Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.
Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage.


Erianthus arundinaceus HSP70 (EaHSP70) Acts as a Key Regulator in the Formation of Anisotropic Interdigitation in Sugarcane (Saccharum spp. hybrid) in Response to Drought Stress.
Plant growth during abiotic stress is a long sought-after trait especially in crop plants in the context of global warming and climate change. Previous studies on leaf epidermal cells have revealed that during normal growth and development, adjacent cells interdigitate anisotropically to form cell morphological patterns known as interlocking marginal lobes (IMLs), involving the cell wall-cell membrane-cortical actin continuum. IMLs are growth-associated cell morphological changes in which auxin-binding protein (ABP), Rho GTPases and actin are known to play important roles. In the present study, we investigated the formation of IMLs under drought stress and found that Erianthus arundinaceus, a drought-tolerant wild relative of sugarcane, develops such growth-related cell morphological patterns under drought stress. Using confocal microscopy, we showed an increasing trend in cortical F-actin intensity in drought-tolerant plants with increasing soil moisture stress. In order to check the role of drought tolerance-related genes in IML formation under soil moisture stress, we adopted a structural data mining strategy and identified indirect connections between the ABPs and heat shock proteins (HSPs). Initial experimental evidence for this connection comes from the high transcript levels of HSP70 observed in drought-stressed Erianthus, which developed anisotropic interdigitation, i.e. IMLs. Subsequently, by overexpressing the E. arundinaceus HSP70 gene (EaHSP70) in sugarcane (Saccharum spp. hybrid), we confirm the role of HSP70 in the formation of anisotropic interdigitation under drought stress. Taken together, our results suggest that EaHSP70 acts as a key regulator in the formation of anisotropic interdigitation in drought-tolerant plants (Erianthus and HSP70 transgenic sugarcane) under moisture stress in an actin-mediated pathway. The possible biological significance of the formation of drought-associated interlocking marginal lobes (DaIMLs) in sugarcane plants upon drought stress is discussed.


Leuko-polymersomes.
Polymersomes are vesicles whose membranes are comprised of self-assembled amphiphilic block co-polymers. Synthetic control of block co-polymer chemistry provides an advantageous diversity of polymersome functions, ranging from tunable materials strength, superior encaspulation of hydrophobic and hydrophilic drugs and optical dyes, and facile functionalization. We have exploited polymersome tunability to make leuko-polymersomes: polymersomes with the adhesive properties of leukocytes. By functionalizing the terminal groups on the outer shell of the vesicle with biotin, we have used modular avidin-biotin chemistry to attach adhesion ligands that mimic the two critical adhesion pathways that leukocytes utilize to achieve adhesion in the fast fluid flow of blood vessels--selectins and integrins. We demonstrate that adhesion is specific and is supported at hydrodynamic flow rates at which leukocytes adhere. We envision the use of such particles for monitoring or treating inflammation, cancer and cardiovascular disease.


Antiproliferative assay of human leucocyte interferon.
An in vitro microtitration system of the antiproliferative effect of human leucocyte interferon (IFN-alpha(Le)) was investigated. The preliminary experiments suggested that the antiproliferative effect of IFN-alpha(Le) was increased by prolonging the incubation period, by reducing the target cell concentration, and might be prescribed by the total IFN amounts in the challenge medium. By employing a system consisted of 1.5 X 10(4) Daudi cells in 0.2 ml of medium containing IFN dilutions and an incubation period of 3 days at 37 degrees C, the antiproliferative effects of twenty-one lots of partially purified IFN-alpha(Le) (PIF-alpha(Le)) preparations were titrated. The interassay variations in the antiproliferative titers of three PIF-alpha(Le) established in the present system were found to be in the same range as those in the antiviral titers estimated by a standard macroplaque reduction assay. The each titration curve was parallel, and the antiproliferative titers, assessed by the reciprocals of the IFN dilutions which suppress the cell growth in 50%, were significantly (p less than 0.01) correlated to the antiviral international units of them.


Seven-Step Total Synthesis of Sporothriolide.
An enantioselective total synthesis of sporothriolide, a bioactive furofurandione-type fungal metabolite, has been achieved in a 21% overall yield from a commercially available β,γ-unsaturated carboxylic acid via seven steps. The key steps of this synthesis include a highly diastereoselective Michael addition of a chiral oxazolidinone derivative to a nitro olefin, the exploitation of an aromatic ring as a masked carboxylic acid functionality, and the base-promoted elimination of nitrous acid to install the α-methylene lactone unit of sporothriolide in the final step.


Evaluation of the common pauraque (Nyctidromus albicollis) cornea using light and scanning electron microscopy.
The common pauraque Nyctidromus albicollis (Gmelin, 1789) is a widespread avian species; however due to its nocturnal habits and reclusive behaviour, little is known about their vision and ecology. Most avian species are visually dependent with advanced visual systems providing high spatial resolution, on the species needs. Each ocular structure has a specific role in contributing towards high visual function, and the cornea is the first refractive structure in the visual process. However, the common pauraque cornea had not been described until the present data. Therefore, this study aims to describe the morphology and morphometry of the common pauraque cornea by means of light and scanning electron microscopy to evaluate the cross-sectional anatomy as well as the ultrastructure of the endothelial cells. Histological similarities with the cornea of other birds have been observed, but the thickness of the common pauraque cornea is much smaller than the other described corneas. A better understanding of the common pauraque cornea can help us better explain the physiology of vision and the visual requirements of this species. In turn, this will help us better understand how this species successfully interacts with its environment, and will improve our knowledge on how to interpret pathological changes in their cornea in a clinical setting.


Inhibition of PKA blocks fibroblast migration in response to growth factors.
Cell migration requires precise coordination of many signaling pathways to achieve directed motility. We report here that NIH3T3 fibroblasts expressing a dominant negative PKA subunit (dnPKA) show diminished migration in response to serum or growth factors. This effect is not a general effect on cell motility, but rather a decreased capacity to enhance migration in response to stimuli. Control (neo) and dnPKA cells show very similar haptotactic migration toward fibronectin, but dnPKA cells show reduced stimulation of migration in response to EGF/PDGF or serum. These effects were not due to alterations in cell growth or adhesion to fibronectin. Forskolin, which elevates cyclic adenosine monophosphate (cAMP) levels, dramatically inhibited neo cell motility in a scrape migration assay, although dnPKA cell migration was unaffected. The MEK selective inhibitor U0126 and the phosphatidyl-inositol-3 kinase (PI3K) inhibitor LY294002 inhibited migrating neo cells and were able to further inhibit residual dnPKA cell migration. Our data show that intermediate or well-controlled levels of PKA activity are required for optimal growth factor-stimulated migration in fibroblasts. PKA may play an important role in the signaling processes that lead to motility.


Activity-Regulated Cytoskeleton-Associated Protein Controls AMPAR Endocytosis through a Direct Interaction with Clathrin-Adaptor Protein 2.
The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing µ2. The Arc-AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. These data provide a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2.


Intramitochondrial filamentous bodies in the thick limb of henle of the rat kidney.
"Intramitochondrial filamentous bodies" (IMFB) were occasionally found within the matrix of some mitochondria of the thick limb of Henle of the rat kidney, but not elsewhere in the tubular system. Three types were recognized: type I, an accumulation of filaments 55 A thick; type II, a bundle of parallel filaments having the same thickness as those of type I and regular spacing, 87 A apart, from center to center; and type III, consisting of type II with regular light bands of 280 A periodicity and a helical border of prismatic tubular cristae. In addition to these, electron-opaque masses showing variable and faint substructures were found in the matrix of mitochondria. It is suggested that all these IMFB may originate from mitochondrial cristae and that type II IMFB may be an intermediate developmental form between type I and type III. After uranyl acetate staining, IMFB and the membranes of prismatic tubular cristae showed highly increased electron opacity. The literature has been reviewed for reports of intramitochondrial filamentous inclusions in various types of cells. These inclusions have been classified according to their structural characteristics and the localization in the mitochondria and compared with IMFB reported herein.


Inverse age-dependent accumulation of decabromodiphenyl ether and other PBDEs in serum from a general adult population.
Polybromodiphenyl ethers (PBDEs), including the decabromodiphenyl congener (BDE-209), were determined in the serum of 731 individuals from a general adult population (18-74 years) collected in 2002 in Catalonia (north-eastern Spain). The BDE-209 was the predominant congener (median 3.7 ng/g lipid) followed by BDE-47 (2.6 ng/g lipid) and BDE-99 (1.2 ng/g lipid). PBDEs in this population (median 15.4 ng/g lipid) ranked amongst the highest of previously described concentrations in populations in Europe, Asia, New Zealand and Australia, yet it was lower than those found in North American reports. Age was clearly the socio-demographic factor of highest influence on the PBDE distributions. However, unlike usual trends of higher accumulation of POPs through age, the higher concentrations were found in young individuals (<30 years) rather than in adults (≥30 years), with differences of 14%, 31% and 46% in the most abundant congeners (i.e. BDE-209, BDE-99 and BDE-47, respectively). This age-dependent distribution of PBDEs (including the case for BDE-209, which is shown for the first time in this study) is explained by the higher and widespread use of these compounds since the 1980s. In view that these compounds remain highly used, this accumulation pattern is likely to evolve, anticipating an increasing level of PBDE concentrations in future general population surveys, yet probably assuming an age-dependent increase pattern. Socio-economic level was also a determinant of BDE-47 concentrations, but only relevant for the least affluent class, suggesting that lifestyle and environmental conditions in the dwelling place may also contribute to exposure. Nonetheless, gender, body mass index, place of birth, parity and education level did not show any statistically significant influence on the observed PBDE distributions.


Weakly diverging to tightly focused Gaussian beams: a single set of analytic expressions: continuation-symmetric beams.
The always diverging-converging laser beams, more rigorously referred to as Gaussian beams, are part of many physical and electro-optical systems. Obviously, a single set of analytic expressions describing these beams in a large span of divergence-convergence angles at the focal plane, and at any distance away from the focal plane, will prove very handy. We have recently published three such analytic sets, one set for linearly polarized beams and two sets for radially polarized beams. However, our published analytic set for linearly polarized beams describes nonsymmetric electric-magnetic field components. Specifically, the strong transverse magnetic field component does not become elliptic at very large divergence angles as it should be, and the other transverse magnetic component, indeed very weak, is missing altogether. Here we present an analytic set of expressions symmetrically describing linearly polarized Gaussian beams. The symmetry applies to the x-electric y-magnetic components and vice versa and to the two electric-magnetic z-components. An important property of the presented set of expressions is power conservation. That is, the electromagnetic power crossing a plane transverse to the propagation direction in a unit time is conserved. Power conservation assures beam description accuracy at any axial distance. The presented analytic expressions, although not strictly satisfying Maxwell's equations, describe Gaussian beams with very reasonable accuracy from low divergence angles up to divergence angles as large as 0.8 rad in a medium with refractive index of 1.5, i.e., up to a NA of 1.1. These expressions should then readily assist in the design of practically all laser-related systems and in the research of diverse physics and electro-optic fields.


Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia.
Individuals with chronic lymphocytic leukemia (CLL) have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role a heterologous boost would have in patients who did not respond to the initial two-dose mRNA vaccine series. SARS-CoV-2 specific immune responses, including antibodies and memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination, as well as postinitial vaccination series and post-third dose in two subjects. One subject seroconverted, had RBD-specific memory B-cells and spike-specific CD4 T-cells while the other did not. Both subjects had a spike-specific CD8 T-cell response after the original mRNA vaccination series that was further boosted after the third dose or remained stable. The results of this study, however small, are especially promising to CLL individuals who did not seroconvert following the initial mRNA vaccination series.


Characteristics and management of domestic waste in the rural area of Southwest China.
With its rapid development, the rural area of Southwest China has been puzzled by the waste management problem, especially for increasing solid waste and water pollution from the domestic waste. Therefore, in order to efficiently and effectively manage the domestic waste in the rural area of Southwest China, 22 villages were selected randomly to analyse the characteristics of domestic waste, the influence factors of characteristics and resident's willingness of participation in domestic waste management by questionnaires, field samplings and laboratory tests. The results of the rural area of Southwest China indicated that the generation of domestic waste was 178 g d(-1) per capita and it was mainly composed of kitchen waste, inert waste, plastics and paper with a total proportion of 81.98%. The waste bulk density, moisture, ash, combustible and lower calorific value were 107 kg m(-3), 37.04%, 25.73%, 37.23% and 8008 kJ kg(-1), respectively. These characteristics were influenced by the topography, the distance from towns or cities, the villagers' ethnicities and income sources to some extent. Moreover, the distance of 50-800 m between each collection facility and the disposal fee of around ¥5.00 per household per month could be accepted. The working hours of participation in waste management is suggested as 5 hours per day with the income of ¥1000 per capita per month. Based on the outcome of this survey, a waste management system consisting of classified collection, centralised treatment and decentralised treatment was proposed. It is important to ensure financial viability and practical considerations of this system.


Cat-scratch disease presenting as abdominal visceral granulomas.
Three cases of atypical, clinically unsuspected cat-scratch disease (CSD), diagnosed by demonstration of the CSD bacillus in an abdominal visceral organ, are presented. In two cases CSD bacilli were demonstrated for the first time in splenic granulomas in a child and in an adult with acquired immunodeficiency syndrome (AIDS)-related complex. In both cases, there was granulomatous hepatitis as well as splenitis. In the third case, the CSD bacillus was present in hepatic granulomas in an adult with granulomatous hepatitis. In all cases, granulomatous inflammation with suppuration in the viscera was identical to that previously described for lymph nodes in CSD. All patients eventually recovered completely. Clinical awareness of the broad spectrum of CSD should avoid the cost and morbidity of prolonged hospitalization, medications, and invasive surgery for a disease that is self-limited and not clearly responsive to antibiotics and that can usually be diagnosed by noninvasive means.


Modulatory Effect of Monochromatic Blue Light on Heat Stress Response in Commercial Broilers.
In a novel approach, monochromatic blue light was used to investigate its modulatory effect on heat stress biomarkers in two commercial broiler strains (Ross 308 and Cobb 500). At 21 days old, birds were divided into four groups including one group housed in white light, a second group exposed to blue light, a 3rd group exposed to white light + heat stress, and a 4th group exposed to blue light + heat stress. Heat treatment at 33°C lasted for five h for four successive days. Exposure to blue light during heat stress reduced MDA concentration and enhanced SOD and CAT enzyme activities as well as modulated their gene expression. Blue light also reduced the degenerative changes that occurred in the liver tissue as a result of heat stress. It regulated, though variably, liver HSP70, HSP90, HSF1, and HSF3 gene expression among Ross and Cobb chickens. Moreover, the Cobb strain showed better performance than Ross manifested by a significant reduction of rectal temperature in the case of H + B. Furthermore, a significant linear relationship was found between the lowered rectal temperature and the expression of all HSP genes. Generally, the performance of both strains by most assessed parameters under heat stress is improved when using blue light.


PERSPECTIVE: DARWIN, PROGRESS, AND ECONOMIC PRINCIPLES.
Darwin's concept of progress was an economic one, with the accumulation of adaptations having a strong analogy to technological innovations. This interpretation makes it easier to understand his differences with Lamarck and others whose views he considered metaphysically objectionable. It also clarifies his relationship to Malthus and such features of his theory as the episodic nature of evolutionary change. His position is consistent with modern theories of biotic invasions and long-term evolutionary trends. It also accords well with current efforts to produce a synthesis between biology and economics.


Matrix-Assisted Three-Dimensional Printing of Cellulose Nanofibers for Paper Microfluidics.
A cellulose nanofiber (CNF), one of the most attractive green bioresources, was adopted for construction of microfluidic devices using matrix-assisted three-dimensional (3D) printing. CNF hydrogels can support structures printed using CAD design in a 3D hydrogel environment with the appropriate combination of rheological properties between the CNF hydrogel and ink materials. Amazingly, the structure printed freely in the bulky CNF hydrogels was able to retain its highly resolved 3D features in an ultrathin two-dimensional (2D) paper using a simple drying process. The dimensional change in the CNF hydrogels from 3D to 2D resulted from simple dehydration of the CNFs and provided transparent, stackable paper-based 3D channel devices. As a proof of principle, the rheological properties of the CNF hydrogels, the 3D structure of the ink, the formation of channels by evacuation of the ink, and the highly localized selectivity of the devices are described.


Tailoring therapy for ischemic cardiomyopathy: is Laplace's law enough?
The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure. Despite several interventions, both pharmaceutical and device based for the treatment of ensuing heart failure, the incidence is increasing in large proportions. Newer molecules like sacubitril show more promise. Despite these novel therapies, several patients relentlessly progress to a stage of advanced heart failure. The use of left-ventricular-assist devices has variable clinical benefit, with some patients progressing to heart transplantation.


Red cell distribution width and Glasgow coma scale score as predictors of in-hospital mortality in maintenance hemodialysis patients diagnosed with spontaneous intracerebral hemorrhage.
Glasgow Coma Scale (GCS) score is being widely used as a useful predictor to investigate patients with head injury. High red cell distribution width (RDW) values have been independently associated with mortality and poor neurological outcome. However, there are few data available for Spontaneous Intracerebral Hemorrhage (SIH) in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the prognostic value of the combined measurement of RDW and GCS score in MHD patients with SIH. We retrospectively studied 46 MHD patients who was admitted to our hospital for nontraumatic SIH from October 2014 to May 2020. Data including demographic information, cause of renal failure, comorbidities at ESRD, clinical and laboratory parameters at admission were collected from medical records. Univariate and multivariate Logistic regression analysis were performed to identify independent risk factors of the in-hospital Mortality in Hemodialysis Patients with SIH. The receiver operating characteristic curve (ROC) and areas under the curve (AUCs) were determined. The sensitivity and specificity of independent risk factors were calculated for a range of different cutoff points. A total of 46 patients were enrolled in the study. The in-hospital mortality rate was 69.57%. We divided subjects into 2 groups based on the clinical outcomes. Compared with survivors (n = 14), non-survivors (n = 32) had longer hemodialysis vintage (P = .017), lower GCS score (P < .001), higher hemoglobin (Hb) (P = .032) and RDW (P = .009). In multivariate logistic regression analysis, GCS score (OR 0.719, 95% CI 0.546-0.946; P = .018) and RDW (OR 4.549, 95% CI 1.243-0.946; P = .018) were independent risk factors of in-hospital mortality in MHD patients with SIH. The area under the ROC curve (AUC) for GCS score was 0.849 (95% CI 0.729-0.970) while that for RDW was 0.743 (95% CI 0.596-0.891). The AUC for the combined prediction was 0.916 (95% CI 0.828-1.000), with a sensitivity of 90.63% and a specificity of 88.46%. In conclusion, high RDW and low GCS score were useful and independent poor prognostic markers for in-hospital mortality of MHD patients with SIH.


Germline polymorphisms of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 in cervical carcinogenesis.
The clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis was investigated. Germline polymorphisms of GSTM1, GSTT1 and p53 codon 72 together with human papillomavirus (HPV) types were examined in a total of 457 blood and cervical smear samples from normal healthy women and the patients with premalignant and malignant cervical lesions. The 167 patients with low-grade squamous intraepithelial lesion (LSIL), 49 with high-grade SIL (HSIL) and 83 with squamous cell carcinoma (SCC) had significantly higher frequency of high-risk HPV than 158 controls. The 49 patients with HSIL and 83 with SCC had statistically higher frequency of null GSTT1 genotype than 158 controls. There was an increased odds ratio for null GSTT1 genotype in HSIL and SCC cases compared with controls among 191 patients with high-risk HPV. The 67 cases with HPV types 16 and/or 18 had higher frequency of the GSTT1 null genotype than 186 with other types of HPV. There was no statistical difference in the polymorphic frequency of GSTM1 and p53 codon 72 genotypes between SILs and controls with or without high-risk HPV. These results suggest that GSTT1 null genotype may increase the risk of cervical cancer particularly in the cases with high-risk HPV types in a Japanese population.


In vitro biomechanical evaluation and comparison of a new prototype locking plate and a limited-contact self compression plate for equine fracture repair.
To determine if the mechanical properties (strength and stiffness) of a new prototype 4.5 mm broad locking plate (NP-LP) are comparable with those of a traditional 4.5 mm broad limited-contact self compression plate (LC-SCP), and to compare the bending and torsional properties of the NP-LP and LC-SCP when used in osteotomized equine third metacarpal bones (MC3). The plates alone were tested in four-point bending single cycle to failure. The MC3-plate constructs were created with mid-diaphyseal osteotomies with a 1 cm gap. Constructs were tested in four-point bending single cycle to failure, four-point bending cyclic fatigue, and torsion single cycle to failure. There were not any significant differences in bending strength and stiffness found between the two implants. The MC3-NP-LP construct was significantly stiffer than the MC3-LC-SCP in bending. No other biomechanical differences were found in bending, yield load in torsion, or mean composite rigidity. Mean cycles to failure for bending fatigue testing were similar for both constructs. The NP-LP was comparable to the LC-SCP in intrinsic, as well as structural properties. The NP-LP construct was more rigid than the LC-SCP construct under four-point bending, and both constructs behaved similarly under four-point bending cyclic fatigue testing and torsion single cycle to failure. The new NP-LP implant fixation is biomechanically comparable to the LC-SCP in a simulated MC3 fracture.


Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in Ondine-Hirschsprung syndrome.
A 5-year-old girl with congenital central hypoventilation syndrome associated with Hirschsprung's disease (Ondine-Hirschsprung syndrome) representing a missense mutation in exon 12 of the receptor tyrosine kinase (RET) proto-oncogene is reported. Using a direct sequencing technique, genomic DNA obtained from the patient's peripheral leukocytes was analyzed for its nucleotide sequences in all 20 exons of the RET proto-oncogene, seven regions of the 1st to the 7th exon of the endothelin-B receptor gene and endothelin 3 gene, including sequences corresponding to proteolytic cleavage sites. The analysis revealed that adenine at the 2116th base in the 12th exon in the RET proto-oncogene was substituted by guanine, supposedly resulting in a mutation of Thr 706 to Ala. No other mutational change was observed in the gene examined in this case. Mutation analysis has not been described previously on the gene in this disease complex. Mutation in this case might impair the maturation of the tyrosine kinase protein and subsequently cause neurocristopathy supposedly originating from the neural crest.


A Perspective on Reagent Diversity and Non-covalent Binding of Reactive Carbonyl Species (RCS) and Effector Reagents in Non-enzymatic Glycation (NEG): Mechanistic Considerations and Implications for Future Research.
This perspective focuses on illustrating the underappreciated connections between reactive carbonyl species (RCS), initial binding in the nonenzymatic glycation (NEG) process, and nonenzymatic covalent protein modification (here termed NECPM). While glucose is the central species involved in NEG, recent studies indicate that the initially-bound glucose species in the NEG of human hemoglobin (HbA) and human serum albumin (HSA) are non-RCS ring-closed isomers. The ring-opened glucose, an RCS structure that reacts in the NEG process, is most likely generated from previously-bound ring-closed isomers undergoing concerted acid/base reactions while bound to protein. The generation of the glucose RCS can involve concomitantly-bound physiological species (e.g., inorganic phosphate, water, etc.); here termed effector reagents. Extant NEG schemes do not account for these recent findings. In addition, effector reagent reactions with glucose in the serum and erythrocyte cytosol can generate RCS (e.g., glyoxal, glyceraldehyde, etc.). Recent research has shown that these RCS covalently modify proteins in vivo via NECPM mechanisms. A general scheme that reflects both the reagent and mechanistic diversity that can lead to NEG and NECPM is presented here. A perspective that accounts for the relationships between RCS, NEG, and NECPM can facilitate the understanding of site selectivity, may help explain overall glycation rates, and may have implications for the clinical assessment/control of diabetes mellitus. In view of this perspective, concentrations of ribose, fructose, Pi, bicarbonate, counter ions, and the resulting RCS generated within intracellular and extracellular compartments may be of importance and of clinical relevance. Future research is also proposed.


Late patient-fitted total orbital reconstruction for facial gunshot wound sequelae.
Late reconstructions of gunshot wounds (GSWs) in the orbital area are a true challenge to the oral and maxillofacial surgeon. Usually, the wall defects are large in size and commonly present loss of orbital volume, which can cause ocular dystopia. The only exceptions are when there is an explosion of the orbital walls-that is, blow-out fractures. We encountered a patient with a two-year sequelae after GSW in the face that caused the destructed orbit to have a 2.5 bigger size than the contralateral orbit, requiring meticulous planning of a patient-specific implant (PSI) to correctly reconstruct the orbit volume and bone projection. The PSI was developed using titanium and it had three pieces that could reconstruct all four walls of the orbit. After surgery, the patient regained orbital volume and malar projection, allowing him to benefit from facial symmetry. The PSI can be used to reconstruct all the orbital walls in cases of complex bone defects.


[Central hemodynamics, gas exchange, and gas oxygen-transporting function in combined anesthesia using xenon during operations under extracorporeal circulation].
The advantages of xenon include its good hemodynamic profile and possible cardioprotective properties. The investigation was undertaken to study central hemodynamics, lung gas exchange, and blood oxygen-transporting function in xenon anesthesia in patients operated on under extracorporeal circulation (EC). Fifteen patients aged 41-69 years operated on for coronary heart disease were examined. The severity of the patients' baseline status corresponded to NYHA functional classes I to IV. The duration of an operation was 251 +/- 10 min; that of EC was 97 +/- 5 min; aortic ligation lasted 59 +/- 3 min. After induction of anesthesia with propofol via concentration-regulated infusion (CRI) and with fentanyl, delivery of xenon was initiated at concentrations of 47 +/- 1 to 52.5 +/- 1%, which was mixed with oxygen. Propofol CRI was used during EC. After the latter, xenon was inhaled at concentrations of 47.7 +/- 1 to 53.3 +/- 1%. The mean arterial pressure (BP(mean)), heart rate (HR), and cardiac index (CI) remained unchanged during xenon anesthesia in the preperfusion period. After EC during xenon anesthesia, CI significantly rose with a moderate increase in HR without inotropic support. BP(mean) was moderately, but statistically significantly decreased. Prior to and following EC, there were no changes in the values of blood oxygen-transporting function.


Purification of prorennin and production of its antibody.
Prorennin, i.e. the zymogen of rennin, was extracted from fresh calf stomach and purified by ammonium sulfate precipitation, ion exchange chromatography and gel filtration. The purified prorennin was homogeneous as judged by SDS-polyacrylamide gel electrophoresis. A specific antibody to the purified prorennin was induced in rabbits. In a double diffusion test and on immunoelectrophoresis the antibody gave a single precipitin line when run against crude and pure zymogen preparations. In the double diffusion test, the antibody also reacted with a purified rennin but not with gastric proteases (pepsin and pepsinogen) or other proteases (trypsin and Mucor rennin). When the antibody was tested against prorennin and rennin in the double diffusion test, a spur was formed at the junction of the precipitin lines against prorennin and rennin. This result confirms that the two proteins share an antigenically common structure in their molecules and that the activation segment of prorennin contains at least one antigenic determinant.


Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry.
To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases.


Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization.
The interactions of peptide and steroid hormone signaling cascades in the ovary are critical for follicular growth, ovulation, and luteinization. Although the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play key regulatory roles, their actions are also dependent on other peptide signaling pathways, including those stimulated by insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta) family members (e.g., inhibin, activin, growth differentiation factor-9, bone morphogenic proteins), fibroblast growth factor, and Wnts (via Frizzled receptors). Each of these factors is expressed and acts in a cell-specific manner at defined stages of follicular growth. IGF-1, estrogen, and FSH comprise one major regulatory system. The Wnt/Frizzled pathways define other aspects relating to ovarian embryogenesis and possibly ovulation and luteinization. Likewise, the steroid receptors as well as orphan nuclear receptors and their ligands impact ovarian cell function. The importance of these multiple signaling cascades has been documented by targeted deletion of specific genes. For example, mice null for the LH-induced genes progesterone receptor (PR) and cyclo-oxygenase-2 (COX-2) fail to ovulate. Whereas PR appears to regulate the induction of novel proteases, COX-2 appears to regulate cumulus expansion. This review summarizes some new aspects of peptide and steroid hormone signaling in the rodent ovary.


Sickness absence and sickness presence in relation to office type: An observational study of employer-recorded and self-reported data from Sweden.
Previous research suggesting that open-plan office environments are associated with higher rates of sickness absence rely on self-reports which can be affected by recall bias. This paper investigates the associations of sickness absence, obtained from employer records as well as self-reports, with office type (cell offices and different sizes of open-plan offices). It additionally studies whether office type is associated with sickness presence. Employees from two private and one public sector organization were recruited to the study. Office type was ascertained by direct observation or from employee responses to an online survey. Control variables were gender, age, public/private sector and education level. Number of days and episodes of sickness absence were calculated from employer absence records and regressed on office type using negative binomial regression (n = 988). Self-reports of sickness absence and presence were regressed on office type using ordered logistic regression (n = 1237). Office type was generally not associated with employer records of number of episodes or days of sickness absence, except that the total number of days of leave was higher in flex offices compared to cell offices (IRR = 2.46, p = 0.007). In general, office type was not associated with self-reported days of sickness absence, apart from participants working in medium-sized open-plan offices who had 0.42 higher log-odds of absence than those working in cell offices (p = 0.004). Office type was not associated with self-reported sickness presence. Office type was not associated with sickness presence nor, in general, with sickness absence, whether obtained from self-reports or company records. It is not possible to conclude from this study that open-plan offices are associated with greater sickness absence or sickness presence compared to cell offices.


Influence of inter-train interval on the plastic effects of rTMS.
High frequency repetitive transcranial magnetic stimulation (rTMS) elicits plastic effects in excitatory and inhibitory circuits. Inter-train intervals (ITI) were initially incorporated into rTMS paradigms to avoid overheating and for safety considerations. Recent studies have shown that inclusion of ITI, as opposed to continuous stimulation, is essential for eliciting excitatory effects, but the optimal ITI remains unknown. Moreover, if ITI duration has no effect, it may be possible to substantially reduce treatment time for rTMS. ITI duration modulates the excitatory and disinhibitory effects of rTMS. rTMS (20 Hz, 2 s trains, 1200 pulses, 100% RMT) was applied in 14 healthy individuals with ITI of 4s (duration: ∼3 min), 8s (∼5 min), 16s (∼9 min) or 32s (16.5 min) in sessions separated by ≥5 days. Effects on cortical excitability and GABAA receptor mediated short interval intracortical inhibition (SICI) were measured for 75 min following rTMS. The time-course of increased cortical excitability following rTMS was independent of ITI duration. There was a striking influence of ITI on SICI, whereby disinhibition increased with shorter ITI duration. Changes in cortical excitability and SICI were independent of each other. These findings provide the first evidence to suggest that ITI may be substantially shortened without loss of rTMS effects, and warrant further investigation where rTMS is applied therapeutically. Furthermore, shorter ITIs result in greater disinhibitory effects which may be desirable in some clinical disorders and accelerated treatment paradigms. The tuning of the plasticity of cortical excitatory and inhibitory circuits to rTMS parameters in human cortex are independent.


[Changes in serum beta-thromboglobulin levels during oral contraception, cardiac valve disease and pulmonary embolism (author's transl)].
beta-thromboglobulin (beta TG), a platelet-specific protein, was measured in the plasma of 53 healthy subjects (20 men and 33 women), 53 women using estrogen-progestogen contraceptives, 31 patients with cardiac valve disease (including 19 with prosthesis) and 71 patients about to undergo scintigraphy for suspected pulmonary embolism. Compared with levels in healthy subjects, beta TG levels were significantly increased in oral contraceptive users and in cardiac patients with or without prosthesis. High beta TG levels were also found in 20 out of 28 patients with pulmonary embolism confirmed by scintigraphy, but also in some of the .9 lung patients with chronic bronchopulmonary disease. Cardiac patients treated with heparin had higher beta TG levels than non heparin-treated patients, which raises queries about a possible influence of heparin on this particular blood protein.


Search for Selection Signatures Related to Trypanosomosis Tolerance in African Goats.
Livestock is heavily affected by trypanosomosis in Africa. Through strong selective pressure, several African indigenous breeds of cattle and small ruminants have acquired varying degrees of tolerance against this disease. In this study, we combined LFMM and PCAdapt for analyzing two datasets of goats from West-Central Africa and East Africa, respectively, both comprising breeds with different assumed levels of trypanotolerance. The objectives were (i) to identify molecular signatures of selection related to trypanotolerance; and (ii) to guide an optimal sampling for subsequent studies. From 33 identified signatures, 18 had been detected previously in the literature as being mainly associated with climatic adaptations. The most plausible signatures of trypanotolerance indicate the genes DIS3L2, COPS7B, PD5A, UBE2K, and UBR1. The last gene is of particular interest since previous literature has already identified E3-ubiquitin ligases as playing a decisive role in the immune response. For following-up on these findings, the West-Central African area appears particularly relevant because of (i) a clear parasitic load gradient related to a humidity gradient, and (ii) still restricted admixture levels between goat breeds. This study illustrates the importance of protecting local breeds, which have retained unique allelic combinations conferring their remarkable adaptations.


TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development.
Healthy bone homeostasis hinges upon a delicate balance and regulation of multiple processes that contribute to bone development and metabolism. While examining hematopoietic regulation by Tle4, we have uncovered a previously unappreciated role of Tle4 on bone calcification using a novel Tle4 null mouse model. Given the significance of osteoblasts in both hematopoiesis and bone development, this study investigated how loss of Tle4 affects osteoblast function. We used dynamic bone formation parameters and microCT to characterize the adverse effects of Tle4 loss on bone development. We further demonstrated loss of Tle4 impacts expression of several key osteoblastogenic genes, including Runx2, Oc, and Ap, pointing toward a potential novel mechanism for Tle4-dependent regulation of mammalian bone development in collaboration with the RUNX family members.


Oviposition-stimulatory activity against Ostrinia zealis by essential oil of root part from Cirsium japonicum DC.
The essential oil components from root part of Cirsium japonicum and oviposition-stimulatory activity against Ostrinia zealis by root essential oil were investigated. The main component of fresh root essential oil was aplotaxene (75.14%) and of dried root stock was found to be palmitic acid (14.42%). The root oil was significantly more active than the control against O. zealis.


Translating public health knowledge into practice: development of a lay health advisor perinatal tobacco cessation program.
The value of lay health advisor (LHA) interventions as an effective approach toward ameliorating racial, ethnic and/socioeconomic health disparities has been noted by researchers and policy makers. Translating scientific knowledge to bring state-of-the-art health promotion/disease prevention innovation to underserved populations is critical for addressing these health disparities. This article examines the experiences of a community-academic partnership in designing, developing, and implementing an evidence-based, LHA-driven perinatal tobacco cessation program for low-income, predominately African American and Hispanic women. A multimethod process evaluation was conducted to analyze three essential domains of program implementation: (1) fit of the tobacco cessation program into the broader project context, (2) feasibility of program implementation, and (3) fidelity to program implementation protocols. Findings indicate that project partners have largely succeeded in integrating an evidence-based tobacco cessation program into a community-based maternal and infant health project. The successful implementation of this intervention appears to be attributable to the following two predominant factors: (1) the utilization of a scientifically validated tobacco cessation intervention model and (2) the emphasis on continuous LHA training and capacity development.


Adult-onset sellar and suprasellar atypical teratoid rhabdoid tumor treated with a multimodal approach: a case report.
We report a very rare case of sellar and suprasellar atypical teratoid rhabdoid tumor (ATRT) in a 42-year-old female patient. The tumor was removed subtotally with a transsphenoidal approach. Histopathologic study showed rhabdoid cells with prominent nucleoli and abundant cytoplasm. Immunohistochemistry for INI1 was completely negative in the tumor cells, consistent with ATRT. After surgery, she received radiotherapy including spinal irradiation with proton beam therapy and subsequent chemotherapy, with no evidence of recurrence for more than 2 years. Up to date, this is the 8th case of an adult-onset ATRT in the sellar or suprasellar region. Despite its rarity, ATRTs should be considered in the differential diagnosis of an unclear malignant sellar or suprasellar lesion in adult patients and the treatment strategies for adult ATRT patients could be differentiated from those of pediatric ATRT patients.


Role of viability imaging in the post-STICH era.
Recent results from prospective randomized controlled trials examining the management of patients with ischemic cardiomyopathy (ICM) have questioned both the added value of revascularization over contemporary optimal medical therapy (OMT) and the use of viability testing as a gate-keeper to revascularization. The purpose of this review is to summarize recent trial evidence before discussing future perspectives in the field. The Surgical Treatment of Ischemic Heart Failure (STICH) trial, PPAR-2 trial and Heart Failure Revascularisation Trial have all reported their results within the past 5 years. None of these trials found revascularization superior to OMT in improving survival of ICM patients. Additionally, the STICH trial's viability substudy suggested that pretreatment viability testing was not beneficial. ICM patients remain a clinical conundrum. The numerous limitations of the recent RCTs have led to uncertainty about optimal management. Revascularization continues to be offered to patients with evidence of myocardial viability. Further studies are required to answer the outstanding questions in the management of patients with ICM.


Measurement of the concentration of radon gas in the Toirano's caves (Liguria).
The radioactive gas radon, intermediate term of the decay series of uranium and thorium, is the main contamination source of underground places and may be a risk for high concentration and long exposure time. European and Italian law requires radon concentration to be measured in workplaces and, if the "action level" of 500 Bq/m3 is reached, proper actions must be made in order to decrease the dose commitment. Considering natural showcaves or artificial cavities open to public, the exposition of the visitors is frequently small, due to the short residence time, but accompanying people, remaining underground for long time, may be subject to appreciable dose and the radon concentration should therefore be monitored. The high humidity in natural caves may impair the use of some measuring devices. Therefore, different detection methods were compared (ZnS scintillation counters, E-PERM electret ionisation chambers, cellulose nitrate alpha-track dosimeters) to select the best procedure for long-term investigation. The LR-115 (Kodak) alpha-track dosimeters were insensitive to humidity and permitted to monitor a great number of places at the same time. Measurements have been carried out in the speleological and archaeological site of the Toirano's Caves (Savona, Liguria, Italy) and several points were monitored for two years. Radon concentration strongly depends on the site and changes during the year, due to the difference between internal and external temperature. The maximum dose commitment during the visitors tour, considering the average yearly value of radon concentration, was found to be between 1.5 and 4 microSv. It was found that no risk exists for visitors, but the evaluation of the dose absorbed by the guides and their classification according to the radiation protection law requires a complete monitoring of the average yearly concentration of radon and of the total time spent by each worker into the cave.


Whole-genome DNA methylation patterns and complex associations with gene structure and expression during flower development in Arabidopsis.
Flower development is a complex process requiring proper spatiotemporal expression of numerous genes. Accumulating evidence indicates that epigenetic mechanisms, including DNA methylation, play essential roles in modulating gene expression. However, few studies have examined the relationship between DNA methylation and floral gene expression on a genomic scale. Here we present detailed analyses of DNA methylomes at single-base resolution for three Arabidopsis floral periods: meristems, early flowers and late flowers. We detected 1.5 million methylcytosines, and estimated the methylation levels for 24 035 genes. We found that many cytosine sites were methylated de novo from the meristem to the early flower stage, and many sites were demethylated from early to late flowers. A comparison of the transcriptome data of the same three periods revealed that the methylation and demethylation processes were correlated with expression changes of >3000 genes, many of which are important for normal flower development. We also found different methylation patterns for three sequence contexts ((m) CG, (m) CHG and (m) CHH) and in different genic regions, potentially with different roles in gene expression.


Nociceptin/orphanin FQ antagonizes lipopolysaccharide-stimulated proliferation, migration and inflammatory signaling in human glioblastoma U87 cells.
Glioblastoma is among the most aggressive brain tumors and has an exceedingly poor prognosis. Recently, the importance of the tumor microenvironment in glioblastoma cell growth and progression has been emphasized. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and endogenous ligands originating from dying cells or the extracellular matrix involved in host defense and in inflammation. G-protein coupled receptors (GPCRs) have gained interest in anti-tumor drug discovery due to the role that they directly or indirectly play by transactivating other receptors, causing cell migration and proliferation. A proteomic analysis showed that the nociceptin receptor (NOPr) is among the GPCRs significantly expressed in glioblastoma cells, including U87 cells. We describe a novel role of the peptide nociceptin (N/OFQ), the endogenous ligand of the NOPr that counteracts cell migration, proliferation and increase in IL-1β mRNA elicited by LPS via TLR4 in U87 glioblastoma cells. Signaling pathways through which N/OFQ inhibits LPS-mediated cell migration and elevation of [Ca2+]i require β-arrestin 2 and are sensitive to TNFR-associated factor 6, c-Src and protein kinase C (PKC). LPS-induced cell proliferation and increase in IL-1β mRNA are counteracted by N/OFQ via β-arrestin 2, PKC and extracellular signal-regulated kinase 1/2; furthermore, the contributions of the transcription factors NF-kB and AP-1 were investigated. Independent of LPS, N/OFQ induces a significant increase in cell apoptosis. Contrary to what was observed in other cell models, a prolonged exposure to this endotoxin did not promote any tolerance of the cellular effects above described, including NOPr down-regulation while N/OFQ loses its inhibitory role.


STING is an essential mediator of the Ku70-mediated production of IFN-λ1 in response to exogenous DNA.
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING. Conversely, parental HEK 293 cells produced IFN-λ1 after they were exposed to exogenous DNA; however, when STING was knocked out in the HEK 293 cells through the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 genome editing system, they lost this response. Through confocal microscopy, we demonstrated that endogenous Ku70 was located in the nucleus and then translocated to the cytoplasm upon DNA exposure to form a complex with STING. Additionally, the DNA binding domain of Ku70 was essential for formation of the Ku70-STING complex. Knocking down STING in primary human macrophages inhibited their ability to produce IFN-λ1 in response to transfection with DNA or infection with the DNA virus HSV-2 (herpes simplex virus-2). Together, these data suggest that STING mediates the Ku70-mediated IFN-λ1 innate immune response to exogenous DNA or DNA virus infection.


Nutrients restriction upregulates adiponectin in epicardial or subcutaneous adipose tissue: impact in de novo heart failure patients.
Background: Hyperadiponectinemia is an indicator of worse outcomes in advanced heart failure (HF), its role in de novo HF is less clear. Objective: Because this protein is a hormone with starvation properties, we wanted to know its association with nutritional state and its regulator factors in de novo HF. Methods: Adiponectin circulating levels were determined by ELISA at discharge in patients admitted for de novo HF (n=74). Nutritional status was determined by CONUT score. Univariate and multivariate Cox regression analyses were employed to calculate the estimated hazard ratio (HR) with 95% confidence interval (CI) for death or all-cause readmission. Stromal vascular cells (SVC) of EAT and subcutaneous adipose tissue (SAT) from patients (n=5) underwent heart surgery were induced to adipogenesis for 18 days. Then, cells were cultured with complete or starved medium for 8 hours. At the end, adiponectin expression levels were analysed by real time polymerase chain reaction. Results: Patients were grouped regarding nutritional status. There was a strong association between high adiponectin levels and failing nutritional status. Those patients with worse nutritional state had the highest adiponectin and proBNP levels at discharge (p<0.01). Both proteins were slightly correlated (p<0.05). However, only high adiponectin levels were independently associated with death or all-cause readmission. Nutrients starvation upregulated adiponectin expression levels in adipogenesis-induced SVC from EAT or SAT. Conclusions: Worse nutritional state in de novo HF patients is associated with higher adiponectin plasma levels. Their levels were upregulated in adipose cells after being nutrients-starved. These results may help us to understand the adiponectin paradox in HF.


Positional control of DNA origami based gold dimer hybrid nanostructures on pre-structured surfaces.
This study explores important parameters for achieving a high-level positional control of DNA-nanoparticle hybrid structures by drop-casting onto a pre-structured silicon surface, in which the active adsorption sites were defined using electron beam lithography. By confining the adsorption sites to the scale of the DNA origami, we create multi-dimensional patterns and study the effect of diffusion and hybrid nanostructure concentration in the liquid on site occupation. We also propose a physical diffusion model that highlights the importance of surface diffusion in facilitating the adsorption of hybrid nanostructure onto active sites, particularly for two and one-dimensional adsorption sites. Our study shows prominent results of the hybrid nanostructure's selective adsorption, indicating high adsorption efficiency and precise control over the position, as well as the spatial orientation. We anticipate similar results in related systems, both in terms of different surfaces and similar DNA structures. Overall, our findings offer promising prospects for the development of large-scale nanoarrays on micrometer-scale surfaces with nanometer precision and orientation control.


DNMT3A-mediated epigenetic silencing of SOX17 contributes to endothelial cell migration and fibroblast activation in wound healing.
Wound healing, especially impaired chronic wound healing, poses a tremendous challenge for modern medicine. Understanding the molecular mechanisms underlying wound healing is essential to the development of novel therapeutic strategies. A wound-healing mouse model was established to analyze histopathological alterations during wound healing, and the expression of SRY-box transcription factor 17 (SOX17), DNA methyltransferase 3 alpha (DNMT3A), and a specific fibroblast marker S100 calcium-binding protein A4 (S100A4) in wound skin tissues was tested by immunofluorescence (IF) assay. Cell proliferation and migration were evaluated using 5-ethynyl-2'-deoxyuridine (EdU) and Transwell migration assays. RT-qPCR and western blotting were used to measure RNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of transforming growth factor-beta (TGF-β). Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) and DNA pull-down assays were performed to confirm the interaction between DNMT3A and the CpG island of the SOX17 promoter. Promoter methylation was examined by pyrosequencing. SOX17 and DNMT3A expression were regularly regulated during the different phases of wound healing. SOX17 knockdown promoted HUVEC migration and the production and release of TGF-β. Through establishing an endothelial cells-fibroblasts co-culture model, we found that SOX17 knockdown in HUVECs activated HFF-1 fibroblasts, which expressed α-smooth muscle actin (α-SMA) and type I collagen (COL1). DNMT3A overexpression reduces SOX17 mRNA levels. ChIP-qPCR and DNA pull-down assays verified the interaction between DNMT3A and CpG island in the SOX17 promoter region. Pyrosequencing confirmed that DNMT3A overexpression increased the methylation level of the SOX17 promoter. DNMT3A-mediated downregulation of SOX17 facilitates wound healing by promoting endothelial cell migration and fibroblast activation.


Interferon Alpha Induces Multiple Cellular Proteins That Coordinately Suppress Hepadnaviral Covalently Closed Circular DNA Transcription.
Covalently closed circular DNA (cccDNA) of hepadnaviruses exists as an episomal minichromosome in the nucleus of an infected hepatocyte and serves as the template for the transcription of viral mRNAs. It had been demonstrated by others and us that interferon alpha (IFN-α) treatment of hepatocytes induced a prolonged suppression of human and duck hepatitis B virus cccDNA transcription, which is associated with the reduction of cccDNA-associated histone modifications specifying active transcription (H3K9ac or H3K27ac), but not the histone modifications marking constitutive (H3K9me3) or facultative (H3K27me3) heterochromatin formation. In our efforts to identify IFN-induced cellular proteins that mediate the suppression of cccDNA transcription by the cytokine, we found that downregulating the expression of signal transducer and activator of transcription 1 (STAT1), structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1), or promyelocytic leukemia (PML) protein increased basal level of cccDNA transcription activity and partially attenuated IFN-α suppression of cccDNA transcription. In contrast, ectopic expression of STAT1, SMCHD1, or PML significantly reduced cccDNA transcription activity. SMCHD1 is a noncanonical SMC family protein and implicated in epigenetic silencing of gene expression. PML is a component of nuclear domain 10 (ND10) and is involved in suppressing the replication of many DNA viruses. Mechanistic analyses demonstrated that STAT1, SMCHD1, and PML were recruited to cccDNA minichromosomes and phenocopied the IFN-α-induced posttranslational modifications of cccDNA-associated histones. We thus conclude that STAT1, SMCHD1, and PML may partly mediate the suppressive effect of IFN-α on hepadnaviral cccDNA transcription.IMPORTANCE Pegylated IFN-α is the only therapeutic regimen that can induce a functional cure of chronic hepatitis B in a small, but significant, fraction of treated patients. Understanding the mechanisms underlying the antiviral functions of IFN-α in hepadnaviral infection may reveal molecular targets for development of novel antiviral agents to improve the therapeutic efficacy of IFN-α. By a loss-of-function genetic screening of individual IFN-stimulated genes (ISGs) on hepadnaviral mRNAs transcribed from cccDNA, we found that downregulating the expression of STAT1, SMCHD1, or PML significantly increased the level of viral RNAs without altering the level of cccDNA. Mechanistic analyses indicated that those cellular proteins are recruited to cccDNA minichromosomes and induce the posttranslational modifications of cccDNA-associated histones similar to those induced by IFN-α treatment. We have thus identified three IFN-α-induced cellular proteins that suppress cccDNA transcription and may partly mediate IFN-α silencing of hepadnaviral cccDNA transcription.


The evolution of Rogers' Science of Unitary Human Beings: 21st century reflections.
The purpose of this article is to reflect on the state of Martha E. Rogers' science of unitary human beings as it has evolved over the past 40 years, with particular attention to the decade since her death. Although Rogers never updated her 1970 book, revised concepts and principles of homeodynamics, as reported in other publications, are discussed. In more than a decade since Rogers' death, nurse scientists have been prolific in explicating the science in scholarly research and writing. An example of theories derived from the science, as well as concepts under study, and research methods are identified. Twenty-first century thoughts on the science of unitary human beings, as expressed by three founders of the Society of Rogerian Scholars, are highlighted from an interview conducted by Fawcett. Rogers suggested that the development of a science of unitary human beings is a never ending process.


The impact of viral respiratory tract infections on long-term morbidity and mortality following lung transplantation: a retrospective cohort study using a multiplex PCR panel.
The major factor affecting morbidity and mortality after lung transplantation (LTX) is bronchiolitis obliterans syndrome. Earlier studies have suggested a connection between the presence of viral agents and morbidity in this patient group, but data are somewhat conflicting. The objective of this study was to investigate the development of bronchiolitis obliterans syndrome and graft loss after LTX in relation to the presence of respiratory viruses during the first year after LTX. The study is a retrospective cohort study of 39 LTX recipients 11Y13 years after surgery. Patients were operated between January 1, 1998 and December 31, 2000 at Sahlgrenska University Hospital. The presence of virus in bronchoalveolar lavage (BAL) fluids from patients during the first year after surgery was analyzed retrospectively using a multiplex polymerase chain reaction test capable of detecting 15 respiratory agents. The time to BOS or graft loss was analyzed in relation to the positive findings in BAL during the first year after LTX. Patients with one or more viruses detected in BAL during the first year after transplantation demonstrated a significantly faster development of BOS (P=0.005) compared with patients with no virus detected. No significant difference in graft survival was found. Our results suggest that the long-term prognosis after LTX may be negatively affected by viral respiratory tract infections during the first year after LTX.


Fluctuating expression of miR-584 in primary and high-grade gastric cancer.
Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics. The expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes. Both experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples. miR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.


Tooth and Alveolar Bone Segmentation From Dental Computed Tomography Images.
Three-dimensional (3D) models of tooth-alveolar bone complex are needed in treatment planning and simulation for computer-aided orthodontics. Tooth and alveolar bone segmentation from computed tomography (CT) images is a fundamental step in reconstructing their models. Due to less application of alveolar bone in conventional orthodontic treatment which may cause undesired side effects, the previous studies mainly focused on tooth segmentation and reconstruction, and did not consider the alveolar bone. In this study, we proposed a method to implement both tooth and alveolar bone segmentation from dental CT images for reconstructing their 3D models. First, the proposed method extracted the connected region of tooth and alveolar bone from CT images using a global convex level set model. Then, individual tooth and alveolar bone are separated from the connected region based on Radon transform and a local level set model. The experimental results showed that the proposed method could successfully complete both the tooth and alveolar bone segmentation from CT images, and outperformed the state of the art tooth segmentation methods in terms of accuracy. This suggests that the proposed method can be used in reconstructing the 3D models of tooth-alveolar bone complex for precise treatment.


Involvement of regulatory T cells in HIV immunopathogenesis.
Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex biology of these cells, including maintenance of immunological tolerance to "self" and regulation of immune responses to pathogens, commensals, and tumors, has become the focus of intense investigation. The ability to control the infection and to delay the progression of the infection to AIDS and/or death is probably regulated by a balance between host factors, such as immunologic response and viral factors. Different rates of disease progression among HIV-1 infected individuals have been observed. In this context, Tregs may play an important role in the immunopathology of HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. In this review, we present the molecular and immunological aspects of Tregs in the HIV system and the association between Tregs and highly active antiretroviral therapy (HAART).


Seroepidemiology of Sarcocystis neurona and Neospora hughesi infections in domestic donkeys (Equus asinus) in Durango, Mexico.
There is currently no information regarding Sarcocystis neurona and Neospora hughesi infections in donkeys in Mexico. Here, we determined the presence of antibodies against S. neurona and N. hughesi in donkeys in the northern Mexican state of Durango. Serum samples of 239 domestic donkeys (Equus asinus) were assayed for S. neurona and N. hughesi antibodies using home-made enzyme-linked immunoassays; six (2.5%) of the 239 donkeys tested seropositive for S. neurona. The seroprevalence of S. neurona infection was comparable among donkeys regardless of their origin, health status, or sex. Multivariate analysis showed that seropositivity to S. neurona was associated with increased age (OR = 2.95; 95% CI: 1.11-7.82; p = 0.02). Antibodies to N. hughesi were found in two (0.8%) of the 239 donkeys. Both exposed donkeys were healthy, 3- and 6-year-old females. This is the first evidence of S. neurona and N. hughesi infections in donkeys in Mexico.


Radiological assessment of the effects of potential root-end filling materials on healing after endodontic surgery.
The effects of three root-end filling materials on healing following endodontic surgery were assessed radiologically and correlated with histological findings reported elsewhere. The materials compared were a light-cured glass ionomer cement (Vitrebond), a reinforced zinc oxide-eugenol cement (Kalzinol) and amalgam. The root canals of 27 two-rooted mandibular premolar teeth of six beagle dogs were inoculated with endodontic pathogenic bacteria to induce periradicular lesions. The roots were apicected and root-end cavities filled with the tested filling materials. The teeth and surrounding jaw were removed after 4 weeks (30 roots) or 8 weeks (24 roots). Radiographs were taken of each jaw section and subjected to image analysis. Healing was evaluated based on measurements of the size of the periradicular radiolucent areas. ANOVA disclosed no statistically significant differences in the size of the periradicular areas either between time periods or between materials. These results did not correlate with the tissue responses in the same material as assessed histologically and previously reported. The use of radiographs alone to assess healing after endodontic surgery in the dog mandible is unsatisfactory, and should not be regarded as a substitute for histological examination for the determination of healing.


Gene features selection for three-class disease classification via multiple orthogonal partial least square discriminant analysis and S-plot using microarray data.
DNA microarray analysis is characterized by obtaining a large number of gene variables from a small number of observations. Cluster analysis is widely used to analyze DNA microarray data to make classification and diagnosis of disease. Because there are so many irrelevant and insignificant genes in a dataset, a feature selection approach must be employed in data analysis. The performance of cluster analysis of this high-throughput data depends on whether the feature selection approach chooses the most relevant genes associated with disease classes. Here we proposed a new method using multiple Orthogonal Partial Least Squares-Discriminant Analysis (mOPLS-DA) models and S-plots to select the most relevant genes to conduct three-class disease classification and prediction. We tested our method using Golub's leukemia microarray data. For three classes with subtypes, we proposed hierarchical orthogonal partial least squares-discriminant analysis (OPLS-DA) models and S-plots to select features for two main classes and their subtypes. For three classes in parallel, we employed three OPLS-DA models and S-plots to choose marker genes for each class. The power of feature selection to classify and predict three-class disease was evaluated using cluster analysis. Further, the general performance of our method was tested using four public datasets and compared with those of four other feature selection methods. The results revealed that our method effectively selected the most relevant features for disease classification and prediction, and its performance was better than that of the other methods.


Social media toolkit.
Skills for Health has launched a free, online social media toolkit to offer healthcare organisations information and advice about using social media.


Analysis of naturally occurring and radiation-induced breakpoint locations in human chromosomes 1, 2 and 4.
The locations of observed breaks in three pairs of painted chromosomes from radiation-exposed and unexposed human peripheral blood lymphocytes are described. No difference in the observed breakpoint locations was seen from people exposed at Chernobyl, from healthy controls or from blood exposed to 2 Gy 137Cs in vitro. However, the distribution of observed breaks within the painted chromosomes was not random. Fewer breaks and rearrangements were observed near the ends of the chromosome arms. Three explanations for these findings were considered: cell selection, non-random efficiency of detection and non-random breakage or repair. Cell selection does not appear to be plausible because the distribution of observed breaks induced in vitro is not different from those induced in vivo. Non-random efficiency of detection is not supported by the data. Non-random breakage or repair appears to be the most likely explanation, although the mechanism(s) by which this occurs is unknown.


Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study.
This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.


Achievements and Challenges in Anti-Doping Research.
The most important element in achieving athlete compliance with anti-doping rules is the certainty of detection. Thus, scientific research plays a mission critical role in achieving clean competition. Many factors contribute to the advances in detection. Incremental advances in the ability to detect prohibited substances and methods, and identification of long-lived metabolites continue to lengthen detection windows. While the athlete biological passport hematological and steroidal modules hold great promise, experience shows that new research is needed to improve the sensitivity and specificity of the approach for current doping techniques. Indirect detection strategies using biomarkers or transcriptomic techniques have been increasingly investigated. The incorporation of more cost-effective sampling strategies using dried blood and plasma spots, oral fluid, and breath analysis show great promise toward increasing the number of tests while remaining within testing budget constraints. Despite the importance of research to ensuring rule compliance, a major challenge for anti-doping research is achieving and maintaining sufficient funding in the reality of the myriad of new substances introduced for disease treatment but abused for performance enhancement. In addition, obtaining metabolism and population reference range data, particularly for new drugs or designer drugs that have not obtained approval for administration to human subjects, remains a significant problem. Nevertheless, research continues to contribute important data to support anti-doping efforts.


The Qingchangligan Formula Alleviates Acute Liver Failure by Regulating Galactose Metabolism and Gut Microbiota.
The Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has significant clinical potential for patients with acute liver failure (ALF). However, the experimental evidence of the effect of QCLGF on ALF and the associated mechanisms remain elusive. We aimed to evaluate the function of QCLGF in ALF and the underlying mechanism. ALF was induced in rats by intraperitoneal injection of D-GalN (1100 mg/kg). The Qingchangligan formula was administered to the rats (6.725 g/kg · d) for 5 days, and the model group and the control group were given the same amount of physiological saline. Then 16S rRNA gene sequencing, high performance gas chromatography-mass spectrometry (GC-MS), and RNA-seq analysis were performed on the samples. The levels of ALT and AST in the ALF rats were abnormal (5322.08 ± 566.27 U/L and 7655.95 ± 1238.08 U/L, respectively) compared with the normal control (98.98 ± 6.90 U/L and 99.63 ± 10.94 U/L, respectively). The levels of ALT and AST in the QCLGF rats (2997.67 ± 469.24 U/L and 4158.40 ± 596.07 U/L, respectively) were closer the normal control group. Liver HE staining showed that the degree of liver damage in the QCLGF rats was lighter than that in the ALF rats. The overall structure of the gut microbiota after ALF was significantly altered, including Proteobacteria, Blautia, Romboutsia, Parabacteroides, UCG-008, Parasutterella, Ruminococcus, norank_f:Lachnospiraceae, the Eubacterium_xylanophilum_group, Oscillibacter, and Eisenbergiella. QCLGF balanced the structure and abundance of intestinal flora. The levels of D(+)galactose, isopropyl beta-D-1-thiogalactopyranoside and D-mannitol were lighter in the plasma of the ALF rats than in the normal control rats, but there were significantly elevated levels of those metabolites in the QCLGF rats. The gene expression changed significantly in the ALF rats. QCLGF regulated the expression of THBS1 and the KEGG pathways of carbohydrate metabolism, lipid metabolism, signal transduction, the immune system, and infectious disease: bacterial. QCLGF may alleviating intestinal flora disorder, regulating galactose metabolism and downregulating the expression of THBS1 to alleviate D-GalN induced acute liver failure.


Management of tyrosine kinase inhibitor resistance in lung cancer with EGFR mutation.
The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved.


Does verruca vulgaris affect social anxiety and self-esteem in adolescents?
Objective Sensitivity about appearance is one of the sine qua non of adolescence and adolescents' self-esteem effecting their socialization processes. We explored if verruca vulgaris, a common visible infectious skin disease, affects social anxiety levels and self-esteem in adolescents compared to controls. Also, the difference in sociodemographic properties between two groups and the effect of clinical properties (the distribution and number of warts) on these parameters were investigated in the patient group. Materials and methods The study group consisted 98 adolescents (49 controls and 49 patients) without other medical/psychiatric diseases. The Sociodemographic form (SDF), the Çapa Social Phobia Scale for Children and Adolescents (ÇCASPS) and the Rosenberg Self-Esteem Scale (RSES) were completed by both groups. Results There was no difference in social anxiety levels and self-esteem between the two groups. Also, the control and patient groups were found matched. However, lower self-esteem was the only factor that increased the risk for social phobia in the patient group. Conclusion Verruca vulgaris distributed in hands and face in adolescents were not found to be related with higher social anxiety and lower self-esteem. However, clinicians should monitor psychiatric symptoms and especially lower self-esteem should be taken into account.


Hepatic gene expression profile in mice perorally infected with Echinococcus multilocularis eggs.
Alveolar echinococcosis (AE) is a severe chronic hepatic parasitic disease currently emerging in central and eastern Europe. Untreated AE presents a high mortality (>90%) due to a severe hepatic destruction as a result of parasitic metacestode proliferation which behaves like a malignant tumor. Despite this severe course and outcome of disease, the genetic program that regulates the host response leading to organ damage as a consequence of hepatic alveolar echinococcosis is largely unknown. We used a mouse model of AE to assess gene expression profiles in the liver after establishment of a chronic disease status as a result of a primary peroral infection with eggs of the fox tapeworm Echinococcus multilocularis. Among 38 genes differentially regulated (false discovery rate adjusted p</=0.05), 35 genes were assigned to the functional gene ontology group <immune response>, while 3 associated with the functional group <intermediary metabolism>. Upregulated genes associated with <immune response> could be clustered into functional subgroups including <macrophages>, <APCs>, <lymphocytes, chemokines and regulation>, <B-cells> and <eosinophils>. Two downregulated genes related to <lymphocytes, chemokines and regulation> and <intermediary metabolism>, respectively. The <immune response> genes either associated with an <immunosupression> or an <immunostimulation> pathway. From the overexpressed genes, 18 genes were subsequently processed with a Custom Array microfluidic card system in order to assess respective expression status at the mRNA level relative to 5 reference genes (Gapdh, Est1, Rlp3, Mdh-1, Rpl37) selected upon a constitutive and stable expression level. The results generated by the two independent tools used for the assessment of gene expression, i.e., microarray and microfluidic card system, exhibited a high level of congruency (Spearman correlation rho = 0.81, p = 7.87e-5) and thus validated the applied methods. Based on this set of biomarkers, new diagnostic targets have been made available to predict disease status and progression. These biomarkers may also offer new targets for immuno-therapeutic intervention.


Neuralgic amyotrophy detected by magnetic resonance neurography: subclinical, bilateral, and multifocal brachial plexus involvement.
Neuralgic amyotrophy (NA) is a painful non-traumatic peripheral nervous system condition affecting the brachial plexus. Signal abnormalities in nerves and muscles have been detected in these patients using magnetic resonance neurography (MRN). Electronic medical records and MRN images obtained in a 3 T scanner, in 14 adult patients diagnosed with NA at our Neurological institution (Neuromuscular Disorders Section), between December 2015 and December 2019 were retrospectively reviewed. The study was first approved by our Institutional Ethics Committee. Subclinical, multifocal, and bilateral nerve signal anomalies were recorded in the brachial plexus of these patients. We identified four different types of nerve constriction without entrapment, which we categorized as follows: incomplete focal (type I), complete focal or hourglass (type II), multifocal or string of pearls (type III) and segmental (type IV). Given that MRN is an accurate diagnostic tool to detect nerve damage, we believe abnormal findings could improve early detection of NA patients.


[Natural coral calcium carbonate as alternative substitute in bone defects of the skull].
A biomaterial derived from natural corals with surgical applications is the calcium carbonate Biocoral. Since 1992 the author has been using this material as a bone graft substitute in maxillofacial surgery. Eighty-nine clinical implantations were done in 68 patients for different indications. The results suggested that coral grafts are well tolerated and are simultaneously partially ossified as the calcified skeleton is resorbed. Clinical cases show that use of this material has been successful.


Reoperations within 48 hours following 7942 pediatric neurosurgery procedures.
OBJECTIVE Various indicators are used to evaluate the quality of care delivered by surgical services, one of which is early reoperation rate. The indications and rate of reoperations within a 48-hour time period have not been previously reported for pediatric neurosurgery. METHODS Between May 1, 2009, and December 30, 2014, 7942 surgeries were performed by the pediatric neurosurgery service in the operating rooms at a single institution. Demographic, socioeconomic, and clinical characteristics associated with each of the operations were prospectively collected. The procedures were grouped into 31 categories based on the nature of the procedure and underlying diseases. Reoperations within 48 hours at the conclusion of the index surgery were reviewed to determine whether the reoperation was planned or unplanned. Multivariate logistic regression was employed to analyze risk factors associated with unplanned reoperations. RESULTS Cerebrospinal fluid shunt-and hydrocephalus-related surgeries accounted for 3245 (40.8%) of the 7942 procedures. Spinal procedures, craniotomy for tumor resections, craniotomy for traumatic injury, and craniofacial reconstructions accounted for an additional 8.7%, 6.8%, 4.5%, and 4.5% of surgical volume. There were 221 reoperations within 48 hours of the index surgery, yielding an overall incidence of 2.78%; 159 of the reoperation were unplanned. Of these 159 unplanned reoperations, 121 followed index operations involving shunt manipulations. Using unplanned reoperations as the dependent variable (n = 159), index operations with a starting time after 3 pm and admission through the emergency department (ED) were associated with a two- to threefold increase in the likelihood of reoperations (after-hour surgery, odds ratio [OR] 2.01 [95% CI 1.43-2.83, p < 0.001]; ED admission, OR 1.97 (95% CI 1.32-2.96, p < 0.05]). CONCLUSIONS Approximately 25% of the reoperations within 48 hours of a pediatric neurosurgical procedure were planned. When reoperations were unplanned, contributing factors could be both surgeon related and system related. Further study is required to determine the extent to which these reoperations are preventable. The utility of unplanned reoperation as a quality indicator is dependent on proper definition, analysis, and calculation.


Prognostic value of DCE-MRI in breast cancer patients undergoing neoadjuvant chemotherapy: a comparison with traditional survival indicators.
To determine associations between dynamic contrast-enhanced MR imaging (DCE-MRI) parameters and survival intervals in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC), surgery, and adjuvant therapies. Further, to compare the prognostic value of DCE-MRI parameters against traditional survival indicators. DCE-MRI and MR tumour volume measures were obtained prior to treatment and post 2nd NAC cycle. To demonstrate which parameters were associated with survival, Cox's proportional hazards models (CPHM) were employed. To avoid over-parameterisation, only those MR parameters with at least a borderline significant result were entered into the final CPHM. When considering disease-free survival positive axillary nodal status (hazard ratio [HR] 6.79), younger age (HR 3.37), negative oestrogen receptor status (HR 3.24), pre-treatment Maximum Enhancement Index (MaxEI) (HR 6.51), and percentage change in MaxEI (HR 1.02) represented the retained CPHM covariates. Similarly, positive axillary nodal status (HR 11.47), negative progesterone receptor status (HR 4.37) and percentage change in AUC90 (HR 1.01) represented the retained predictive variables for overall survival. Multivariate survival analysis has demonstrated that DCE-MRI parameters obtained prior to NAC and/or post 2nd cycle can provide independent prognostic information that can complement traditional prognostic indicators available prior to treatment. • MR-derived DCE-MRI parameters obtained prior to treatment have prognostic value. • Early treatment-induced reductions in DCE-MRI parameters represents a positive prognostic indicator. • DCE-MRI parameters provide independent prognostic information that can complement traditional prognostic indicators.


Self-assembly behavior of alkylated isophthalic acids revisited: concentration in control and guest-induced phase transformation.
The engineering of two-dimensional crystals by physisorption-based molecular self-assembly at the liquid-solid interface is a powerful method to functionalize and nanostructure surfaces. The formation of high-symmetry networks from low-symmetry building blocks is a particularly important target. Alkylated isophthalic acid (ISA) derivatives are early test systems, and it was demonstrated that to produce a so-called porous hexagonal packing of plane group p6, i.e., a regular array of nanowells, either short alkyl chains or the introduction of bulky groups within the chains were mandatory. After all, the van der Waals interactions between adjacent alkyl chains or alkyl chains and the surface would dominate the ideal hydrogen bonding between the carboxyl groups, and therefore, a close-packed lamella structure (plane group p2) was uniquely observed. In this contribution, we show two versatile approaches to circumvent this problem, which are based on well-known principles: the "concentration in control" and the "guest-induced transformation" methods. The successful application of these methods makes ISA suitable building blocks to engineer a porous pattern, in which the distance between the pores can be tuned with nanometer precision.


The Miller Assessment for Preschoolers: clinical use with children with developmental delays.
In this pilot study, we investigated the clinical use of the Miller Assessment for Preschoolers (MAP) (Miller, 1982) with a sample of children with suspected or confirmed developmental delays. A retrospective chart audit was performed for 95 subjects, 30 girls and 65 boys, 34 to 68 months of age. Clinically related diagnoses were classified into six medical/developmental groups and a no-diagnosis group. When an analysis of variance was used to compare the six medical/developmental groups with the no-diagnosis group, some of the MAP score patterns differed significantly (p less than .01). These score patterns provide preliminary evidence for the MAP's effectiveness in screening children with developmental delays.


Demarcation of Intensity From 3 to 5 Zones Aids in Understanding Physiological Performance Progression in Highly Trained Under-23 Rowing Athletes.
Watts, SP, Binnie, MJ, Goods, PSR, Hewlett, J, Fahey-Gilmour, J, and Peeling, P. Demarcation of intensity from 3 to 5 zones aids in understanding physiological performance progression in highly trained under-23 rowing athletes. J Strength Cond Res 37(11): e593-e600, 2023-The purpose of this investigation was to compare 2 training intensity distribution models (3 and 5 zone) in 15 highly trained rowing athletes ( n = 8 male; n = 7 female; 19.4 ± 1.1 years) to determine the impact on primary (2,000-m single-scull race) and secondary (2,000-m ergometer time trial, peak oxygen consumption [V̇O 2 peak], lactate threshold 2 [LT2 power]) performance variables. Performance was assessed before and after 4 months training, which was monitored through a smart watch (Garmin Ltd, Olathe, KS) and chest-strap heart rate (HR) monitor (Wahoo Fitness, Atlanta, GA). Two training intensity distribution models were quantified and compared: a 3-zone model (Z1: between 50% V̇O 2 peak and lactate threshold 1 (LT1); Z2: between LT1 and 95% LT2; Z3: >95% LT2) and a 5-zone model (T1-T5), where Z1 and Z3 were split into 2 additional zones. There was significant improvement in LT2 power for both male (4.08% ± 1.83, p < 0.01) and female (3.52% ± 3.38, p = 0.02) athletes, with male athletes also demonstrating significant improvement in 2,000-m ergometer time trial (2.3% ± 1.92, p = 0.01). Changes in V̇O 2 peak significantly correlated with high-quality aerobic training (percent time in T2 zone; r = 0.602, p = 0.02), whereas changes in LT2 power significantly correlated with "threshold" training (percent time in T4 zone; r = 0.529, p = 0.04). These correlations were not evident when examining intensity distribution through the 3-zone model. Accordingly, a 5-zone intensity model may aid in understanding the progression of secondary performance metrics in rowing athletes; however, primary (on-water) performance remains complex to quantify.