Telescopic eyepieces in indirect ophthalmoscopy.
A new attachment that can be used with optimized ophthalmoscopes is described. Readily removable and interchangeable eyepieces containing small, lightweight Galilean telescopes approximately double the magnification. The influence of this device on some of the optical properties of binocular indirect ophthalmoscopy including magnification, field of view, brightness of the fundus image, and stereopsis, are reviewed briefly.


[Phase II study of 5-FU tablet in bladder tumor].
A phase II study of 5-FU tablet at a dose of 200 to 300 mg/day (b.i.d. or t.i.d.) for 28 patients with tumor of urinary bladder was undertaken by a cooperative study group consisting of 7 institutions including Okayama University. The clinical response rate in 25 evaluable cases was 20.0 (5/25) (CR: 2 cases, PR: 3 cases, MR: 4 cases, NC: 11 cases and PD: 5 cases). Efficacy rates of 5-FU tablet were higher in patients having smaller lesions or those who received no previous chemotherapy. Some adverse effects were observed in 6 of 27 cases (22.2%), all of which were gastrointestinal symptoms. Abnormal laboratory tests were seen in 18.5%, but all of these abnormalities were mild. 5-FU tablet administered to patients with tumor of urinary bladder was found to be highly distributed in tumor tissue. It is considered from the above results that 5-FU tablet is one of the useful agents for tumor of urinary bladder.


Leptin and its Receptors in Human Placenta of Small, Adequate, and Large for Gestational Age Newborns.
Alterations in birth weight impact postnatal outcome and adult metabolic health. Therefore, fetal growth regulation is crucial for preventing chronic metabolic diseases. Leptin has been suggested to play an important role in placental and fetal growth, albeit its specific mechanisms of action have not been elucidated. The aim of this study was to analyze leptin concentrations in placenta, cord blood, and maternal blood of SGA, AGA, and LGA (small, adequate and large for gestational age, respectively) newborns, as well as placental leptin receptor (LEPRa and LEPRb) protein expression. We performed a cross-sectional comparative study in 3 groups of healthy mothers and their term newborns at delivery (SGA, AGA, and LGA, n=20 per group). Placental, maternal blood, and cord blood leptin content were measured by ELISA. Placental LEPRa and LEPRb protein expression were determined by Western Blot. Maternal leptin concentrations correlated positively with maternal weight before and at the end of gestation, without differences between groups. Cord leptin is higher in LGA and lower in SGA, whereas placental leptin is higher in SGA. Placental leptin was inversely correlated with placental weight, independently from maternal weight and gestational age. Both LEPRa and LEPRb expression are lower in SGA, while LEPRa positively correlated with placental weight and birthweight. The current findings indicate that placental leptin and its receptors are differentially expressed in SGA, AGA, and LGA newborns. We suggest that placental leptin and LEPR protein expression may influence placental growth and thus, birth weight.


Dietary effect on platelet aggregation in men with and without a family history of essential hypertension.
Platelet aggregation induced by 5 microM adenosine 5'-diphosphate (ADP) was significantly higher in men with a family history of essential hypertension than in men without such a history when they were fed a low fat-cholesterol diet with low salt. Platelet aggregation activity was remarkably increased in both groups when the diet was changed from low salt into high salt. Platelet aggregation activity was higher in the group with a positive family history of hypertension on the low fat-cholesterol plus high salt diet than in the group without a family history under the same conditions. The activity was slightly increased in both groups when fed a high fat-cholesterol diet with low salt. There was no significant difference in the platelet aggregation between the two groups. The activity was significantly increased in both groups on the high fat-cholesterol diet after the diet was changed from low salt to high salt. Under both the low and high fat-cholesterol diets, the mean blood pressure was significantly elevated in response to excessive salt intake in the group with a family history of essential hypertension, but it was not elevated in the group without such a family history.


A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).
The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.


Modeling fermentations with recombinant microorganisms: formulation of a structured model.
A simple structured model is described and compared with experimental data for fermentations with recombinant. Escherichia coli. The model is a so-called compartment, model, where the different biomass components are lumped together in a few intracellular variables. The model is able to describe, in a biologically reasonable fashion, a majority of the observations that have been made through fermentations with recombinant microorganisms. The model is especially suited for description of dynamic changes in plasmid copy number, e.g., runaway plasmid replication.


Chronic Traumatic Encephalopathy: The cellular sequela to repetitive brain injury.
This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities. The pathological hallmarks of CTE have been well characterised and have been linked to the pathophysiologic mechanisms in this review. Human studies are limited due to ethical implications of exposing subjects to head trauma. Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE. The neuronal loss and axonal dysfunction mediated by these pathognomonic mechanisms lead to the broad psycho-cognitive symptoms seen in CTE.


Spontaneous cessation of Friend murine leukemia virus production by leukemia cell line Y57: overgrowth by nonproducer cells.
Cell line Y57, obtained from a (C57BL/10 X A.BY)F1 mouse made leukemic with Friend virus complex (FV), spontaneously ceased FV production in vitro after 20 passages. By limiting dilution cloning, the incidence of non-virus-producing cells was found to increase with sequential passage. Nonproducer cells apparently arose spontaneously and were able to increase in number relative to producer cells because the growth rate of nonproducer cells was more rapid than the rate at which virus could reinfect them. Nonproducer clones all contained the defective spleen focus-forming virus in a latent but rescuable form but showed defects in helper virus env and gag gene product synthesis. Stable long-term virus-producing clones were obtained both by cloning at early in vitro passages or by cloning immediately after reinfection of nonproducer cells with FV.


Role of Wnt signaling during inflammation and sepsis: A review of the literature.
Despite the development of modern intensive care and new antimicrobial agents, the mortality of patients with severe sepsis and septic shock remains high. Systemic inflammation is a consequence of activation of the innate immune system. It is characterized by the intravascular release of proinflammatory cytokines and other vasoactive mediators, with concurrent activation of innate immune cells. The Wnt signaling pathway plays a critical role in the development of multicellular organisms. Abnormal Wnt signaling has been associated with many human diseases, ranging from inflammation and degenerative diseases to cancer. This article reviews the accumulating evidence that the Wnt signaling pathway plays a distinct role in inflammation and sepsis.


Work Function Modification of Tungsten-Doped Indium Oxides Deposited by the Co-Sputtering Method.
We have studied the work function modification of tungsten-doped indium oxides (IWOs) through the co-sputtering of indium oxide (In2O3) and indium tungsten oxide (In2O3 80 wt% + WO3 20 wt%) via a radio frequency (RF) magnetron sputtering system. By controlling the elemental deposition of IWOs, the resultant work functions varied from 4.37 eV to 4.1 eV. The IWO thin films showed excellent properties for application as transparent conducting oxide materials in the region of 0 to 2.43 at.% of tungsten versus the total metal content. The carrier concentration of n-type IWO thin films varied from 8.39 x 10(19) cm(-3) to 8.58 x 10(21) cm(-3), while the resistivity varied from 3.15 x 10(-4) Ωcm to 2.26 x 10(-3) Ωcm. The largest measured optical band gap was 3.82 eV determined at 2.43 at.% of tungsten atoms relative to the total amount of metal atoms, while the smallest optical band gap was 3.6 eV at 4.78 at.% of tungsten. IWO films containing more than 2.43 at.% of tungsten atoms relative to the total number of metal atoms revealed an average transmittance of over 80% within the visible light region.


Alpha-1-antitrypsin protease inhibitor SZ phenotype and liver cirrhosis.
In the light of recent findings concerning the importance of intermediate alpha 1-antitrypsin deficiency in the development of chronic liver disease and of hepatocellular carcinoma, we report the case of a 56-year-old woman affected by cirrhosis with significant features of liver cell dysplasia associated with intermediate alpha 1-antitrypsin deficiency (protease inhibitor SZ phenotype). In our paper we emphasize the importance of a precocious diagnosis and identification of individuals carrying the Z allele, also heterozygous.


Genetic polymorphisms of the IGF-II gene intron 8 coding region and its association with growth and carcass traits in yak.
Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth and is involved in stimulating fetal cell division, differentiation, and metabolic regulation. IGF-II is considered a candidate gene for genetic markers of growth and carcass traits. Therefore, in this study, the associations of single nucleotide polymorphisms (SNPs) in the IGF-II gene region with growth and carcass characteristics in five yak breeds were investigated. Two SNPs, G(330)C and A(358)G, were identified by sequencing intron 8 of the IGF-II gene in homozygotes. Two alleles, A and B, and three genotypes, AA, AB, and BB, were identified by polymerase chain reaction. Genotypic frequencies of IGF-II allele B were 0.8623, 0.8936, 0.8535, 0.8676, and 0.8300 for Datong yak, Gannan yak, Tianzhu white yak, Qinghai Plateau yak, and Xinjiang yak, respectively. Allele and the genotype of IGF-II were strongly associated with growth and carcass traits. Least square analysis revealed a significant effect (P < 0.01) of genotypes AA and AB compared with genotype BB on live-weight (at 12, 13-24, and 25-36 months of age), average daily weight gain (P < 0.01) and carcass weight (P < 0.05). Animals with genotype AB had a higher mean rib eye area, and a lower mean yield grade. The results indicated that the IGF-II gene acts by a primarily additive biological mechanism by adding weight independently of skeletal growth.


Health Risk Assessment of Photoresists Used in an Optoelectronic Semiconductor Factory.
Photoresist materials are indispensable in photolithography, a process used in semiconductor fabrication. The work process and potential hazards in semiconductor production have raised concerns as to adverse health effects. We therefore performed a health risk assessment of occupational exposure to positive photoresists in a single optoelectronic semiconductor factory in Taiwan. Positive photoresists are widely used in the optoelectronic semiconductor industry for photolithography. Occupational exposure was estimated using the Stoffenmanager® model. Bayesian modeling incorporated available personal air sampling data. We examined the composition and by-products of the photoresists according to descriptions published in the literature and patents; the main compositions assessed were propylene glycol methyl ether acetate (PGMEA), novolac resin, photoactive compound, phenol, cresol, benzene, toluene, and xylene. Reference concentrations for each compound were reassessed and updated if necessary. Calculated hazard quotients were greater than 1 for benzene, phenol, xylene, and PGMEA, indicating that they have the potential for exposures that exceed reference levels. The information from our health risk assessment suggests that benzene and phenol have a higher level of risk than is currently acknowledged. Undertaking our form of risk assessment in the workplace design phase could identify compounds of major concern, allow for the early implementation of control measures and monitoring strategies, and thereby reduce the level of exposure to health risks that workers face throughout their career.


(η-All-yl)bromido(1-phenyl-1H-imidazole-κN)palladium(II).
The title compound, [PdBr(C(3)H(5))(C(9)H(8)N(2))], was synthesized by the reaction of the allyl-palladium(II) bromide dimer and 1-phenyl-1H-imidazole. The Pd atom is coordinated by one allyl group [in η(3) mode, the central CH group of the allyl group is disordered over two sets of sites in a 0.668 (5):0.332 (5) ratio], one bromide anion and a 1-phenyl-1H-imidazole ligand. Intra-molecular face-to-face π-π stacking inter-actions occur between adjacent phenyl or imidazole groups, with centroid-centroid distances in the range 3.877 (1)-3.6596 (6) Å, forming a supra-molecular chain along [100].


Coordinate transformation method for modeling three-dimensional photonic structures with curved boundaries.
The coordinate transformation method (C method) is a powerful tool for modeling photonic structures with curved boundaries of discontinuities. As a modal method upon the Fourier basis, the C method has superior computational efficiency and rich physical intuitiveness compared to other full-wave numerical methods. But presently the C method is limited to two-dimensional (2D) structures if the boundaries between adjacent z-invariant layers are of generally different profiles [with (x,y,z) being the Cartesian coordinate]. Here we report a nontrivial extension of the C method to the general case of three-dimensional (3D) structures with curved boundaries of different profiles between adjacent layers. This extension drastically enlarges the applicability of the C method to the various interesting structures in nanophotonics and plasmonics. The extended 3D-C method adopts a hybrid coordinate transformation which includes not only the z-direction coordinate transformation in the classical C method but also the x- and y-direction matched coordinates adopted in the Fourier modal method (FMM), so as to exactly model the curved boundaries in all the three directions. The method also incorporates the perfectly matched layers (PMLs) for aperiodic structures and the adaptive spatial resolution (ASR) for enhancing the convergence. A modified numerically-stable scattering-matrix algorithm is proposed for solving the equations of boundary condition between adjacent z-invariant layers, which are derived via a transformation of the full 3D covariant field-components between the different curvilinear coordinate systems defined by the different-profile top and bottom boundaries of each layer. The validity of the extended 3D-C method is tested with several numerical examples.


Early histopathologic changes in purple glove syndrome.
An 86-year-old African-American man presented with tonic-clonic seizures. Intravenous phenytoin was urgently administered into the dorsum of the right hand. The patient developed a raised purple area of discoloration around the intravenous insertion site within 2 h and edema and vesiculobullous lesions of the distal forearm, hands, and fingers within 8 h. Microscopic sections from a biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild superficial and deep perivascular lymphoid infiltrate, associated with numerous thrombi of small vessels throughout the dermis. The findings were judged to be consistent with soft-tissue injury associated with intravenous administration of phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for its distinctive purple discoloration and swelling of the hands in the distribution of a glove, is an uncommon complication of intravenous phenytoin administration through small dorsal veins of the hands. It is comprised by pain, discoloration, and edema in the vicinity of intravenous infusion of phenytoin through dorsal veins of the hand. The histopathologic features of fully developed lesions have been reported; however, early-stage findings have not been previously described, and the histogenesis of this lesion is controversial. The presence of thrombi in this early-stage lesion suggests that thrombosis plays a role in the initial pathogenesis of this condition.


Fabrication of 1-D Photonic Crystal Cavity on a Nanofiber Using Femtosecond Laser-induced Ablation.
We present a protocol for fabricating 1-D Photonic Crystal (PhC) cavities on subwavelength-diameter tapered optical fibers, optical nanofibers, using femtosecond laser-induced ablation. We show that thousands of periodic nano-craters are fabricated on an optical nanofiber by irradiating with just a single femtosecond laser pulse. For a typical sample, periodic nano-craters with a period of 350 nm and with diameter gradually varying from 50 - 250 nm over a length of 1 mm are fabricated on a nanofiber with diameter around 450 - 550 nm. A key aspect of such a nanofabrication is that the nanofiber itself acts as a cylindrical lens and focuses the femtosecond laser beam on its shadow surface. Moreover, the single-shot fabrication makes it immune to mechanical instabilities and other fabrication imperfections. Such periodic nano-craters on nanofiber, act as a 1-D PhC and enable strong and broadband reflection while maintaining the high transmission out of the stopband. We also present a method to control the profile of the nano-crater array to fabricate apodized and defect-induced PhC cavities on the nanofiber. The strong confinement of the field, both transverse and longitudinal, in the nanofiber-based PhC cavities and the efficient integration to the fiber networks, may open new possibilities for nanophotonic applications and quantum information science.


The development of the vibrissal cortical column: a 2-deoxyglucose study in the rat.
A column of SI cortex responding to stimulation of a single vibrissa can be visualized with [14C]2-deoxyglucose (2-DG) autoradiography. The development of C3 vibrissal column was investigated in rat pups aged 2, 4, 6, 8, 12 and 21 days. A patch of label corresponding to higher glucose utilization appeared at postnatal day (p.d.) 4 to 6 in the cortical plate. Between p.d. 6 and 12 it developed into a spindle-shaped column. The infragranular layers showed metabolic activation later than the upper laminae. The suitability of the 2-DG technique for studies of infant mammalian brain is discussed.


Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever.
Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at -20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD.


NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma.
The purpose of this study was to investigate the role of NAC1 in the development of endometrial cancer. NAC1 expression and localization were assessed with immunohistochemistry in the normal cyclic human endometrium, hyperplastic endometrium, and endometrial cancer. Expression of NAC1 in the glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases, endometrial hyperplasia, and endometrial carcinoma. NAC1 expression was down-regulated during endometrial carcinogenesis. There were significant correlations between positive NAC1 expression and pathological grade (P=0.037). No significant associations were found between NAC1 expression and the other clinicopathological characteristics including patient age, FIGO staging, depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, menopause, or body mass index. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and JHEM2 cell lines, all of which overexpressed NAC1. Ectopic overexpression of the NAC1 gene stimulated cell proliferation in the HEC1B, and JHEM1 endometrial cancer cell lines, which have lower endogenous NAC1 expression. Endometrial carcinomas with NAC1 overexpression are clinically aggressive, high-grade carcinomas. Therefore, detection of NAC1 overexpression in endometrial cancers may identify patients who will benefit from NAC1 targeted therapy.


Antibody reactive with Actinobacillus actinomycetemcomitans leukotoxin in early-onset periodontitis patients.
The objective of this study was to determine whether a relationship exists between antibody reactive with the Actinobacillus actinomycetemcomitans leukotoxin and the severity of periodontal disease. Serum concentrations of antibody reactive with the leukotoxin were determined for 119 early-onset periodontitis patients and 59 non-periodontitis subjects using limiting dilution analysis on Western blots. Immunoglobulin G (IgG) antibody reactive with the A. actinomycetemcomitans leukotoxin ranged from undetectable to 29 micrograms/ml (mean = 3.13 +/- 0.97 micrograms/ml for the generalized early-onset periodontitis and 2.17 +/- 0.86 micrograms/ml for the localized juvenile periodontitis patients vs 0.32 +/- 0.24 ng/ml for 59 non-periodontitis controls), and the dominant subclass was IgG1. Analysis of the relationship between antibody reactive with A. actinomycetemcomitans sonicate, A. actinomycetemcomitans leukotoxin and attachment loss patterns indicates that seropositive generalized early-onset periodontitis patients had decreased attachment loss compared with patients lacking this antibody. The statistical relationship appeared to be stronger for the sonicate than the purified leukotoxin. These data suggest that antibody reactive with A. actinomycetemcomitans leukotoxin may be protective in early-onset periodontitis, but given that the sonicate appeared better than the leukotoxin alone, it is not likely that leukotoxin is the only antigen of importance to host defense.


Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas.
Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification.


[Establishment and characterization of a new human renal cell carcinoma cell line (KG-2) and metastatic model in nude mice].
A new cultured cell line (KG-2) derived from human renal cell carcinoma and a metastatic model in nude mice were studied. KG-2 was cultured from renal cell carcinoma (clear cell carcinoma) of the left kidney. In vitro doubling time of KG-2 was approximately 50 hours. KG-2 cells produced tumors in both the subcutaneous and renal sub-capsular space in nude mice, with tumorigenicity of 75%, showing no difference between the two sites. Histologically, tumors formed in the subcutaneous sites were hypovascular granular cell carcinoma. Moreover, each tumor was encapsulated by a thick fibrous capsule and never produced distant metastasis or invasion into the surrounding tissue. However, tumors formed in the subrenal capsular space were clear cell carcinoma. These tumors were hypervascular, and produced distant metastases. The most common metastatic site was the lung. Immunohistochemical analysis using anti-human collagenase type IV antibody on tumors formed in subcutaneous and subrenal capsular sites demonstrated that the expression of this enzyme in tumors formed in the subrenal capsular space was much higher than that in tumors formed in the subcutaneous site. Additionally, immunohistochemical study using anti-mouse collagen type IV antibody, a major components of the vascular wall, demonstrated many small densely growing vessels in tumors formed in the subrenal capsular space. In contrast, few vessels were produced in tumors formed in subcutaneous sites. These findings suggest that factors relating to the different injection sites may regulate the production of collagenase type IV secreted by KG-2 cells and neovascularity in nude mice. This metastatic model may be useful in the study of the mechanism of cancer metastases.


Timing of evolutionary innovation: scenarios of evolutionary diversification in a species-rich fungal clade, Boletales.
Acquisition of mutualistic symbiosis could provide hosts and/or symbionts with novel ecological opportunities for evolutionary diversification. Such a mechanism is one of the major components of coevolutionary diversification. However, whether the origin of mycorrhizal symbiosis promotes diversification in fungi still requires clarification. Here, we aimed to reveal evolutionary diversification in a clade comprising ectomycorrhizal (ECM) fungi. Based on a phylogenic tree inferred from the sequences of 87 single-copy genes, we reconstructed the origins of ECM symbiosis in a species-rich basidiomycetous order, Boletales. High-resolution phylogeny of Boletales revealed that ECM symbiosis independently evolved from non-ECM states at least four times in the group. Among them, only the second most recent event, occurring in the clade of Boletaceae, was inferred to involve an almost synchronous rapid diversification and rapid transition from non-ECM to ECM symbiosis. Our results contradict the hypothesis of evolutionary priority effect, which postulates the greatest ecological opportunities in the oldest lineages. Therefore, the novel resources that had not been pre-empted by the old ECM fungal lineages - supposedly the coevolving angiosperm hosts - could be available for the young ECM fungal lineages, which resulted in evolutionary diversification occurring only in the young ECM fungal lineages.


Nursing students' attitudes toward sexually active older persons.
This study investigated the attitudes of senior baccalaureate nursing students toward geriatric sexuality. Two separate experiments used vignettes as an unobtrusive measure of attitudes toward sexual activity in an older man or woman who was depicted as either married or widowed. All subjects read a vignette concerning a 68-year-old person who was temporarily living in a nursing home. Half read that the person was sexually active; there was no mention of sexual activity for the remaining subjects. Subjects evaluated the person on a 10-item questionnaire, employing 0-to-9 bipolar rating scales for such traits as well-adjustedness, cheerfulness, and mental alertness. Regardless of the stimulus person's gender, or marital status, subjects showed a significant bias favoring the sexually active older person in both experiments. Implications for nursing practice are discussed.


Vitamin C blocks TNF-alpha-induced NF-kappaB activation and ICAM-1 expression in human neuroblastoma cells.
Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), activates the NF-kappaB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-alpha in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-alpha-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kappaB activation and IkappaBalpha degradation induced by TNF-alpha. Taken together, these results suggest that vitamin C downregulates TNF-alpha-induced ICAM-1 expression via the inhibition of NF-kappaB activation.


Fifteen-year follow-up of transplantation of a cadaveric polycystic kidney: a case report.
Kidneys from donors affected by autosomal-dominant polycystic kidney disease (ADPKD) are in general considered unsuitable for transplantation. To the best of our knowledge, only 12 cases of ADPKD transplanted renal units have been reported in the English literature; most have only short-term follow-up. We provide a review of these patients and share our experience with an ADPKD patient who received a 21-year-old deceased donor ADPKD-affected renal transplant and has been closely followed for 15 years. Based on the current literature, this report is the longest follow-up of a ADPKD donor transplant. Over the 15-year follow-up period, there have been no complications related to the ADPKD-affected donor kidney, including three kidney transplant biopsies. The graft continues to function well with the serum creatinine currently 1.2 mg/dL. Serial axial imaging has demonstrated that the cystic disease has slowly progressed in the donor renal unit, with the largest cyst having only increasing from 1.2 to 2.9 cm in diameter. Metachronous, bilateral laparoscopic nephrectomies of the native kidneys were performed owing to intractable pain from cystic enlargement. Normal functioning deceased donor kidneys that show signs of early ADPKD should be considered acceptable for donation in select cases. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.


Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors.
Bacterial vaginosis (BV) is characterized by a highly structured polymicrobial biofilm, which is strongly adhered to the vaginal epithelium and primarily consists of the bacterium Gardnerella vaginalis. However, despite the presence of other BV-associated bacteria, little is known regarding the impact of other species on BV development. To gain insight into BV progress, we analyzed the ecological interactions between G. vaginalis and 15 BV-associated microorganisms using a dual-species biofilm model. Bacterial populations were quantified using a validated peptide nucleic acid fluorescence in situ hybridization approach. Furthermore, biofilm structure was analyzed by confocal laser scanning microscopy. In addition, bacterial coaggregation ability was determined as well as the expression of key virulence genes. Remarkably, our results revealed distinct biofilm structures between each bacterial consortium, leading to at least three unique dual-species biofilm morphotypes. Furthermore, our transcriptomic findings seem to indicate that Enterococcus faecalis and Actinomyces neuii had a higher impact on the enhancement of G. vaginalis virulence, while the other tested species had a lower or no impact on G. vaginalis virulence. This study casts a new light on how BV-associated species can modulate the virulence aspects of G. vaginalis, contributing to a better understanding of the development of BV-associated biofilms.


Canted Antiferromagnetism on Rectangular Layers of Fe2+ in Polymorphic CaFeSeO.
From stoichiometric amounts of CaO, Fe, and Se, pure powders and single crystals of quaternary [Formula: see text] can be obtained by solid-state reaction and self-flux growth, respectively. The as-synthesized compound exhibits a polymorphic crystal structure, where the two modifications have different stacking sequences of [Formula: see text] layers. The two polymorphs have similar unit cells but different crystal symmetries (Cmc21 and Pnma), of which the former is non-centrosymmetric. Fe is divalent (d6) and high-spin, as proven by X-ray spectroscopy, Mössbauer spectroscopy, and powder neutron diffraction data. The latter two, in combination with magnetic susceptibility and specific heat data, reveal a long-range antiferromagnetic spin order (TN = 160 K) with a minor spin canting. CaFeSeO is an electronic insulator, as confirmed by resistivity measurements and density functional theory calculations. The latter also suggest a relatively small energy difference between the two polymorphs, explaining their intimate intergrowth.


A lithium-air battery and gas handling system demonstrator.
The lithium-air (Li-air) battery offers one of the highest practical specific energy densities of any battery system at >400 W h kgsystem-1. The practical cell is expected to operate in air, which is flowed into the positive porous electrode where it forms Li2O2 on discharge and is released as O2 on charge. The presence of CO2 and H2O in the gas stream leads to the formation of oxidatively robust side products, Li2CO3 and LiOH, respectively. Thus, a gas handling system is needed to control the flow and remove CO2 and H2O from the gas supply. Here we present the first example of an integrated Li-air battery with in-line gas handling, that allows control over the flow and composition of the gas supplied to a Li-air cell and simultaneous evaluation of the cell and scrubber performance. Our findings reveal that O2 flow can drastically impact the capacity of cells and confirm the need for redox mediators. However, we show that current air-electrode designs translated from fuel cell technology are not suitable for Li-air cells as they result in the need for higher gas flow rates than required theoretically. This puts the scrubber under a high load and increases the requirements for solvent saturation and recapture. Our results clarify the challenges that must be addressed to realise a practical Li-air system and will provide vital insight for future modelling and cell development.


Soybean (Glycine max) transformation using mature cotyledonary node explants.
Agrobacterium tumefaciens-mediated transformation of soybeans has been steadily improved since its development in 1988. Soybean transformation is now possible in a range of genotypes from different maturity groups using different explants as sources of regenerable cells, various selectable marker genes and selective agents, and different A. tumefaciens strains. The cotyledonary-node method has been extensively investigated and across a number of laboratories yields on average greater than 1% transformation efficiency (one Southern-positive, independent event per 100 cotyledonary-node explants). Continued improvements in the cotyledonary-node method concomitant with further increases in transformation efficiency will enhance broader adoption of this already productive transformation method for use in crop improvement and functional genomics research efforts.


Supplementation of culture medium with knockout serum replacement improves the survival of bovine secondary follicles when compared with other protein sources during in vitro culture.
The present study evaluated the effect of knockout serum replacement (KSR), fetal bovine serum (FBS) and bovine serum albumin (BSA) on the viability and growth of bovine secondary follicles cultured in vitro for 12 days. To this end, secondary follicles were isolated (185-202 μm) and cultured in vitro in TCM-199+ medium supplemented with KSR (5% and 10%), FBS (5% and 10%) or BSA (3 mg/ml) at 38.5°C with 5% CO2 in air. Follicular diameters were evaluated on days 0, 4, 8 and 12. After 12 days of culture, follicular survival analysis was performing by using calcein-AM and ethidium homodimer. Before and after culture, follicles were fixed in paraformaldehyde for histological evaluation. Follicular diameter at different days of culture were compared using the Kruskal-Wallis test, while the percentages of viable follicles were analyzed by chi-squared test (P < 0.05). Results showed that follicles cultured in the presence of KSR at both concentrations presented higher follicular survival rates than those cultured in control medium alone or supplemented with FBS or BSA. Conversely, the presence of KSR, BSA or FBS did not increase follicular diameter after 12 days of culture. Histology analysis showed that, among the tested treatments, follicles cultured in the presence of KSR had preserved rounded oocytes, juxtaposed granulosa cells and intact basal membrane. In conclusion, supplementation of culture medium with KSR increases the follicular survival of bovine secondary follicles cultured in vitro.


[Demonstration of dual liver systems after experimental auxiliary partial liver transplantation using the alternative of sequential hepatobiliary scintigraphy].
Hepatobiliary sequential scintigraphies by 99m Tc-ROTOP-EHIDA were carried out for judging the dual liver system after experimental auxiliary transplantation of a part of the liver. A functional advantage of the host liver in contrast to the transplant was found in all cases investigated. Ischemic transplant damages could be detected in all experiments and were scintigraphically recognised at an early stage. In addition to transplants with a functioning entire parenchyma, the investigations showed transplants with functionally active parenchyma zones and such ones without any functional evidence. A quantifiable determination of the global functional capacity of the hepatobiliary system of both livers was possible and also the evidence on residual functions. The different behaviour of the kinetics of the radio-pharmacon with normal function and in case of hepatic ischemia is discussed.


Long-term cognitive and neuroanatomical stability in patients with anoxic amnesia: A Case Report.
Anoxia can result in selective hippocampal damage with associated impairments in declarative memory. Whilst memory impairments and brain structures are thought to be stable, there are little data regarding the effects of ageing or change over time in patients with amnesia from anoxic brain injury. To assess change over time, we compared structural magnetic resonance imaging (MRI) with data obtained over ten years previously in two well-characterized patients with amnesia (JRW and RS) who experienced an anoxic brain injury. Six healthy, age-matched control participants were recruited to compare brain volumes with the patients at Time 2. Wechsler adult intelligence scale-revised and Wechsler memory scale-revised scores were compared to scores on the same tests administered 13 and 19 years prior. Patients with amnesia had significantly smaller hippocampal volumes than controls, but comparable medial temporal lobe and ventricular volumes. Memory, intellectual function and brain volumes were stable over time. Patients with an amnesia due to anoxia have memory impairments and smaller hippocampal volumes compared to controls; however, memory, intelligence and structural volumes remain stable over time. At ages 50 and 57, they do not appear to have early age-associated cognitive decline that is sometimes observed in patients with traumatic brain injury.


Effects of N-Methyl-D-aspartate (NMDA) antagonists ketamine, methoxetamine, and phencyclidine on the odor span test of working memory in rats.
The glutamate hypothesis proposes that N-Methyl-D-aspartate (NMDA) receptor hypofunction underlies cognitive and perhaps other schizophrenic symptoms. The present study used the odor span task to assess the effects of NMDA antagonists on remembering multiple stimuli in rodents. This task uses an incrementing nonmatching-to-sample procedure in which responses to a new olfactory stimulus are reinforced on each trial, whereas responses to previously presented stimuli are not. NMDA antagonists have been associated with memory impairments in a variety of animal models; however, there are inconsistencies across different NMDA antagonists and tasks used. The current study compared the acute effects of phencyclidine (PCP), ketamine (KET), and the novel NMDA antagonist methoxetamine (MXE) on responding in the odor span task and a simple discrimination control task. PCP and MXE impaired odor span accuracy at doses that did not impair simple discrimination in most rats; however, the effects of KET were less selective. Within-session analyses indicated that the effects of PCP and MXE depended on the number of stimuli to remember, that is, impairment only occurred when the memory load was relatively high. These effects of PCP and MXE were consistent with the hypothesis that NMDA antagonists may interfere with working memory, but the basis for less selective results with KET are unclear. (PsycINFO Database Record


Geographic Variation, Economic Activity, and Labor Market Characteristics in Trajectories of Suicide in the United States, 2008 to 2020.
Suicide rates have increased in the U.S. over the past 15 years with substantial geographic variation in these increases; yet there have been few attempts to cluster counties by the magnitude of suicide rate changes by intercept and slope or to identify the economic precursors of increases. We used Vital Statistics data and growth mixture models to identify clusters of counties by their magnitude of suicide growth from 2008 to 2020 and examined associations with county economic and labor indices. Our models identified five clusters, each differentiated by intercept and slope magnitude, with the highest rate cluster (4% of counties) mainly in sparsely populated areas in the West and Alaska, starting the time series at 25.4 suicides/100,000, and exhibiting the steepest increase in slope (0.69/100,000 per year). There was no cluster for which the suicide rate was stable or declining. Counties in the highest rate cluster were more likely to have agriculture and service economies, and less likely to have urban professional economies. Given the increased burden of suicide, with no clusters of counties improving over time, additional policy and prevention efforts are needed, particularly targeted at rural areas in the West.


Toxicity of [14C] phorate applied systemically to the aphids Myzus persicae (Sulz) and Brevicoryne brassicae (l.) grown on brussels sprout plants.
The effect of foliar application of [14C] phorate on the larvae of M. persicae and B. brassicae was studied. Regression analysis of the toxic components in the foliage and the probit kill showed that B. brassicae was more susceptible to the insecticide than M. persicae. The level of radioactivity extracted from the leaves, aphids and their honeydew shows that there was no correlation between the applied dose and the mortality. The amounts of honeydew produced by colonies before and after application of the insecticide were measured. The ratio of honeydew calculated shows that in M. persicae there was a slight increase in the honeydew production as the insecticide was increased from sublethal doses. At higher doses over the lethal range of the insecticide, honeydew production declined gradually in both the species.


Vaccination-associated immune thrombocytopenia possibly due to ChAdOx1 nCoV-19 (Covishield) coronavirus vaccine.
Immune thrombocytopenia (ITP) is an acquired haemorrhagic diathesis of immune-mediated destruction, impaired production or increased splenic sequestration of platelets. It can be idiopathic (primary) or secondary (infections, medications, HIV infection, malignancies, connective tissue diseases or rarely secondary to vaccination). ITP postvaccination is termed vaccine-associated ITP (VITP) and is known to be caused by vaccines against various infectious agents such as measles-mumps-rubella, Haemophilus influenzae, pneumococcus, hepatitis B virus and human papilloma virus. Cases of VITP post SARS-CoV-2 vaccination have also been reported in the literature. Various hypotheses on the occurrence of the same are theorised, but no single theory has been proven to cause VITP conclusively. Management includes routine treatment of ITP with use of agents such as steroids, intravenous immunoglobulins, or on rare occasions a thrombopoietic agent or vinca alkaloids. We present a case of VITP possibly due to ChAdOx1 nCoV-19 (Covishield) vaccination in a middle-aged woman who responded to steroid therapy.


Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas.
The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical carcinoma cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosome regions 20pter----20q13 and 3p25----3qter, regions that also contain the protooncogenes c-src-1 and c-raf-1, respectively. The HPV 16 integration site in the SiHa cervical carcinoma-derived cell line is in chromosome region 13q14----13q32. The HPV 18 integration site in SW756 cervical carcinoma cells is in chromosome 12 but is not closely linked to the Ki-ras2 gene. Finally, in two cervical carcinoma cell lines, HeLa and C4-I, HPV 18 DNA is integrated in chromosome 8, 5' of the c-myc gene. The HeLa HPV 18 integration site is within 40 kilobases 5' of the c-myc gene, inside the HL60 amplification unit surrounding and including the c-myc gene. Additionally, steady-state levels of c-myc mRNA are elevated in HeLa and C4-I cells relative to other cervical carcinoma cell lines. Thus, in at least some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells.


Urinary excretion of 5-S-cysteinyldopa in healthy Japanese.
Urinary excretion of 5-S-cysteinyldopa was investigated in 20 healthy Japanese (10 men and 10 women). The values of excretion varied between 46 and 193 microgram/24 h. The mean (+/- S.D.) was 96 1 +/- 9.8 microgram/24 h. It was higher in the men than in the women, being 13 +/- 15 vis-a-vis 80.8 +/- 11.4 microgram/24 h. This finding indicates that 5-S-cysteinyldopa is formed and excreted by active melanocytes even in Mongoloids. The excretion of dopa and dopamine was found not correlative with the excretion of 5-S-cysteinyldopa.


Listening to Cancer Patients' Narratives During Residency: A Pilot Study on a Communication Skills' Workshop Involving Patients-Partners.
The field of cancer care still lacks best practices in communication. Few postgraduate training programs offer formal training to develop such skills. The patient partnership has been used in medical education to increase the sensitivity of the subjective experiences of patients. In our Canadian center, residents and patient-partners participated in an educational workshop on communication focusing on patient's narrative. The aim of this pilot qualitative study was to explore the experiences of participants in the workshop. Using theoretical sampling, we recruited 6 residents and 6 patient-partners. Semi-structured interviews were conducted and transcribed. A thematic analysis was performed. From analysis, 4 themes emerged: (1) lack of communication skills training; (2) barriers to effective communication in cancer care; (3) the empathy of patient-partners towards the communication challenges faced by residents; and (4) the participants' reactions to the workshop. Based on our findings, our communication skills workshop centered on narrative medicine and involving patient-partners appears feasible. Future research could study its pedagogical value and the optimal learning environment required.


Measurements of phantom scatter factors for small field sizes in high energy x rays.
An alternate method to measure the phantom scatter factor in small fields is provided for high energy photon beams. The measurement technique is based on the density scaling theorem described by O'Connor [Phys. Med. Biol. 1, 352-369 (1957)]. The phantom scatter factor (Sp) is measured in balsa and cedar wood to give effective field sizes in 3 x 3 to 0.5 x 0.5 cm2 water. The extrapolated zero area phantom scatter factor from the average data of balsa and cedar is 0.45. This indicates that the variation of output is largely due to a sharp decrease in the phantom scatter factor for small field sizes.


Proton effects on diazafluorene derivatives with sulfur-rich substituents, a structural, spectroscopic and theoretical study.
Proton effects on an intramolecular donor-acceptor molecular system 4',5'-diaza-9'-(4,5-dialkylthio-1,3-dithiol-2-ylidene)fluorenes (methylthio = L(1) (1), ethylthio = L(2) (2)) have been experimentally and theoretically studied. Structures of L(2) (2) and three protonated salts, [L(2) x H]CF(3)SO(3) (3), [L(1) x H]CF(3)SO(3) (4), and [L(1) x H]ClO(4) (5), were characterized by single-crystal X-ray determination. In all these salts the cations are found to be monoprotonated even in an excessive amount of acid. The protonated imine group forms strong N-H...O or N-H...N hydrogen bonds, which enhance the interaction between cations and anions and play an important role in the molecular packing. The measurement of UV-vis spectra indicates a two-step red shift of the absorption bands, which corresponds to the two-step protonation of L in solution. The intramolecular charge-transfer (ICT) property is enhanced when the compounds are protonated. Compound L is also a proton sensible fluorescent system with two-step remarkable changes in band energy and intensity. The study on the effect of protonation is further complemented by theoretical calculation with the DFT/TDDFT method.


Two unusual cases of microvascular thrombosis in the immediate posttransplant period.
We present two unusual cases of microvascular thrombosis in the immediate posttransplant period resulting in graft loss. The first was a 20-year-old female with a cadaveric renal transplant with immediate graft dysfunction due to microthrombi of probable donor origin, with nonrecovery of renal function nine months' posttransplant. The second was a 23-year-old male with unrelated live kidney transplant with hyperacute rejection due to anti-endothelial antibodies.


Hardware/Software Data Acquisition System for Real Time Cell Temperature Monitoring in Air-Cooled Polymer Electrolyte Fuel Cells.
This work presents a hardware/software data acquisition system developed for monitoring the temperature in real time of the cells in Air-Cooled Polymer Electrolyte Fuel Cells (AC-PEFC). These fuel cells are of great interest because they can carry out, in a single operation, the processes of oxidation and refrigeration. This allows reduction of weight, volume, cost and complexity of the control system in the AC-PEFC. In this type of PEFC (and in general in any PEFC), the reliable monitoring of temperature along the entire surface of the stack is fundamental, since a suitable temperature and a regular distribution thereof, are key for a better performance of the stack and a longer lifetime under the best operating conditions. The developed data acquisition (DAQ) system can perform non-intrusive temperature measurements of each individual cell of an AC-PEFC stack of any power (from watts to kilowatts). The stack power is related to the temperature gradient; i.e., a higher power corresponds to a higher stack surface, and consequently higher temperature difference between the coldest and the hottest point. The developed DAQ system has been implemented with the low-cost open-source platform Arduino, and it is completed with a modular virtual instrument that has been developed using NI LabVIEW. Temperature vs time evolution of all the cells of an AC-PEFC both together and individually can be registered and supervised. The paper explains comprehensively the developed DAQ system together with experimental results that demonstrate the suitability of the system.


[The problem of chronic gastritis].
Scientific review and own data about chronic gastritis problem: prevalence, short history data, question of aetiology and pathogenesis, clinical features, methods of instrumental and laboratory diagnostics including developed by the author, interrelation between chronic gastritis, gastric ulcer, gastric cancer and functional gastric dyspepsia syndrome are represented. Issues of chronic gastritis classification, principles of treatment and its efficiency are shown.


Design and performance evaluation of polyvinyl alcohol/polyimide coated optical fibre grating-based humidity sensors.
Optical fibre grating based sensors make a significant contribution to relative humidity measurement for various applications and a number of different designs and sensor configurations have been produced and discussed in the literature. Recent developments have included using sensitive polymers and indeed other materials that experience a variation of their physical and optical properties as a result of the absorption of moisture and which thus creates a modification of the characteristic spectral features of the gratings used. The strain and the effective refractive index of the gratings are affected by the change induced by the polymer and these effects were calibrated against the relative humidity variations that initially induce variations in the polymer layer. In this work, an evaluation is made of the performance characteristics of two different moisture sensitive polymers, i.e., polyimide and polyvinyl alcohol, as the basis of such sensors, while at the same time using different types of fibre gratings i.e., fibre Bragg gratings and long period gratings. Their performance is discussed in light of the operation of similar types of polymer-coated and other grating based sensors reported in the literature.


Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.
Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value.


Children's Hope in South Africa: A Population-Based Study.
A growing body of research has provided evidence for the cognitive motivational construct of hope as a psychological strength, particularly for children in adverse social circumstances. In children, hope is defined as a set of cognitions focused on children's agency to contemplate workable goals, to identify pathways to achieve those goals and the intrinsic beliefs about their capacity to activate sustained movement toward those goals. Using data from the third wave of the Children's Worlds International Survey on Children's Well-Being, the study aimed to explore children's hope amongst a random population-based sample of children in South Africa. The study further aimed to explore children's level of hope across the nine provincial regions of South Africa. Data were collected using Snyder et al.'s (1997) Children's Hope Scale (CHS). Confirmatory factor analysis (CFA) was used to analyze the data, with multi-group CFA used to analyze the data across provincial regions. The study found an appropriate fit structure for the CHS using the overall pooled sample. The mean score on the CHS for the national sample was of 4.781 (SD = 1.082). Measurement invariance demonstrated the tenability of scalar invariance, which indicates comparability across correlations, regressions and mean scores. Mean scores ranged from 4.511 (SD = 1.163) for the Northern Cape to 4.982. (SD = 0.974) for the Western Cape. Five provinces (Eastern Cape, Northern Cape, Free State, Mpumalanga, and KwaZulu Natal) scored below the national mean, while four provinces (North West, Western Cape, Limpopo, and Gauteng) scored above.


Protein-releasing conductive anodized alumina membranes for nerve-interface materials.
Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.


[Case of NK/T-cell lymphoma of the larynx with hemophagocytic syndrome].
We report the case of a 67-year-old man with NK/T cell lymphoma of the larynx accompanied by hemophagocytic syndrome (HPS) who reported throat paresthesia and was referred for evaluation of a laryngeal tumor extending from the left false vocal cord to the arytenoids. Two separate biopsies from the larynx yielded a histological diagnosis of NK/T-cell lymphoma, nasal and nasal type. Since he showed pancytopenia and remittent fever soon after admission, bone marrow was examined and showed severe hemophagocytosis, leading to a diagnosis of HPS. He died of circulatory and respiratory distresses due to HPS about one month after admission. HPS develops with symptoms of fever, cytopenia, and liver dysfunction, and is characterized by systemic proliferation of benign hemophagocytic histiocytosis in the bone marrow, lymph nodes, liver, and spleen. To the best of our knowledge, this is only the second case of NK/T-cell lymphoma of the larynx with hemophagocytic syndrome to be reported in the Japanese literature.


Female-biased dispersal and patrilocal kin groups in a mammal with resource-defence polygyny.
In most mammals, dispersal rates are higher in males than in females. Using behavioural and genetic data of individually marked bats, we show that this general pattern is reversed in the greater sac-winged bat (Saccopteryx bilineata). Dispersal is significantly female biased and male philopatry in combination with rare male immigration causes a patrilineal colony structure. Female dispersal helps avoid father-daughter inbreeding, as male tenure exceeds female age at first breeding in this bat species. Furthermore, our data suggest that females may engage in extra-harem copulations to mate with genetically dissimilar males, and thus avoid their male descendants as mating partners. Acquaintance with the natal colony might facilitate territory takeover since male sac-winged bats queue for harem access. Given the virtual absence of male immigration and the possible lower reproductive success of dispersing males, we argue that enhancing the likelihood of settlement of male descendants could be adaptive despite local mate competition. We conclude that resource defence by males is important in promoting male philopatry, and argue that the potential overlap of male tenure and female first conception is the driving force for females to disperse.


Sutureless large incision cataract extraction: Indications and results from two teaching hospital eye departments in the United Kingdom.
To highlight the role of Sutureless Large Incision Cataract Extraction (SLICE) in the United Kingdom for the treatment of cataracts at high risk for intra- or postoperative complications. Two University Hospitals in the United Kingdom Retrospective case note review of planned SLICE performed over a 12-month period. SLICE was performed on 11 eyes of 11 patients (mean age, 79 years) having preoperative vision of hand motions (10 eyes) with very dense or mobile cataracts and high risk for phacoemulsification. Mean follow up was 12 weeks, with no operative or postoperative complications. Nine patients (without ocular or systemic comorbidity) achieved best corrected vision of 0.3 LogMAR (20/40) or better. SLICE is safe and effective for dense or mobile cataracts and can play a role in patients where conventional phacoemulsification carries higher risks of complications.


Nebivolol prevents desensitization of β-adrenoceptor signaling and induction of cardiac hypertrophy in response to isoprenaline beyond β1-adrenoceptor blockage.
The importance of chronic stimulation of β-adrenoceptors in the development of cardiac dysfunction is the rationale for the use of β-blockers in the treatment of heart failure. Nebivolol is a third-generation β-blocker, which has further properties including stimulation of endothelial nitric oxide synthase and/or β3-adrenoceptors. The aim of this study was to investigate whether nebivolol has additional effects on β-adrenoceptor-mediated functional responses along with morphologic and molecular determinants of cardiac hypertrophy compared with those of metoprolol, a selective β1-adrenoceptor blocker. Rats infused by isoprenaline (100 μg·kg(-1)·day(-1), 14 days) were randomized into three groups according to the treatment with metoprolol (30 mg·kg(-1)·day(-1)), nebivolol (10 mg·kg(-1)·day(-1)), or placebo for 13 days starting on day 1 after implantation of minipump. Both metoprolol and nebivolol caused a similar reduction on heart rate. Nebivolol mediated a significant improvement on cardiac mass, coronary flow, mRNA expression levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) and atrial natriuretic peptide and phospholamban (PLN)/SERCA2a and phospho-PLN/PLN ratio compared with metoprolol and placebo. Nebivolol prevented the detrimental effects of isoprenaline infusion on isoprenaline (68% of control at 30 μM), BRL37344 (63% of control at 0.1 μM), and forskolin (64% of control at 1 μM) responses compared with metoprolol (isoprenaline, 34% of control; BRL37344, no response; forskolin, 26% of control) and placebo (isoprenaline, 33% of control; BRL37344, 28% of control; forskolin, 12% of control). Both β-blockers improved the changes in mRNA expressions of β1- and β3-adrenoceptors. Our results suggest that nebivolol partially protects the responsiveness of β-adrenoceptor signaling and the development of cardiac hypertrophy independent of its β1-adrenoceptor blocking effect.


IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil.
We evaluated the influence of the IL8 T-738A (nonidentified rs), IL8 T-353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single-nucleotide polymorphisms on leprosy. The AA genotype of IL8 T-353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age-of-onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1-13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1-5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age-of-onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.


The investigator as volunteer subject.
It is particularly within the past three decades that increased attention has been focused on human experimentation, both in regard to the scientific design that ensures the greatest chance of success and to conformity to ethical principles that are most likely to receive public approbation. The story of man's experimentation on man dates back to prehistoric times. In the past two centuries, these investigations have been carried out at an increasing level of sophistication. In this saga, the narratives of the auto-experimenters define a special group of investigators, to many of whom the term "heroic" can be applied. When investigators involve themselves as subjects of their research, a situation of informed consent is often assumed to exist. Discussions concerning voluntarism and ethical propriety have been much less voluminous when the investigators have themselves been subjects that when this is not so. It is within the past half century that physiologists particularly have often been auto-experimenters, and Dr. Earl Wood belongs to the best of this illustrious group.


Linking acute infection to chronic lung disease. The role of IL-33-expressing epithelial progenitor cells.
Respiratory infection is a common feature of the major human airway diseases, such as asthma and chronic obstructive pulmonary disease, but the precise link between acute infection and chronic lung disease is still undefined. In a mouse model of this process, parainfluenza virus infection is followed by long-term induction of IL-33 expression and release and in turn innate immune cell generation of IL-13 and consequent airway disease signified by excess mucus formation. IL-33 induction was traceable to a subset of secretoglobin-positive airway epithelial cells linked to progenitor/stem cell function. In corresponding studies of humans with chronic obstructive pulmonary disease, an increase in IL-33 production was also detected in concert with up-regulation of IL-13 and airway mucus formation. In this case, increased IL-33 production was localized to a subset of airway basal cells that maintain an endogenous capacity for increased pluripotency and ATP-regulated release of IL-33 even ex vivo. The results provide evidence of a sustainable epithelial cell population that may be activated by environmental danger signals to release IL-33 and thereby lead to IL-13-dependent disease. The progenitor nature of this IL-33-expressing ATP-responsive cell population could explain an acquired susceptibility to chronic airway disease. The findings may therefore provide a new paradigm to explain the role of viral infection and the innate immune system in chronic lung disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production. Further studies are needed to address the basis for this type of postviral reprogramming and the means to correct it and thereby restore airway mucosal immune function to normal.


HER-2-directed, small-molecule antagonists.
Inactivation of the human epidermal growth factor receptor-2 (HER-2) tyrosine kinase holds significant promise as a cancer treatment hypothesis, making it a high-value target for drug discovery. Screening and structure-based efforts have led to the development of several classes of ATP analog inhibitors of the HER-2 tyrosine kinase. These efforts have been further enhanced by detailed structural information regarding its sibling kinase, the EGF receptor, and structural properties that can be exploited to confer activity and even selectivity toward HER-2 kinase. Signaling and structural studies also suggest a critical involvement of the kinase inactive HER-3 in the regulation of HER-2, creating unique challenges in the efforts to inactivate the latter.


Monolithic molecularly imprinted solid-phase extraction for the selective determination of trace cytokinins in plant samples with liquid chromatography-electrospray tandem mass spectrometry.
Cytokinins (CTKs) are a class of growth-regulating hormones involved in various physiological and developmental processes. More novel analytical methods for the accurate identification and quantitative determination of trace CTKs in plants have been desired to better elucidate the roles of CTKs. In this work, a novel method based on monolithic molecularly imprinted solid-phase extraction followed by liquid chromatography-electrospray tandem mass spectrometry (mMI-SPE-LC-MS/MS) was developed for accurate determination of four CTKs in plant samples. The molecularly imprinted polymer monolith was prepared by using kinetin as the template in syringes and exhibited specific recognition ability for the four CTKs in comparison with that of non-imprinted polymer monolith. Several factors affecting the extraction performance of mMI-SPE, including the pH of loading sample solution, the nature and volume of elution solvent, the flow rate of sample loading, and sample volume, were investigated, respectively. Under the optimized conditions, the proposed mMI-SPE-LC-MS/MS method was successfully applied in the selective extraction and determination of four CTKs in plant tissues, and it offers detection limits (S/N = 3) of 104, 113, 130, and 89 pg/mL and mean recoveries of 85.9%, 79.3%, 73.5%, and 70.1% for kinetin, kinetin glucoside, trans-zeatin, and meta-topolin (mT), respectively, with the corresponding RSDs less than 15%.


Recovery of lactic acid by repeated batch electrodialysis and lactic acid production using electrodialysis wastewater.
Repeated batch electrodialysis for lactic acid recovery was investigated using lactic acid solution and fermentation broth. In both cases, lactate fluxes averaged more than 7.0 moles/m2.h, lactate recovery reached more than 99% for all the batch runs, and specific energy consumption per unit lactate transported was lower than 0.25 kWh/kg-lactate. When electrodialysis wastewater was used as a fermentation medium, supplemented with 100 g/l glucose, up to 92.4 g/l lactic acid was produced with a productivity of 0.67 g/l.h. In addition, when electrodialysis wastewater was supplemented with 150 g/l whole-corn flour hydrolyzate and 5 g/l corn steep liquor, 2.5-fold and 1.8-fold increases in lactic acid productivity and maximum cell growth, respectively, were achieved, as compared with lactic acid fermentation using electrodialysis wastewater supplemented with glucose only.


An unprecedented chemospecific and stereoselective tandem nucleophilic addition/cycloaddition reaction of nucleophilic carbenes with ketenimines.
The first study of the reaction between nucleophilic carbenes and ketenimines is reported. The interaction of thiazole and benzothiazole carbenes with ketenimines proceeded in a chemospecific and stereoselective manner to produce thiazole- and benzothiazole-spiro-pyrrole derivatives generally in good yields. The reaction was proposed to proceed via a tandem nucleophilic addition of carbene to the C=N bond of ketenimine followed by a stepwise [3+2] cycloaddition of the 1,3-dipolar intermediate with the C=C bond of ketenimine. This reaction provides a powerful protocol for the construction of novel polyfunctional thiazole-spiro-pyrrole or benzothiazole-spiro-pyrrole compounds that are not readily accessible by other methods.


Double-blind study of tolerability and antibody production of unmodified and chemically modified allergen vaccines of Phleum pratense.
The physicochemical modification of allergen extracts provides a chance for administering higher doses of allergen vaccines. To evaluate the safety of a chemically modified (depigmented-glutaraldehyde polymerized) therapeutic vaccine of Phleum pratense administered at doses that are 10 times higher than those used in clinical practice, in comparison with conventional doses of the corresponding non-modified alum-adsorbed vaccine. The design of the study was randomized, double-blind, parallel and included two groups of patients. Twenty-three patients were treated weekly during nine visits for the build-up phase, followed by two weekly maintenance doses (a total of 11 injections per patient). Twelve patients received a vaccine containing the standardized unmodified extract, at a maximum concentration of 308.5 mcg of freeze dried material/mL (Group A). Eleven patients received a standardized modified allergen extract (Group B). The maximum dose used was 2400 mcg/mL. Safety was evaluated recording all adverse events. Skin test results and specific antibody levels were evaluated at the beginning and at the end of the study. Group A patients experienced three local immediate (two clinically irrelevant and one with a diameter>5 cm) and 18 delayed reactions (15 irrelevant and three with a diameter>10 cm), while Group B experienced six local immediate and 12 delayed reactions (all clinically irrelevant). Nine Group A patients experienced 12 systemic reactions (one immediate of grade 1, one of grade 2; and one delayed of grade 1; four of grade 2 and three of grade 3), while Group B patients experienced one immediate systemic reaction of grades 1, and 1 delayed reaction of grade 1. The modified extract of P. pratense is safe to treat sensitive patients, even at concentrations that are 10 times higher than those regularly administered in clinical practice. The majority of the local reactions were clinically irrelevant. No systemic reactions of grade 2, 3 or 4 were reported using the modified extract.


Inter and intra-individual differences in steering wheel hand positions during a simulated driving task.
This paper describes an experimental study focusing onto the way drivers use the steering wheel while performing a 2D tracking task. The stimulus during this task was a steering wheel angle signal recorded in real situations involving turns and straight lines performed at about 30 km/h. The hand positions of 20 volunteers were recorded in 6 steering scenarios involving 7 road geometries using a 3D motion capture system. The hand movement data were analysed via a descriptive/inferential procedure: each hand was considered using nine indicators - eight membership value averages linked to eight fuzzy angle windows and a frequency value related to the off steering wheel position - while the indicators were investigated using multiple correspondence analysis and non-parametric global and post-hoc tests. Results showed that inter-individual differences were larger than intra-individual differences. Considering 2 × 9 = 18 windows, the inter-individual differences mainly appeared during two main kinds of steering hand strategies: with versus without crossing hands, the latter being the most often used (17 among 20 participants). The intra-individual data showed that some drivers maintained a nearly identical strategy for all road geometries, while other drivers changed their hand position with the direction and/or maximum angle value of the turn. Practitioner Summary: Understanding hand position strategy could be used to design steering wheel assistance in relation to a driver's physical resources with a view to adapting the steering wheel to disabled drivers.


Emotion perception deficits following traumatic brain injury: a review of the evidence and rationale for intervention.
While the cognitive disturbances that frequently follow severe traumatic brain injury (TBI) are relatively well understood, the ways in which these affect the psychosocial functioning of people with TBI are yet to be determined and have thus received little attention in treatment research. Growing evidence indicates that a significant proportion of individuals with TBI demonstrate an inability to recognize affective information from the face, voice, bodily movement, and posture. Because accurate interpretation of emotion in others is critical for the successful negotiation of social interactions, effective treatments are necessary. Until recently, however, there have been no rehabilitation efforts in this area. The present review examines the literature on emotion perception deficits in TBI and presents a theoretical rationale for targeted intervention. Several lines of research relevant to the remediation of emotion perception in people with TBI are considered. These include work on emotion perception remediation with other cognitively impaired populations, current neuropsychological models of emotion perception and underlying neural systems, and recent conceptualizations of remediation processes. The article concludes with a discussion of the importance of carrying out efforts to improve emotion perception within a contextualized framework in which the day-to-day relevance of training is clear to all recipients.


The prognostic potential of keratin 18 in breast cancer associated with tumor dedifferentiation, and the loss of estrogen and progesterone receptors.
The differential expression profiling with breast normal and tumor tissues, and a breast cancer cell line led to identification of cytokeratin 18 (KT18) gene over-expressed in breast cancer. The expression pattern of KT18 in breast cancer was compared to those of conventional tumor markers such as proliferating cell nuclear antigen (PCNA) and minichromosome maintenance protein 3 (MCM3). Their expression patterns in breast cancer were almost identical, suggesting that KT18 might be useful for detection of proliferating fractions in the breast cancer. The immunohistochemical analyses on the tissue microarray consisting of invasive ductal carcinomas revealed that the up-regulation of KT18 is observed in a majority of breast carcinomas whereas its down-regulation also occurs at a less frequency. Of particular interest, KT18 down-regulation was associated with histologically poorly differentiated carcinomas than well differentiated carcinomas. In addition, it was also significantly associated with the loss of estrogen receptor (ER) and progesterone receptor (PR), the prognostic markers of the breast cancer (P < 0.05), while not with HER2, tumor size, and lymph node metastasis. This result suggests that KT18 correlated with ER and PR may be utilized for the prognosis of breast cancer. Furthermore, the forced down-regulation of KT18 enhanced the growth of tumor xenografts in vivo and invasiveness in vitro. Therefore, our findings suggest that loss of KT18 expression might be a good indicator of the poor prognosis of the breast cancer and it may play an active role in the breast tumorigenesis.


[Basal blood level of thyrotropic hormone in diabetes mellitus patients].
The basal blood level of the thyrotropic hormone (TTH) was radioimmunologically determined in 160 patients with diabetes mellitus. A significant increase of its average level was established versus that in the control group of healthy subjects. The changes found showed no dependence on sex, age, duration and type of disease, light deviations from the standard body weight and the differences in drug treatment. A light correlation was established between the thyrotropinemia and glycemia as well as an insignificant dynamics of the hormonal blood level after the compensation of the diabetes. The higher TTH level established in the patients without retinopathy requires further studies on the significance of that fact.


Effective dynamic properties of random complex media with spherical particles.
The effective dynamic bulk modulus and density are presented for random media consisting of particles in a viscous host fluid, using a core-shell, self-consistent effective medium model, under the large compressional wavelength assumption. These properties are relevant to acoustic or dynamic processes in nano- and micro-particle fluids including particle density determination, resonant acoustic mixing, and acoustic characterisation. Analytical expressions are obtained for the effective bulk modulus and mass density, incorporating the viscous nature of the fluid host into the core-shell model through wave mode conversion phenomena. The effective density is derived in terms of particle concentration, particle and host densities, particle size, and the acoustic and shear wavenumbers of the liquid host. The analytical expressions obtained agree with prior known results in the limit of both static and inviscid cases; the ratio of the effective bulk modulus to that of the fluid is found to be quasi-static. Numerical calculations demonstrate the dependence of the effective mass density on frequency, particle size (from nano- to micro-regime), and concentration. Herein it is demonstrated both theoretically and numerically that the viscosity, often neglected in the literature, indeed plays a significant role in the effective properties of nanofluids.


High performance shape memory polymer networks based on rigid nanoparticle cores.
Smart materials that can respond to external stimuli are of widespread interest in biomedical science. Thermal-responsive shape memory polymers, a class of intelligent materials that can be fixed at a temporary shape below their transition temperature (T(trans)) and thermally triggered to resume their original shapes on demand, hold great potential as minimally invasive self-fitting tissue scaffolds or implants. The intrinsic mechanism for shape memory behavior of polymers is the freezing and activation of the long-range motion of polymer chain segments below and above T(trans), respectively. Both T(trans) and the extent of polymer chain participation in effective elastic deformation and recovery are determined by the network composition and structure, which are also defining factors for their mechanical properties, degradability, and bioactivities. Such complexity has made it extremely challenging to achieve the ideal combination of a T(trans) slightly above physiological temperature, rapid and complete recovery, and suitable mechanical and biological properties for clinical applications. Here we report a shape memory polymer network constructed from a polyhedral oligomeric silsesquioxane nanoparticle core functionalized with eight polyester arms. The cross-linked networks comprising this macromer possessed a gigapascal-storage modulus at body temperature and a T(trans) between 42 and 48 degrees C. The materials could stably hold their temporary shapes for > 1 year at room temperature and achieve full shape recovery <or= 51 degrees C in a matter of seconds. Their versatile structures allowed for tunable biodegradability and biofunctionalizability. These materials have tremendous promise for tissue engineering applications.


Mental Health of LGBTQ Older Adults.
More than 54 million people in the United States are aged ≥65 years, including an estimated 2.4 million people who identify as lesbian, gay, bi-sexual, transgender, or queer (LGBTQ). As a group, LGBTQ older adults experienced criminalization, discrimination, and social stigma the majority of their lives, with rates of victimization and stigma increasing with age. LGBTQ older adults continue to experience social and health disparities compared to heterosexual individuals. To meet the needs of LGBTQ older adults, it is necessary to understand the impact of politics, culture, and social norms as they came of age. Unique mental health needs, such as social isolation, loneliness, disenfranchised grief, and long-term social support, are discussed through the lens of the minority stress model. Implications and recommendations for health care, research, and policy, such as creating a safe and welcoming environment and providing culturally competent care for LGBTQ older adults, are discussed. [Journal of Psychosocial Nursing and Mental Health Services, 60(4), 7-10.].


Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening.
Severe combined immunodeficiency (SCID) is characterized by severely impaired T-cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pretransplantation care, and transplantation protocols for NBS identified infants with SCID, as well as infants with other T-lymphopenic disorders detected by using NBS. We developed approaches to management based on the study of infants identified by means of NBS for SCID who received care at the University of California, San Francisco (UCSF). From August 2010 through October 2016, 32 patients with NBS-identified SCID and leaky SCID from California and other states were treated, and 42 patients with NBS-identified non-SCID T-cell lymphopenia were followed. Our center's approach supports successful outcomes; systematic review of our practice provides a framework for diagnosis and management, recognizing that more data will continue to shape best practices.


Monte carlo simulation of heterotypic cell aggregation in nonlinear shear flow.
In this paper, we develop a population balance model for cell aggregation and adhesion process in a nonuniform shear flow. Some Monte Carlo simulation results based on the model are presented for the heterotypic cell-cell collision and adhesion to a substrate under dynamic shear forces. In particular, we focus on leukocyte (PMN)-melanoma cell emboli formation and subsequent tethering to the vascular endothelium (EC) as a result of cell-cell aggregation. The simulation results are compared with the results of experimental measurement. Discussions are made on how we could further improve the accuracy of the population balance type modelling.


Postoperative peritonitis due to gastric and duodenal fistulas. Operative management by continuous intraluminal infusion and aspiration: report of 23 cases.
A new surgical procedure is presented for the management of postoperative peritonitis due to a leak from a suture line in the stomach or the duodenum. At re-operation, an intraluminal unit made of three silicone tubes is inserted through the fistula into the bowel lumen. Extraluminal drains are placed near the fistula. A Witzel jejunostomy is constructed in order to provide continuous high energy enteral support. Intraluminal infusion and aspiration starts immediately after operation. Twenty-three patients have been treated according to this technique. Five died (22 per cent): one from mediastinitis and four from complications unrelated to the fistula. Three (13 per cent) patients developed recurrent abdominal abscesses and underwent re-operation for drainage with no mortality. In the first 2 weeks after operation, most of the discharge was collected by the extraluminal drains. Thereafter the intraluminal unit collected the majority of the fluid, thus allowing the extraluminal drains to be removed. At an average time of 27 days after operation the intraluminal unit was withdrawn. The external fistula created by this technique healed spontaneously in 15 of the 18 survivors, and was surgically closed in three, with no complication. This procedure prevents the recurrence of intra-abdominal sepsis and local complications due to the enzymatic action of the gastroduodenal secretions.


Extracellular vesicle biomarkers in circulation for the diagnosis of gastric cancer: A systematic review and meta‑analysis.
The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.


Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia.
Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM. A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β). COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients. Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.


Regioselective Generation of Single-Site Iridium Atoms and Their Evolution into Stabilized Subnanometric Iridium Clusters in MWW Zeolite.
Preparation of supported metal catalysts with uniform particle size and coordination environment is a challenging and important topic in materials chemistry and catalysis. In this work, we report the regioselective generation of single-site Ir atoms and their evolution into stabilized subnanometric Ir clusters in MWW zeolite, which are located at the 10MR window connecting the two neighboring 12MR supercages. The size of the subnanometric Ir clusters can be controlled by the post-synthesis treatments and maintain below 1 nm even after being reduced at 650 °C, which cannot be readily achieved with samples prepared by conventional impregnation methods. The high structure sensitivity, size-dependence, of catalytic performance in the alkane hydrogenolysis reaction of Ir clusters in the subnanometric regime is evidenced.