Application of NIR Spectroscopy Coupled with PLS Regression for Quantification of Total Polyphenol Contents from the Fruit and Aerial Parts of Citrullus colocynthis.
Citrullus colocynthis (L.) Schrad is extensively used to treat diabetes, obesity, fever, cancer, amenorrhea, jaundice, leukemia, rheumatism, and respiratory diseases. Chemical studies have indicated the presence of several cucurbitacins, flavones, and other polyphenols in this plant. These phytochemical constituents are responsible for the interesting antioxidant and other biological activities of C. colocynthis. In the present study, for the first time, near infrared (NIR) spectroscopy coupled with partial least square (PLS) regression analysis was used to quantify the polyphenolic phytochemicals of C. colocynthis. The fruit and aerial parts of the C. colocynthis were extracted individually in methanol followed by fractionation in n-hexane, chloroform, ethyl acetate, n-butanol, and water. Near infrared (NIR) spectra were obtained in absorption mode in the wavelength range 700-2500 nm. The PLS regression model was then built from the obtained spectral data to quantify the total polyphenol contents in the selected plant samples. The PLS regression model obtained had a R2 value of 99% with a 0.98 correlationship value and a good prediction with a root mean square error of prediction (RMSEP) value of 1.89% and correlation of 0.98. These results were further confirmed through UV-vis spectroscopy and it is found that the ethyl acetate fraction has the maximum value for polyphenol contents (101.7 mg/100 g; NIR, 100.4 mg/100 g; UV-vis). The polyphenolic phytochemicals of the fruit and aerial parts of C. colocynthis have been quantified successfully by using multivariate analysis in a non-destructive, economical, precise, and highly sensitive method, which uses very simple sample preparation. Copyright © 2017 John Wiley & Sons, Ltd.


A retrospective observational examination following the COVID-19 pandemic: Was everything necessary done in the management of hip fractures?
Hip fragility fracture-related mortality depends on several variables. The management of such cases during the COVID-19 pandemic is an important issue that needs to be evaluated. The aim of this study is to evaluate the management of such cases during the COVID-19 pandemic in a single trauma center in Turkey. In this retrospective study, the length of stay (LoS) and 30-day mortality rates in patients with hip fragility fractures, in the ICU - clinic combined follow- ups (ICU/Clinic group) combined follow-ups and in the clinic follow-ups (Clinic Only group) were compared between pre-pandemic and pandemic period. The data of 393 patients, 164 (41.7%) men and 229 (58.3%) women, with a mean age of 81.22±8.37 (45-100) years, were analyzed. The total LoS during the pandemic was determined to be shorter than the pre-pandemic period in both the patient groups that followed up in the Clinic Only and those in ICU/Clinic (p<.001, p=.007). The 30-day mortality rates of the groups were similar. The length of the hospital stay of hip fragility fracture patients was seen to be shorter during the COVID-19 pandemic, but this early discharge did not affect the 30-day mortality rates.


Transcoronary transplantation of progenitor cells after myocardial infarction.
Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow (BMC) or circulating blood (CPC) may improve left ventricular function after acute myocardial infarction. The effects of cell transplantation in patients with healed myocardial infarction are unknown. After an initial pilot trial involving 17 patients, we randomly assigned, in a controlled crossover study, 75 patients with stable ischemic heart disease who had had a myocardial infarction at least 3 months previously to receive either no cell infusion (23 patients) or infusion of CPC (24 patients) or BMC (28 patients) into the patent coronary artery supplying the most dyskinetic left ventricular area. The patients in the control group were subsequently randomly assigned to receive CPC or BMC, and the patients who initially received BMC or CPC crossed over to receive CPC or BMC, respectively, at 3 months' follow-up. The absolute change in left ventricular ejection fraction was significantly greater among patients receiving BMC (+2.9 percentage points) than among those receiving CPC (-0.4 percentage point, P=0.003) or no infusion (-1.2 percentage points, P<0.001). The increase in global cardiac function was related to significantly enhanced regional contractility in the area targeted by intracoronary infusion of BMC. The crossover phase of the study revealed that intracoronary infusion of BMC was associated with a significant increase in global and regional left ventricular function, regardless of whether patients crossed over from control to BMC or from CPC to BMC. Intracoronary infusion of progenitor cells is safe and feasible in patients with healed myocardial infarction. Transplantation of BMC is associated with moderate but significant improvement in the left ventricular ejection fraction after 3 months.


The effect of neuromuscular blockade on oxygen supply, consumption, and total chest compliance in patients with high oxygen requirements undergoing mechanical ventilation.
We investigated the effects of neuromuscular blockade with atracurium on oxygen consumption, oxygen delivery and total chest compliance in 20 sedated intensive care patients who required mechanical ventilation with an inspired oxygen fraction of at least 0.6. The reverse Fick method was used to measure oxygen consumption. Total chest compliance was measured from the ventilator pneumotachograph and pressure transducer. Measurements were made before neuromuscular blockade, at a standard level of neuromuscular blockade, and after demonstrated recovery of neuromuscular function. There was no statistical difference in any of the parameters measured. However there were large changes in oxygen consumption (range -35% to +17%) and total chest compliance (range -19.7% to +9.7%) in individuals. We conclude that in the setting of critical oxygenation, neuromuscular blockade cannot be assumed to reduce oxygen requirements or improve total lung compliance. If, however, neuromuscular blockade is selected as an adjunct to therapy, we recommend that the indices of oxygenation are calculated.


A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins.
How the cuticles of the roughly 4.5 million species of ecdysozoan animals are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover the spatiotemporal blueprint for how the chitin-based pharyngeal cuticle of the nematode Caenorhabditis elegans is built. We demonstrate that the blueprint correctly predicts expression patterns and functional relevance to cuticle development. We find that as larvae prepare to molt, catabolic enzymes are upregulated and the genes that encode chitin synthase, chitin cross-linkers, and homologs of amyloid regulators subsequently peak in expression. Forty-eight percent of the gene products secreted during the molt are predicted to be intrinsically disordered proteins (IDPs), many of which belong to four distinct families whose transcripts are expressed in overlapping waves. These include the IDPAs, IDPBs, and IDPCs, which are introduced for the first time here. All four families have sequence properties that drive phase separation and we demonstrate phase separation for one exemplar in vitro. This systematic analysis represents the first blueprint for cuticle construction and highlights the massive contribution that phase-separating materials make to the structure.


Ubiquity of Sicyopterus lagocephalus (Teleostei: Gobioidei) and phylogeography of the genus Sicyopterus in the Indo-Pacific area inferred from mitochondrial cytochrome b gene.
Sicyopterus lagocephalus is a Gobiidae Sicydiinae (Teleostei) thought to inhabit Indo-Pacific island rivers from Comoros Islands in the Indian Ocean to Australs Islands (French Polynesia) in the Pacific Ocean. Its biological cycle comprises a marine planctonic larval phase of several months allowing it to migrate from island to island, but the other species of the genus, with such a larval stage, have generally a more restricted range and are often endemic. To understand the organisation of a species with such a wide distribution, mtDNA cytochrome b sequences were amplified for 55 specimens of this genus covering most of its distribution range together with six close endemic species and other gobiids used as outgroups. The main result is the confirmation of the ubiquity of S. lagocephalus that occurs over a range of 18,000 km in the Indian and Pacific Oceans. Two clades were identified within this species, one clustering most of French Polynesian haplotypes and the other clustering most of Mascarene (including Comoros) haplotypes. The overall pattern of distribution and phylogenetic relationship suggests that the lineages leading to endemic species originated earlier than S. lagocephalus. This latter seems to be a secondary migrant species, having colonised both Indian and Pacific Oceans with a few exceptions, situated at the border of the range (Madagascar, Marquesas, Rapa). According to the results, the phylogeny of the Sicyopterus group, the age of the different lineages and the past history of the colonisation of the Indo-Pacific islands are discussed.


Development of omega-3-rich Camelina sativa seed oil emulsions.
Camelina sativa seed is an underutilized oil source rich in omega-3 fatty acids; however, camelina oil is not fully explored for food applications. Its high omega-3 content makes it susceptible to oxidation, which may limit food applications. Therefore, the main objective of this study was to investigate the potential of camelina seed oil to form physically and oxidatively stable emulsions as a potential delivery system for omega-3 fatty acids. Effects of homogenization conditions, namely, pressure (15 MPa-30 MPa), number of passes (1,3,5, and 7), and type of homogenizers (high pressure and high shear) on the structural properties and stability of camelina seed oil emulsions stabilized with whey protein isolate were studied. High homogenization pressure (30 MPa) and number of passes (>3) reduced the particle size (278 nm) and formed more physically and oxidatively stable emulsions compared to high shear homogenization; high shear homogenization generated bigger oil particles (~2,517 nm). Apparent viscosity and consistency index (k) decreased with increasing pressure, number of passes, and shear rate. Emulsions prepared with high pressure homogenization at both 15 and 30 MPa with 3 and more passes did not exhibit any peroxide formation over 28 days. Results indicated that camelina seed oil is a promising alternative oil source to form stable omega-3-rich emulsions for food applications.


Comparative analysis of adult and fetal human small intestinal microvilli.
The aim was to study the development of human small intestinal microvillus membranes. We compared the protein patterns of human fetal and adult small intestinal microvillus membranes using the high-resolution technique of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. We also examined the synthesis of brush border membrane proteins from the adult small intestine using small intestinal biopsy organ culture 35S-methionine uptake and subsequent gel electrophoresis. We observed that the fetal and colonic microvillus membranes were similar, but differed in certain respects from adult small intestinal microvillus membranes. The jejunal biopsy organ culture revealed that synthesised brush border membrane proteins could be recognized by gel electrophoresis.


A boy born with multiple lesions of atrophoderma.
The Atrophodermas include a large group of disorders appearing as localized or widespread depressed skin areas and characterized by underlying dermal atrophy. The present study aims to report a peculiar form of previously unreported focal dermal atrophy. We studied over a period of 5 years a boy who manifested, since birth, multiple hypopigmented cutaneous atrophic lesions of the atrophoderma type in a mosaic distribution over the body and the legs. This boy did no develop other cutaneous or systemic stigmata except for an idiopathic thrombocytopenic purpura (ITP) manifested at age 2 years. Full serum, metabolic and infective analyses; full ophthalmological examination; ultrasound examination of the heart and internal organs; skeletal x-rays; brain magnetic resonance imaging; and DNA analysis of the PORCN (Focal Dermal Hypoplasia - FDH) gene in this boy yielded normal results. Pathological analysis of multiple skin specimens from an affected area revealed slightly reduced dermal thickness; hyperpigmentation of the basal layer; homogenized and disarrayed collagen bundles; perivascular chronic infiltrates of lymphocytes and histiocytes; and normal skin appendages. Currently, the child is healthy; he has mildly improved skin status with less-evident skin depression throughout the lesion areas and no further complication has been recorded. The histological and clinical appearance of the skin lesions and the course were against any known disorder in the group of the atrophodermas. The cutaneous lesions seen in this boy represent a possibly new congenital skin disorder characterized by multiple, benign areas of focal dermal atrophy in a mosaic distribution.


Characteristics of olfactory ensheathing cells and microarray analysis in Tupaia belangeri (Wagner, 1841).
Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.


Hypermetabolic Calcified Lymph Nodes on 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography in a Case of Treated Ovarian Cancer Recurrence: Residual Disease or Benign Formation?
The contribution of positron emission tomography/computed tomography (PET/CT) with 18F-fludeoxyglucose (FDG) in evaluating ovarian cancer recurrence even after a prolonged disease-free interval, and in therapy response is well-described. Calcifications observed in CT, although usually attributed to benign conditions, may actually represent active disease. Such an example of calcified formations is psammoma bodies. We present a case of 56-y. o. patient with ovarian cancer relapse at the supraclavicular area 18 years after complete response and disease-free interval. The patient received chemotherapy and underwent 18F-FDG-PET/CT for the evaluation of treatment response. Both CT corrected and uncorrected PET images showed hypermetabolism in the massively calcified lymph nodes in the neck, mediastinum, axilla and abdomen, indicative of active residual disease.


Endovascular treatment of M2 dissecting aneurysm presenting with subarachnoid haemorrhage.
A 63-year-old woman presented with a ruptured dissecting aneurysm (DA) at the right M2 region of the angular branches. This report describes a rare case of middle cerebral artery DA presenting with a subarachnoid haemorrhage (SAH); the patient was successfully treated with endovascular internal trapping of the DA, without a bypass surgery.


Low- and high-grade glioma endothelial cells differentially regulate tumor growth.
A key feature distinguishing high-grade glioma (HGG) from low-grade glioma (LGG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor endothelial cells (TEC) from HGG are molecularly and functionally distinct from normal brain EC and secrete higher levels of pro-tumorigenic factors that promote glioma growth and progression. However, it remains unclear whether TEC from LGG also express pro-tumorigenic factors, and to what extent they functionally contribute to glioma growth. Transcriptomic profiling was conducted on tumor endothelial cells (TEC) from grade II/III (LGG, IDH-mutant) and grade IV HGG (IDH-wildtype). Functional differences between LGG- and HGG-TEC were evaluated using growth assays, resistance to anti-angiogenic drugs and radiation therapy. Conditioned media and specific factors from LGG- and HGG-TEC were tested on patient-derived gliomasphere lines using growth assays in vitro and in co-transplantation studies in vivo in orthotopic xenograft models. LGG-TEC showed enrichment of extracellular matrix and cell cycle-related gene sets and sensitivity to anti-angiogenic therapy whereas HGG-TEC displayed an increase in immune response-related gene sets and anti-angiogenic resistance. LGG- and HGG-TEC displayed opposing effects on growth and proliferation of IDH-wildtype and mutant tumor cells. Asporin (ASPN), a small leucine rich proteoglycan enriched in LGG-TEC was identified as a growth suppressor of IDH-wildtype GBM by modulating TGFΒ1-GPM6A signaling. Our findings indicate that TEC from LGG and HGG are molecularly and functionally heterogeneous and differentially regulate the growth of IDH-wildtype and mutant tumors.


Heterogeneity in fairness views: a challenge to the mutualistic approach?
This commentary argues that the observed heterogeneity in fairness views, documented in many economic experiments, poses a challenge to the partner choice theory developed by Baumard et al. It also discusses the extent to which their theory can explain how people consider inequalities due to pure luck.


Salsalate reduces atherosclerosis through AMPKβ1 in mice.
Salsalate is a prodrug of salicylate that lowers blood glucose in people with type 2 diabetes. AMP-activated protein kinase (AMPK) is an αβγ heterotrimer which inhibits macrophage inflammation and the synthesis of fatty acids and cholesterol in the liver through phosphorylation of acetyl-CoA carboxylase (ACC) and HMG-CoA reductase (HMGCR), respectively. Salicylate binds to and activates AMPKβ1-containing heterotrimers that are highly expressed in both macrophages and liver, but the potential importance of AMPK and ability of salsalate to reduce atherosclerosis have not been evaluated. ApoE-/- and LDLr-/- mice with or without (-/-) germline or bone marrow AMPKβ1, respectively, were treated with salsalate, and atherosclerotic plaque size was evaluated in serial sections of the aortic root. Studies examining the effects of salicylate on markers of inflammation, fatty acid and cholesterol synthesis and proliferation were conducted in bone marrow-derived macrophages (BMDMs) from wild-type mice or mice lacking AMPKβ1 or the key AMPK-inhibitory phosphorylation sites on ACC (ACC knock-in (KI)-ACC KI) or HMGCR (HMGCR-KI). Salsalate reduced atherosclerotic plaques in the aortic roots of ApoE-/- mice, but not ApoE-/- AMPKβ1-/- mice. Similarly, salsalate reduced atherosclerosis in LDLr-/- mice receiving wild-type but not AMPKβ1-/- bone marrow. Reductions in atherosclerosis by salsalate were associated with reduced macrophage proliferation, reduced plaque lipid content and reduced serum cholesterol. In BMDMs, this suppression of proliferation by salicylate required phosphorylation of HMGCR and the suppression of cholesterol synthesis. These data indicate that salsalate suppresses macrophage proliferation and atherosclerosis through an AMPKβ1-dependent pathway, which may involve HMGCR phosphorylation and cholesterol synthesis. Since rapidly-proliferating macrophages are a hallmark of atherosclerosis, these data indicate further evaluation of salsalate as a potential therapeutic agent for treating atherosclerotic cardiovascular disease.


[The Oncologic and Palliative Network Landshut: a problem-solving approach to oncological and palliative care in structurally weak rural areas, with special emphasis on outpatient and inpatient networking].
The Oncologic and Palliative Network Landshut is a problem-solving approach to structurally weak rural areas to improve an a dequate care of critically ill patients, especially by a close involvement of outpatient and inpatient care providers. These networks not only improve the medical and nursing care of patients, but can also be cost-effective.


Remarkable response to neoadjuvant therapy with methotrexate, vinblastine, adriamycin, and Cisplatin for undifferentiated bladder carcinoma: a case report and literature review.
We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.


Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4+ Foxp3+ Regulatory T Cells.
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4+ conventional (CD4+CD25-Foxp3-, Tconv) and regulatory (CD4+CD25+Foxp3+, Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4+ Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4+ Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT.


Diagnosis and management of plantar fasciitis.
Plantar fasciitis, a chronic degenerative process that causes medial plantar heel pain, is responsible for approximately 1 million physician visits each year. Individuals with plantar fasciitis experience pain that is most intense during their first few steps of the day or after prolonged standing. The authors provide an overview of the diagnosis and management of a common problem encountered in the primary care setting. Routine imaging is not initially recommended for the evaluation of plantar fasciitis but may be required to rule out other pathologic conditions. Overall, plantar fasciitis carries a good prognosis when patients use a combination of several conservative treatment modalities. Occasionally, referral to a specialist may be necessary.


Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion.
Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1AJUBA, SNAI3SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified.


Successful in situ treatment of infected aortic arch prosthesis by omental wrapping.
A 67-year-old man who underwent total aortic arch graft replacement with coronary artery bypass grafting developed postoperative Serratia mediastinitis. Re-operative debridement and irrigation were carried out. An infected aortic arch prosthesis was successfully treated by in situ disinfection followed by complete omental wrapping.


Quality of life in people with cognitive impairment: nursing homes versus home care.
The evaluation of quality of life (QoL) among older adults has become increasingly important, and living arrangements play a pivotal role in determining the QoL of people with cognitive impairment (PWCI). Although informal care (home-based) is favored, transition to formal care (residential care) often becomes necessary, especially in the later stages of cognitive impairment. The primary objective was to compare the QoL of PWCI in the community and nursing homes. Additionally, factors differentiate the QoL of PWCI in these two settings were identified. This is a quasi-experimental study design involving 219 older adults with cognitive impairment, aged 60-89 years old from both nursing home and home care. Participants completed the EUROPE Health Interview Survey-QoL (WHO-8), the Short Mini-Mental State Examination (SMMSE), the Barthel Index (BI), the Geriatric Depression Scale (GDS-15), and the Friendship Scale (FS). There were significant differences in QoL, depression, social connectedness (p < 0.01) and cognitive functions (p = 0.01) between home care recipients and nursing home participants. No significant differences were observed with regards to health condition, co morbidities and physical functions between study cohorts. Older adults with cognitive impairment living at home experienced higher QoL, had better cognitive function, were less depressed and reported higher social connectedness compared to those living in institutional care. Therefore, support should be provided in enabling home care and empowering caregivers to provide better care for PWCI.


Collagen fiber alignment does not explain mechanical anisotropy in fibroblast populated collagen gels.
Many load-bearing soft tissues exhibit mechanical anisotropy. In order to understand the behavior of natural tissues and to create tissue engineered replacements, quantitative relationships must be developed between the tissue structures and their mechanical behavior. We used a novel collagen gel system to test the hypothesis that collagen fiber alignment is the primary mechanism for the mechanical anisotropy we have reported in structurally anisotropic gels. Loading constraints applied during culture were used to control the structural organization of the collagen fibers of fibroblast populated collagen gels. Gels constrained uniaxially during culture developed fiber alignment and a high degree of mechanical anisotropy, while gels constrained biaxially remained isotropic with randomly distributed collagen fibers. We hypothesized that the mechanical anisotropy that developed in these gels was due primarily to collagen fiber orientation. We tested this hypothesis using two mathematical models that incorporated measured collagen fiber orientations: a structural continuum model that assumes affine fiber kinematics and a network model that allows for nonaffine fiber kinematics. Collagen fiber mechanical properties were determined by fitting biaxial mechanical test data from isotropic collagen gels. The fiber properties of each isotropic gel were then used to predict the biaxial mechanical behavior of paired anisotropic gels. Both models accurately described the isotropic collagen gel behavior. However, the structural continuum model dramatically underestimated the level of mechanical anisotropy in aligned collagen gels despite incorporation of measured fiber orientations; when estimated remodeling-induced changes in collagen fiber length were included, the continuum model slightly overestimated mechanical anisotropy. The network model provided the closest match to experimental data from aligned collagen gels, but still did not fully explain the observed mechanics. Two different modeling approaches showed that the level of collagen fiber alignment in our uniaxially constrained gels cannot explain the high degree of mechanical anisotropy observed in these gels. Our modeling results suggest that remodeling-induced redistribution of collagen fiber lengths, nonaffine fiber kinematics, or some combination of these effects must also be considered in order to explain the dramatic mechanical anisotropy observed in this collagen gel model system.


Non-invasive risk stratification within 48 h of hospital admission in patients with unstable coronary disease.
In this study we evaluated the prognostic value of three methods of early risk estimation in patients with unstable coronary disease. The methods evaluated were: clinical risk estimation at hospital admission, continuous ST analysis with computerized vectorcardiography for 24 h and serial measurements of creatinine kinase-MB for 48 h. Twenty-seven (14%) of the 195 patients died or had a non-fatal infarction within one year. Clinical risk evaluation correctly identified a subgroup of patients with low risk but did not otherwise predict outcome. Fifty-six (29%) patients had ST vector magnitude episodes on vectorcardiography, 70 (38%) had three or more episodes of ST change vector magnitude and 74 (38%) had a peak creatinine kinase-MB value of 6 microgram.l-1 or more. The even rate for patients with ST vector magnitude episodes (23%) was significantly higher than for those without (10%; P < 0.05). For patients with and without three or more episodes of ST change vector magnitude the event rate was 23% and 9% respectively (P < 0.05) and for patients with and without creatinine kinase-MB > or = 6 microgram.l-1 the event rate was 23% and 8% respectively (P < 0.01). The positive predictive value of having none, either one or both of the ST or creatinine kinase-MB markers positive was incremental. Continuous vectorcardiographic monitoring of ischaemia in combination with serial creatinine kinase-MB measurement considerably improves risk stratification in unstable coronary disease.


Clinical outcomes of implants placed in ridge-preserved versus nonpreserved sites: A 4-year randomized clinical trial.
Consistent bone changes occur after tooth removal, often compromising the success of implants placed within the socket left to natural healing The long-term effect of ridge preservation on implant outcomes is still unclear. The aim of the study was to assess success and survival rates of implants placed in extraction sockets, with spontaneous healing, or grafted with cortical porcine bone, or collagenated corticocancellous porcine bone. Ninety patients in need for a single premolar/molar tooth extraction and an implant treatment were selected for the present study. Patients were randomly distributed among 3 groups: sites that healed naturally (ctrl), or sites that received ridge preservation with either cortical (cort) or collagenated corticocancellous porcine bone (coll). Three months after, all the experimental sites were reentered to insert implants. Marginal bone levels were recorded; soft tissues were analyzed and summarized with the Pink Esthetic Score (PES). Forty-two patients out of 90 (initial cohort study) completed the entire follow-up of 4 years. Cumulative survival and success rates for all implants were 100% at a 4-year evaluation. Mean marginal bone loss (MBL) was 1.14 ± 0.23 mm in the cort group, 1.13 ± 0.29 mm in the coll group, and 1.92 ± 0.07 mm in the ctrl group. There were no significant differences between the 2 grafting materials but MBL was significantly greater in the nongrafted sites (P value < .001). The PES resulted significantly better (9.42 ± 0.75) for the cort group than for the coll group (8.53 ± 1.18) and ctrl group (6.07 ± 1.89) at 4-year evaluation. Ridge preservation was more effective than natural healing in preserving marginal bone and in achieving better esthetic outcomes around implants 4 years after placement. The cortical porcine bone showed better clinical outcomes than collagenated corticocancellous porcine bone.


Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease.
GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease etiologies and compared with the levels in normal donor livers. GP73-expressing cells were identified immunohistochemically. GP73 expression in vitro was studied by Western blotting and immunofluorescence microscopy in HepG2 and SK-Hep-1 cells and in the HepG2-derived, hepatitis B virus (HBV)-transfected HepG2215 and HepG2T14.1 cell lines. Whole organ levels of GP73 were low in normal livers. Significant increases were found in liver disease due to viral causes (HBV, HCV) or nonviral causes (alcohol-induced liver disease, autoimmune hepatitis). In normal livers, GP73 was constitutively expressed by biliary epithelial cells but not by hepatocytes. Hepatocyte expression of GP73 was dramatically up-regulated in diseased livers, regardless of the etiology, whereas biliary epithelial cell expression did not change appreciably. GP73 was present at high levels in HepG2215 cells (a cell line that supports active HBV replication), but was absent in HepG2T14.1 cells (an HBV-transfected cell line that does not support HBV replication) and in HBV-free HepG2 cells. In SK-Hep-1 cells, GP73 expression was increased in response to interferon gamma (IFN-gamma), and inhibited by tumor necrosis factor alpha (TNF-alpha). In conclusion, increased expression of GP73 in hepatocytes appears to be a general feature of advanced liver disease, and may be regulated via distinct pathways that involve hepatotropic viruses or cytokines.


Small molecule inhibition of human cGAS reduces total cGAMP output and cytokine expression in cells.
The cGAS-STING pathway is a major mechanism that mammalian cells utilize to detect cytoplasmic dsDNA from incoming viruses, bacteria, or self. CYCLIC GMP-AMP SYNTHASE (cGAS) is the sensor protein that directly binds dsDNAs. cGAS synthesizes cyclic GMP-AMP (cGAMP), which binds to the adaptor STIMULATOR OF INTERFERON GENES (STING), activating an INTERFERON REGULATORY FACTOR 3 (IRF3)-mediated immune response. Constitutive activation can result in interferonopathies such as Aicardi-Goutieres Syndrome (AGS) or other lupus-like autoimmune disorders. While inhibitors targeting mouse or human cGAS have been reported, the identification of a small molecule that targets both homologs of cGAS has been challenging. Here, we show that RU.521 is capable of potently and selectively inhibiting mouse and human cGAS in cell lines and human primary cells. This inhibitory activity requires the presence of cGAS, but it cannot suppress an immune response in cells activated by RNA, Toll-like receptor ligands, cGAMP, or recombinant interferon. Importantly, when RU.521 is applied to cells, the production of dsDNA-induced intracellular cGAMP is suppressed in a dose-dependent manner. Our work validates the use of RU.521 for probing DNA-induced innate immune responses and underscores its potential as an ideal scaffold towards pre-clinical development, given its potency against human and mouse cGAS.


Early experience with an implantable cardioverter.
We tested the efficacy and safety of a fully programmable cardioverter weighing 95 g, in terminating sustained ventricular tachycardia. The device was implanted tranvenously under local anesthesia in seven patients. On command from a programmer or automatically, the cardioverter delivered shocks through a lead inserted to the apex of the right ventricle. It also served as a demand ventricular pacemaker and could perform programmed ventricular stimulation or overdrive pacing. Cardioversion of ventricular tachycardia required less than 0.5 J (mean) and was well tolerated by the patients, who were awake and not sedated. In one patient, a shock terminated ventricular tachycardia with the device in the automatic mode but produced atrial fibrillation with a rapid ventricular response that was intermittently recognized as ventricular tachycardia, triggering additional shocks. One such shock in the ST segment produced ventricular fibrillation that was terminated transthoracically in the emergency room, without residual impairment. We conclude from these preliminary observations that cardioversion of sustained ventricular tachycardia by means of an implantable catheter device is feasible, but for the present its use in the automatic mode must be cautious and selective. The unit's small size, ease of implantation, usefulness for noninvasive electrophysiologic studies, programmability, and bradycardia pacing functions are advantages. The next-generation device must be able to defibrillate and provide better differentiation of arrhythmias.


Lack of association between helicobacter pylori and gastric atrophy or intestinal metaplasia in elderly patients.
Helicobacter pylori (Hp) is associated with gastritis and peptic ulcers. It may also induce gastric atrophy (GA) and intestinal metaplasia (IM), and these changes may be the precursors of gastric carcinoma. The aim of this study was to determine if GA or IM is associated with Hp infection in elderly patients. Consecutive patients admitted for gastroscopy were recruited. Multiple biopsies were taken for histology and rapid urease (CLO) tests along with IgG enzyme-linked immunosorbent assay antibodies and (13)C-urea breath tests. Statistical analysis was by chi(2) tests. 114 patients were recruited, the average age was 78.9 + or - 5.4 years. Histology was available on 105 patients, 80 (76.2%) had gastritis, and 61/80 (76.25%) had evidence of definite current Hp infection. Seven patients had reflux gastritis, and these were excluded from the analysis described below. 20 patients had GA and 24 IM. The relationship between Hp and GA or IM was investigated by dividing patients into four groups: Group 1 patients (n = 57) were taken to be definitely currently infected (GA 7 patients, IM 11, both 1). Group 2 patients (n = 18) had old infection (GA 2, IM 4, both 3). Group 3 patients (n = 16) have never been infected previously (GA 1, IM 1, both 3). Group 4 patients (n = 4) had a poor immunological response to Hp (GA 1, IM 1, both 0). There were no significant differences in the numbers of patients with GA or IM in any group as compared with any other, with the exception of less patients with histological evidence of combined GA and IM among patients with definite current infection as compared with those with either previous infection (p = 0.04) or 'never' infection (p = 0.03). We conclude that the mucosal changes of GA or IM are not consistently associated with Hp infection in the elderly.


Moving an Evidence-Based Parenting Program Into the Community.
Attachment and Biobehavioral Catch-up (ABC) is a parenting program developed to enhance sensitivity among parents of infants who experience early adversity. In several randomized clinical trials, the intervention's efficacy has been demonstrated. Moving interventions into the community with adequate fidelity is challenging, though, and intervention effects are often much smaller than when tested in randomized clinical trials. To enhance the likelihood that ABC is delivered with high fidelity, a microanalytic fidelity assessment was developed. Using this fidelity tool as a central component of training, supervision, and certification, changes in parent sensitivity for 108 families with children ages 6 months to 2 years were as large as those seen in laboratory settings. These findings are discussed with regard to implications for moving other evidence-based interventions into the community.


Donor-site Chyle Leakage after Breast Reconstruction Using a Deep Inferior Epigastric Artery Perforator Flap.
Postoperative chyle leakage is an uncommon type of lymphorrhea characterized by a milky white lymphatic fluid. Here, we report a case of postoperative donor-site chyle leakage after breast reconstruction using a deep inferior epigastric artery perforator (DIEP) flap. A 50-year-old woman underwent unilateral secondary breast reconstruction using a DIEP flap. On postoperative day (POD) 3, 50 mL of clear white liquid was observed in the abdominal suction drain over 12 hours. On POD 6, the amount of white-colored fluid in the left side suction drain increased to 190 mL/d with high triglyceride 674 mg/dL. The computed tomography scan showed no fluid collections intraabdominally, within the rectus abdominis muscle, or in the subcutaneous area. Based on the diagnosis of donor-site subcutaneous chyle leakage, the patient was treated with a low-fat diet, a medium-chain triglyceride diet, and compression of the contralateral groin area. The fluid became clear and decreased in quantity, and we removed the drain on POD 9. No abdominal fluid was observed after the discharge. Combined treatment with a low-fat diet and compression of the groin area may be effective for donor-site chyle leakage after breast reconstruction using the DIEP flap.


Time/dose relationships in experimental radiation cataractogenesis.
The response of the mammalian lens to fractionated radiation exposures was evaluated as a model system for predicting delayed radiation effects on normal tissue. Only the heads of male Ha/ICR mice were irradiated with 14 different time-dose schedules and followed for cataractous changes. A log-log plot of dose vs time yielded a line with a slope of 0.303 and ordinate intercept of 1050 R; a similar plot for dose vs fraction number yielded a slope of 0.382 and ordinate intercept of 835 R. Results suggest that the lenticular response to radiation may be a useful model for studying late effects.


Failing kidneys: Hotspots, blind spots and biopolitics of indifference.
Chronic kidney disease of non-traditional cause (CKDnt) is commonly associated with monocropping agriculture, heat stress and impoverished working conditions, referred to as CKDnt "hotspots." The condition is also emerging in various sites of environmental contamination, raising questions as to whether multiple variants of the condition exist as a result of different ecologies and different human-environment interactions. This paper examines the emergence of CKDnt around Lake Chapala in Mexico, where we document local efforts to gain recognition and reparation for CKDnt. We follow the ways patients, families and activists have mobilized specific and interlocking infrastructural failures to enact complaint and confront state inaction and neglect of their bodies, communities, and environments. Though their labors have formally achieved little, we discuss how they make visible a biopolitics of indifference, one bound to the production of structural "blindspots."


Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves the survival of clinical stage II/III esophageal squamous cell carcinoma patients.
The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed to improve survival through locoregional control, leading to prevention of micrometastasis. We investigated whether or not neoadjuvant CRT led to survival benefits in TNM stage II/III esophageal cancer patients. We retrospectively reviewed 62 patients with stage II or III esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant CRT. All patients received esophagectomy 4-7 weeks after CRT consisting of 40 Gy irradiation and chemotherapy (5-FU, 500 mg/m2/day, days 1-5 and cisplatin, 10-20 mg/body, days 1-5). Clinical response and survival rates were analyzed using Kaplan-Meier methods, with p<0.05 considered as significant. The clinical effect rate of CRT for both primary tumors and metastatic nodes was 82.3%. Operative and hospital mortality rates were 1.65 and 6.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.6 and 49.2%, respectively. A significant difference was noted between stages II and III for both OS and DFS. The 5-year OS rates were 64.2% for stage II, 33.1% for stage III (T4 and non-T4) and 46.9% for stage III (non-T4 only) patients. The depth of tumor invasion (T3 vs. T4), resectability (R0 vs. R1, R2), lymph node metastasis (positive vs. negative), and the effect of CRT were proven to be independent prognostic factors for univariate analysis, with resectability and the effect of CRT for multivariate analysis. These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant CRT appears to be a promising option for these patients.


Cherenkoscopy based patient positioning validation and movement tracking during post-lumpectomy whole breast radiation therapy.
To investigate Cherenkov imaging (Cherenkoscopy) based patient positioning and movement tracking during external beam radiation therapy (EBRT). In a phase 1 clinical trial, including 12 patients undergoing post-lumpectomy whole breast irradiation, Cherenkov emission was imaged with a time-gated ICCD camera synchronized to the LINAC pulse output, during different fractions of the treatment. Patients were positioned with the aid of the AlignRT system in the beginning of each treatment session. Inter-fraction setup variation was studied by rigid image registrations between images acquired at individual treatments to the average image from all imaged treatment fractions. The amplitude of respiratory motion was calculated from the registration of each frame of Cherenkov images to the reference. A Canny edge detection algorithm was utilized to highlight the beam field edges and biological features provided by major blood vessels apparent in the images. Real-time Cherenkoscopy can monitor the treatment delivery, patient motion and alignment of the beam edge to the treatment region simultaneously. For all the imaged fractions, the patient positioning discrepancies were within our clinical tolerances (3 mm in shifts and 3 degree in pitch angle rotation), with 4.6% exceeding 3 mm but still within 4 mm in shifts. The average discrepancy of repetitive patient positioning was 1.22 mm in linear shift and 0.34 degrees in rotational pitch, consistent with the accuracy reported by the AlignRT system. The edge detection algorithm enhanced features such as field edges and blood vessels. Patient positioning discrepancies and respiratory motion retrieved from rigid image registration were consistent with the edge enhanced images. Besides positioning discrepancies caused by globally inaccurate setups, edge enhanced blood vessels indicate the existence of deformations within the treatment region, especially for large patients. Real-time Cherenkoscopy imaging during EBRT is a novel imaging tool that can be used for treatment monitoring, patient positioning and motion tracking.


Policing Farm Animal Welfare in Federated Nations: The Problem of Dual Federalism in Canada and the USA.
In recent European animal welfare statutes, human actions injurious to animals are new "offences" articulated as an injury to societal norms in addition to property damage. A crime is foremost a violation of a community moral standard. Violating a societal norm puts society out of balance and justice is served when that balance is returned. Criminal law normally requires the presence of mens rea, or evil intent, a particular state of mind; however, dereliction of duties towards animals (or children) is usually described as being of varying levels of negligence but, rarely can be so egregious that it constitutes criminal societal injury. In instrumental justice, the "public goods" delivered by criminal law are commonly classified as retribution, incapacitation and general deterrence. Prevention is a small, if present, outcome of criminal justice. Quazi-criminal law intends to establish certain expected (moral) standards of human behavior where by statute, the obligations of one party to another are clearly articulated as strict liability. Although largely moral in nature, this class of laws focuses on achieving compliance, thereby resulting in prevention. For example, protecting the environment from degradation is a benefit to society; punishing non-compliance, as is the application of criminal law, will not prevent the injury. This paper will provide evidence that the integrated meat complex of Canada and the USA is not in a good position to make changes to implement a credible farm animal protection system.


Closing the detection loophole in Bell experiments using qudits.
We show that the detection efficiencies required for closing the detection loophole in Bell tests can be significantly lowered using quantum systems of dimension larger than two. We introduce a series of asymmetric Bell tests for which an efficiency arbitrarily close to 1/N can be tolerated using N-dimensional systems, and a symmetric Bell test for which the efficiency can be lowered down to 61.8% using four-dimensional systems. Experimental perspectives for our schemes look promising considering recent progress in atom-photon entanglement and in photon hyperentanglement.


A note on the early history of electrical stimulation of the human brain.
We address inconsistencies in two areas concerning who was first to electrically stimulate a human's brain. First, Boring (1950) and others attributed priority to Eduard Hitzig based on information mentioned somewhat incidentally in Fritsch and Hitzig's (1870) classic work using dogs. Others cited Fritsch and Hitzig but attributed priority to Roberts Bartholow (1874). Second, our examination of translations of Fritsch and Hitzig, especially of footnote 16 in Hitzig's report (1870) of a human case, revealed errors, omissions, and inconsistencies. To aid our inquiry, we requested and received new translations of footnote 16 and of Hitzig's report.


Research and practice opportunities at the intersection of health education, health behavior, and genomics.
Researchers and practitioners in health behavior and health education (HBHE) can play a pivotal leadership role in the integration of genomic advances to improve the public's health. The purpose of this article is to outline research and practice opportunities at the intersection of genomics and HBHE. We begin this article by briefly summarizing the existing evidence in the literature pertaining to the public's use of genetic services, the effectiveness of genetic counseling, and the impact of genetic testing. Following this, we outline and expand on several areas that we believe are ripe for further exploration, understanding, and public health application:(a) public understanding of genetic information, (b) interventions for health behavior change, and (c) public health assurance and advocacy. This analysis has identified the need to consider potential application efforts in genomics and HBHE from an ecological perspective, with an emphasis on multiple levels of intervention and analysis.


Crop failure in Dalocha, Ethiopia: a participatory emergency response.
This case study of an NGO's response to a food crisis due to crop failure focuses on the extent of active community participation at each stage of the project. With the current debate on the relationship between relief and development, and in particular the focus on encouraging more active community participation in relief responses, this study has relevance both in the Ethiopian context and beyond. In this example the participation process was greatly facilitated by the prior relationship between the international NGO and the communities, and also by the high level of staff input into the project. Where resources or conditions are less favourable, as might be the case in similar responses by local NGOs or government agencies, the paper suggests that the participatory approach can be adapted or partially implemented and still result in a more effective and locally relevant operation.


Public health professionals' perceptions of mental health services in Equatorial Guinea, Central-West Africa.
Mental health disorders constitute 13% of global disease burden, the impacts of which are disproportionality felt in sub-Saharan Africa. Equatorial Guinea, located in Central-West Africa, has the highest per-capita investment in healthcare on the African continent, but only two studies have discussed mental health issues in the country and none of have examined the perspective of professionals working in the field. The purpose of this study was to gain a preliminary understanding of Equatoguinean health care professionals' perspectives on the mental health care system. Nine adult participants (directors or program managers) were interviewed in July 2013 in Malabo, Equatorial Guinea from government agencies, aid organizations, hospitals, and pharmacies. Interviews were designed to collect broad information about the mental healthcare system in Equatorial Guinea including the professionals' perspectives and access to resources. This research was reviewed and approved by an ethical oversight committee. All individuals interviewed indicated that the mental health system does not currently meet the needs of the community. Professionals cited infrastructural capacity, stigmatization, and a lack of other resources (training programs, knowledgeable staff, medications, data) as key factors that limit the effectiveness of mental healthcare. This study provides a preliminary understanding of the existing mental health care needs in the country, highlighting opportunities for enhanced healthcare services.


Polyomavirus nephropathy in native kidneys of a solitary pancreas transplant recipient.
Latent polyomavirus (PV) infection of the urinary tract can be reactivated by immunosuppression. When this occurs in the renal allograft, permanent loss of allograft function can occur. Polyomavirus reactivation could potentially affect the native kidneys of nonrenal transplant recipients and cause renal dysfunction. This article describes a case of PV nephropathy in the native kidneys of a solitary-pancreas transplant recipient. This patient had a progressive increase in serum creatinine. Screening urine cytology showed numerous cells with cytopathic changes suggestive of polyomavirus infection. Biopsy of the native kidneys of this patient showed renal tubular cells with intranuclear inclusions characteristic of PV infection, which was confirmed by immunohistochemistry. Electron microscopy showed intranuclear viral particles. Patchy inflammation and fibrosis also were noted. Polyomavirus reactivation can occur in the native kidneys of nonrenal solid organ transplant recipients. This should be considered in the differential diagnosis of renal impairment in these patients. The effects of PV reactivation on long-term native kidney function are not known.


Spatial extent of an outbreak in animal epidemics.
Characterizing the spatial extent of epidemics at the outbreak stage is key to controlling the evolution of the disease. At the outbreak, the number of infected individuals is typically small, and therefore, fluctuations around their average are important: then, it is commonly assumed that the susceptible-infected-recovered mechanism can be described by a stochastic birth-death process of Galton-Watson type. The displacements of the infected individuals can be modeled by resorting to brownian motion, which is applicable when long-range movements and complex network interactions can be safely neglected, like in the case of animal epidemics. In this context, the spatial extent of an epidemic can be assessed by computing the convex hull enclosing the infected individuals at a given time. We derive the exact evolution equations for the mean perimeter and the mean area of the convex hull, and we compare them with Monte Carlo simulations.


Rationalisation and racialisation in the Rainbow Nation: inequalities and identity in the South African bone marrow transplant network.
This article examines discourses and practises in the professional network of people and organisations in South Africa that comprise the bone marrow/haematopoietic stem cell transplantation (BMT) network. A prominent discursive inter-relationship asserts that some genetically inherited Human Leukocyte Antigen (HLA) types appear in certain ethnic populations more commonly than others, meaning that patients are most likely to find a transplant match with someone in the same ethnic group. The South African BMT network efforts to increase the number of donors from ethnic groups not well represented on the registry are crucial given South Africa's unique and diverse gene pool. This inter-relationship is at the heart of a complex interweaving of genomics, ethnicity, culture, South African nationhood, and the limits of bodily integrity. It necessitates serious engagement in health resource inequalities and burgeoning biosocial identities in a diverse South Africa, especially given its history and its contemporary political agenda of transformation. The analysis of fieldwork is particularly informed by Troy Duster's concept of feedback loops and Paul Rabinow's work on biosociality. Drawing from this analysis, the article also suggests possibilities for policy and practical application.


Supplementary immunization activities (SIAs) in South Africa: comprehensive economic evaluation of an integrated child health delivery platform.
Supplementary immunization activity (SIA) campaigns provide children with an additional dose of measles vaccine and deliver other interventions, including vitamin A supplements, deworming medications, and oral polio vaccines. To assess the cost-effectiveness of the full SIA delivery platform in South Africa (SA). We used an epidemiologic cost model to estimate the cost-effectiveness of the 2010 SIA campaign. We used province-level campaign data sourced from the District Health Information System, SA, and from planning records of provincial coordinators of the Expanded Programme on Immunization. The data included the number of children immunized with measles and polio vaccines, the number of children given vitamin A supplements and Albendazole tablets, and costs. The campaign cost $37 million and averted a total of 1,150 deaths (95% uncertainty range: 990-1,360). This ranged from 380 deaths averted in KwaZulu-Natal to 20 deaths averted in the Northern Cape. Vitamin A supplementation alone averted 820 deaths (95% UR: 670-1,040); measles vaccination alone averted 330 deaths (95% UR: 280-370). Incremental cost-effectiveness was $27,100 (95% UR: $18,500-34,400) per death averted nationally, ranging from $11,300 per death averted in the Free State to $91,300 per death averted in the Eastern Cape. Cost-effectiveness of the SIA child health delivery platform varies substantially across SA provinces, and it is substantially more cost-effective when vitamin A supplementation is included in the interventions administered. Cost-effectiveness assessments should consider health system delivery platforms that integrate multiple interventions, and they should be conducted at the sub-national level.


Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons.
Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index (r = -.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function (r = -.205 and r = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.


Usefulness of bipolar scissors for rectal cancer surgery with autonomic nerve preservation.
Pelvic autonomic nerve preservation for rectal cancer has become more common in recent years. Therefore, we evaluated the usefulness of bipolar scissors for this procedure. This study included 30 consecutive patients with lower rectal cancer who underwent pelvic autonomic nerve preservation at our hospital between April 1998 and August 2001. The bipolar scissors group comprised 10 patients who received the procedure using bipolar scissors, while the conventional group included 20 patients who received the procedure without the use of bipolar scissors. The two groups were compared in terms of operating time, blood loss, postoperative urinary and sexual function. Blood loss in the bipolar scissors group was 394.4 +/- 201.8mL, which was a significantly lower volume than that in the conventional group (881.8 +/- 582.9ml) (p=0.0049). All the patients in the bipolar scissors group (10/10=100%) and 19 cases in the conventional group (19/20=95.0%) answered that they were satisfied with the results of their voiding function. In the bipolar scissors group, 100% were capable of erection (5/5) and 80.0% preserved ejaculation (4/5). In the conventional group, 100.0% (10/10) and 77.8% (7/9) preserved erection and ejaculation, respectively. The use of bipolar scissors is quite beneficial when patients with rectal cancer receive pelvic autonomic nerve preservation.


Potential energy surface and second virial coefficient of methane-water from ab initio calculations.
Six-dimensional intermolecular potential energy surfaces (PESs) for the interaction of CH4 with H2O are presented, obtained from ab initio calculations using symmetry-adapted perturbation theory (SAPT) at two different levels of intramonomer correlation and the supermolecular approach at three different levels of electron correlation. Both CH4 and H2O are assumed to be rigid molecules with interatomic distances and angles fixed at the average values in the ground-state vibration. A physically motivated analytical expression for each PES has been developed as a sum of site-site functions. The PES of the CH4-H2O dimer has only two symmetry-distinct minima. From the SAPT calculations, the global minimum has an energy of -1.03 kcal/mol at a geometry where H2O is the proton donor, HO-H...CH4, with the O-H-C angle of 165 degrees, while the secondary minimum, with an energy of -0.72 kcal/mol, has CH4 in the role of the proton donor (H3C-H...OH2). We estimated the complete basis set limit of the SAPT interaction energy at the global minimum to be -1.06 kcal/mol. The classical cross second virial coefficient B12(T) has been calculated for the temperature range 298-653 K. Our best results agree well with some experiments, allowing an evaluation of the quality of experimental results.


Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats.
Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.


Na+/K+/Cl- cotransporter activates MAP-kinase cascade downstream to protein kinase C, and upstream to MEK.
In this study, we demonstrated that the specific inhibitors of the Na+/K+/Cl- cotransporter (NKCC1), bumetanide and furosemide, inhibited extracellular regulated kinase (ERK) phosphorylation in Balb/c 3T3 fibroblasts, stimulated with a variety of mitogens. In addition to fibroblast growth factor (FGF) shown before, the various mitogens tested in the present study (endothelial growth factor (EGF), platelet-derived growth factor (PDGF), insulin, thrombin, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA)). Enter, the Ras/Raf/MEK/ERK cascade via different growth factors receptors and through one of the two main routes. The results of the present study provide evidence that have led us to conclude that the target protein which is controlled by the Na+/K+/Cl- cotransporter, is downstream of tyrosine kinase receptors, as well as of the G-protein-coupled receptor (GPCR). Several additional lines of evidence supported the above conclusion: (i) furosemide inhibits phosphorylation of MAPK kinase (MEK) induced by receptor tyrosine kinase (RTK) ligands, such as PDGF, FGF, and EGF. (ii) Furosemide also inhibited ERK phosphorylation, induced by thrombin, a GPCR. (iii) Furosemide inhibited MEK and ERK phosphorylation even when ERK phosphorylation was induced by direct activation of protein kinase C (PKC) by TPA, which bypasses early steps of the mitogenic cascade. In addition, we found that furosemide did not affect PKC phosphorylation induced directly by TPA. Taken together, the results of the present study indicate that the signal transduction protein, controlled by the Na+/K+/Cl- cotransporter, must be downstream of the PKC, and at/or upstream to MEK in the Ras/Raf/MEK/ERK cascade.


Citizen engagement initiatives in precision health in the European Union member states: a scoping review.
Precision health requires citizens that are empowered to orient health decisions towards their personal values, aware of the benefits and risks, and committed to sharing their personal data to trustful institutions. Effective citizen engagement initiatives are fundamental for the success of a precision health approach. To provide an overview of citizen engagement initiatives in precision health in European Union (EU) member states. Scoping review. The electronic databases PubMed, Web of Science, CINAHL and Embase were searched to include articles published in English. Furthermore, desk research was conducted in English, Dutch, French, Italian and Spanish. Articles or reports regarding ongoing initiatives of citizen engagement in precision health conducted in EU member states and published from January 2015 to July 2020 were considered eligible. A quality assessment of the retrieved entries using Critical Appraisal Skills Programme tool was conducted. We identified nine documents, which reported eight ongoing citizen engagement initiatives, with substantial variability. Government agencies, non-governmental organisations and scientific societies were the main organisers and funders. Most of the initiatives were conducted in the UK. Genomics was the most emphasised aspect of precision health in these initiatives. Among the identified initiatives, both in-person and digital means were reported. Our work provides an overview of current citizen engagement initiatives in the EU that can be useful for stakeholders interested in designing and developing precision health projects enriched by meaningful citizen participation. CRD42020193866.


Colorectal cancer detection by gold nanoparticle based surface-enhanced Raman spectroscopy of blood serum and statistical analysis.
The capabilities of using gold nanoparticle based surface-enhanced Raman spectroscopy (SERS) to obtain blood serum biochemical information for non-invasive colorectal cancer detection were presented in this paper. SERS measurements were performed on two groups of blood serum samples: one group from patients (n = 38) with pathologically confirmed colorectal cancer and the other group from healthy volunteers (control subjects, n = 45). Tentative assignments of the Raman bands in the measured SERS spectra suggested interesting cancer specific biomolecular changes, including an increase in the relative amounts of nucleic acid, a decrease in the percentage of saccharide and proteins contents in the blood serum of colorectal cancer patients as compared to that of healthy subjects. Both empirical approach and multivariate statistical techniques, including principal components analysis (PCA) and linear discriminant analysis (LDA) were employed to develop effective diagnostic algorithms for classification of SERS spectra between normal and colorectal cancer serum. The empirical diagnostic algorithm based on the ratio of the SERS peak intensity at 725 cm(-1) for adenine to the peak intensity at 638 cm(-1) for tyrosine achieved a diagnostic sensitivity of 68.4% and specificity of 95.6%, whereas the diagnostic algorithms based on PCA-LDA yielded a diagnostic sensitivity of 97.4% and specificity of 100% for separating cancerous samples from normal samples. Receiver operating characteristic (ROC) curves further confirmed the effectiveness of the diagnostic algorithm based on PCA-LDA technique. The results from this exploratory study demonstrated that gold nanoparticle based SERS serum analysis combined with PCA-LDA has tremendous potential for the non-invasive detection of colorectal cancers.


Application of UV-derivative spectra for determination of four antihyperlipidaemic drugs in pharmaceutical formulations.
A method for the determination of bezafibrate, ciprofibrate, fenofibrate and gemfibrozil in pharmaceutical formulations by first-, second- and third- derivative spectrophotometry is described, using "peak-peak" and "peak-zero" measurements. The calibration graphs were linear in the range 2-20 microg x mL(-1) for all the compounds investigated. No interference was found from tablet excipients at the selected wavelengths and assay conditions. The developed methods were found to be validated and showed good precision and reproducibility (RSD = 1.57%, 0.78%, 1.45%, and 1.36%, respectively).


Blunt thoracic aortic injury resulting in free rupture into the pleural space and cardiac arrest, managed successfully with endovascular stenting.
Blunt thoracic aortic injury (BTAI) is an uncommon yet serious diagnosis in trauma patients, with high on-scene mortality. BTAI typically occurs from rapid deceleration such as in motor vehicle collisions or high-altitude falls shearing the aorta just proximal to the ligamentum arteriosum. We report a case of a man in his 50s falling from a height of 15 m who presented hypotensive with retrosternal chest pain. Mobile chest X-ray showed a widened mediastinum with left-sided haemothorax. CT revealed a contained free aortic rupture just inferior to the origin of the left subclavian artery with bleeding into the mediastinum and left pleural space. The patient underwent urgent thoracic endovascular aortic repair (TEVAR) but arrested on-table due to a left-sided tension haemothorax requiring chest-drain decompression and haemostatic resuscitation. After return of spontaneous circulation, TEVAR was successfully performed. BTAI is a dynamic process; hence, timely imaging and minimally invasive surgical treatment are key to patients surviving grade III and IV aortic injuries.


Nutritional status and hyperglycemia in the peritransplant period: a review of associations with parenteral nutrition and clinical outcomes.
Hematopoietic stem cell transplantation is an established treatment option for various hematological diseases. This therapy involves complex procedures and is associated with several systemic complications. Due to the toxic effects of the conditioning regimen used in allogeneic transplantations, patients frequently suffer from severe gastrointestinal complications and are unable to feed themselves properly. This complex clinical scenario often requires specialized nutritional support, and despite the increasing number of studies available, many questions remain regarding the best way to feed these patients. Parenteral nutrition has been traditionally indicated when the effects on gastrointestinal mucosa are significant; however, the true benefits of this type of nutrition in reducing clinical complications have been questioned. Hyperglycemia is a common consequence of parenteral nutrition that seems to be correlated to poor transplantation outcomes and a higher risk of infections. Additionally, nutrition-related pre-transplantation risk factors are being studied, such as impaired nutritional status, poorly controlled diabetes mellitus and obesity. This review aims to discuss some of these recent issues. A real case of allogeneic transplant was used to illustrate the scenario and to highlight the most important topics that motivated this literature review.


The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.
Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by fine-structure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning.


Seagrass soil archives reveal centennial-scale metal smelter contamination while acting as natural filters.
The upper Spencer Gulf in South Australia hosts the world's largest single stream Pb-Zn smelter, which has caused environmental and health issues related to elevated metal concentrations in the surrounding environment. The area also has extensive seagrass meadows, occupying >4000 km2. We reconstructed the fluxes of heavy metals over the last ~3000 years through a multi-parameter study of the soil archives formed by the seagrass Posidonia australis. Pb, Zn and Cd concentrations increased up to 9-fold following the onset of smelter operations in the 1880s, and the stable Pb isotopic signatures confirmed the smelter has been the main source of lead pollution in the seagrass soils until present. Preliminary estimates suggest that over the past 15 years seagrass meadows within 70 km2 of the smelter accumulated ~7-15% of the smelter emissions in their soils. Here we demonstrate that seagrass meadows act as pollution filters and sinks while their soils provide a record of environmental conditions, allowing baseline conditions to be identified and revealing the time-course of environmental change.


Feline leukemia - unique and cross-relating antigens on individual virus-producing tumors identified by complement-dependent antibody.
Following exposure to feline leukemia virus (FeLV), cats that resist leukemia produce complement dependent antibodies (CDA) which lyse leukemia cells in the presence of cat complement. The CDA activity has been shown to be directed to feline oncornavirus-associated cell membrane antigen (FOCMA) found on the surface of most feline leukemias. Despite the retrovirus etiology of feline leukemia, and the ubiquity of FOCMA expression by individual tumors, we found that CDA activity did not cross-react when five feline leukemia lines were compared (FL74, F422, 3272, 3281, and 79-14940). Profiles for CDA mediated lysis of the leukemia target lines were determined for sera from 149 FeLV exposed cats, and animals were identified whose sera would selectively lyse almost any possible combination of tumors from one to five lines tested. Cross absorption and cold target inhibition studies were performed on selected sera, and a spectrum of different antigens was identified which included both individual determinants and antigens shared by some of the tumor lines. Leukemias FL74 and F422 carried a cross-reactive determinant which was distinct from a second antigen shared by 3272 and 3281; lines F422, 3272 and 3281 each also carried a unique antigen. Leukemia 79-14940 did not cross-react with other target tumor lines. Targets of CDA mediated lysis on leukemia cells maybe associated with normal feline cell surface antigens, because CDA titers were sometimes reduced after serum absorption with normal cat spleen cells. The relevance of multiple FOCMA determinants is discussed in terms of tumor escape from immunity.


Effects of normal aging on event-related desynchronization/synchronization during a memory task in humans.
Event-related desynchronization (ERD) and event-related synchronization (ERS) of the 1-20Hz EEG frequencies were studied using wavelet transforms in young (n = 10, mean age 22) and elderly subjects (n = 10, mean age 65) performing an auditory Sternberg memory task with words as stimuli. In both age groups, encoding of the four-word memory set elicited ERS in the theta and alpha frequency range. Theta ERS, and ERD in the alpha and beta bands were observed during retrieval. During encoding, the elderly showed greater alpha ERS and smaller theta ERS. During retrieval, smaller alpha ERD and theta ERS was found in the elderly subjects. Also, in the elderly, beta ERD was elicited in the late time window during retrieval. The statistically significant differences between the age groups were more marked during retrieval than during encoding. The results indicate that although the two groups performed equally well behaviorally in the task and the elderly subjects were cognitively intact, normal aging affects oscillatory theta, alpha and beta responses particularly during retrieval from working memory. The ERD/ERS patterns of the elderly resemble those of children found in a recent study, which might suggest that those memory-related brain processes that evolve later in childhood are the first to be affected in older age.


[First experiences with detection of the tcdB gene of Clostridioides difficile using Simplexa C. difficile Direct Kit].
Clostridioides difficile (formerly Clostridium difficile) is one of the main pathogens causing nosocomial infections today. It colonizes the intestines of patients receiving antibiotic therapy, causing unpleasant or even life-threatening conditions (diarrhea, toxic megacolon). Rapid and correct detection of strain toxigenicity is essential for treatment and isolation of patients. Simplexa C. difficile Direct Kit is a real-time PCR kit detecting the tcdB gene of C. difficile. The kit does not require DNA isolation; stool eluates are directly used for the reaction. The study aimed to verify the analytical properties of the kit by its comparison with culture and in-house multiplex PCR methods. A total of 164 stool samples were prospectively tested using two immunoenzymatic kits (C. diff Quik Chek Complete and LIAISON C. difficile GDH, Toxins AandB). In 39 samples, the results were discrepant or unclear (GDH+TOX-). These samples were tested using in-house multiplex PCR and the Simplexa kit. The Simplexa kit had 94.7% sensitivity, 100% specificity, 100% positive predictive value and 95.2% negative predictive value. These parameters were calculated from the numbers of true-/false-positive and true-/false-negative results. True results were determined based on the consensus of culture and in-house multiplex PCR results. Another outcome of the study was comparison of the Quik Chek and LIAISON kits. The analytical properties of the Simplexa kit were tested on 39 samples. These samples were selected for their unclear (GDH+TOX-) or discrepant results yielded by immunoenzymatic methods. Compared with culture and subsequent in-house PCR detection of the tcdB gene, the Simplexa kit showed properties declared by the manufacturer. An important advantage of the kit was the absence inhibitions when stool eluates were directly used for PCR reactions.


C3G localizes to the mother centriole in a cenexin-dependent manner and regulates centrosome duplication and primary cilium length.
C3G (also known as RAPGEF1) plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein that colocalizes with cenexin (also known as ODF2) at the mother centriole in interphase cells. C3G interacts with cenexin through its catalytic domain, and the two proteins show interdependence for localization to the centrosome. C3G depletion causes a decrease in cellular cenexin levels. Centrosomal localization of C3G is lost as myocytes differentiate to form myotubes. Depletion of C3G by CRISPR/Cas9 results in the formation of supernumerary centrioles, whereas overexpression of C3G, or expression of a catalytically active C3G deletion construct, inhibits centrosome duplication. Cilium length is increased in C3G knockout cells, and this phenotype is reverted upon reintroduction of C3G or its catalytic domain alone. Association of C3G with the basal body is dynamic, decreasing upon serum starvation and increasing upon re-entry into the cell cycle. C3G inhibits cilium formation and length, and this inhibition is dependent on C3G catalytic activity. We conclude that C3G regulates centrosome duplication and maintains ciliary homeostasis, properties that could be important for its role in embryonic development.


[Blighted ovum in subfertile patients undergoing assisted reproductive technology].
To explore the incidence and risk factors of blighted ovum in subfertile patients undergoing assisted reproductive technology (ART). This retrospective analysis was conducted among 2378 patients who were pregnant following embryo transfer at our center from January, 2012 to December, 2015, including cases of early pregnancy losses and simultaneous live births. The cases with early pregnancy losses were divided into embryonic pregnancy and blighted ovum groups based on the presence or absence of an embryonic pole before dilation and curettage. The clinical data of the 3 groups were analyzed for comparisons of the maternal age, paternal age, BMI, AFC, basal FSH, bFSH/bLH, duration of infertility, Gn dosage, Gn days, serum estradiol on the day of HCG administration, endometrium thickness, number of oocyte retrieved, proportion of high-quality embryos transferred, serum β-HCG value on the 10th to 14th days of embryo transfer, infertility type and miscarriage times. The incidences of blighted ovum were compared between cases with different cycles, embryo stages, infertile factors and methods of fertilization. Maternal age and paternal age, BMI, duration of infertility, infertility type and miscarriage times differed significantly between cases with blighted ovum and those with live births. Serum β-HCG level was the lowest in blighted ovum group followed by embryonic pregnancy group and then by live birth group. Blastocyst transfer was associated with a significantly higher incidence of blighted ovum as compared with cleavage embryo transfer (11.6% vs 5.6%, P=0.000). No significant difference was found in the other parameters among the 3 groups (P>0.05). Adjusted logistic regression analysis showed that maternal age, β-HCG level and blastocyst transfer were risk factors of blighted ovum. Advanced maternal age, low β-HCG level and blastocyst transfer may increase the risk of blighted ovum possibly in association with gene imprinting errors during the early stage of embryo development.


Estimation of Respiratory Rates Using the Built-in Microphone of a Smartphone or Headset.
This paper proposes accurate respiratory rate estimation using nasal breath sound recordings from a smartphone. Specifically, the proposed method detects nasal airflow using a built-in smartphone microphone or a headset microphone placed underneath the nose. In addition, we also examined if tracheal breath sounds recorded by the built-in microphone of a smartphone placed on the paralaryngeal space can also be used to estimate different respiratory rates ranging from as low as 6 breaths/min to as high as 90 breaths/min. The true breathing rates were measured using inductance plethysmography bands placed around the chest and the abdomen of the subject. Inspiration and expiration were detected by averaging the power of nasal breath sounds. We investigated the suitability of using the smartphone-acquired breath sounds for respiratory rate estimation using two different spectral analyses of the sound envelope signals: The Welch periodogram and the autoregressive spectrum. To evaluate the performance of the proposed methods, data were collected from ten healthy subjects. For the breathing range studied (6-90 breaths/min), experimental results showed that our approach achieves an excellent performance accuracy for the nasal sound as the median errors were less than 1% for all breathing ranges. The tracheal sound, however, resulted in poor estimates of the respiratory rates using either spectral method. For both nasal and tracheal sounds, significant estimation outliers resulted for high breathing rates when subjects had nasal congestion, which often resulted in the doubling of the respiratory rates. Finally, we show that respiratory rates from the nasal sound can be accurately estimated even if a smartphone's microphone is as far as 30 cm away from the nose.


Cemento-fibrous dysplasia of the periodontal membrane (studies of the European hamster maxillary incisor).
The periodontal membrane of European hamster maxillary incisors showed histologic changes consisting of an irregularly orientated, less vascularized connective tissue which included abundant cementicle-like structures. The changes were multifocal and bilateral, growing towards the alveolar bone (Grade 1), causing atrophy of the alveolar bone due to compression (Grade 2) and reaching the periosteal membranes (Grade 3). In a few animals, the lesions were seen after one year. They were seen in 80% of hamsters more than 2 years old. Carcinogenic exposure did not alter the latency and incidence of the alterations. The lesions were thought to be a spontaneously occurring disease representing a nodular cemento-fibrous dysplasia of the periodontium. As, morphologically, no exact attribution to other odontogenic or mesenchymal growth could be made, the entity of this periodontal lesion was considered. Although the changes observed in the periodontal membrane of the maxillary incisors of the European hamster were not exactly comparable to odontogenic cemental lesions in man, they may serve as a model to further clarify the nature of fibro-osseous lesions.


[Neurohypophyseal diabetes insipidus. Anatomo-clinical correlations].
Eighteen patients aged between 14 and 60 years suffering from diabetes insipidus were studied. Diabetes insipidus was diagnosed by means of Robertson's test. All patients underwent C.T. scanning and evaluation of PRL basally and after TRH (200 mcg e.v.). Twelve patients (66%) showed neurological lesions (secondary central diabetes insipidus). Six of these patients had hyperprolactinaemia. Our data suggest that most of central diabetes insipidus are associated with central system nervous (S.N.C.) damage. In same cases the presence of hyperprolactinaemia suggests a brain damage. Therefore neuroradiological study is very important in all cases of neurohypophyseal diabetes insipidus.


Active colorimetric lipid-coated polyaniline nanoparticles for redox state sensing in cancer cells.
Herein, lipid-coated polyaniline (LiPAni) nanoparticles were fabricated to monitor the redox state of cancer cells. To confirm the characteristics of LiPAni, we firstly analyzed the size and chemical structures of the LiPAni nanoparticles. The absorbance properties of the LiPAni nanoparticles were observed to vary with the pH conditions. Furthermore, cell viability tests conducted with breast cancer cell lines showed that the cell viability of the cells with LiPAni nanoparticles was dramatically increased compared to those with the Tween80-coated polyaniline nanoparticles (TPAni) as a control. Subsequently, the colors of the LiPAni nanoparticles were observed and analyzed using spectroscopic methods. Finally, in order to investigate the more accurate sensing of the redox state using the color changes of the LiPAni nanoparticles with cancer cell lines, dark field microscopic images and scattering spectra were recorded at the single nanoparticle scale. For the TPAni nanoparticles, there was only a change in brightness and no change in color, but for the LiPAni nanoparticles, there was a change of color from yellow to pink in the dark field images.


Mild conditions for deuteration of primary and secondary arylamines for the synthesis of deuterated optoelectronic organic molecules.
Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C). These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications.


Interleukin-2 receptor gene expression by bronchoalveolar lavage lymphocytes in pulmonary sarcoidosis.
Current concepts of the immunopathogenesis of sarcoidosis favor a central role of activated, interleukin-2 (IL-2) producing helper T-cells at sites of inflammation. Normally, activated T-cells release IL-2 and express IL-2 receptors (IL-2R). IL-2R+ cells, however, are not uniformly found in patients with clinically active disease. To determine whether the lack of IL-2R+ cells is caused by a dysregulation of the IL-2R gene or by the mode of T-cell activation in pulmonary sarcoidosis, we quantified IL-2 and IL-2R m-RNA transcripts, IL-2 release, and IL-2R surface protein in peripheral blood lymphocytes of patients with sarcoidosis and normal control subjects before and after in vitro stimulation as a function of time. Additionally, we determined the percentage of IL-2R+ bronchoalveolar lavage (BAL) and peripheral blood lymphocytes in our study population and evaluated the in vivo transcriptional activity of the IL-2R gene. In peripheral blood lymphocytes, maximal IL-2R mRNA accumulation is found between 6 and 24 h, and maximal accumulation of IL-2 mRNA is found between 24 and 48 h. No differences emerged between normal subjects and patients with sarcoidosis. In six of 19 patients, we observed elevated numbers of IL-2R+ BAL lymphocytes and found IL-2R mRNA in those cells. These results are in accordance with the concept of a compartmentalized T-cell activation in sarcoidosis, resulting in IL-2 and IL-2R positive BAL cells and quiescent peripheral blood lymphocytes.


Finding malignant findings from radiological reports using medical attributes and syntactic information.
Radiology reports are written primarily in natural language. Automated extraction of malignant findings from narrative reports is an important technique for clinical support or alert generation for physicians. This paper proposes a method for automatically extracting malignant findings from narrative radiological reports written in Japanese. First, sentences are parsed and a medical attribute of each phrase is determined. Next, sub-trees related to radiological findings are extracted from a dependency tree using medical attributes. Finally, the malignant findings in each sub tree are extracted with their positive or negative assertions, each of which is determined by the multiplication of pos/neg signs along a path in a sub-tree. The recall and precision for the extraction of malignant findings with their positive or negative assertions were 76% and 91% respectively. The experimental results showed the validity of the proposed method for extracting malignant findings with correct assertions.