expression patterns of gibberellic acid (GA) and flowering time pathways that determine plant height and flowering time in rice validated the preferential transcriptome expression of the parents with positive GCA effect. Furthermore, H3K36me3 modification bias in the Pseudo-Response Regulators (PRR) gene family was observed in the positive GCA effect parents and demonstrated that the phenotype and transcriptome bias in the positive GCA effect parents have been epigenetically regulated by either global modification or specific signaling pathways in rice. The results revealed that the transcriptome profiles and DEGs in the F1s were highly related to phenotype bias to the positive GCA-effect parent. The transcriptome bias toward high GCA parents in F1 hybrids attributed to H3K36me3 modification both on global modification level and specific signaling pathways. Our results indicated the transcriptome profile and epigenetic modification level bias to high GCA parents could be the molecular basis of GCA.


Long-term Effectiveness of the National Diabetes Quality Assessment Program in South Korea.
This study examined the long-term effectiveness of the national diabetes quality assessment program (NDQAP) in diabetes. From the Health Insurance Review and Assessment Service database, 399,984 individuals with diabetes who visited a primary care clinic from 1 July 2012 to 30 June 2013 were included and followed up until 31 May 2021. The NDQAP included five quality assessment indicators: regular outpatient visits, continuity of prescriptions, regular testing of glycated hemoglobin and lipids, and regular fundus examination. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes complications and all-cause mortality by the achievement of quality assessment indicators. During the mean follow-up duration of 7.6 ± 1.8 years, 20,054 cases (5.0%) of proliferative diabetic retinopathy (PDR), 6,281 end-stage kidney diseases (ESKD; 1.6%), 1,943 amputations (0.5%), 9,706 myocardial infarctions (MIs; 2.4%), 26,975 strokes (6.7%), and 35,799 all-cause mortality (8.9%) occurred. Each achievement of quality assessment indicator was associated with a decreased risk of diabetes complications and all-cause mortality. Individuals who were managed in high-quality institutions had a lower risk of PDR (HR 0.82; 95% CI 0.80-0.85), ESKD (HR 0.77; 95% CI 0.73-0.81), amputation (HR 0.75; 95% CI 0.69-0.83), MI (HR 0.85; 95% CI 0.82-0.89), stroke (HR 0.86; 95% CI 0.84-0.88), and all-cause mortality (HR 0.96; 95% CI 0.94-0.98) than those who were not managed in high-quality institutions. In Korea, the achievement of NDQAP indicators was associated with a decreased risk of diabetes complications and all-cause mortality.


Projected impacts of future climate change, ocean acidification, and management on the US Atlantic sea scallop (Placopecten magellanicus) fishery.
Ocean acidification has the potential to significantly impact both aquaculture and wild-caught mollusk fisheries around the world. In this work, we build upon a previously published integrated assessment model of the US Atlantic Sea Scallop (Placopecten magellanicus) fishery to determine the possible future of the fishery under a suite of climate, economic, biological, and management scenarios. We developed a 4x4x4x4 hypercube scenario framework that resulted in 256 possible combinations of future scenarios. The study highlights the potential impacts of ocean acidification and management for a subset of future climate scenarios, with a high CO2 emissions case (RCP8.5) and lower CO2 emissions and climate mitigation case (RCP4.5). Under RCP4.5 and the highest impact and management scenario, ocean acidification has the potential to reduce sea scallop biomass by approximately 13% by the end of century; however, the lesser impact scenarios cause very little change. Under RCP8.5, sea scallop biomass may decline by more than 50% by the end of century, leading to subsequent declines in industry landings and revenue. Management-set catch limits improve the outcomes of the fishery under both climate scenarios, and the addition of a 10% area closure increases future biomass by more than 25% under the highest ocean acidification impacts. However, increased management still does not stop the projected long-term decline of the fishery under ocean acidification scenarios. Given our incomplete understanding of acidification impacts on P. magellanicus, these declines, along with the high value of the industry, suggest population-level effects of acidification should be a clear research priority. Projections described in this manuscript illustrate both the potential impacts of ocean acidification under a business-as-usual and a moderately strong climate-policy scenario. We also illustrate the importance of fisheries management targets in improving the long-term outcome of the P. magellanicus fishery under potential global change.


Expression of mammary tumor virus proteins in preneoplastic outgrowth lines and mammary tumors of BALB/cV mice.
A subline of BALB/c mice, designated BALB/cV, has been segregated which exhibits an intermediate mammary tumor incidence and which harbors a unique milk-transmitted virus. Six stable hyperplastic alveolar nodule outgrowth lines were established from chemical carcinogen-treated and hormonally stimulated mice. Tumor incidences exhibited by the individual preneoplastic lines ranged from 22 to 95%; no differences in tumor-producing capability were observed when lines were transplanted in virus-negative (BALB/c) or virus-positive (BALB/cV) animals. Viral antigen expression was monitored using antisera prepared against C3H mouse mammary tumor virus (MMTV) proteins. The preneoplastic lines exhibited more virus antigenpositive cells in a peroxidase-antiperoxidase immunocytochemical assay than did primary tumors which arose from the hyperplastic alveolar nodule transplants. Analysis of BALB/cV preneoplastic and tumor tissue by metabolic labeling and by protein electroblotting methodologies revealed that viral precursor and structural proteins were expressed in both types of tissue; the polypeptides were similar in molecular weight to those encoded by exogenous MMTVs. These studies demonstrate that the coding capacity of the BALB/cV isolate of MMTV is similar to that of known MMTV isolates and that each of the BALB/cV structural polypeptides shares group-specific antigenic determinants with the analogous protein encoded by MMTV from the C3H mouse. The hyperplastic outgrowth lines established in the BALB/cV subline provide an additional system for the study of mammary tumorigenesis.


Data on Aging.
Federal payment for hospitalization and partial medical care of certain citizens 65 and over is proposed in H.R. 4222. There are several important aspects of this proposed legislation which merit consideration, notably (1) How great is the actual need? and (2) Who would actually be covered by the proposed measure?1. The need for subsidized hospitalization and medical care is believed to be distinctly limited. A national study of the total life situation of those 65 and over (by Wiggins and Schoeck) showed that 90 per cent of the respondents reported no unmet medical needs of which they were aware. About 96 per cent reported no medical debts. This would leave presumably 4 per cent with such debts.2. The proposed legislation would cover those eligible for benefits under the Social Security Act and the Railroad Retirement Act, but not other elderly persons. The Wiggins-Schoeck Report has been bitterly assailed by supporters of H.R. 4222 as being nonrepresentative and incomplete. Its authors (in a recent letter to Science) point out that it is indeed representative of the older population currently designated in H.R. 4222, and that it intentionally omitted those segments which would not be covered by H.R. 4222. In other words the data on needs of elderly persons as uncovered by Wiggins and Schoeck is pertinent to the legislation at hand. For this reason it is believed that physicians will be interested in reading the reply of these authors to the criticisms of their survey.With the permission of Science and of the authors, it is reprinted herewith.


Degenerate and specific PCR assays for the detection of bovine leukaemia virus and primate T cell leukaemia/lymphoma virus pol DNA and RNA: phylogenetic comparisons of amplified sequences from cattle and primates from around the world.
Degenerate and specific PCR assays were developed for bovine leukaemia virus (BLV) and/or primate T cell leukaemia/lymphoma viruses (PTLV). The degenerate assays detected all major variants of the BLV/PTLV genus at a sensitivity of 10-100 copies of input DNA; the specific systems detected 1-10 copies of input target. Sensitivity was 100% in specific DNA-PCR assays done on peripheral blood from seropositive BLV-infected cattle and HTLV-I- or HTLV-II-infected humans, and 62% in RNA/DNA-PCR assays on sera from BLV seropositive cattle. The pol fragments from 21 different BLV strains, isolated from cattle in North and Central America, were cloned and sequenced, and compared to other published BLV and PTLV pol sequences. BLV and PTLV sequences differed by 42%. Sequence divergence was up to 6% among the BLV strains, and up to 36% among the PTLV strains (with PTLV-I and PTLV-II differing among themselves by 15% and 8%, respectively). Some cows were infected with several BLV strains. Among retroviruses, BLV and PTLV sequences formed a distinct clade. The data support the interpretation that BLV and PTLV evolved from a common ancestor many millennia ago, and some considerable time before the PTLV-I and PTLV-II strains diverged from each other. The dissemination of the BLV strains studied probably resulted from the export of European cattle throughout the world over the last 500 years. The relatively similar mutation rates of BLV and PTLV, after their various points of divergence, suggest that there could be a much wider genetic range of BLV than has currently been defined.


Vitamin D and multiple sclerosis: Potential pathophysiological role and clinical implications.
Multiple sclerosis (MS) is thought to arise due to an interplay of genetic and environmental risk factors. Vitamin D, besides maintaining bone health and calcium metabolism, is thought to play an immunomodulatory role in the central nervous system. Studies have shown that patients with the highest level of Vitamin D (99-152 nmol/l) had a significantly lower risk of MS than the subgroup with the lowest levels (15-63 nmol/l). Furthermore, populations having a high oral intake of vitamin D had a decreased risk of MS. Hypovitaminosis D is one of the environmental risk factors for MS based on numerous physiological, experimental and epidemiologic data, which can be corrected to provide an effective therapeutic option for this debilitating disease.


Elevation of vitreous leptin in diabetic retinopathy and retinal detachment.
Leptin is a cytokine that regulates energy metabolism and is linked to diabetes mellitus through its metabolic actions. Leptin is angiogenic and promotes wound healing, and therefore this investigation was conducted to determine whether leptin is associated with neovascular and fibrotic complications of diabetes and other retinopathies. Serum and vitreous samples were collected from patients classified by the presence and type of diabetic retinopathy or other ocular diseases. Leptin was measured in serum and vitreous by radioimmunoassay, and leptin and leptin receptor were localized in epiretinal membranes immunohistochemically. Leptin levels in serum and vitreous were higher in patients with diabetes than in those without, and vitreous leptin concentrations were especially elevated in patients with proliferative diabetic retinopathy or retinal detachment. Leptin and leptin receptor were detected in fibrovascular epiretinal membrane of patients with diabetes. Leptin in human vitreous is elevated in proliferative diabetic retinopathy, and retinal detachment and is present in fibrovascular epiretinal tissue. These data suggest an involvement of leptin in retinal disease.


Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese.
To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.


A Glucose Sensing System Based on Transmission Measurements at Millimetre Waves using Micro strip Patch Antennas.
We present a sensing system operating at millimetre (mm) waves in transmission mode that can measure glucose level changes based on the complex permittivity changes across the signal path. The permittivity of a sample can change significantly as the concentration of one of its substances varies: for example, blood permittivity depends on the blood glucose levels. The proposed sensing system uses two facing microstrip patch antennas operating at 60 GHz, which are placed across interrogated samples. The measured transmission coefficient depends on the permittivity change along the signal path, which can be correlated to the change in concentration of a substance. Along with theoretical estimations, we experimentally demonstrate the sensing performance of the system using controlled laboratory samples, such as water-based glucose-loaded liquid samples. We also present results of successful glucose spike detection in humans during an in-vivo Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be developed into a non-invasive glucose monitor for continuous monitoring of glucose levels for people living with diabetes, as it can detect as small as 1.33 mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.


Spatial structure of the novel light-sensitive photoprotein berovin from the ctenophore Beroe abyssicola in the Ca(2+)-loaded apoprotein conformation state.
The bright bioluminescence of ctenophores, found in oceans worldwide, is determined by Ca(2+)-regulated photoproteins, functionally identical to and sharing many properties of hydromedusan photoproteins. In contrast, however, the ctenophore photoproteins are extremely sensitive to UV and visible light over the range of their absorption spectrum. The spatial structure of a novel light-sensitive photoprotein from the ctenophore Beroe abyssicola in its apoform bound with three calcium ions is determined at 2.0Å. We demonstrate that the apoberovin is a slightly asymmetrical compact globular protein formed by two domains with a cavity in the center, which exactly retains the fold architecture characteristic of hydromedusan photoproteins despite their low amino acid sequence identity. However, the structural alignment of these two photoprotein classes clearly shows that despite the high similarity of shape and geometry of their coelenterazine-binding cavities, their interiors differ drastically. The key residues appearing to be crucial for stabilizing the 2-hydroperoxycoelenterazine and for formation of the emitter in hydromedusan photoproteins, are replaced in berovin by amino acid residues having completely different side chain properties. Evidently, these replacements must be responsible for the distinct properties of ctenophore photoproteins such as sensitivity to light or the fact that the formation of active photoprotein from apophotoprotein, coelenterazine, and oxygen is more effective at alkaline pH.


Developing the Cyber Victimization Experiences and Cyberbullying Behaviors Scales.
The reported prevalence rates of cyber victimization experiences and cyberbullying behaviors vary. Part of this variation is likely due to the diverse definitions and operationalizations of the constructs adopted in previous research and the lack of psychometrically robust measures. Through 2 studies, the authors developed (Study 1) and evaluated (Study 2) the cyber victimization experiences and cyberbullying behaviors scales. Participants in Study 1 were 393 (122 boys, 171 girls) and in Study 2 were 345 (153 boys, 192 girls) 11-15-year-olds who completed measures of cyber victimization experiences, cyberbullying behaviors, face-to-face victimization experiences, face-to-face bullying behaviors, and social desirability. The 3-factor cyber victimization experiences scale comprised threat, shared images, and personal attack. The 3-factor cyberbullying behaviors scale comprised sharing images, gossip, and personal attack. Both scales demonstrated acceptable internal consistency and convergent validity.


Paramagnetic NMR in solution and the solid state.
The field of paramagnetic NMR has expanded considerably in recent years. This review addresses both the theoretical description of paramagnetic NMR, and the way in which it is currently practised. We provide a review of the theory of the NMR parameters of systems in both solution and the solid state. Here we unify the different languages used by the NMR, EPR, quantum chemistry/DFT, and magnetism communities to provide a comprehensive and coherent theoretical description. We cover the theory of the paramagnetic shift and shift anisotropy in solution both in the traditional formalism in terms of the magnetic susceptibility tensor, and using a more modern formalism employing the relevant EPR parameters, such as are used in first-principles calculations. In addition we examine the theory first in the simple non-relativistic picture, and then in the presence of spin-orbit coupling. These ideas are then extended to a description of the paramagnetic shift in periodic solids, where it is necessary to include the bulk magnetic properties, such as magnetic ordering at low temperatures. The description of the paramagnetic shift is completed by describing the current understanding of such shifts due to lanthanide and actinide ions. We then examine the paramagnetic relaxation enhancement, using a simple model employing a phenomenological picture of the electronic relaxation, and again using a more complex state-of-the-art theory which incorporates electronic relaxation explicitly. An additional important consideration in the solid state is the impact of bulk magnetic susceptibility effects on the form of the spectrum, where we include some ideas from the field of classical electrodynamics. We then continue by describing in detail the solution and solid-state NMR methods that have been deployed in the study of paramagnetic systems in chemistry, biology, and the materials sciences. Finally we describe a number of case studies in paramagnetic NMR that have been specifically chosen to highlight how the theory in part one, and the methods in part two, can be used in practice. The systems chosen include small organometallic complexes in solution, solid battery electrode materials, metalloproteins in both solution and the solid state, systems containing lanthanide ions, and multi-component materials used in pharmaceutical controlled-release formulations that have been doped with paramagnetic species to measure the component domain sizes.


Neuropathological and biochemical assessments of an Alzheimer's disease patient treated with the γ-secretase inhibitor semagacestat.
Amyloid deposition has been implicated as the key determinant of Alzheimer's disease (AD) pathogenesis. Interventions to antagonize amyloid accumulation and mitigate dementia are now under active investigation. We conducted a combined clinical, biochemical and neuropathological assessment of a participant in a clinical trial of the γ-secretase inhibitor, semagacestat. This patient received a daily oral dose of 140 mg of semagacestat for approximately 76 weeks. Levels of brain amyloid-β (Aβ) peptides were quantified using enzyme-linked immunosorbent assays (ELISA). Western blot/scanning densitometry was performed to reveal BACE1, presenilin1, amyloid precursor protein (APP) and its proteolysis-produced C-terminal peptides APP-CT99 and APP-CT83 as well as several γ-secretase substrates. To serve as a frame of reference, the ELISA and Western analyses were performed in parallel on samples from neuropathologically confirmed non-demented control (NDC) and AD subjects who did not receive semagacestat. Neuropathology findings confirmed a diagnosis of AD with frequent amyloid deposits and neurofibrillary tangles in most areas of the cortex and subcortical nuclei as well as cerebellar amyloid plaques. Mean levels of Tris-soluble Aβ40 and glass-distilled formic acid (GDFA)/guanidine hydrochloride (GHCl)-extractable Aβ40 in the frontal lobe and GDFA/GHCl-soluble Aβ40 in the temporal lobe were increased 4.2, 9.5 and 7.7-fold, respectively, in the semagacestat-treated subject compared to those observed in the non-treated AD group. In addition, GDFA/GHCl-extracted Aβ42 was increased 2-fold in the temporal lobe relative to non-treated AD cases. No major changes in APP, β- and γ-secretase and CT99/CT83 were observed between the semagacestat-treated subject compared to either NDC or AD cases. Furthermore, the levels of γ-secretase substrates in the semagacestat-treated subject and the reference groups were also similar. Interestingly, there were significant alterations in the levels of several γ-secretase substrates between the NDC and non-treated AD subjects. This is the first reported case study of an individual enrolled in the semagacestat clinical trial. The subject of this study remained alive for ~7 months after treatment termination, therefore it is difficult to conclude whether the outcomes observed represent a consequence of semagacestat therapy. Additional evaluations of trial participants, including several who expired during the course of treatment, may provide vital clarification regarding the impacts and aftermath of γ-secretase inhibition.


[Use of formalinized homologous bone in reconstructive operations on the mandible].
An experience with 69 osteoplastic operations with formalinized homografts in 66 patients having various affections and injuries of the lower jaw is summarized. The grafts were preserved in 0.5% formalin solution or gel containing 0.25% formalin and 0.25% betapropiolactone as sterilizing agents. Positive issues during the follow-up from 4 months to 4 years 7 months were noted in 60 operative procedures, negative--in 9. It is concluded that the formalinized homobone shows good osteoplastic properties and may be used as a plastic material in reparative operations on the lower jaw bone.


The intracellular degradation of poly(epsilon-caprolactone).
Poly(epsilon-caprolactone) [PEC], a biodegradable aliphatic polyester, undergoes a two-stage degradation process: The first lengthy phase involves nonenzymatic hydrolytic cleavage of ester groups, the second phase beginning when the polymer is more highly crystalline, and of low molecular weight. The cellular events of the second phase were examined by implanting gelatin capsules containing 25 mg of low molecular weight (Mn 3000) PEC powders, 106 to 500 micron, in rats. PEC fragments ultimately were degraded in phagosomes of macrophages and giant cells, the process requiring less than 13 days for completion at some sites. PEC was also identified within fibroblasts. These studies support the intracellular degradation of PEC as the principal pathway of degradation once the molecular weight of the aged polymer is reduced to 3000 or less.


Feasibility study of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected non-small-cell lung cancer: FAST-nab.
The aim of this study was to determine the feasibility of adjuvant administration of nab-paclitaxel (nab-P) plus carboplatin and for completely resected patients with stage IB, II, and IIIA non-small-cell lung cancer (NSCLC) (FAST-nab study, UMIN000011225). Twenty-nine eligible NSCLC patients received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-P (100 mg/m) on days 1 and 8, followed by carboplatin area (area under the curve=6) on day 1. Twenty-two (75.9%) of the 29 patients enrolled completed four cycles of this regimen. The most common grade 3 or 4 adverse event experienced during the nab-P plus carboplatin was neutropenia (34.5%), followed by anemia (13.8%). No grade 3 or 4 nonhematologic adverse event was observed during this chemotherapy. The median time to disease recurrence survival was 21 (95% confidence interval: 16-26) months. The administration of modified nab-P plus carboplatin was considered an attractive alternative regimen that was safe and well tolerated as a postoperative adjuvant chemotherapy for completed resected NSCLC.


Transmembrane-4-superfamily proteins CD151 and CD81 associate with alpha 3 beta 1 integrin, and selectively contribute to alpha 3 beta 1-dependent neurite outgrowth.
Proteins in the transmembrane-4-superfamily (TM4SF) form many different complexes with proteins in the integrin family, but the functional utility of these complexes has not yet been demonstrated. Here we show that TM4SF proteins CD151, CD81, and CD63 co-distribute with alpha3beta1 integrin on neurites and growth cones of human NT2N cells. Also, stable CD151-alpha3beta1 and CD81-alpha3beta1 complexes were recovered in NT2N detergent lysates. Total NT2N neurite outgrowth on laminin-5 (a ligand for alpha3beta1 integrin) was strongly inhibited by anti-CD151 and -CD81 antibodies either together ( approximately 85% inhibition) or alone ( approximately 45% inhibition). Notably, these antibodies had no inhibitory effect on NT2N neurites formed on laminin-1 or fibronectin, when alpha3beta1integrin was not engaged. Neurite number, length, and rate of extension were all affected by anti-TM4SF antibodies. In summary: (1) these substrate-dependent inhibition results strongly suggest that CD151 and CD81 associations with alpha3beta1 are functionally relevant, (2) TM4SF proteins CD151 and CD81 make a strong positive contribution toward neurite number, length, and rate of outgrowth, and (3) NT2N cells, a well-established model of immature central nervous system neurons, can be a powerful system for studies of integrin function in neurite outgrowth and growth cone motility.


The resolution dependence of optimal exposures in liquid nitrogen temperature electron cryomicroscopy of catalase crystals.
Electron beam damage is the fundamental limit to resolution in electron cryomicroscopy (cryo-EM) of frozen, hydrated specimens. Radiation damage increases with the number of electrons used to obtain an image and affects information at higher spatial frequencies before low-resolution information. For the experimentalist, a balance exists between electron exposures sufficient to obtain a useful signal-to-noise ratio (SNR) in images and exposures that limit the damage to structural features. In single particle cryo-EM this balance is particularly delicate: low-resolution features must be imaged with a sufficient SNR to allow image alignment so that high-resolution features recorded below the noise level can be recovered by averaging independent images. By measuring the fading of Fourier components from images obtained at 200 kV of thin crystals of catalase embedded in ice, we have determined the electron exposures that will maximize the SNR at resolutions between 86 and 2.9A. These data allow for a rational choice of exposure for single particle cryo-EM. For example, for 20A resolution, the SNR is maximized at approximately 20e(-)/A(2), whereas for 3A resolution, it is maximized at approximately 10 e(-)/A(2). We illustrate the effects of exposure in single particle cryo-EM with data collected at approximately 12-15 and approximately 24-30 e(-)/A(2).


Adaptive pattern recognition in the analysis of cardiotocographic records.
The recognition of accelerative and decelerative patterns in the fetal heart rate (FHR) is one of the tasks carried out manually by obstetricians when they analyze cardiotocograms for information respecting the fetal state. An approach based on artificial neural networks formed by a multilayer perceptron (MLP) is developed. However, since the system utilizes the FHR signal as direct input, an anterior stage must be incorporated that applies a principal component analysis (PCA) so as to make the system independent of the signal baseline. Furthermore, the introduction of multiresolution into the PCA has resolved other problems that were detected in the application of the system. Presented in this paper are the results of validation of these systems designated the PCA-MLP and multiresolutlon principal component analysis (MR-PCA) systems against three clinical experts.


Pore-Scale Modeling of Fluid-Fluid Interfacial Area in Variably Saturated Porous Media Containing Microscale Surface Roughness.
A pore-scale model is developed to simulate fluid-fluid interfacial area in variably saturated porous media, with a specific focus on incorporating the effects of solid-surface roughness. The model is designed to quantify total (film and meniscus) fluid-fluid interfacial area (Anw ) over the full range of wetting-phase fluid saturation (Sw ) based on the inherent properties of the porous medium. The model employs a triangular pore space bundle of cylindrical capillaries (BCC) framework, modified with three surface roughness-related parameters. The first parameter (surface roughness factor) represents the overall magnitude of surface roughness, whereas the other two parameters (interface growth factor and critical adsorptive film thickness) reflect the micro-scale structure of surface roughness. A series of sensitivity analyses was conducted for the controlling variables, and the efficacy of the model was tested using air-water interfacial area data measured for three natural porous media. The model produced good simulations of the measured Anw data over the full range of saturation. The results demonstrate that total interfacial areas for natural media are typically much larger than those for ideal media comprising smooth surfaces due to the substantial contribution of surface roughness to wetting-film interfacial area. The degree to which fluid-fluid interfacial area is influenced by roughness is a function of fluid-retention characteristics and the nature of the rough surfaces. The full impact of roughness may be masked to some degree due to the formation of thick wetting films, which is explicitly quantified by the model. Application of the model provides insight into the importance of the interplay between pore-scale distribution and configuration of wetting fluid and the surface properties of solids.


Smoking habit and labial microcirculation.
Smoking habit is an important risk factor in oral diseases. In the last years, many studies tried to evaluate smoking effects on the microcirculation. It had never been used such a simple not invasive technique, like the video-capillaroscopic one. The aim of the research is to analyse "in vivo", the microcirculation labial characteristics, and to evaluate the smoking effects by means of computerised videocapillaroscopy techniques. 35 healthy no-smoker patients and 35 healthy smoker patients were examined. The characteristics of the microcirculation in the areas of labial mucous were examined using computerised videomicroscopic techniques. For each patient we evaluated the visibility, the course, the tortuosity and any images characteristic of capillary loops, besides the possible presence of microhaemorrhages, the average calibre of capillary loops and the number of capillary loops visible per square millimetre. The investigation was non invasive and repeatable for each patient. In both groups the investigation of labial mucous revealed a course of capillary loops parallel to the surface. In smoker patients, it was possible to underline capillaries of a smaller calibre (P<.001), and a higher number of detectable capillaries compared with no-smoker patients (P<.001). We observed an important correlation between the capillary tortuosity and the smoking habit (P<.001). Our research highlighted, that today it is possible to carry out a capillaroscopic investigation of labial mucous in a simple and reliable way. Furthermore, smoking habit represents a real risk factor of oral disease, greatly affecting the microcirculation.


Characteristic Immune Dynamics in COVID-19 Patients with Cardiac Dysfunction.
Background: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE). Peripheral blood immunophenotyping, cardiac (pro-BNP; troponin) and inflammatory biomarkers were simultaneously evaluated. Results: Cardiac dysfunction (DYS) was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. High-sensitivity cardiac troponin (hs-cTn) was detectable in 43.3% of the patients with a median value of 13.00 ng/L. There were no significant differences between DYS and nDYS patients regarding mortality, organ dysfunction, cardiac (including hs-cTn) or inflammatory biomarkers. Patients with DYS showed persistently lower lymphocyte counts (median 896 [661−1837] cells/µL vs. 2141 [924−3306] cells/µL, p = 0.058), activated CD3 (median 85 [66−170] cells/µL vs. 186 [142−259] cells/µL, p = 0.047) and CD4 T cells (median 33 [28−40] cells/µL vs. 63 [48−79] cells/µL, p = 0.005), and higher effector memory T cells (TEM) at baseline (CD4%: 10.9 [6.4−19.2] vs. 5.9 [4.2−12.8], p = 0.025; CD8%: 15.7 [7.9−22.8] vs. 8.1 [7.7−13.7], p = 0.035; CD8 counts: 40 cells/µL [17−61] vs. 10 cells/µL [7−17], p = 0.011) than patients without cardiac dysfunction. Conclusion: Our study suggests an association between the immunological trait and cardiac dysfunction in severe COVID-19 patients.


Activated Ras alters lens and corneal development through induction of distinct downstream targets.
Mammalian Ras genes regulate diverse cellular processes including proliferation and differentiation and are frequently mutated in human cancers. Tumor development in response to Ras activation varies between different tissues and the molecular basis for these variations are poorly understood. The murine lens and cornea have a common embryonic origin and arise from adjacent regions of the surface ectoderm. Activation of the fibroblast growth factor (FGF) signaling pathway induces the corneal epithelial cells to proliferate and the lens epithelial cells to exit the cell cycle. The molecular mechanisms that regulate the differential responses of these two related tissues have not been defined. We have generated transgenic mice that express a constitutively active version of human H-Ras in their lenses and corneas. Ras transgenic lenses and corneal epithelial cells showed increased proliferation with concomitant increases in cyclin D1 and D2 expression. This initial increase in proliferation is sustained in the cornea but not in the lens epithelial cells. Coincidentally, cdk inhibitors p27Kip1 and p57Kip2 were upregulated in the Ras transgenic lenses but not in the corneas. Phospho-Erk1 and Erk2 levels were elevated in the lens but not in the cornea and Spry 1 and Spry 2, negative regulators of Ras-Raf-Erk signaling, were upregulated more in the corneal than in the lens epithelial cells. Both lens and corneal differentiation programs were sensitive to Ras activation. Ras transgenic embryos showed a distinctive alteration in the architecture of the lens pit. Ras activation, though sufficient for upregulation of Prox1, a transcription factor critical for cell cycle exit and initiation of fiber differentiation, is not sufficient for induction of terminal fiber differentiation. Expression of Keratin 12, a marker of corneal epithelial differentiation, was reduced in the Ras transgenic corneas. Collectively, these results suggest that Ras activation a) induces distinct sets of downstream targets in the lens and cornea resulting in distinct cellular responses and b) is sufficient for initiation but not completion of lens fiber differentiation.