New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.
Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.


Vibrio lentus protects gnotobiotic sea bass (Dicentrarchus labrax L.) larvae against challenge with Vibrio harveyi.
Due to the mounting awareness of the risks associated with the use of antibiotics in aquaculture, treatment with probiotics has recently emerged as the preferred environmental-friendly prophylactic approach in marine larviculture. However, the presence of unknown and variable microbiota in fish larvae makes it impossible to disentangle the efficacy of treatment with probiotics. In this respect, the recent development of a germ-free culture model for European sea bass (Dicentrarchus labrax L.) larvae opened the door for more controlled studies on the use of probiotics. In the present study, 206 bacterial isolates, retrieved from sea bass larvae and adults, were screened in vitro for haemolytic activity, bile tolerance and antagonistic activity against six sea bass pathogens. Subsequently, the harmlessness and the protective effect of the putative probiotic candidates against the sea bass pathogen Vibrio harveyi were evaluated in vivo adopting the previously developed germ-free sea bass larval model. An equivalence trial clearly showed that no harmful effect on larval survival was elicited by all three selected probiotic candidates: Bacillus sp. LT3, Vibrio lentus and Vibrio proteolyticus. Survival of Vibrio harveyi challenged larvae treated with V. lentus was superior in comparison with the untreated challenged group, whereas this was not the case for the larvae supplemented with Bacillus sp. LT3 and V. proteolyticus. In this respect, our results unmistakably revealed the protective effect of V. lentus against vibriosis caused by V. harveyi in gnotobiotic sea bass larvae, rendering this study the first in its kind.


Staying informed without a cost: No effect of positive news media on stress reactivity, memory and affect in young adults.
We read, see and hear news from various media sources every day. A large majority of the news is negative. A previous study from our laboratory showed that reading negative news is associated with both increased stress reactivity (measured via the stress hormone cortisol) and recall of the negative news segments in women. The present study investigated the effects of positive news on cortisol stress reactivity, memory and affect using a methodology highly similar to the study on negative news that was previously used by our team. Sixty-two healthy participants aged between 18 and 35 years (81% women) were randomly exposed to either positive or neutral news segments, followed by a laboratory stressor. We assessed participants' affect three times during the procedure and measured cortisol in saliva eight times (at 10-minute intervals). Twenty-four hours later, participants were contacted by phone to assess their recall of the news segments. Results showed that exposure to positive news, relative to neutral news, did not modulate participants' cortisol levels in response to the laboratory stressor. Positive news had no impact on memory recall of the news and did not change participants' positive or negative affect. Bayes factors suggested that these nonsignificant results are not attributable to low statistical power. Contrary to negative news, positive and neutral news do not modulate stress reactivity, memory and affect. These results suggest that people can stay informed without physiological and psychological costs when the news to which they are exposed adopt a positive or neutral approach.


A conceptual and empirical review of the meaning, measurement, development, and teaching of intervention competence in clinical psychology.
Through the course of this paper we discuss several fundamental issues related to the intervention competence of psychologists. Following definitional clarification and proposals for more strictly distinguishing competence from adherence, we interpret Dreyfus and Dreyfus's [Dreyfus, H.L., & Dreyfus, S.E. (1986). Mind over machine: The power of human intuition and expertise in the age of the computer. New York: Free Press.] five stage theory of competence development (from novice to expert) within a strictly clinical framework. Existing methods of competence assessment are then evaluated, and we argue for the use of new and multiple assessment modalities. Next, we utilize the previous sections as a foundation to propose methods for training and evaluating competent psychologists. Lastly, we discuss several potential impediments to large scale competence assessment and education, such as the heterogeneity of therapeutic orientations and what could be termed a lack of transparency in clinical training.


Comparative analysis of two blood culture systems (Isolator and a 12-tube system) by cumulative differences in detection power at different times during incubation.
A lysis-centrifugation blood culture system (Isolator) and a conventional system (4 tubes of nutrient broth, 4 tubes of semisolid agar, and 4 tubes of thioglycollate agar) were compared after different lengths of incubation by cumulative scoring of differences in detection power. After the first half day of incubation, the Isolator system was already significantly faster in detecting isolates of clinical significance (15 vs. 4, P = 0.02). Maximum difference in first or only detection system was seen after two days of incubation and was based on an overall superior detection of Staphylococcus aureus (11 vs. 0, P = 0.001), and an earlier detection of Enterobacteriaceae (30 vs. 13, P = 0.01) in the Isolator system. On the contrary, the detection of Streptococcus pneumoniae was significantly inferior in the Isolator system (0 vs. 10, P = 0.002). The earlier finding of clinically significant microorganisms in the Isolator system certainly contributes to good patient-care. A drawback of the Isolator system was the finding of clinically insignificant coagulase-negative staphylococci in 11%, compared with 1% in the conventional system. This led to a considerable waste of time and materials in the laboratory. The comparison of the two blood culture systems, based on statistical analysis of cumulative differences in detection power, expressed as the earliest or only findings, gives the optimal information, and is in our opinion the clinically most relevant comparison.


Axial interactions during neurogenesis in dysraphic mice.
The spatial relationships of midline axial structures were compared in normal and dysraphic embryos of the loop-tail (Lp) mutant mouse at 9 days of gestation, and the distribution of two glycoproteins, fibronectin and laminin, was determined in this region by means of immunofluorescence histochemistry. At various levels of the trunk in abnormal embryos, the notochord, ventral midline of the neural folds, dorsal aorta(e) and/or gut were variably separated from one another, in contrast to the closer contact that occurred among these midaxial structures at comparable trunk levels in normal embryos. Positive anti-fibronectin and anti-laminin reactions were noted within areas of contact in the normal embryos and at the interfaces of tissue separation in the abnormal embryos. Although the intensity of the immunofluorescent reaction could not be assessed or compared quantitatively, the presence and distribution of fibronectin and laminin in the abnormal embryos suggest that these two glycoproteins may not be causally or fundamentally involved in producing the abnormal spatial relationships and separation of the midaxial structures.


The value of a spaceflight clinical decision support system for earth-independent medical operations.
As NASA prepares for crewed lunar missions over the next several years, plans are also underway to journey farther into deep space. Deep space exploration will require a paradigm shift in astronaut medical support toward progressively earth-independent medical operations (EIMO). The Exploration Medical Capability (ExMC) element of NASA's Human Research Program (HRP) is investigating the feasibility and value of advanced capabilities to promote and enhance EIMO. Currently, astronauts rely on real-time communication with ground-based medical providers. However, as the distance from Earth increases, so do communication delays and disruptions. Moreover, resupply and evacuation will become increasingly complex, if not impossible, on deep space missions. In contrast to today's missions in low earth orbit (LEO), where most medical expertise and decision-making are ground-based, an exploration crew will need to autonomously detect, diagnose, treat, and prevent medical events. Due to the sheer amount of pre-mission training required to execute a human spaceflight mission, there is often little time to devote exclusively to medical training. One potential solution is to augment the long duration exploration crew's knowledge, skills, and abilities with a clinical decision support system (CDSS). An analysis of preliminary data indicates the potential benefits of a CDSS to mission outcomes when augmenting cognitive and procedural performance of an autonomous crew performing medical operations, and we provide an illustrative scenario of how such a CDSS might function.


Galvanic corrosion inhibition from aspect of bonding orbital theory in Cu/Ru barrier CMP.
In this report, the galvanic corrosion inhibition between Cu and Ru metal films is studied, based on bonding orbital theory, using pyridinecarboxylic acid groups which show different affinities depending on the electron configuration of each metal resulting from a π-backbonding. The sp2 carbon atoms adjacent to nitrogen in the pyridine ring provide π-acceptor which forms a complex with filled d-orbital of native oxides on Cu and Ru metal film. The difference in the d-orbital electron density of each metal oxide leads to different π-backbonding strength, resulting in dense or sparse adsorption on native metal oxides. The dense adsorption layer is formed on native Cu oxide film due to the full-filled d-orbital electrons, which effectively suppresses anodic reaction in Cu film. On the other hand, only a sparse adsorption layer is formed on native Ru oxide due to its relatively weak affinity between partially filled d-orbital and pyridine groups. The adsorption behaviour is investigated through interfacial interaction analysis and electrochemical interaction evaluation. Based on this finding, the galvanic corrosion behaviour between Cu and Ru during chemical mechanical planarization (CMP) processing has been controlled.


[What is the cost of vascular operations? A prospective cost analysis of conventional and combined endovascular interventions].
Current and future legislation demand improved efficiency in the medical services. The aim of this study was to analyse the costs of vascular surgery in order to reveal potential ways of reducing expense. Taking into account the staff, equipment and operating theatre supplies, we analyzed 58 elective operations comprising 47 conventional and 11 combined endovascular procedures. The mean overall costs calculated for the different operations were: 5.269 DM for a transfemoral embolectomy (n = 3), 8.504 DM for a patchplasik of the profunda arteria (n = 8), 10.265 DM for a femoro-popliteal bypass with a prosthesis (n = 6)--13.180 DM with a vein (n = 2), 9.864 DM for conventional iliac artery reconstruction (n = 7)--iliac endovascular combined procedure (n = 4) 14.494 DM, 14.951 DM for a Y-prosthesis in case of stenosis (n = 3)--13.288 DM in case of infrarenal aortic aneurysm (IAA, n = 4), 11.954 DM for a tube prosthesis in case of IAA (n = 3), 23.571 DMY-stent prothesis for IAA (n = 5), 19.914 DM stent for a thoracic aneurysm (n = 2), 7.153 DM a carotid thrombendarterectomy (n = 6), 5.503 DM for varicosis surgery (n = 5). Because of the high cost of materials, the total outlay for combined endovascular procedures appeared to be high when compared to conventional vascular surgery. Substantial savings concerning the operation may only be achieved if facility structure and qualification of staff meets the particular requirements.


Concanavalin A-stimulated proliferation of T cell subset-depleted lymphocyte populations isolated from Fasciola hepatica-infected cattle.
Over 14 weeks, peripheral blood lymphocytes (PBL) were isolated from eight adult cattle which had been orally infected with Fasciola hepatica via trickle infection over a 10-day period. Two age, breed and sex-matched cattle served as controls. CD4+, CD8+ and gammadelta+ T cells were depleted from whole PBL populations by magnetic bead depletion. Lymphocyte proliferation assays demonstrated a transient, but marked elevation in responsiveness to Concanavalin A (Con A) between weeks 2 and 4 post-infection in PBL from infected animals. Proliferative responses to Con A were significantly greater in PBL from infected cattle than uninfected/control cattle over the initial period of the experiment. Con A-stimulated proliferation of PBL isolated from infected cattle followed a similar pattern to PBL responses to F. hepatica antigen. In both whole and subset-depleted lymphocyte populations from infected cattle, proliferative responses to Con A decreased from day 28 post-infection. Depletion of CD4+, CD8+ and gammadelta+ T cell subpopulations significantly augmented responses soon after infection. These findings suggest that the capacity of bovine PBL to proliferate in response to Con A stimulation, was in some way attenuated by F. hepatica infection and proliferative responses due to non-specific activation was suppressed by the coordinated activities of various lymphocyte subsets.


Nonimmune fetal ascites: a series of 79 cases.
The purpose of this study was to analyze the precision of ultrasonography in defining the cause and prognosis in fetal ascites. We conducted a retrospective study of 79 cases of fetal ascites. The mortality rate was 57% overall and ranged from 100% (7/7 cases) for metabolic storage disease to 0% (0/3 cases) in chylous ascites. Ascites before 24 weeks of gestation or combined with fetal hydrops indicates poor prognosis (respectively, 78.6% vs 45% mortality rate after 24 weeks; P<.01; and 77% vs 50.8% without hydrops; P<.02). Ascites was organic in 45 cases, infectious in 13 cases, idiopathic in 12 cases, and genetic in 9 cases. The cause was defined ultrasonographically in 28 of the 45 organic ascites and in 8 of the 25 isolated ascites. Urinary cause was the most frequent and the most successfully specified cause (14/15 cases). Routine ultrasonography detects fetal ascites, but the cause is extremely variable and difficult to specify. When associated with fetal hydrops, the prognosis is poor.


CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes: Applications for cardiovascular disease modelling and cardiotoxicity screening.
Cardiovascular diseases (CVDs) are leading causes of death worldwide, and drug-induced cardiotoxicity is among the most common cause of drug withdrawal from the market. Improved models of cardiac tissue are needed to study the mechanisms of CVDs and drug-induced cardiotoxicity. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) have provided a major advance to our ability to study these conditions. Combined with efficient genome editing technologies, such as CRISPR/Cas9, we now have the ability to study with greater resolution the genetic causes and underlying mechanisms of inherited and drug-induced cardiotoxicity, and to investigate new treatments. Here, we review recent advances in the use of hPSC-CMs and CRISPR/Cas9-mediated genome editing to study cardiotoxicity and model CVD.


Clinical results of meniscus repair in patients 40 years and older.
The critical role that the meniscus plays in the knee along with the advantages of preserving as much of the meniscus as possible have both been well documented. Whenever possible, meniscus repair has become the procedure of choice for treatment of meniscal tears. However, some researchers have reported less favorable results in older patients. To determine the results of meniscus repair in older patients, patients 40 years and older who underwent arthroscopically assisted meniscus repair were prospectively followed up. Thirty-seven patients were included in the study, all of which had a minimum 2-year follow-up (average, 26.5 months). The average age of the patients at the time of the repair was 44.2 years (range, 40 to 52 years); 26 were males and 11 were females. There were 19 left knees and 18 right knees included in the study. Twenty-two patients had associated anterior cruciate ligament reconstructions. Physical examination at follow-up included swelling, joint line tenderness, locking, and McMurray testing and radiographs. Five of 37 menisci repaired (13.5%) were symptomatic at latest follow-up. All of these patients had joint line tenderness and two had a positive McMurray test. Three of these patients had repeat arthroscopy confirming that the meniscus had not healed. Because of the small number of patients with symptoms at follow-up, the authors feel that meniscus repair in patients 40 years and older is an effective treatment for peripherally located meniscus tears. With 86.5% of the patients having good clinical results, these findings are comparable with other studies with a younger population and signify that repair of peripheral tears is indicated in this age group especially in conjunction with anterior cruciate ligament reconstruction. The findings suggest that the location and meniscal tear, rather than the age of the patient, determine the potential for successful repair.


Drosophila melanogaster as an emerging translational model of human nephrolithiasis.
The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventive measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis. It may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. We comprehensively reviewed the English language literature using PubMed®. When necessary, authoritative texts on relevant subtopics were consulted. The genetic composition, anatomical structure and physiological function of Drosophila malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis have been developed, including genetically linked and environmentally induced stones. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urological community with a unique opportunity to increase our understanding of this enigmatic disease.


Unexpected isolated native pulmonary valve endocarditis; really benign as thought?
Isolated pulmonary valve endocarditis is extremely rare, accounting for <2% of cases. Major predisposing factors are intravenous drug use, implanted cardiac devices, congenital heart diseases, and central venous catheters. Most patients respond well to appropriate antibiotherapy. We report a case with an isolated native pulmonary valve endocarditis due to methicillin-resistant staphylococcus-aureus infection which developed after a tooth abscess in a previously healthy non-drug user young male. After one week antibiotherapy, surgery was required due to acute severe pulmonary insufficiency and right heart-failure. After the operation, he had a multi-organ failure despite veno-arterial extracorporeal membrane oxygenation, antibiotherapy, and other supportive treatments, therefore the case concluded with mortality. Our case showed that pulmonary valve endocarditis may occur in patients without risk factors in case of portal of entry for bacteremia and it may carry worse prognosis than previously known. Virulence of the microorganism and vegetation size are the major predictors of prognosis. Pulmonary valve endocarditis should be kept in mind even in patients without any known risk factors.


[Study of the possibility of stabilizing a levorin microbiological standard].
The effect of a number of factors, providing increased stability of the levorin microbiological standard was studied. It was shown that air-tight packing and inert gas atmosphere (antibiotic storage in ampoules sealed under nitrogen) significantly increased the antibiotic stability. It was also shown that hydrochinone had the highest positive effect on levorin stability.


Feeding practices and early weaning in the neonatal period: a cohort study.
To describe feeding practices and the risk factors for the mixed breastfeeding and early weaning in the neonatal period. Cohort study, which we collected socioeconomic, demographic, health care and feeding data from 415 mother/child binomials born in four public maternity hospitals in Natal/Brazil. They were followed-up at 48 hours, 7 and 28 days after birth. The association was established using Pearson's Chi-square test and Poisson's regression, after adjusting it to other variables. The prevalence of mixed breastfeeding in the first 2 days was 47,2% and early weaning in 7 and 28 days was 8,4% and 16,2% in that order. The main reasons for mixed breastfeeding and early weaning were: colostrum deficiency (33.8%), difficulty in latching/sucking (23.5%) and "little milk" (70.0%). The use of formula/milk/porridge remained associated with maternal age ≤ 20 years (RR = 0.64; 95%CI: 0.47-0.86), age 20-29 years (RR = 0,70; 95%CI: 0,57-0,87), primiparity (RR = 1.37; 95%CI: 1.11-1.60) and cesarean delivery (RR = 1.20; 95%CI: 1.00-1.45) at 2 days; absence of paternal support (RR = 4.98; 95%CI: 2.54-9.79) and pacifier use (RR = 3.21; 95%CI: 1.63-6.32) at 7 days; and only pacifier use (RR = 2.48; 95%CI: 1.53-4.02) at 28 days. Early weaning was associated with maternal and health care factors, thus suggesting the need to readjust good practices and educational actions to achieve the exclusive offer to the maternal breast in the neonatal period.


Anaerobic oxidation of methane coupled to thiosulfate reduction in a biotrickling filter.
Microorganisms from an anaerobic methane oxidizing sediment were enriched with methane gas as the substrate in a biotrickling filter (BTF) using thiosulfate as electron acceptor for 213days. Thiosulfate disproportionation to sulfate and sulfide were the dominating sulfur conversion process in the BTF and the sulfide production rate was 0.5mmoll-1day-1. A specific group of sulfate reducing bacteria (SRB), belonging to the Desulforsarcina/Desulfococcus group, was enriched in the BTF. The BTF biomass showed maximum sulfate reduction rate (0.38mmoll-1day-1) with methane as sole electron donor, measured in the absence of thiosulfate in the BTF. Therefore, a BTF fed with thiosulfate as electron acceptor can be used to enrich SRB of the DSS group and activate the inoculum for anaerobic oxidation of methane coupled to sulfate reduction.


Sulphonated azo dye decolorization by Alcaligenes faecalis subsp. phenolicus MB207: Insights from laboratory and computational analysis.
Microbial decolorization of azo dyes, mediated by an enzymatic mechanism is an intricate cost-effective, and eco-friendly treatment method of genotoxic azo pollutants. Scientists are on the constant lookout for microbes, enzymes, and mechanisms that could aid remediation of the environment at a fast pace. Alcaligenes faecalis subsp. phenolicus MB207 is one such bacteria, consisting of azoreductase (AzoR) and laccase/multicopper oxidase enzyme responsible for sulphonated mono-azo dye (Methyl orange) and di-azo dye (Congo red) degradation. AzoR degrades dyes by a ping-pong setup while multicopper oxidase achieves this through a non-specified radical approach. We have coupled experimental analysis with bioinformatics for deciphering intricacies of this procedure in tiny scale enzymatic machines of this biotope. The degradation assays were followed by molecular docking of the enzyme-substrate complexes. Key anchoring bonds were detected and mapped H-bonding, electron exchange, ionic interactions, as well as hydrophobic interactions, provided insights into dye-enzyme and NADH-enzyme binding. This study establishes a foundation of the molecular basis of dye interaction with azoR and multicopper oxidase in A. facealis subsp. phenolicus MB207.


A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy.
Intravenous immunoglobulin (IVIG) has become the standard treatment for multifocal motor neuropathy (MMN) based on limited data. To critically assess the efficacy, safety, and tolerability of 10% liquid IVIG (IVIG), 44 adults with MMN were randomized 1 : 1 to either double-blind treatment of IVIG followed by placebo for 12 weeks each or the reverse. Open-label IVIG was administered for 12 weeks at the beginning and end of the study for clinical stabilization, and between double-blinded periods to prevent a carry-over effect. To avoid potential worsening, switching to open-label IVIG was permitted if deterioration occurred during blinded treatment. Mean maximal grip strength of the more affected hand declined 31.38% during placebo and increased 3.75% during IVIG (p = 0.005). In 35.7% of participants, Guy's Neurological Disability scores for upper limbs worsened during placebo and not during IVIG, whereas the converse was true in 11.9% (p = 0.021). Sixty-nine percent (69.0%) switched prematurely from placebo to open-label IVIG and 2.4% switched from blinded to open-label IVIG (p < 0.001). One serious adverse reaction (pulmonary embolism) and 100 non-serious reactions (69 mild, 20 moderate, and 11 severe) to IVIG occurred. IVIG was effective in improving disability and muscle strength, and was safe and well tolerated in adults with MMN.


Saltwater icephobicity: Influence of surface chemistry on saltwater icing.
Most studies on icephobicity focus on ice formation with pure water. This manuscript presents studies to understand the influence of surfaces on saltwater ice nucleation and propagation. Experiments are conducted to quantify the influence of surface chemistry on saltwater ice nucleation and to understand the utility of superhydrophobic surfaces for saltwater icephobicity. These experiments are conducted with pure water and two sodium chloride solutions, which represent the salinity of seawater and briny produced water. It is seen that the presence of salt slows down the ice front propagation velocity significantly. Saltwater droplet impact dynamics on superhydrophobic surfaces are also different from pure water. Saltwater droplets retract more and a greater fraction of impacting liquid is repelled from the superhydrophobic surface. It is seen that the greater bounciness of saltwater droplets is a result of slower ice nucleation propagation kinetics. These experiments indicate that superhydrophobic surfaces will have better resistance to impact icing with saltwater than pure water and can remain useful at temperatures as low as -40 °C. Overall, this work is a starting point for further studies on heterogeneous nucleation in saltwater and serves as a bridge between the widely studied freshwater icephobic surfaces and saltwater-related applications.


Signaling pathways and therapeutic perspectives related to environmental factors associated with multiple sclerosis.
Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of unknown etiology. Both genetic-susceptibility and environment exposures, including vitamin D deficiency, Epstein-Barr viral and Herpesvirus (HHV-6) infections are strongly implicated in the activation of T cells and MS-pathogenesis. Despite precise knowledge of how these factors could be operating alone or in combination to facilitate and aggravate the disease progression, it is clear that prolonged induction of inflammatory molecules and recruitment of other immune cells by the activated T cells results in demyelination and axonal damage. It is imperative to understand the risk factors associated with MS progression and how these factors contribute to disease pathology. Understanding of the underlying mechanisms of what factors triggers activation of T cells to attack myelin antigen are important to strategize therapeutics and therapies against MS. Current review provides a detailed literature to understand the role of both pathogenic and non-pathogenic factors on the impact of MS.


SSR markers for Filago subg. Filago (Gnaphalieae: Asteraceae) and cross-amplification in three other subgenera.
Microsatellite primers were developed for the first time in the genus Filago (Gnaphalieae: Asteraceae). These markers will facilitate low-scale phylogenetic, phylogeographic, and population genetic studies within the genus Filago. Ten pairs of polymorphic microsatellite primers (as well as five pairs of monomorphic primers) were identified and optimized on two species of Filago (F. gaditana and F. carpetana) using a microsatellite-enrichment library method and 454 GS-FLX technique. The polymorphic primers amplified tri- to hexanucleotide repeats and showed one to six alleles per locus for both species. Transferability was performed in 29 samples corresponding to nine representative species of Filago. The results indicate the utility of the newly developed markers, which will be useful to delve into the phylogenetic relationships among the taxa within Filago. These microsatellites will enable studies of phylogeographic, reproductive, and genetic variation.


Cytomegalovirus granulomatous hepatitis.
Three patients with granulomatous hepatitis due to cytomegalovirus are described. They are compared to the three previously described patients with this disease, and their clinical and serologic characteristics are discussed. Similarities and differences between infectious mononucleosis (Epstein-Barr virus) and cytomegalovirus infections are adduced. That cytomegalovirus may be a cause of granulomatous hepatitis in the adult is stressed.


A case of generalized granuloma trichophyticum.
A 59-year-old man visited our hospital. The patient had suffered from generalized tinea superficialis for thirty years, had been treated with several topical antifungal preparations and was administered griseofulvin at another hospital. Clinical manifestations were as follows: There were large pigmentations on the chest, abdomen, and lower extremities. He had several irregular shaped ulcers on the back, left forearm, and right axilla, and glossy granular lesions on the dorsum of the left foot. Generalized eruptions consisting of indurative pustules, red papules, scars, atrophies and depigmentations were also visible. The biopsy specimens taken from the ulcers, the indurative pustules and granular lesions of the dorsum of the left foot were cultured and Trichophyton rubrum was isolated. Laboratory studies showed slight eosinophilia, Mantoux reaction 56 X 40 mm, Trichophytin reaction 5 X 5 mm, IgE 4000 IU/dl. Histological findings were as follows: Fungal elements were observed in the horny layer, in the spindle cell layer, and in the dermis. Histologic features were both abscesses and granulomas with giant cells. According to the pathologic features of the lesions, the parasitic forms of the fungus changed. Abscesses and granulation tissues containing histiocytes and many multinucleated giant cells were observed in the dermis. Various sizes of arthrospores and various shapes of hyphae were stained by PAS. Most of these fungal elements dissolved in the abscesses and granulomas. However, a few survived.


Oxidative desulfurization of benzothiophene and thiophene with WOx/ZrO2 catalysts: effect of calcination temperature of catalysts.
Oxidative desulfurization (ODS) of model fuel containing benzothiophene (BT) or thiophene (Th) has been carried out with WO(x)/ZrO2 catalyst, which was calcined at various temperatures. Based on the conversion of BT in the model fuel, it can be shown that the optimum calcination temperature of WOx/ZrO2 catalyst is around 700 °C. The most active catalyst is composed of tetragonal zirconia (ZrO2) with well dispersed polyoxotungstate species and it is necessary to minimize the contents of the crystalline WO3 and monoclinic ZrO2 for a high BT conversion. The oxidation rate was interpreted with the first-order kinetics, and it demonstrated the importance of electron density since the kinetic constant for BT was higher than that for Th even though the BT is larger than Th in size. A WOx/ZrO2 catalyst, treated suitably, can be used as a reusable active catalyst in the ODS.


Genome-wide methylation analysis identifies novel prognostic methylation markers in colon adenocarcinoma.
Previous studies have indicated that abnormal methylation is a critical and early event in the pathogenesis of most types of human cancer, which contributes to tumorigenesis. However, there has been little focus on the potential of DNA methylation patterns as predictive markers for the prognosis of colon adenocarcinoma (COAD). In the present study, a genome-wide comparative analysis of DNA methylation profiles was performed between 315 COAD samples and 38 matched tumor-adjacent normal tissue samples. A total of 675 differentially methylated regions (DMRs) associated with 630 genes were identified, including 654 hypermethylated regions (UMRs) and 21 hypomethylated regions, which were capable of distinguishing COAD samples from non-malignant tissue samples. Although most of the DMRs appeared to be located within the gene body or promoter regions, UMRs were mostly located within CpG islands. Functional analysis suggested that genes associated with DMRs were enriched in many of the core cancer-signaling pathways known to be important in COAD biology. A survival analysis was also performed, which identified 7 DMRs as potential candidate markers with the ability to classify patients into high and low-risk groups with significantly different overall survival. The present study provides a better understanding of the molecular mechanisms underlying COAD, and demonstrates the utility of aberrant DNA methylation in the prognosis of COAD.


Advances in immunomodulatory therapy for severe acute pancreatitis.
Severe acute pancreatitis (SAP) has a complex course and a worse prognosis. Immune response imbalance is an important cause of severe pancreatitis or even death in patients. Immunomodulation therapy can regulate the imbalance of inflammatory response, alleviate SAP-related organ damage and improve the prognosis of patients. There are some problems in early immune regulation measures, such as single target and simple way. In recent years, new treatment methods, such as regulating the maturation and apoptosis of immune cells, the application of mesenchymal stem cells (MSCs) and multifactor combination therapy, have provided new ideas and hope for the future treatment of SAP. This article reviews the development of SAP immunoregulation and its recent progress.


Pathways from adolescent screen time to eating related symptoms: a multilevel longitudinal mediation analysis through self-esteem.
Screen time and self-esteem have been shown to be important correlates of eating disorders in adolescence. However, there is an absence of longitudinal studies that distinguish between time-varying factors, accounting for parallel developmental changes and common underlying vulnerability. A total of 3,801 adolescents were administered self-report measures, annually, over the course of 5 years. The association of screen time (social media use, television watching, video gaming) on eating related symptoms was analyzed using a longitudinal Bayesian multilevel path analysis framework. Self-esteem was examined as a mediating factor in this model. This study investigated direct and indirect associations at between-person, concurrent within-person, and lagged-within-person levels, while controlling for gender. The findings revealed that all types of screen time exposure were significantly associated with eating related symptoms at between and within-person levels. A significant association at the lagged-within person level was only revealed for social media use. Self-esteem was found to be a significant mediating factor between screen time and eating related symptoms. An increase in social media use one year was associated with increased of eating related symptoms two years later through lower self-esteem. Implications for prevention are discussed.


Modulation of CYP1A and genotoxic effects in European seabass (Dicentrarchus labrax) exposed to weathered oil: a mesocosm study.
The aim of this study was to assess medium-term toxicity of weathered oil on European seabass. A mesocosm system reproducing an oil spill at sea was applied. Fish were collected after 48 h, 7, 30 and 60 days. Cyp1a gene transcription, EROD and UDPGT activities, bile PAHs metabolites and micronuclei frequency were investigated. A progressive disappearance of low molecular weight n-alkanes and PAHs in the water of the mesocosm occurred during the experimentation. Fishes exposed to oil displayed a significant increase of cyp1a expression and EROD activity during the entire experiment as well as higher concentrations of PAHs metabolites in bile. Micronulei frequency resulted significantly higher during all experiment in oil exposed sea bass compared to controls. The results highlight the environmental risk associated with the release of oil products at sea and confirm the adopted parameters as useful tools for studying the impact of accidental oil spills on fish.


Results of treatment of 20 patients with implant-retained auricular prostheses.
A prospective study of 20 patients receiving rehabilitation for a missing external ear revealed the failure of three flanged implants in a total of 60 placed for the support of a prosthesis and 10 for retention of a bone-anchored hearing aid. Factors limiting an optimal outcome were health of the cutaneous cuff around the abutments, bonding of the silicone ear to the acrylic-resin substructure, and the ability to minimize disfigurement of a congenitally deformed face.


Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment.
Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells' heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1 CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.


Lack of phenotype for LTP and fear conditioning learning in calpain 1 knock-out mice.
We previously proposed the hypothesis that calpain activation played an important role in long-term potentiation (LTP) of synaptic transmission in hippocampus. Two forms of calpain are predominant in brain tissues, calpain 1 (mu-calpain), activated by micromolar calcium concentration and calpain 2 (m-calpain), activated by millimolar calcium concentration in vitro. In the present study, we tested the role of calpain 1 in LTP and in learning and memory using calpain 1 knock-out mice. Changes in learning and memory were assessed using both context and tone fear conditioning. No differences in freezing responses were observed between the knock-out and the wild-type animals during the acquisition phase of the training, eliminating the possibility that the knock-out animals could be differentially affected by the foot shock. Likewise, no differences in freezing responses elicited by either the context or the tone were observed during the retention phase. No differences in short-term potentiation (STP) or LTP were observed in hippocampal slices from the knock-out and matched wild-type mice. Several interpretations might explain these negative results. First, it is conceivable that calpain 2 plays a more dominant role in neurons, and that calpain 1 makes a minor contribution as opposed to its suspected predominant role in the hematopoietic system. Alternatively, it is conceivable that some as yet unknown compensatory mechanisms take effect, and that calpain 2 or another calpain isoform substitutes for the missing calpain 1.


Workforce diversity in cardiothoracic surgery: An examination of recent demographic changes and the training pathway.
The purpose of our study was to examine changes in the demographic makeup of resident physicians in integrated 6-year cardiothoracic surgery and traditional thoracic surgery residency programs from 2013 to 2022 compared with other surgical subspecialties and determine potential leaks in the training pathway. Data from US Graduate Medical Education reports from 2013 to 2022 and medical student enrollment data from the Association of American Medical Colleges were obtained. Average percentages of women and underrepresented minorities were calculated in 2 5-year intervals: 2013 to 2017 and 2018 to 2022. Average percentages of women, Black, and Hispanic medical students and residents were calculated for the 2019 to 2022 period. Pearson χ2 tests were conducted to determine significant differences in proportions of women, Black/African American, and Hispanic trainees across time (α = 0.05). Thoracic surgery and I6 residents saw a significant increase in the proportion of women trainees across the 2 time periods (19.9% (210 out of 1055) to 24.6% (287 out of 1169) (P < .01) and 24.1% (143 out of 592) to 28.9% (330 out of 1142) (P < .05)), respectively. There was no significant change in the proportion of Black and Hispanic trainees in thoracic surgery fellowship or integrated 6-year cardiothoracic residency programs. Hispanic trainees were the only group whose proportion of cardiothoracic surgery trainees was not significantly lower than their medical school proportion. Women and Black trainees had significantly lower proportions of thoracic surgery residents and integrated 6-year cardiothoracic residency program residents than their proportions in medical school (P < .01). Cardiothoracic surgery has not significantly increased the number of Black and Hispanic trainees during the past decade. The lower proportion of Blacks and women in thoracic surgery residency and fellowship programs compared with their proportion in medical schools is concerning and is an opportunity for intervention.


Monitoring respiratory activity in neonates using diaphragmatic electromyograph.
The monitoring of the development of respiratory function in low-birth-weight or sick neonates is important in its overall treatment. The most direct approach to obtaining information on respiratory function is to monitor the activity of the diaphragmatic muscular system rather than measure the resultant change in lung volume or ventilator output, which cannot be guaranteed to be directly related to the neonate's own respiratory activity. The system was designed to assess the feasibility of monitoring respiratory activity in such neonates by measuring the diaphragmatic electromyograph. It is hoped that this system can be used to monitor the development of lung function and possibly, if reliability proves adequate, the synchronisation and control of ventilator assistance. To monitor the EMG, the dominant effect of the ECG was removed using a digital processor. Initial clinical measurements indicate that neonatal respiratory activity can be monitored by measuring the diaphragmatic EMG. Comparative measurements show the EMG method is faster in detecting the inspiratory phase of a breath. Measurements on ventilated neonates showed the presence of intermittent respiratory activity. It also is proposed that clinically relevant information may be deduced from the analysis of the morphology of the detected EMG waveform.


Sleep and aminophylline treatment of apnea in preterm infants.
The influence of short-term aminophylline treatment on sleep behaviour was studied in six preterms infants with recurrent apnea. The incidence of apnea, respiratory pauses, and bradycardias which were closely related to the phases of active sleep, decreased during aminophylline treatment. However, the amount of active sleep remained unaffected. The mode of action of aminophylline is discussed in view of the previously proposed neurophysiological concept of apnea of prematurity.


Environmental factors in cardiovascular disease.
Environmental exposure is an important but underappreciated risk factor contributing to the development and severity of cardiovascular disease (CVD). The heart and vascular system are highly vulnerable to a number of environmental agents--ambient air pollution and the metals arsenic, cadmium, and lead are widespread and the most-extensively studied. Like traditional risk factors, such as smoking and diabetes mellitus, these exposures advance disease and mortality via augmentation or initiation of pathophysiological processes associated with CVD, including blood-pressure control, carbohydrate and lipid metabolism, vascular function, and atherogenesis. Although residence in highly polluted areas is associated with high levels of cardiovascular risk, adverse effects on cardiovascular health also occur at exposure levels below current regulatory standards. Considering the widespread prevalence of exposure, even modest contributions to CVD risk can have a substantial effect on population health. Evidence-based clinical and public-health strategies aimed at reducing environmental exposures from current levels could substantially lower the burden of CVD-related death and disability worldwide.


The prevalence of hepatitis delta virus infection in acute and chronic liver diseases in Turkey: an analysis of clinical studies.
The objective of this study was to review the studies on hepatitis D virus-related liver diseases and to evaluate the national and regional outcomes in order to identify the hepatitis D virus infection in Turkey. This retrospective study included 2182 acute viral hepatitis, 6613 inactive HBsAg carriers, 5961 chronic hepatitis B, 1264 liver cirrhosis and 748 hepatocellular carcinoma cases, who were evaluated for anti-hepatitis D virus positivity at several centers in Turkey since 1980's. ELISA method was used and the results were statistically evaluated. The anti-hepatitis D virus positivity was 3.0% in 1416 acute viral hepatitis and 8.1% in 766 acute hepatitis B cases. This ratio was significantly higher in Diyarbakir than in Istanbul and Ankara for acute viral hepatitis (p<0.001). The mean anti-hepatitis D virus was 4.9% in inactive HBsAg carriers and significantly decreased from 1980 to 2005 (4.1% and 2.9%, respectively p<0.001). The anti- hepatitis D virus was 20% in chronic hepatitis B and 32.5% in liver cirrhosis cases. The positivity were significantly lower in Istanbul and Izmir compared to Diyarbakr and Van (p<0.001). Antihepatitis D virus positivity was decreased in all regions for the last two decades (p<0.001). The rates decreased from 31% to 11% for chronic hepatitis B and from 43.3% to 24% for liver cirrhosis (p<0.001). The mean anti-hepatitis D virus was 23% in hepatocellular carcinoma cases, which was significantly lower in Istanbul and Izmir compared to Diyarbakr and Elaz currency (p<0.0001). The hepatitis D virus infection is a critical problem in our country, particularly in the Eastern and Southeastern Anatolia. In recent years, the hepatitis D virus infection is decreasing countrywise, however the rate still remains to be critical.


Longitudinal studies of experimental otitis media with Haemophilus influenzae in the gerbil.
Haemophilus influenzae non-typable strain 119 was found to cause severe otitis media with sequellae when inoculated into the middle ear cavities of the Mongolian gerbil, Meriones unguiculatus. Acute inflammation was followed by the development of highly vascular granulation tissue and formation of new bone within the middle ear bulla. These changes persisted throughout the 14-week study in the untreated animals. The gerbil was variably susceptible to otitis media caused by inoculating 30-3000 bacterial cells and 100% susceptible to greater than 3000 cells. The susceptibility of the gerbil to common etiological agents of otitis media allows its use as an appropriate model of the disease.


Orchestration of a blood-derived and ADARB1-centred network in Alzheimer's and Parkinson's disease.
The peripheral immune system is thought to influence the pathogenesis of the central nervous system in Alzheimer's disease (AD) and Parkinson's disease (PD). This study aimed to investigate the characteristics of peripheral leukocytes in AD and PD by comprehensively analyzing the transcriptomic and metabolic features in the blood (NCONTROL = 15; NAD = 11; NPD = 13). The study found an ADARB1-centered module that was associated with diagnosis, phenethylamine, and glutamate. The module consisted of ADARB1, a vital RNA-editing enzyme, LINC02960, and 109 miRNAs. The study also predicted that the ADARB1 and involved regulators were targeted by miRNAs in the ADARB1 module. The integrated analysis of transcriptome and metabolic panel revealed a central role of ADARB1, miR-199b-5p, miR-26a, miR-450b-5p, miR-34c-5p, glutamate and phenethylamine in the regulatory relationships. The study highlights a set of synergetic non-coding RNA related to ADARB1 in the blood ecosystem of AD and PD with dynamic glutamate and phenethylamine, providing new insights into the pathogenesis of these diseases.


Ocular myasthenia gravis mimicking pseudointernuclear ophthalmoplegia and variable esotropia.
A 70-year-old man with known vascular disease, who had bilateral internuclear ophthalmoplegia, and an 18-month-old girl with a long-term variable esotropia culminating in a postinfectious oculopharyngeal neuropathy both responded with a positive edrophonium chloride (Tensilon) test, strongly suggesting the diagnosis of myasthenia gravis. Both subsequently received maintenance doses of neostigmine methylsulfate (Prostigmin).


Review on adherence of the literature to official recommendations on albuminuria harmonization and standardization.
Albuminuria standardization is a key issue to produce reliable and equivalent results between laboratories. We investigated whether official recommendations on albuminuria harmonization are followed in the literature. The PubMed database was searched from June 1 to September 26, 2021. The search terms included urine albumin, urine albumin-to-creatinine ratio (uACR), and albuminuria. A total of 159 articles were considered eligible; 50.9 % reported the type of urine collection. Specifically, 58.1 % collected a random spot urine specimen, 21 % collected a first morning void, and 6.2 % collected a 24-h specimen. Overall, 15 % of articles reported data on sample shipping, storage, and centrifugation and 13.3 % mentioned the preanalytical phase without any data on albuminuria. The method for albuminuria was properly described in 31.4 % of articles; of these, 54.9 % used immunological methods, and 8.9 % contained errors or missing data. Most articles (76.7 %) expressed test results as albuminuria-to-creatininuria ratio. Different decision levels were utilized in 130 articles; of these, 36 % used a decision level of ≤30 mg/g creatininuria and 23.7 % used three decision levels (≤30, 30-300, and ≥300 mg/g). The failure to follow guidelines on albuminuria harmonization was mainly found in the preanalytical phase. The poor awareness of the importance of preanalytical steps on test result may be a possible explanation.


Transcriptome changes in age-related macular degeneration.
Age-related macular degeneration (AMD) is a debilitating, common cause of visual impairment. While the last decade has seen great progress in understanding the pathophysiology of AMD, the molecular changes that occur in eyes with AMD are still poorly understood. In the current issue of Genome Medicine, Newman and colleagues present the first systematic transcriptional profile analysis of AMD-affected tissues, providing a comprehensive set of expression data for different regions (macula versus periphery), tissues (retina versus retinal pigment epithelium (RPE)/choroid), and disease state (control versus early or advanced AMD). Their findings will serve as a foundation for additional systems-level research into the pathogenesis of this blinding disease.


Nucleation and transport organize microtubules in metaphase spindles.
Spindles are arrays of microtubules that segregate chromosomes during cell division. It has been difficult to validate models of spindle assembly due to a lack of information on the organization of microtubules in these structures. Here we present a method, based on femtosecond laser ablation, capable of measuring the detailed architecture of spindles. We used this method to study the metaphase spindle in Xenopus laevis egg extracts and found that microtubules are shortest near poles and become progressively longer toward the center of the spindle. These data, in combination with mathematical modeling, imaging, and biochemical perturbations, are sufficient to reject previously proposed mechanisms of spindle assembly. Our results support a model of spindle assembly in which microtubule polymerization dynamics are not spatially regulated, and the proper organization of microtubules in the spindle is determined by nonuniform microtubule nucleation and the local sorting of microtubules by transport.


[Recombinations during DNA cloning].
RecA-independent recombinations accompanying the processes of plasmids preparation and cloning into Escherichia coli cells are induced within the short direct and inverted repeats of several types.


Longitudinal metabolomic profiles reveal sex-specific adjustments to long-duration spaceflight and return to Earth.
Spaceflight entails a variety of environmental and psychological stressors that may have long-term physiological and genomic consequences. Metabolomics, an approach that investigates the terminal metabolic outputs of complex physiological alterations, considers the dynamic state of the human body and allows the identification and quantification of down-stream metabolites linked to up-stream physiological and genomic regulation by stress. Employing a metabolomics-based approach, this study investigated longitudinal metabolic perturbations of male (n = 40) and female (n = 11) astronauts on 4-6-month missions to the International Space Station (ISS). Proton nuclear magnetic resonance (1H-NMR) spectroscopy followed by univariate, multivariate and machine learning analyses were used on blood serum to examine sex-specific metabolic changes at various time points throughout the astronauts' missions, and the metabolic effects of long-duration space travel. Space travel resulted in sex-specific changes in energy metabolism, bone mineral and muscle regulation, immunity, as well as macromolecule maintenance and synthesis. Additionally, metabolic signatures suggest differential metabolic responses-especially during the recovery period-with females requiring more time to adjust to return to Earth. These findings provide insight into the perturbations in glucose and amino acid metabolism and macromolecule biosynthesis that result from the stressors of long-duration spaceflight. Metabolomic biomarkers may provide a viable approach to predicting and diagnosing health risks associated with prolonged space travel and other physiological challenges on Earth.


A unique chromatin complex occupies young α-satellite arrays of human centromeres.
The intractability of homogeneous α-satellite arrays has impeded understanding of human centromeres. Artificial centromeres are produced from higher-order repeats (HORs) present at centromere edges, although the exact sequences and chromatin conformations of centromere cores remain unknown. We use high-resolution chromatin immunoprecipitation (ChIP) of centromere components followed by clustering of sequence data as an unbiased approach to identify functional centromere sequences. We find that specific dimeric α-satellite units shared by multiple individuals dominate functional human centromeres. We identify two recently homogenized α-satellite dimers that are occupied by precisely positioned CENP-A (cenH3) nucleosomes with two ~100-base pair (bp) DNA wraps in tandem separated by a CENP-B/CENP-C-containing linker, whereas pericentromeric HORs show diffuse positioning. Precise positioning is largely maintained, whereas abundance decreases exponentially with divergence, which suggests that young α-satellite dimers with paired ~100-bp particles mediate evolution of functional human centromeres. Our unbiased strategy for identifying functional centromeric sequences should be generally applicable to tandem repeat arrays that dominate the centromeres of most eukaryotes.


Microsurgical reconstruction in the head and neck region: an 18-year experience with 500 consecutive cases.
Microvascular free tissue transfer has become a significant factor in the reconstruction of head and neck cancer patients. Various donor sites are available to enable anatomical and functional repair of a defect. All free vascularized tissue transfers performed during the period from March 1982 to September 2000 were retrieved from this hospital's database and analysed with regard to the surgical defect, chosen donor site and complications. During the 18-year period a total of 1,164 patients with head and neck cancer were treated in this institution. A total of 500 free-flap reconstructions were performed for 479 patients. In the majority of patients (n = 451) reconstruction was indicated following ablative tumour surgery. With regard to donor site selection, the first choice of free jejunum was used in 181 patients, followed by the radial forearm flap in 140 patients. Among the 500 free-flap reconstructions, a total flap loss rate of 6% was observed. Patient age (p = 0.004) and tobacco use (p = 0.043) were significant risk factors for complications overall, whereas patient age (p = 0.021) and operating time (p = 0.043) were significantly correlated with local complications. Immediate repair of head and neck defects using free tissue transfer is a successful and reliable method and is becoming the gold standard at many institutions. The complication rate is low once experience with these techniques has been acquired.


Creating an Optimal Approach for Diagnosing Sleep Apnea.
Sleep apnea is nowadays recognized as a treatable chronic disease and awareness of it has increased, leading to an upsurge in demand for diagnostic testing. Conventionally, diagnosis depends on overnight polysomnography in a sleep clinic, which is highly human-resource intensive and ignores the night-to-night variability in classical sleep apnea markers, such as the apnea-hypopnea index. In this review, the authors summarize the main improvements that could be made in the sleep apnea diagnosis strategy; how technological innovations and multi-night home testing could be used to simplify, increase access, and reduce costs of diagnostic testing while avoiding misclassification of severity.


A new biologically, osmotically, and oncotically balanced gel that shows calcifications blocked by silicone.
The radiodensity of silicone gel-filled breast implants is well documented. It has been suggested that silicone gel may block the transmission of x-rays sufficiently to prevent visualization of microcalcifications that are frequently an indicator of malignancy. A new biologically, oncotically balanced gel has been developed that has increased radiotranslucency to approximately the density of normal breast tissue, increased lubrication qualities, and is quickly and safely eliminated by the body should the shell rupture. We present a case wherein a patient's mammogram was read as negative two years prior to breast reaugmentation due to Baker IV capsular contracture. During surgery, complete calcification of the capsule was discovered, as well as two ruptured prostheses; neither condition had been detected by the mammogram. These capsules, with their calcifications and scar intact, were removed in toto and radiographically compared through standard silicone gel-filled breast implants and through implants containing the new biologically, osmotically, oncotically balanced gel. The calcifications were completely obscured by the silicone gel-filled prosthesis and completely visible when viewed through the bio-oncotic gel-filled prosthesis. Postoperative mammograms confirmed the radiolucency of the new gel-filled prostheses. This new gel appears to be a reasonable alternative to silicone gel for filling breast implants.


[The multi-disciplinary treatment of adult head trauma, from treatment to reintegration].
The treatment of patients with head trauma in neurological rehabilitation units must implement a coordinated care approach, involving rehabilitation and early reintegration. This integration is overseen by a specialised and multi-disciplinary team.


Thermal injury on the foot and ankle of a paraplegic: report of a case from exposure to sunshine.
The case of a paraplegic patient who sustained a fullthickness thermal injury to his left foot from exposure to sunshine is described. Electromagnetic energy from the sun can cause enough damage to full thickness of the skin when the heat is intense enough or not dissipated sufficiently. The lesson of it is that paralyzed and anesthetic individuals should be cautious about sunbathing.


[The gene pool of the Belgorod oblast population: II. "Family name portraits" in groups of districts with different degrees of subdivision and the role of migrations in their formation].
The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The "family name portraits" of districts with low (0.00003 less sign f* < 0.00022, f*(r) = 0.00015) and moderate (0.00023 < f*(r) < 0.00042, f*(r) = 0.00029) inbreeding levels are similar both to each other and to the "family name portrait" of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*(r) < 0.00125, f*(r) = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision.


Dataset on the proteomic response during ferroptosis induction via tamoxifen induced GPX4 KO in mouse embryonic fibroblasts.
Ferroptosis is a type of programmed cell death distinct from apoptosis and necroptosis that plays an essential role in pathophysiological conditions such as neurodegenerative diseases and tumorigenesis. Massive lipid oxidation in an iron-dependent manner is a hallmark of ferroptosis.This modality of cell death is also characterized by perturbation of several metabolic pathways, predominantly fatty acid metabolism, thiol metabolism, iron homeostasis and the mevalonate pathway. We aimed to acquire data from different timepoints of ferroptotic death in order to get information about the primary and delayed phases of the ferroptotic response. For this purpose, we used model Pfa1 cells, which are 4-OH-TAM-inducible Gpx4-/- mouse immortalized fibroblasts [1]. GPX4 is one of the main intracellular ferroptosis regulators and inhibiting it is a classic approach to induce ferroptosis. Measuring protein fold changes at different ferroptotic stages and in nontreated Pfa1 cells could give useful information on the activation of genes involved in ferroptosis and non-genomic protein regulation during ferroptotic progression. Bottom-up proteomic data were acquired from samples obtained 24 and 48 hours after genetic induction of ferroptosis. Chromato-mass spectra were registered in DDA mode and are suitable for further label-free quantification. These data might be a valuable proteome basis for further investigation of ferroptosis and complement other available omics.


Educational attainment among long-term survivors of cancer in childhood and adolescence: a Norwegian population-based cohort study.
The number of young cancer survivors has increased over the past few decades due to improvement in treatment regimens, and understanding of long-term effects among the survivors has become even more important. Educational achievements and choice of educational fields were explored here. Five-year cancer survivors born in Norway during 1965-1985 (diagnosed <19 years) were included in our analysis by linking Norwegian population-based registries. Cox regression was applied to study the educational attainment among survivors of central nervous system (CNS) tumours, those assumed to have received CNS-directed therapy, and other cancer survivors relative to the cancer-free population. Logistic regression was used to compare the choice of educational fields between the cancer survivors at undergraduate and graduate level and the cancer-free population. Overall, a lower proportion of the cancer survivors completed intermediate (67 vs. 70 %), undergraduate (31 vs. 35 %) and graduate education (7 vs. 9 %) compared with the cancer-free population. Deficits in completion of an educational level were mainly observed among survivors of CNS-tumours and those assumed to have received CNS-directed therapy. Choices of educational fields among cancer survivors were in general similar with the cancer-free population at both undergraduate and graduate levels. Survivors of CNS-tumours and those assumed to have received CNS-directed therapy were at increased risk for educational impairments compared with the cancer-free population. Choices of educational fields were in general similar. Careful follow-up of the survivors of CNS-tumours and those assumed to have received CNS-directed therapy is important at each level of education.


Effects of heavy grazing on the microclimate of a humid grassland mountain ecosystem: Insights from a biomass removal experiment.
In high-altitude Andean grasslands (páramo), overgrazing leads to alterations in both vegetation and microclimate. These alterations need to be identified to devise land management strategies that will preserve and enhance ecosystem processes. To elucidate this issue, we designed an overgrazing experiment: we selected two plots covered with native grass (pajonal), in one of which we mowed to the ground surface. We left the second plot undisturbed to serve as a control. For both plots, we continuously monitored albedo and ancillary energetic components to generate quarterly and yearly comparisons for the following parameters: (a) impacts on albedo and resilience of grass; (b) radiative forcing of albedo; and (c) land surface temperature feedback during the recovery period. In the first quarter following removal, when the soil was covered with light litter, median albedo increased 38.81% (0.16 ± 0.02), then began a gradual decrease, which continued until its full recovery 1.75 years later (0.10 ± 0.01). During the first year of the experiment, a strong mean negative instantaneous radiative forcing was observed (-7.08 ± 6.03 Wm-2), signifying a reduction in net shortwave energy. This forcing returned to normal, pre-intervention conditions (-0.55 ± 0.97 Wm-2) after 1.75 years, equal to the energetic recovery period of the grass. Both the amount (from 133.0 ± 44.72 to 119.67 ± 39.30 Wm-2) and the partitioning (net shortwave decreased 5%; net longwave increased 9.7%) of net energy were altered after removal, evidence of cooling feedback during the recovery period. This feedback indicated that the decrease in albedo (1.25%) or instantaneous radiative forcing (-4.67 Wm-2) resulted in a decrease in land surface temperature of 1 °C. Thus, our overgrazing experiment without soil destruction followed by a natural recovery time has identified the energetic recovery period for grass in the páramos; suggesting the albedo as a good indicator of grass resilience.


Chemical synthesis of on demand-activated SUMO-based probe by a photocaged glycine-assisted strategy.
The transiently-activated SUMO probes are conducive to understand the dynamic control of SENPs activity. Here, we developed a photocaged glycine-assisted strategy for the construction of on demand-activated SUMO-ABPs. The light-sensitive groups installed at G92 and G64 backbone of SUMO-2 can temporarily block probes activity and hamper aspartimide formation, respectively, which enabled the efficient synthesis of inert SUMO-2 propargylamide (PA). The probe could be activated to capture SENPs upon photo-irradiation not only in vitro but also in intact cells, providing opportunities to further perform intracellular time-resolved proteome-wide profiling of SUMO-related enzymes.


The frequencies and disparities of adverse childhood experiences in the U.S.
Adversity experienced during childhood manifests deleteriously across the lifespan. This study provides updated frequency estimates of ACEs using the most comprehensive and geographically diverse sample to date. ACEs data were collected via BRFSS (Behavioral Risk Factor Surveillance System). Data from a total of 211,376 adults across 34 states were analyzed. The ACEs survey is comprised of 8 domains: physical/emotional/sexual abuse, household mental illness, household substance use, household domestic violence, incarcerated household member, and parental separation/divorce. Frequencies were calculated for each domain and summed to derive mean ACE scores. Findings were weighted and stratified by demographic variables. Group differences were assessed by post-estimation F-tests. Most individuals experienced at least one ACE (57.8%) with 21.5% experiencing 3+ ACEs. F-tests showed females had significantly higher ACEs than males (1.64 to 1.46). Multiracial individuals had a significantly higher ACEs (2.39) than all other races/ethnicities, while White individuals had significantly lower mean ACE scores (1.53) than Black (1.66) or Hispanic (1.63) individuals. The 25-to-34 age group had a significantly higher mean ACE score than any other group (1.98). Generally, those with higher income/educational attainment had lower mean ACE scores than those with lower income/educational attainment. Sexual minority individuals had higher ACEs than straight individuals, with significantly higher ACEs in bisexual individuals (3.01). Findings highlight that childhood adversity is common across sociodemographic, yet higher in certain categories. Identifying at-risk populations for higher ACEs is essential to improving the health outcomes and attainment across the lifespan.


Ectoine from halophilic microorganisms induces the expression of hsp70 and hsp70B' in human keratinocytes modulating the proinflammatory response.
The heat shock proteins (Hsps) have an important role in the cytoprotection and repair of cells and tissues. One potential mechanism of protection is the ability of Hsp to inhibit genetic expression of proinflammatory cytokines, the transcription of which is dependent on nuclear factor-kappa B (NF-kappaB) activation. In this study, we evaluated the ability of ectoine, a novel natural biomolecule produced by halophilic microorganisms, to activate the hsp70 and hsp70B'. By reverse transcriptase-polymerase chain reaction and Western blot analysis, we demonstrated increased hsp70B' gene expression in human keratinocytes treated with ectoine and heat stressed. In contrast, in the absence of heat shock, ectoine was unable to induce hsp70B' but had the ability to induce another member of the Hsp family, the hsp70. The latter is not only elevated in response to stress but is also present at basal level in unstressed cells. In addition, ectoine had no effect on proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor-alpha and on NF-kappaB and IkappaB-alpha pathway, whereas it downregulated the expression of cited proinflammatory cytokines, in lipopolysaccharides-treated keratinocytes. These results highlighted the ability of ectoine to protect cells from stress conditions and to prevent cell damage by maintaining an elevated level of the Hsp70. Overall, these data might suggest the use of this compatible solute in cosmetic and even pharmaceutical preparations aiming to activate a cytoprotective heat shock response in human cells.


Dimension and Complexity in Human Movement and Posture.
There has been considerable effort over the last 25 years to understand the emergence of complexity in motor output and how this relates to properties of the individual (e.g., age, disease state, etc.), environment (e.g., information) and task (e.g., movement, posture, isometric force). This paper addresses the behavioral dimension of motor complexity in movement and posture from a degrees of freedom (DF) perspective together with the change of complexity through aging, disease and fatigue. The dimension of behavior for a given perceptual-motor output is shown to be relatively low, dependent on the interaction between the individual, environmental, and task constraints and varies within a limited adaptive range for a given motor task. The determination of dimension in movement and posture has taken us beyond the traditional motor performance scores of behavior but it is not a sufficient characterization of the adaptive and emergent processes of complexity.


The role of neurotrophins in the maintenance of the spinal cord motor neurons and the dorsal root ganglia proprioceptive sensory neurons.
The aim of this study was to approach the question of neuronal dependence on neurotrophins during embryonic development in mice in a way other than gene targeting. We employed amyogenic mouse embryos and fetuses that develop without any skeletal myoblasts or skeletal muscle and consequently lose motor and proprioceptive neurons. We hypothesized that if, in spite of the complete inability to maintain motor and proprioceptive neurons, the remaining spinal and dorsal root ganglia tissues of amyogenic fetuses still contain any of the neurotrophins, that particular neurotrophin alone is not sufficient for the maintenance of motor and proprioceptive neurons. Moreover, if the remaining spinal and dorsal root ganglia tissues still contain any of the neurotrophins, that particular neurotrophin alone may be sufficient for the maintenance of the remaining neurons (i.e., mostly non-muscle- and a few muscle-innervating neurons). To test the role of the spinal cord and dorsal root ganglia tissues in the maintenance of its neurons, we performed immunohistochemistry employing double-mutant and control tissues and antibodies against neurotrophins and their receptors. Our data suggested that: (a) during the peak of motor neuron cell death, the spinal cord and dorsal root ganglia distribution of neurotrophins was not altered; (b) the distribution of BDNF, NT-4/5, TrkB and TrkC, and not NT-3, was necessary for the maintenance of the spinal cord motor neurons; (c) the distribution of BDNF, NT-4/5 and TrkC, and not NT-3 and Trk B, was necessary for the maintenance of the DRG proprioceptive neurons; (d) NT-3 was responsible for the maintenance of the remaining neurons and glia in the spinal cord and dorsal root ganglia (possibly via TrkB).


A new approach for measuring the erythrocyte life span with a nonradioisotope.
The possibility of substituting a nonradioactive isotope of chromium for 51Cr was studied. Blood, from five dogs with varying erythrocyte life spans, was labeled with 50Cr and 51Cr and transfused autologously. Erythrocyte-bound 50Cr was determined by inductively coupled argon plasma mass spectrometry and 51Cr by measuring radioactivity. Erythrocyte life span determination derived from the two isotopes did not differ significantly. Our results suggest that 50Cr can provide a nonradioactive alternative to 51Cr for labeling erythrocytes for life span studies.


An analysis of nursing students' decision-making in teams during simulations of acute patient deterioration.
The aim of this study was to examine the decision-making of nursing students during team based simulations on patient deterioration to determine the sources of information, the types of decisions made and the influences underpinning their decisions. Missed, misinterpreted or mismanaged physiological signs of deterioration in hospitalized patients lead to costly serious adverse events. Not surprisingly, an increased focus on clinical education and graduate nurse work readiness has resulted. A descriptive exploratory design. Clinical simulation laboratories in three Australian universities were used to run team based simulations with a patient actor. A convenience sample of 97 final-year nursing students completed simulations, with three students forming a team. Four teams from each university were randomly selected for detailed analysis. Cued recall during video review of team based simulation exercises to elicit descriptions of individual and team based decision-making and reflections on performance were audio-recorded post simulation (2012) and transcribed. Students recalled 11 types of decisions, including: information seeking; patient assessment; diagnostic; intervention/treatment; evaluation; escalation; prediction; planning; collaboration; communication and reflective. Patient distress, uncertainty and a lack of knowledge were frequently recalled influences on decisions. Incomplete information, premature diagnosis and a failure to consider alternatives when caring for patients is likely to lead to poor quality decisions. All health professionals have a responsibility in recognizing and responding to clinical deterioration within their scope of practice. A typology of nursing students' decision-making in teams, in this context, highlights the importance of individual knowledge, leadership and communication.


Preoperative status and treatment of osteoradionecrosis of the jaw: a retrospective study of 252 cases.
Osteoradionecrosis of the jaw (ORNJ) is one of the most devastating and progressive complications of head and neck radiotherapy. It can cause emaciation, deformity, and pathological fractures, resulting in decreased quality of life. The aim of this study was to evaluate the preoperative index and outcomes of treatment for ORNJ. A retrospective study of 252 ORNJ cases treated at one institution between January 2010 and January 2018 was made. The abnormal items from the preoperative examination and follow-up after different treatments were recorded, and the differences between the noteworthy items were compared using univariate and multivariate models. Most ORNJ patients in the middle and late stages had abnormal items, such as hypoproteinaemia, anaemia, and leucocytosis. Partial mandibulectomy with flap reconstruction was significantly more effective than without reconstruction. Advanced ORNJ patients tended to have more abnormal items, which might have a negative influence on treatment. For better outcomes, it is essential and effective to completely remove the necrotic lesion and reconstruct it with a flap. The surgeons should provide sufficient perioperative management and strive for suitable surgical treatment.


Nutrient balance in the preterm infant. 3. Effect of balance duration on outcome measurements.
To determine the effect of balance duration on outcome measurements 18 84-h balances were performed in a group of formula-fed preterm infants (birth weight = 1,362 +/- 125 g; gestational age = 32.3 +/- 1.7 weeks). Each 84-h balance was broken into contiguous 48- and 36-h periods. Comparisons (paired t tests, paired variance tests, and linear regression analysis) were made between the 48-h and 36-h (paired t and F tests) and between the 48-h and 84-h collections (simple linear regression). Nitrogen absorption (mean +/- SD) during 48-h collection (365 +/- 58 mg/kg/day and 87 +/- 3%) was not significantly different from that of the 36-h collection (381 +/- 66 mg/kg/day and 84 +/- 4%). Nitrogen retention during the 48-h collection (301 +/- 59 mg/kg/day, 72 +/- 6%) also was not significantly different from that of the 36-h collection (318 +/- 64 mg/kg/day, 72 +/- 6%). Moreover, nitrogen absorption and retention during the 48-h collection were significantly related (p less than 0.0001 for linear regression comparisons) to that of the 84-h collection. Similar observations were noted for calcium, phosphorus, magnesium, zinc, and copper absorption and retention. We conclude that a 48-h collection may be used in place of an 84-h collection without compromising the accuracy of the balance data in the enterally fed preterm infant.


Lysyl oxidase promotes liver metastasis of gastric cancer via facilitating the reciprocal interactions between tumor cells and cancer associated fibroblasts.
Liver is one of the most preferred destinations of distant metastasis in gastric cancer (GC). As effective treatment is still limited, the prognosis of GC patients bearing liver metastasis is poor. We filter out lysyl oxidase (LOX) to study its function in the tumor microenvironment (TME) and seek for potential therapeutic targets. Transcription analysis on 6 cases of liver metastasis of GC patients with respective paired primary tumors and adjacent normal livers was performed. The filtration out of LOX was done using 5 datasets. 69 GC liver metastasis tissues were utilized to perform immunohistochemistry (IHC) and analyze prognosis. Computed Tomography (CT) combined 3D organ reconstruction bioluminescence imaging was performed to precisely evaluate the metastatic tumor burden on liver of intrasplenic injection mouse model. Human and mouse cancer associated fibroblasts (CAFs) in liver metastasis were separated to culture to study the interaction of LOX and TGF-β1. Patients-derived xenograft (PDX) model was established using liver metastasis of patients to evaluate the therapeutic value of LOX inhibitor β-aminopropionitrile (BAPN). CAFs-derived LOX at liver metastatic niche of GC promotes niche formation and outgrowth thus predicts poor prognosis. Meanwhile tumor cells in niche secrete TGF-β1 to nourish CAFs and stimulate them to produce more LOX in turn. The mechanism involved in LOX-mediated proliferation facilitation is enhancement of Warburg effect. The inhibitor of LOX, BPAN could hamper the effect brought by LOX in vivo and in vitro. Our study has unveiled a positive feedback loop between CAFs and tumor cells in liver metastasis niche of GC. The core molecule is LOX which facilitates Warburg effect. Targeting LOX with its inhibitor BAPN might serve as a potential therapeutic strategy. FUND: This research was supported by the National Natural Science Foundation of China (31872740), the 100-member plan of the Shanghai Municipal Commission of Health and Family Planning (2017BR043), Shanghai Science and Technology Commission Project(17ZR1416800), Renji Hospital Training Fund (PYMDT-003, PYIII-17-015), National Natural Science Foundation of China (81672358), the Shanghai Municipal Education Commission-Gao feng Clinical MedicineGrant Support (20181708), Program of Shanghai Academic/Technology Research Leader(19XD1403400), Science and Technology Commission of Shanghai Municipality (18410721000), Shanghai Municipal Health Bureau (2018BR32), China Postdoctoral Science Foundation (2018M640403), National Natural Science Foundation of China (81701945) and Youth project of Shanghai Municipal Health Commission(20164Y0045).


Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5.
Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P = .76 and P = .90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P = .42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.


Dual-targeted therapeutic strategy combining CSC-DC-based vaccine and cisplatin overcomes chemo-resistance in experimental mice model.
Emerging evidence suggests that one of the main reasons of chemotherapy treatment failure is the development of multi-drug resistance (MDR) associated with cancer stem cells (CSCs). Our aim is to identify a therapeutic strategy based on MDR-reversing agents. CSC-enriched Ehrlich carcinoma (EC) cell cultures were prepared by drug-resistant selection method using different concentrations of cisplatin (CIS). Cell cultures following drug exposure were analyzed by flow cytometry for CSC surface markers CD44+/CD24-. We isolated murine bone marrow-derived dendritic cells (DCs) and then used them to prepare CSC-DC vaccine by pulsation with CSC-enriched lysate. DCs were examined by flow cytometry for phenotypic markers. Solid Ehrlich carcinoma bearing mice were injected with the CSC-DC vaccine in conjunction with repeated low doses of CIS. Tumor growth inhibition was evaluated and tumor tissues were excised and analyzed by real-time PCR to determine the relative gene expression levels of MDR and Bcl-2. Histopathological features of tumor tissues excised were examined. Co-treatment with CSC-DC and CIS resulted in a significant tumor growth inhibition. Furthermore, the greatest response of downregulation of MDR and Bcl-2 relative gene expression were achieved in the same group. In parallel, the histopathological observations demonstrated enhanced apoptosis and absence of mitotic figures in tumor tissues of the co-treatment group. Dual targeting of resistant cancer cells using CSC-DC vaccine along with cisplatin represents a promising therapeutic strategy that could suppress tumor growth, circumvent MDR, and increase the efficacy of conventional chemotherapies.


Embryonic development of the ganglion plexuses and the concentric layer structure of human gut: a topographical study.
In this study, we performed a detailed topographical study on the development of ganglion plexuses and the smooth muscle layers of human embryonic and fetal gut. Neuron and glia differentiation was investigated with anti-PGP9.5 and anti-S100 antibodies respectively. The differentiation of smooth muscle and interstitial cells of Cajal (ICC) was studied with anti-smooth muscle alpha-actin and anti-C-Kit antibodies respectively. By week 7, rostro-caudal neural crest cell (NCC) colonization of the gut was complete, and NCCs have differentiated into neurons and glia. At the foregut, neurons and glia were aggregated into ganglion plexus in the myenteric region, and the longitudinal and circular muscle layers have started to differentiate; however, neurons and glia were not found in the submucosa. At the hindgut, neurons and glia were dispersed within the mesenchyme. Myenteric plexus, longitudinal and circular muscle layers formed along the entire gut by week 9. Scattered and individual neurons and glia, and small ganglion plexuses were detected in the foregut and midgut submucosa by week 12. Ganglion plexus was not seen in the hindgut submucosa until week 14. Muscularis mucosae was formed at the foregut and midgut by week 12 but was only discernible at the hindgut 2 weeks later. As the gut wall developed, ganglion plexus increased in size with more neurons and glia, and the formation of intra-plexus nerve fascicle. ICCs were localized in the ganglion plexus as early as week 7. ICCs were initially dispersed in the plexus and were preferentially localized at the periphery of the plexus by week 20. The specification of the annular layers of human embryonic and fetal gut follows a strict spatio-temporal pattern in a rostro-caudal and centripetal manner suggesting that interaction between (1) homotypic and/or heterotypic cells; and (2) cells and the extracellular matrix is critical for the embryonic development of the gut mesenchyme and the enteric nervous system.


Theoretical and Experimental Analyses on the Sound Absorption Coefficient of Rice and Buckwheat Husks Based on Micro-CT Scan Data.
In this study, the sound absorption coefficients of rice and buckwheat husks were estimated. Computed tomography (CT) images were processed to determine the circumference and surface area of voids in the granular material, and the normal incident sound absorption coefficients were derived. In addition, the tortuosity, which expresses the complexity of the sound wave propagation through the structure, was measured for each material. The theoretical sound absorption coefficients were then compared to the measured sound absorption coefficients with and without consideration of the tortuosity. A correction factor was used to bring the surface area of the granular material closer to the actual surface area and observed that the tortuosity obtained theoretical values that matched the trend of the measured values. These results indicate that using CT images to estimate the sound absorption coefficient is a viable approach.


Incidence of deep sternal wound infection is not reduced with autologous platelet rich plasma in high-risk cardiac surgery patients.
Deep sternal wound infections (DSWI) remain a devastating complication in cardiac surgery applying full sternotomy. As the risk profile in cardiac surgery changed toward an older and sicker population, the incidence of DSWI increases. Platelet rich plasma (PRP) holds promise in tissue regeneration with respect to bone regeneration, reduction of bleeding, and accelerated wound healing. The effect of PRP on DSWI was investigated in high-risk patients undergoing cardiac surgery with full sternotomy. 196 consecutive patients at risk of DSWI were randomized to application of autologous PRP before sternal wiring (n = 97) or control (n = 99). All patients underwent cardiac surgery on cardiopulmonary bypass with cardioplegic cardiac arrest. Endpoint was occurrence of DSWI requiring revision surgery. Demographic, intraoperative, and perioperative variables as well as risk factors were comparable between groups. Incidence of DSWI was not different between the PRP-group and the control-group (6/97 (6.2%) vs. 3/99 (3.0%); n.s.). Local application of autologous PRP in cardiac surgery patients with full sternotomy at high risk for sternal complications did not reduce the incidence of DSWI.


Age estimation by modified Suchey-Brooks method using three-dimensional reconstructed CT images of Chinese Han population.
The method proposed by Suchey-Brooks for adult age estimation based on the surface morphology of the pubic symphysis has been widely accepted. The applicability of the method varies considerably in different populations. The present study established a virtual reference sample and aimed to develop population-specific criteria that can be used for age estimation in different skeletal samples. First, The dry bone specimens from 100 individuals were compared with their corresponding three-dimensional (3D) reconstruction model and showed high inter-method agreement (k = 0.743-0.811), suggesting that the virtual bone model and physical bone specimens have comparable performances in describing the surface morphology of the pubic symphysis. We retrospectively collected clinical computed tomography (CT) data from 895 Chinese patients to create a virtual reference sample of the pubic symphysis. Based on the original Suchey-Brooks method, each of the 895 reference samples was assigned a phase, for each sex and phase, data on the mean age, standard deviation, and 95% age range of the corresponding sample were obtained, which was then used as the "method modified for Chinese" (modified method) and compared to the "SB method". Compared to the SB method, modified method had a lower inaccuracy in dry bones for males over 35 years and females over 45 years, in dry bone CT test sample for males over 55 years and females over 45 years, and in postmortem CT test sample for males over 35 years and females over 55 years. The modified method can improve the accuracy of age estimation for older samples over 40 years. It has shown considerable reliability when applied as a population-specific criterion, but its accuracy is still not sufficient, and caution is needed when using it.


The development of tissue around various prosthetic implants used as replacements for ligaments and tendons.
Currently, no ideal prosthesis is available for the repair or replacement of tendons and ligaments. Although filamentous carbon is a useful fibrogenic material, it does not fulfill the ideal requirements of a soft-tissue prosthesis. A number of other synthetic fibers were examined for biocompatibility and fibrogenic properties in both cell culture and in vivo implantation. It was found that the less extensible materials could adversely affect the normal morphology of the induced collagen. None of the materials examined exhibited mechanical properties similar to those of collagen; therefore, a composite prosthesis was designed to incorporate three criteria: mechanical characteristics similar to those of the normal tissue, fibrogenic capability to induce replacement collagen, and replacement collagen developing with normal morphologic characteristics. A prototype prosthesis for the Achilles tendon in rabbits, evaluated by mechanical and histologic methods, shows that these criteria can be fulfilled and thus form the basis for future prosthetic tendon and ligament research.


Estimating sex and age from a face: a forensic approach using machine learning based on photo-anthropometric indexes of the Brazilian population.
The facial analysis permits many investigations, some of the most important of which are craniofacial identification, facial recognition, and age and sex estimation. In forensics, photo-anthropometry describes the study of facial growth and allows the identification of patterns in facial skull development, for example, by using a group of cephalometric landmarks to estimate anthropological information. Previous works presented, as indirect applications, the use of photo-anthropometric measurements to estimate anthropological information such as age and sex. In several areas, automation of manual procedures has achieved advantages over and similar measurement confidence as a forensic expert. This manuscript presents an approach using photo-anthropometric indexes, generated from frontal faces cephalometric landmarks of the Brazilian population, to create an artificial neural network classifier that allows the estimation of anthropological information, in this specific case age and sex. This work is focused on four tasks: (i) sex estimation on ages from 5 to 22 years old, evaluating the interference of age on sex estimation; (ii) age estimation from photo-anthropometric indexes for four age intervals (1 year, 2 years, 4 years, and 5 years); (iii) age group estimation for thresholds of over 14 and over 18 years old; and; (iv) the provision of a new data set, available for academic purposes only, with a large and complete set of facial photo-anthropometric points marked and checked by forensic experts, measured from over 18,000 faces of individuals from Brazil over the last 4 years. The proposed binary classifier obtained significant results, using this new data set, for the sex estimation of individuals over 14 years old, achieving accuracy values higher than 0.85 by the F1 measure. For age estimation, the accuracy results are 0.72 for the F1 measure with an age interval of 5 years. For the age group estimation, the F1 measures of accuracy are higher than 0.93 and 0.83 for thresholds of 14 and 18 years, respectively.