Brain age prediction using the graph neural network based on resting-state functional MRI in Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease that significantly impacts the quality of life of patients and their families. Neuroimaging-driven brain age prediction has been proposed as a potential biomarker to detect mental disorders, such as AD, aiding in studying its effects on functional brain networks. Previous studies have shown that individuals with AD display impaired resting-state functional connections. However, most studies on brain age prediction have used structural magnetic resonance imaging (MRI), with limited studies based on resting-state functional MRI (rs-fMRI). In this study, we applied a graph neural network (GNN) model on controls to predict brain ages using rs-fMRI in patients with AD. We compared the performance of the GNN model with traditional machine learning models. Finally, the post hoc model was also used to identify the critical brain regions in AD. The experimental results demonstrate that our GNN model can predict brain ages of normal controls using rs-fMRI data from the ADNI database. Moreover the differences between brain ages and chronological ages were more significant in AD patients than in normal controls. Our results also suggest that AD is associated with accelerated brain aging and that the GNN model based on resting-state functional connectivity is an effective tool for predicting brain age. Our study provides evidence that rs-fMRI is a promising modality for brain age prediction in AD research, and the GNN model proves to be effective in predicting brain age. Furthermore, the effects of the hippocampus, parahippocampal gyrus, and amygdala on brain age prediction are verified.


Endogenous anxiogenic peptide, ODN-diazepam-binding inhibitor, and benzodiazepines enhance the production of interleukin-1 and tumor necrosis factor by human monocytes.
Benzodiazepines (BZD) have been described to interact with specific peripheral-type receptors on phagocytes. The present study demonstrates that pico- to nanomolar concentrations of BZD compounds enhance the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by human monocytes, as determined by specific immunoreactive and biological assays for these cytokines. BZD remained ineffective in the absence of LPS. The activity of BZD was restricted to peripheral (Ro 5-4864) and mixed (diazepam, Valium) type ligands, while anxiogenic (beta-carbolines) or anxiolytic (clonazepam) central type ligands had no effect. Interestingly, peptide fragments of the endogenous anxiogenic ligand diazepam-binding inhibitor (DBI), such as octadecaneuropeptide (ODN-DBI) and the octaneuropeptide corresponding to its COOH-terminal sequence, very efficiently modulated the LPS-induced production of both monokines. Similar results were obtained directly within whole blood samples. These results indicate that widely prescribed pharmacological compounds and endogenous anxiety modulators affect molecular mediators of human host defense mechanisms and inflammatory reactions.


Retrospective, multicenter study of surgical treatment for carotid body tumors with or without preoperative embolization.
Carotid body tumor (CBT) is the most common head and neck paraganglioma. Whether preoperative embolization benefits CBT patients who will receive surgical resection is still controversial. In this multi-center retrospective study, we collected data from patients with CBT who received surgical treatment without (group A) or with preoperative embolization (group B) from 2011 to 2019. The primary outcome was the rate of death or stroke after 3 years of follow-up. The secondary outcomes of the study were length of operation (LOO), intraoperative blood loss (IBL), length of stay (LOS), rate of recurrence, and rate of cranial nerve (CN) injuries. Descriptive statistics were used to analyze the demographics, clinical characteristics, complications, and follow-up results of the patients. Between January 2011 and October 2019, 261 consecutive patients (107 male and 154 female) entered analysis. After 3 years of follow-up, no patient died in both groups. Only three patients with stroke were detected: 2/226 (0.9%) in group A vs. 1/35 (2.9%) in group B (p = .308). The LOO in group A was 132.6 ± 64.6 min compared with 152.9 ± 40.4 min in group B (p = .072). IBL in group A was 375.4 ± 497.8 ml compared with 448.0 ± 270.8 ml in group B (p = .400). LOS in group A was 8.3 ± 2.0 days compared with 7.4 ± 1.7 days in group B (p = .016). Seventy-two CN injuries were detected: 65/226 (28.8%) in group A vs. 7/35 (20.0%) in group B (p = .281). There were 65 temporary CN injuries (59 in group A vs. 6 in group B) (p = .254) and seven permanent CN injuries (6 in group A vs. 1 in group B) (p = .945). Three most frequently injured cranial nerves were the pharyngeal branch and superior laryngeal nerve (12.3%), recurrent laryngeal nerve (7.7%) and vagus nerve (7.3%). There was insufficient evidence to support the efficacy of preoperative embolization. CBT resection alone had a similar rate of stoke, recurrence, and CN injuries when compared with CBT resection with preoperative arterial embolization. Meanwhile, CBT resection alone did not increase LOO and IBL.


Laminin fragment E4 inhibition studies: basement membrane assembly and embryonic lung epithelial cell polarization requires laminin polymerization.
Laminins (LMs), the main constituents of basement membranes (BMs), are heterotrimeric glycoproteins composed of alpha, beta, and gamma chains held together by disulfide bonds. In the presence of Ca2+, some laminins, such as laminin-1 self-assemble into a polymer through the interaction of their three NH2 termini. Here we exposed lung organotypic cultures to a proteolytic fragment of laminin-1 that blocks laminin polymerization. This fragment, referred as E4, comprises the outer globular region of laminin beta1 chain. Inhibition of laminin polymerization in lung organotypic cultures resulted in impaired basement membrane assembly and failure of epithelial cells to polarize. In addition, we found that in control organotypic cultures, the bronchial smooth muscle cells were arranged in concentric layers around the newly formed epithelium. However, in E4-treated cultures, the smooth muscle cells were in disarray. Exposure of organotypic cultures to laminin-1 proteolytic fragment P1', that comprises part of alpha1, beta1, and gamma1 chains, but does not overlap with fragment E4, had no effect in basement membrane assembly. Exposure to fragment E4 also caused an increased release of laminin-1 into the culture medium, suggesting a failure to retain laminin at the epithelial-mesenchymal interface. These studies provide the first direct evidence linking epithelial cell polarization to laminin polymerization at the epithelial-mesenchymal interface and assign a key role to the outer globular region of laminin beta1 chain.


Prediction of the Potential Mechanism of Triptolide in Improving Diabetic Nephropathy by Utilizing A Network Pharmacology and Molecular Docking Approach.
Triptolide (TP) is a major active component of colquhounia root tablet, which has been long been used in China to treat diabetic nephropathy (DN) due to its marked anti‑inflammatory, antiproteinuric, and podocyte‑protective effects. This study investigated the anti-proteinuria activity and related signaling cascade of TP in DN by utilizing a network pharmacology and molecular docking approach. From the GeneCard, DisGeNET, and National Center for Biotechnology Information Gene databases, 1458 DN targets were obtained and input together with 303 TP targets into Venny2.1.0 for mapping and comparing. In total, 113 common targets of TP and DN were obtained, of which 7 targets were found to play an important role through theoretical inhibitory constant analysis. The common targets were further analyzed by Kyoto Encyclopedia of Genes and Genomes to identify the pathways related to the therapeutic effect of TP on DN. Among them, the seven targets were found to play key roles in six signaling pathways. The molecular docking results also showed TP had good binding ability to the seven targets. Analysis of the common targets and key pathways showed that TP can improve DN via its anti-nephritis, anti-renal fibrosis, antioxidant, and podocyte-protective effects, which might elucidate the mechanism by which TP improves renal function and reduces proteinuria in DN.


Subcutaneous pedicled propeller flap technique for microscopic reconstruction of eyelid defects.
To describe the subcutaneous pedicled propeller flap technique for the microscopic reconstruction of eyelid defects and evaluate its outcomes. The clinical data of 23 patients (23 eyes) who underwent microscopic reconstruction of eyelid defects with the subcutaneous pedicled propeller flap technique were retrospectively analyzed. All patients underwent eyelid tumor resection and one-stage microscopic reconstruction with the subcutaneous pedicled propeller flap for anterior- or posterior-layer eyelid defects. The survival rate of the propeller flap, eyelid function and appearance, tumor recurrence rate, and patient satisfaction were evaluated after the surgery. The patients consisted of 12 men and 11 women, aged 31-82y (mean, 58.9y). The longest follow-up time was 5y, and the shortest was 3mo. All the propeller flaps survived well. There was no significant difference in color and luster between the flap and adjacent tissues, and there was no dog ear phenomenon. No obvious scarring was observed. There were no obvious abnormalities of eyelid morphology or function, and no adverse complications such as exposure keratitis, entropion, ectropion, ptosis, and eyelid retraction. No tumor recurrence was found at the time of the last follow-up. All patients were satisfied with the surgical results. The subcutaneous pedicled propeller flap technique for the microscopic reconstruction of eyelid defects has satisfactory outcomes in terms of eyelid function and esthetics, and merits clinical application.


Spatial organization of frequency response areas and rate/level functions in the developing AI.
The current study was conducted to extend our understanding of changes in spatial organization and response properties of cortical neurons in the developing mammalian forebrain. Extracellular multiunit responses to tones were recorded from a dense array of penetrations covering entire isofrequency contours in the primary auditory cortex (AI) of pentobarbital anesthetized kittens. Ages ranged from postnatal day 14 (P14), shortly after acquisition of normal auditory response thresholds, through postnatal day 111 (P111), when the kittens were largely mature. Spatial organization of the AI was tonotopically ordered by P14. The tonotopic gradient decreased with chronological maturation. At P14 the gradient was about 3.5 kHz/mm. By P111 it had declined to about 2.5 kHz/mm, so that the cortical region encompassing a fixed 3- to 15-kHz frequency range enlarged along its posterior-anterior dimension. Response properties of developing AI neurons changed in both frequency selectivity and intensity selectivity. The mean frequency tuning bandwidth increased with age. Initially, tuning bandwidths were narrow throughout the entire AI. With progressive maturation, broader bandwidths were observed in areas dorsal and ventral to a central region in which neurons remained narrowly tuned. The resulting spatial organization of tuning bandwidth was similar to that reported in adult cats. The majority of recording sites manifested nonmonotonic rate/level functions at all ages. However, the proportion of sites with monotonic rate/level functions increased with age. No spatial organization of rate/level functions (monotonic and nonmonotonic) was observed through P111. The relatively late development of bandwidth tuning in the AI compared with the early presence of tonotopic organization suggests that different developmental processes are responsible for structuring these two dimensions of acoustic selectivity.


[Investigation on reproductive tract infection among floating married women of childbearing age in Fengtai district in Beijing].
In order to develop plans for effective intervention measures, prevalence and health-seeking behavior related to reproductive tract infection among floating married women of childbearing age in Fengtai district in Beijing were studied. Cross-sectional study was carried out. Two thousand and sixty-nine eligible women were randomly selected from strata based on their home provinces. From June to July 2001, the subjects were given face-to-face interview at the Fengtai family planning clinic in Beijing using standard questionnaire followed by gynecologic examination and laboratory tests. Thirty point three percent of the subjects were found to have reproductive tract infections (RTI) by laboratory tests. Prevalence rates of bacterial vaginosis, candida and trichomonas vaginitis were 22.2%, 4.9% and 2.1% respectively. Prevalence rates of chlamydia, gonorrhea, condyloma acuminatum and syphilis were 2.2%, 1.6%, 0.5% and 0.2% respectively. Of these infected women, only 43.1% (270/626) were symptomatic, and 61.5% (166/270) of these women with symptoms had sought treatment. Compared to other results in the literature, we found a relatively high prevalence of RTI in our study population. Only a small proportion of these infected women were symptomatic but only few of them sought treatment. We suggested that the provision of more family planning service and promotion of RTI knowledge to the floating women of childbearing age.


Athletes as health testing examinees.
Health-testing examination data of 91 male and 54 female athletes were studied, together with age-matched controls, on serum biochemistry, ECG findings, hematology, and some data on gynecological physiology. Analysis of serum biochemical values revealed statistically significant differences in 14 of 18 routine test items as compared with the age-matched controls. In ECG findings, the combination of bradycardia and left ventricular hypertrophy was most frequently found in male athletes, whereas that of bradycardia and sinus arrhythmia was observed predominantly in female athletes. The incidence of anemia and menstrual dysfunction was higher in female athletes than in controls, especially in the basketball team. In the same team, a high rate of deviant ECG records and a different distribution of the age at menarche were also observed.


Role of vascularised tissue transfer after oncological resection in the upper extremity.
We reviewed 12 patients who had had vascularised tissue transfer after oncological resection in the upper extremity. All patients had immediate reconstruction, and one had a double tissue transfer. Tissues used were skin flaps, free muscles, and vascularised fibulas, for resurfacing the wound, motor recovery, and reconstruction of large bony defects, respectively. All the patients returned early to their daily activities. Although local recurrences were encountered in two patients, they were again rendered disease-free by salvage operations. Two patients had secondary reconstructions using pedicle latissimus dorsi flaps for late problems, including one of the two patients who developed a local recurrence. The mean functional score using the system devised by the Musculoskeletal Tumor Society was 84%. All the upper extremities were successfully rescued with satisfactory function. Vascularised tissue transfer was invaluable for achieving both curative resection of the tumour and a useful upper extremity.


[The role of driver and subclonal mutations in pathogenesis of primary myelofibrosis].
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone marrow biopsy shows features of abnormal proliferation of terminally differentiated megakaryocytes and subsequent bone marrow fibrosis. The molecular landscape of PMF includes phenotypic driver mutations (JAK2 V617F, CALR and MPL) which represent major diagnostic criteria, and subclonal mutations that also occur in several other myeloid diseases, but have a prognostic value in disease progression of MF. The most important subclonal mutations affect the genes ASXL1, TET2, IDH1/2, EZH2 and TP53. Triple negative genotype and the high molecular risk genotype and CALR-/ASXL1+ are associated with adverse survival with the latest indicating stem cell transplantation independently of the DIPSS-plus score.


Intersections between COVID-19 and socio-economic mental health stressors in the lives of South African adolescent girls and young women.
In contexts where poverty and mental health stressors already interact to negatively impact the most vulnerable populations, COVID-19 is likely to have worsened these impacts. Before the COVID-19 pandemic, adolescent girls and young women (AGYW) in South Africa already faced intersecting mental health stressors and vulnerabilities. It is critical to understand how additional challenges brought on by COVID-19 have intersected with existing vulnerabilities and mental health risks AGYW faced, particularly given the intersections between psychological distress and increased risk behaviours that impact sexual and reproductive health. We aimed to examine socio-economic and mental health impacts of COVID-19 on South African AGYW in order to understand how additional challenges brought on by COVID-19 have intersected with existing challenges, compounding AGYW vulnerabilities. Using qualitative and quantitative methods, framed by the syndemic theory, we examined the intersections between mental health and the COVID-19 epidemic amongst AGYW in six districts of South Africa characterised by high rates of HIV, teenage pregnancy and socio-economic hardship. Between November 2020 and March 2021 we conducted a cross-sectional telephone survey with 515 AGYW, and in-depth interviews with 50 AGYW, aged 15 to 24 years. Our findings reveal how COVID-19 restrictions led to increased experiences of stress and anxiety. Poor mental health was compounded by strained family relationships, increased fear of domestic violence, household unemployment, economic stress and food insecurity. Respondents described feelings of boredom, frustration, isolation, loneliness, fear and hopelessness. However, despite the multitude of challenges, some AGYW articulated emotional resilience, describing ways in which they coped and retained hope. Various psycho-social risk factors already disproportionally affect the mental health of AGYW in these communities; the COVID-19 pandemic intersects with these pre-existing social and environmental factors. Understanding strategies AGYW have used to positively cope with the uncertainty of COVID-19 amongst an array of pre-existing mental health stressors, is key in informing efforts to respond to their needs. Multisectoral interventions are needed to address the drivers of poor mental health among AGYW, and bolster healthy coping mechanisms; interventions seeking to mitigate the mental health impacts on this vulnerable population need to be responsive to the unpredictable pandemic environment.


Combined retinal-retina pigment epithelial hamartoma presenting as a vitreous hemorrhage.
A 2-year-old healthy white boy had a vitreous hemorrhage in the left eye but no history or external signs of trauma. Computed tomographic and ultrasonographic examinations were not diagnostic. A pars plana vitrectomy performed when the patient was 2 1/2 years old revealed a posterior pole lesion diagnosed clinically as a combined retinal-retina pigment epithelial hamartoma. Such lesions may be symptomatic because of decreased vision, macular puckering, and strabismus; vitreous hemorrhage has not previously been reported as the presenting clinical sign or the predominant cause for reduced vision.


Sensation Seeking and Online Gaming Addiction in Adolescents: A Moderated Mediation Model of Positive Affective Associations and Impulsivity.
Based on the Dual Systems Model (Somerville et al., 2010; Steinberg, 2010a) and the biosocial-affect model (Romer and Hennessy, 2007) of adolescent sensation seeking and problem behaviors, the present study examined how (affective associations with online games as a mediator) and when (impulsivity as a moderator) did sensation seeking influence online gaming addiction in adolescence. A total of 375 Chinese male adolescents (mean age = 16.02 years, SD = 0.85) from southern China completed anonymous questionnaires regarding sensation seeking, positive affective associations with online games, impulsivity, and online gaming addiction. Our findings revealed that sensation seeking, positive affective associations with online games and impulsivity were each significantly and positively associated with online gaming addiction in adolescents. Positive affective associations mediated the relationship between sensation seeking and online gaming addiction. Further, impulsivity moderated the relationship between positive affective associations and online gaming addiction, such that the association between positive affective association and online gaming addiction was stronger for high than for low impulsivity adolescents. These findings underscore the importance of integrating the biosocial-affect model and the Dual Systems Model to understand how and when sensation seeking impacts adolescent online gaming addiction.


Liposomal polyamine-dialkyl phosphate conjugates as effective gene carriers: chemical structure, morphology, and gene transfer activity.
Synthetic cationic lipids are promising transfection agents for gene therapy. We report here that polyamine conjugates of dialkyl phosphates, combined with natural lipids and assembled in the form of liposomes (polycationic liposome: PCL), possess high transfection activity in the COS-1 cell line. Furthermore, we describe the functional morphology of the PCL/DNA complexes as revealed by atomic force microscopy (AFM). The conjugates were synthesized from dialkyl phosphates (with alkyl chain lengths of 12, 14, or 16 carbons) by reaction with the polyamine molecules, spermidine, spermine, or polyethylenimine (PEI(1800)). [Dewa, T., et al. Bioconjugate Chem. 2004, 15, 824]. The PCL composed of the spermidine and C16 conjugate combined with phospholipid and cholesterol (conjugate/phospholipid/cholesterol = 1/1/1 as a molar ratio) exhibited 3.6 times higher activity than that of a popular commercial product. Systematic tests revealed clear correlations of the transgene activity with physical properties of the polyamine, in particular, that longer alkyl chains and the lower molecular weight polyamines (spermidine, spermine) favor high efficacy at the higher nitrogen/phosphate ratio = 24 (N/P, stoichiometric ratio of nitrogen in the conjugate to phosphate in DNA). The low molecular weight polyamine-based PCLs, which formed 150-400 nm particles with plasmid DNA (lipoplexes), exhibited approximately 3-fold higher gene transfer activity than micellar aggregates (lacking phospholipid and cholesterol) of the corresponding conjugate. In contrast, the PEI-based PCL formed large aggregates (approximately 1 microm), that, like the micellar aggregate form, had low activity. Activity of the low molecular weight polyamine-based PCLs increased linearly with the N/P of the lipoplex up to N/P = 24. Formation of lipoplexes was examined by agarose gel electrophoresis, dynamic light scattering (DLS), and AFM. At the lower N/P = 5, large aggregates of complex (approximately 1 microm), in which DNA molecules were loosely packed, were observed. At higher N/P, lipoplexes were converted into smaller particles (150-400 nm) having a lamellar structure, in which DNA molecules were tightly packed. Such morphological features of the lipoplex correlate with the dependence of transfection on the N/P in that the lamellar structures gave superior transfection. AFM also indicated that the lipoplexes disassembled significantly, releasing DNA, when the lipoplexes were exposed to acidic conditions (pH 4). The significance for transfection activity of the metamorphosis of bilayer lipoplexes is discussed relative to that of the less active micellar aggregate form, which is unresponsive to pH change.


Imaging pyrometry for most color cameras using a triple pass filter.
A simple combination of the Planck blackbody emission law, optical filters, and digital image processing is demonstrated to enable most commercial color cameras (still and video) to be used as an imaging pyrometer for flames and explosions. The hardware and data processing described take advantage of the color filter array (CFA) that is deposited on the surface of the light sensor array present in most digital color cameras. In this work, a triple-pass optical filter incorporated into the camera lens allows light in three 10-nm wide bandpass regions to reach the CFA/light sensor array. These bandpass regions are centered over the maxima in the blue, green, and red transmission regions of the CFA, minimizing the spectral overlap of these regions normally present. A computer algorithm is used to retrieve the blue, green, and red image matrices from camera memory and correct for remaining spectral overlap. A second algorithm calibrates the corrected intensities to a gray body emitter of known temperature, producing a color intensity correction factor for the camera/filter system. The Wien approximation to the Planck blackbody emission law is used to construct temperature images from the three color (blue, green, red) matrices. A short pass filter set eliminates light of wavelengths longer than 750 nm, providing reasonable accuracy (±10%) for temperatures between 1200 and 6000 K. The effectiveness of this system is demonstrated by measuring the temperature of several systems for which the temperature is known.


[Prosthetic management in cases of generalized destruction of dental crowns].
Disturbances in stomatognathic system (ss) emerging as a result of generalized destruction of dental crowns of noncarious origin have been described in the article. Principles of two-stage rehabilitation of ss have been presented. Three own cases creating examples of two-stage prosthetic rehabilitation have been described.


Effect of icariin on fracture healing in an ovariectomized rat model of osteoporosis.
Osteoporosis is frequently asymptomatic, presenting a significant clinical and economic burden, particularly following an osteoporosis-associated fracture. Icariin has been reported to inhibit osteoporosis in vitro, and the present study investigated whether icariin also promoted bone fracture healing in ovariectomized osteoporotic (OVX) rats in vivo. A total of 30 female rats were randomly divided into three groups (n=10 per group): i) Sham surgery; ii) OVX; and iii) OVX with icariin (OVX + ICA) groups. At 3 months after the ovariectomy, a unilateral cross-tibia fracture was made at the proximal right tibia. Animals were then sacrificed after 5 weeks of oral treatment. X-rays were taken at 1 week, 3 weeks and 5 weeks of treatment, and dual energy X-ray absorptiometry was used to measure the bone mineral density (BMD). Changes to the osteocalcin (BGLAP), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and estradiol levels in blood were measured. Callus formation and bone union were observed, the BMD was significantly higher and the BGLAP, ALP and TRAP levels were reduced, but no significant increase was observed in the blood estradiol level in the OVX + ICA group compared with the OVX group. The present findings indicate that icariin has potential as a novel alternative therapeutic agent for fracture healing in postmenopausal osteoporosis.


Size-Resolved Field Performance of Low-Cost Sensors for Particulate Matter Air Pollution.
Particulate matter (PM) air pollution is a major health hazard. The health effects of PM are closely linked to particle size, which governs its deposition in (and penetration through) the respiratory tract. In recent years, low-cost sensors that report particle concentrations for multiple-sized fractions (PM1.0, PM2.5, PM10) have proliferated in everyday use and scientific research. However, knowledge of how well these sensors perform across the full range of reported particle size fractions is limited. Unfortunately, erroneous particle size data can lead to spurious conclusions about exposure, misguided interventions, and ineffectual policy decisions. We assessed the linearity, bias, and precision of three low-cost sensor models, as a function of PM size fraction, in an urban setting. Contrary to manufacturers' claims, sensors are only accurate for the smallest size fraction (PM1). The PM1.0-2.5 and PM2.5-10 size fractions had large bias, noise, and uncertainty. These results demonstrate that low-cost aerosol sensors (1) cannot discriminate particle size accurately and (2) only report linear and precise measures of aerosol concentration in the accumulation mode size range (i.e., between 0.1 and 1 μm). We recommend that crowdsourced air quality monitoring networks stop reporting coarse (PM2.5-10) mode and PM10 mass concentrations from these sensors.


Dendritic cells conditioned by activin A-induced regulatory T cells exhibit enhanced tolerogenic properties and protect against experimental asthma.
Previously, we demonstrated that regulatory T (Treg) cells induced by the cytokine activin-A suppress TH2-mediated allergic responses and linked airway disease. Still, the effects of activin-A-induced regulatory T (Act-A-iTreg) cells on the regulation of dendritic cell (DC)-driven allergic inflammation remain elusive. Here we investigated whether Act-A-iTreg cells can modulate DC responses and endow them with enhanced tolerogenic functions. Using adoptive cell transfer studies in mouse models of allergic airway disease, we examined the effects of Act-A-iTreg cells on DC phenotype, maturation status, and TH2 cell priming potential. Genome-wide gene expression profiling characterized the transcriptional networks induced in tolerogenic DCs by Act-A-iTreg cells. The ability of DCs conditioned by Act-A-iTreg cells (Act-A-iTreg cell-modified DCs) to protect against experimental asthma, and the mechanisms involved were also explored. Act-A-iTreg cell-modified DCs exhibited a significantly impaired capacity to uptake allergen and stimulate naive and TH2 effector responses on allergen stimulation in vivo accompanied by markedly attenuated inflammatory cytokine release in response to LPS. Gene-profiling studies revealed that Act-A-iTreg cells dampened crucial TH2-skewing transcriptional networks in DCs. Administration of Act-A-iTreg cell-modified DCs ameliorated cardinal asthma manifestations in preventive and therapeutic protocols through generation of strongly suppressive forkhead box P3+ Treg cells. Finally, programed death protein 1/programmed death ligand 1 signaling pathways were essential in potentiating the generation of DCs with tolerogenic properties by Act-A-iTreg cells. Our studies reveal that Act-A-iTreg cells instruct the generation of a highly effective immunoregulatory circuit encompassing tolerogenic DCs and forkhead box P3+ Treg cells that could be targeted for the design of novel immunotherapies for allergic disorders.


FDG-Avid Focal Liver Reaction From Proton Therapy in a Patient With Primary Esophageal Adenocarcinoma.
A 25-year-old man with IgA deficiency was treated with 2 months of chemotherapy and proton therapy for gastroesophageal junction adenocarcinoma. Restaging PET/CT 18 days posttherapy demonstrated 2 new foci of increased FDG uptake in the left hepatic lobe, which were favored to represent radiation injury as opposed to new metastases. Follow-up MRI with contrast 2 weeks later demonstrated hypoenhancement and T1/T2 hypointensity in the liver, without restricted diffusion, which correlated with the dominant FDG-avid focus. The hepatic lesions resolved on subsequent FDG PET/CT and MRI studies, confirming the diagnosis of acute radiation injury.


De novo versus transformed atypical and anaplastic meningiomas: comparisons of clinical course, cytogenetics, cytokinetics, and outcome.
The clinical course of atypical and anaplastic meningiomas is heterogeneous. As malignant gliomas, aggressive meningiomas may arise de novo or transform from a benign tumor. This study aims to compare differences in clinical behavior, cytogenetics, cytokinetics, receptor status, and outcome between de novo malignant meningiomas and meningiomas that progressed to malignancy. Data from 36 patients with atypical or anaplastic meningiomas were selected for retrospective analysis and divided into two subgroups: 1) de novo atypical or anaplastic tumors and 2) tumors that progressed from a lower grade. We analyzed data concerning patients' sex, age, tumor location, number of operations, status of hormone receptors, proliferative indices, cytogenetic findings, additional therapy, and survival. For meningiomas with progression, we calculated the interval between initial diagnosis and tumor progression. For atypical meningiomas, the subgroups had significant differences in status of progesterone receptors, proliferative indices, cytogenetics, and patients' outcome. The anaplastic group had similar differences, but they did not reach statistical significance because of the small numbers. There was a loss of part or monosomy of chromosome 10 and an increased monosomy or derivative chromosome 1 combined with monosomy of chromosome 14. These phenomena occurred mainly in patients with malignant transformation who had a worse outcome. De novo malignant meningiomas and meningiomas with malignant transformation may represent distinct subgroups of atypical and anaplastic meningiomas.


Micropatterned supported membranes as tools for quantitative studies of the immunological synapse.
In living cells, membrane receptors transduce ligand binding into signals that initiate proliferation, specialization, and secretion of signaling molecules. Spatial organization of such receptors regulates signaling in several key immune cell interactions. In the most extensively studied of these, a T cell recognizes membrane-bound antigen presented by another cell, and forms a complex junction called the "immunological synapse" (IS). The importance of spatial organization at the IS and the quantification of its effect on signaling remain controversial topics. Researchers have successfully investigated the IS using lipid bilayers supported on solid substrates as model antigen-presenting membranes. Recent technical developments have enabled micron- and nanometre-scale patterning of supported lipid bilayers (SLBs) and their application to immune cell studies with provocative results, including spatial mutation of the IS. In this tutorial review, we introduce the IS; discuss SLB techniques, including micropatterning; and discuss various methods used to perturb and quantify the IS.


Do standard doses of frequently prescribed drugs cause preventable adverse effects in women?
Adverse effects from prescription medications are a leading cause of disability and death in the United States, and more than 75% of these adverse effects are dose related. This analysis examines women's experience with dose-related adverse effects of several major medication groups, induding oral contraceptives, hormone replacement therapy, anti-inflammatory drugs, antihypertensives, statins, and others. The original recommended doses for oral contraceptives and conjugated estrogens were 100% to 800% higher than the doses recommended today. Unnecessarily high doses of ibuprofen and terfenadine were linked to serious and lethal dose-related adverse effects, and proven effective lower doses of celecoxib, fluoxetine, omeprazole, and many other medications were not initially marketed or recommended. Much of the data on effective low doses of drugs is not readily available to physicians or patients. The lack of information on or recommendations for the lowest, proven-effective doses of many major medications may in part explain the continued high incidence of dose-related adverse effects. The findings in this article suggest that women, especially elderly women, may be prone to adverse effects linked to unnecessarily high drug doses.


Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages.
The novel SARS-CoV-2 variant, Omicron (B.1.1.529), is being testified, and the WHO has characterized Omicron as a variant of concern due to its higher transmissibility and very contagious behavior, immunization breakthrough cases. Here, the comparative proteomic study has been conducted on spike-protein, hACE2 of five lineages (α, β, δ, γ and Omicron. The docking was performed on spike protein- hACE-2 protein using HADDOCK, and PRODIGY was used to analyze the binding energy affinity using a reduced Haddock score. Followed by superimposition in different variant-based protein structures and calculated the esteem root mean square deviation (RMSD). This study reveals that Omicron was seen generating a monophyletic clade. Further, as α variant is the principal advanced strain after Wuhan SARS-CoV-2, and that is the reason it was showing the least likeness rate with the Omicron and connoting Omicron has developed of late with the extreme number of mutations. α variant has shown the highest binding affinity with hACE2, followed by β strain, and followed with γ. Omicron showed a penultimate binding relationship, while the δ variant was seen as having the least binding affinity. This proteomic basis in silico analysis of variable spike proteins of variants will impart light on the development of vaccines and the identification of mutations occurring in the upcoming variants.


Ankle foot orthoses for young children with cerebral palsy: a scoping review.
To describe research on outcomes associated with early Ankle Foot Orthosis (AFO) use, AFO use patterns, and parent and clinician perspectives on AFO use among young children with cerebral palsy. Arksey and O'Malley's five-stage method was used to conduct a scoping review. MEDLINE (Ovid), PubMed, CINAHL, Cochrane Database of Systematic Reviews, EMBASE, PEDro, Web of Science and Scopus were searched for studies evaluating AFO use with children under the age of six years. Descriptive information was extracted and outcomes categorized according to the International Classification of Functioning, Disability and Health (ICF). Quality assessments were conducted to evaluate methodological rigor. Nineteen articles were included in the review; 14 focused on body functions and structures, seven on activity level outcomes and no studies addressed participation outcomes. Evaluations of the effects of AFOs on gross motor skills other than gait were limited. Overall, the body of evidence is comprised of methodologically weak studies with common threats to validity including inadequate descriptions of study protocols, AFO construction, and comparison interventions. Research evaluating the effects of AFOs on age-appropriate, functional outcomes including transitional movements, floor mobility and participation in early childhood settings is needed to inform practice regarding early orthotic prescription. Implications for rehabilitationLack of rigorous evidence about the effects of AFOs in young children limits the ability of research to guide practice in pediatric rehabilitation.More rigorous research that evaluates a broader range of age-appropriate outcomes, including those focused on participation in meaningful activities, could further inform clinical practice.While clinicians often discuss expectations and goals with individual families, qualitative research that provides more insight into the experiences of families could guide AFO prescription and monitoring practices.


Hormonal and cardiorenal responses to acute saline loading in mild congestive heart failure--the effect of angiotensin converting enzyme inhibition.
We investigated cardiorenal responses to acute saline loading in patients with mild congestive heart failure (CHF) with and without angiotensin-converting enzyme (ACE) inhibition. Saline loading (infusion of 250 ml of normal saline) was performed on 10 patients with mild CHF and 10 control subjects. Although saline loading reduced plasma renin activity and plasma angiotensin II to a similar extent in both groups, it increased cardiac output, renal blood flow, and the ratio of renal blood flow to cardiac output in the mild CHF group but not in the control group. After saline loading, urinary sodium excretion was higher in the control than in the mild CHF group. In the mild CHF group, saline loading was performed again after an ACE inhibitor (delapril) had been administered for 5 days. Although delapril increased cardiac output and renal blood flow under basal conditions, saline loading did not affect these variables. Delapril improved urinary sodium excretion after saline loading. Thus, the renin-angiotensin-aldosterone axis may contribute to cardiorenal hemodynamics and renal sodium handling in patients with mild CHF. This effect may attenuate the natriuretic response to acute saline loading, and administration of an ACE inhibitor improves this attenuation.


Association between ALT/AST and Muscle Mass in Patients with Type 2 Diabetes Mellitus.
The alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio is thought to be related to metabolic disorders and insulin resistance. Type 2 diabetes mellitus (T2DM) is a high-risk population for low muscle mass. This study was performed to evaluate the association between ALT/AST and muscle mass in subjects with T2DM. This cross-sectional study enrolled 1068 subjects (566 males and 502 females) with T2DM. General information, medical history, and blood samples were collected. Skeletal muscle index (SMI) was detected using dual-energy X-ray absorptiometry. Logistic regression analysis was utilized to determine the correlation of ALT/AST and low muscle mass in subjects with T2DM. Multiple linear regression analysis was utilized to evaluate the association between ALT/AST, SMI and other metabolic characteristics. Of all subjects, 115 men (20.3%) and 71 women (14.1%) presented low muscle mass. ALT/AST was related to an increased risk for low muscle mass in both genders. Multiple linear regression analysis displayed that SMI was negatively associated with ALT/AST, age, glycosylated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL) in male group. While in female group, SMI was positively associated with systolic blood pressure (SBP) and negatively associated with ALT/AST and age. Furthermore, ALT/AST was associated with age and BMI in both genders. ALT/AST was negatively associated with muscle mass in subjects with T2DM.


Molecular Dynamics Investigation on the Inhibition of MDM2-p53 Interaction by Polyphenols.
Inhibition of the MDM2-p53 interaction has become a new therapeutic strategy to activate wild type p53 in tumors. Quercetin and taxifolin bind to p53 binding hydrophobic groove of MDM2, and alter the conformation of groove as evidenced by 65 ns molecular dynamics simulation. Quercetin showed hydrogen bonding with Gly 16, Ser 17, Phe 55 and Val 93 along with π-π interaction with His96 and π-σ with Phe 55. Taxifolin also showed similar interactions except π-σ interaction with Phe 55. Further, we found that binding of ligands lead to the dissociation of MDM2-p53 complex. These ligands form stable hydrophobic interactions with MDM2 which led to complete disruption of MDM2-p53 hydrophobic interactions and dissociation of p53 from the complex. It was found that the π-π stacking between Tyr 51 of MDM2 and ligands is the critical event in MDM2-p53 dissociation.


Fractional nonablative laser resurfacing: is there a skin tightening effect?
Fractional photothermolysis, an approach to laser skin resurfacing that creates microscopic thermal wounds in skin separated by islands of spared tissue, was developed to overcome the high incidence of adverse events and prolonged healing times associated with full coverage ablative laser procedures. To examine whether fractional nonablative laser resurfacing induces skin tightening. A literature review was performed to evaluate the clinical and histologic effects of fractional nonablative laser resurfacing and full coverage ablative resurfacing procedures. Fractional nonablative lasers produce excellent outcomes with minimal risk and morbidity for a variety of clinical conditions, including photodamaged skin, atrophic scars, surgical and burn scars. Efforts to induce robust fibroplasia in histologic specimens and skin tightening in the clinical setting have yielded inconsistent results. A better understanding of the histology of fractional laser resurfacing will help to optimize clinical outcomes.


Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation.
Common genetic variants at the RIN3 locus on chromosome 14q32 predispose to Paget's disease of bone (PDB) but the mechanisms by which they do so are unknown. Here, we analysed the skeletal phenotype of female mice with targeted inactivation of the mouse Rin3 gene (Rin3-/-) as compared with wild-type littermates. The Rin3-/- mice had higher trabecular bone volume (BV/TV%) compared with wild type. Mean ± standard deviation values at the distal femur at 8 weeks were 9.0 ± 2.5 vs. 7.0 ± 1.5 (p = 0.002) and at 52 weeks were 15.8 ± 9.5 vs. 8.5 ± 4.2 (p = 0.002). No differences were observed in femoral cortical bone parameters with the exception of marrow diameter which was significantly smaller in 52-week-old Rin3-/- mice compared to wild type: (0.43 mm ± 0.1 vs. 0.57 mm ± 0.2 (p = 0.001). Bone histomorphometry showed a lower osteoclast surface / bone surface (Oc.S/BS%) at 8 weeks in Rin3-/- mice compared to wild type (24.1 ± 4.7 vs. 29.7 ± 6.6; p = 0.025) but there were no significant differences in markers of bone formation at this time. At 52 weeks, Oc.S/BS did not differ between genotypes but single labelled perimeter (SL.Pm/B.Pm (%)) was significantly higher in Rin3-/- mice (24.4 ± 6.4 vs. 16.5 ± 3.8, p = 0.003). We conclude that Rin3 negatively regulates trabecular bone mass in mice by inhibiting osteoclastic bone resorption and favouring bone formation. Our observations also suggest that the variants that predispose to PDB in humans probably do so by causing a gain-in-function of RIN3.


Theoretical and empirical derivation of cardiovascular allometric relationships in children.
Basic fluid dynamic principles were used to derive a theoretical model of optimum cardiovascular allometry, the relationship between somatic and cardiovascular growth. The validity of the predicted models was then tested against the size of 22 cardiovascular structures measured echocardiographically in 496 normal children aged 1 day to 20 yr, including valves, pulmonary arteries, aorta and aortic branches, pulmonary veins, and left ventricular volume. Body surface area (BSA) was found to be a more important determinant of the size of each of the cardiovascular structures than age, height, or weight alone. The observed vascular and valvar dimensions were in agreement with values predicted from the theoretical models. Vascular and valve diameters related linearly to the square root of BSA, whereas valve and vascular areas related to BSA. The relationship between left ventricular volume and body size fit a complex model predicted by the nonlinear decrease of heart rate with growth. Overall, the relationship between cardiac output and body size is the fundamental driving factor in cardiovascular allometry.


[Interest of sentinel lymph node biopsy for the staging of ductal carcinoma in situ].
The aim of this study was to define the interest of sentinel lymph node biopsy (SLNB) for the staging of ductal carcinoma in situ (DCIS) and DCIS with micro-invasion (DCISM) in patients with breast carcinoma. From June 1999 to December 2002 we listed, in a retrospective study, 52 patients treated surgically for a DCIS or a DCISM. All except one had an histology before surgery, and all had SLNB. Intraoperative imprint cytology of the sentinel lymph node (SLN) was performed then there were analysed by staining with hematoxylin-eosin. Patients with positive SLN underwent complete axillary dissection. It was removed an average of three SLNs by patient (extreme 1 to 6). Metastases in the SLN were detected in four (7,7%) of the 52 patients, including three cases had only micrometastases in the SLN. In the four patients treated with complete axillary dissection, the SLN were the only positives nodes. The SLNB for DCIS and DCISM increases the involvement rate of lymph node. Because of the widespread for early detection of breast cancer, it is noted a regular increase in the rate of DCIS. Even if the attitude to be had towards the lymph node metastases in these cases is not yet well defined, and so only 2% of the patients approximately die of this pathology, it is interesting because of increase in absolute value of mortality, to try to improve the prognosis criteria to modify the treatment of this pathology.


MRI analysis of structural changes in skeletal muscles and surrounding tissues following long-term walking exercise with training equipment.
Muscular recovery after exercise is an important topic in sports medicine, and accurate and quantitative measurements of changes in muscle are required to assess muscular recovery. In the present study, we report a new analytical method to measure muscular changes quantitatively. The technique consists of three independent methods: image processing of two-dimensional MR images, morphological analysis using three-dimensional MR images, and diffusion tensor MRI. Using this method, we investigated changes in the quadriceps and biceps femoris and gluteus maximus muscles and surrounding tissues before and after 1 mo of exercise wearing training equipment. The subjects were 21 healthy adult female volunteers, 14 of whom wore training equipment and 7 who wore normal equipment. The percentage of adipose tissue in muscle after exercise in subjects who wore training equipment was on average 4.4% (P < 0.001) lower than that before exercise, and the peak point of the dorsal hip after exercise with use of the equipment was on average 10.8 mm higher than that before exercise. Further, the fractional anisotropy of water diffusion in muscles increased by an average of 0.039 (P < 0.001) after exercise with use of training equipment. In contrast, there was no significant difference before and after exercise in subjects who wore normal equipment. These results show that walking exercise while wearing training equipment thickens and tightens the muscular fiber tissues. This noninvasive measurement approach may allow quantitation of the athletic ability of the muscles, which is not measured conventionally, and is an effective method for analyzing skeletal muscles.


Educational attainment, continued learning experience, and cognitive function among older men.
This article assesses the effects of educational attainment, posteducational training experience, and occupational status on cognitive function among older men, controlling for demographic and health factors. Conditional relationships between educational attainment and factors that importantly influence cognitive function are also investigated. Data from a nationally representative sample of 1,839 older men are used to explore life-course effects of occupational and training experiences during the 1960s, 1970s, and 1980s. A positive relationship is found between formal educational attainment and cognitive function, but this association is conditional on subsequent training experience, ethnicity, and symptoms of depression. Training experiences are also positively associated with cognitive function. Continued pursuit of education and training may offer opportunities to promote cognitive function throughout the life course, especially among those with low educational attainment early in life.


Genetic polymorphisms of matrix metalloproteinases and protein levels in chronic obstructive pulmonary disease in a Mexican population.
To evaluate association of single nucleotide polymorphisms (SNPs) in the MMP1, MMP2, MMP9 and MMP12 genes and serum MMP-2 and MMP-9 levels in smoking chronic obstructive pulmonary disease (COPD) patients. Genotyping using real-time PCR in 330 smokers with COPD (COPD), 658 smokers without COPD (SNC) and 150 nonsmokers (NCNS), the analysis of samples used was χ(2) test. Using ELISA, the proteins were evaluated. Multiple comparisons were made by ANOVA. rs243864 (OR: 7.44; 95% CI: 3.62-15.26) and rs11646643 (OR: 1.58; 95% CI: 1.07-2.34) of the MMP-2 gene and rs3918253 (OR: 1.72; 95% CI: 1.08-2.71) of the MMP-9 gene, were associated with the risk of COPD. Serum MMP-2 level in the COPD group was lower compared with SNC (p < 0.05). Serum MMP-9 level was elevated in the COPD group compared with SNC (p < 0.05). Polymorphisms in MMP2 and MMP9 but not in MMP1 and MMP12 are associated with the risk of COPD in the Mexican mestizo population.


[Communication and language problems in children with nemaline myopathy].
Nemaline myopathy is a rare disease with an incidence of 1 in every 50,000 live births. It is the most prevalent of the congenital myopathies, a heterogeneous set of neuromuscular disorders present at birth or manifesting at a very early age, which affect the skeletal muscles and give rise to weakness, hypotonia and psychomotor retardation, although cognitive development remains normal. To review the studies conducted to date on the communication difficulties and dysphagia of children with nemaline myopathy and their possible management based on speech therapy. All the children presented dysphagia, with severe feeding problems during the first three years of life that nevertheless are somewhat mitigated as time goes by. In 50% of cases a gastrostomy will be used, although some oral ingestion is maintained in many of them. Nemaline myopathy gives rise to a clearly dysarthric pattern. The weakness of the muscles involved in ventilation and of the face, with a limited ability to close the mouth, leads to hypophonia, nasality and marked unintelligibility. Studies conducted on treatments based on speech therapy suggest that, in the most disabling cases of dysarthria, alternative systems of communication should be used in the first years of life so as to eliminate the frustration caused by the lack of meaningful expression. Later, communicators based on written language can be used. In the remaining cases, the aim must be to improve speech intelligibility. Speech therapy can contribute to improve the quality of life of these children with two types of treatment: management of their dysphagia and improvement of their communication problems through speech or technical aids. These is insufficient scientific evidence of the effectiveness of these treatments.


Exotic Optical Fibers and Glasses: Innovative Material Processing Opportunities in Earth's Orbit.
Exotic optical fibers and glasses are the platform material for photonics applications, primarily due to their superior signal transmission (speed, low attenuation), with extending bandwidth deep into the infrared, exceeding that of silica fibers. Gravitational effects (convection sedimentation) have a direct impact on the phase diagram of these materials and influence melting properties, crystallization temperatures, and viscosity of the elemental mix during the manufacturing process. Such factors constitute limits to the yield, transmission quality, and strength and value of these fibers; they also constrain the range of applications. Manufacturing in a gravity-free environment such as the Earth's Orbit also helps with other aspects of the fabrication process (i.e., improved form factor of the manufacturing unit, sustainability). In this article, revolutionary developments in the field of photonics over the past decade merge with the paradigm shift in the privatization of government-owned capabilities supporting a more diverse infrastructure (parabolic, suborbital, orbital), reduced price, and increased frequency to access space and the microgravity environment. With the increased dependence on data (demand, bandwidth, efficiency), space and the microgravity environment provide opportunities for optimized performance of these exotic optical fibers and glasses underlying the development of enabling technologies to meet future data demand. Existing terrestrial markets (Internet, telecommunications, market transactions) and emerging space markets (on-orbit satellite servicing, space manufacturing, space resources, space communications, etc.) seem to converge, and this innovative material processing opportunity of exotic optical fibers and glasses might just be that "killer app": technologically competitive, economically viable, and with the ability to close the business case.


[Characteristics of potentially inappropriate prescribing of drugs in elderly polypathological patients].
To analyse potentially inappropriate prescribing (PIP) in elderly polypathological patients (PP). Multicentre observational, prospective study of 672 patients aged 75 years and older hospitalised in Internal Medicine between April 2011 and March 2012. The Beers, STOPP-START and ACOVE criteria were used to detect potentially inappropriate prescribing and the results of PP and non-PP patients were compared. Of the 672 patients included, 419 (62%) were polypathological, of which 89.3% met PIP criteria versus 79.4% of non-polypathological patients (p <0.01). 40.3% of polypathological patients met at least one Beers criteria, 62.8% at least one STOPP criteria, 62.3% at least one START criteria and 65.6% at least one ACOVE criteria. The rate of potentially inappropriate prescribing was higher in polypathological patients regardless of the tool used. Given the high rate of potentially inappropriate prescribing in polypathological patients, strategies to improve prescribing adequacy must be developed.


Investigation of the Plasma Nitrite Levels and Oxidant-Antioxidant Status in Obstructive Sleep Apnea Syndrome.
Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. In the present study, we assessed the nitrite level, which is an indirect indicator of nitric oxide (NO), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), which may be associated with endotel dysfunction. We investigated the difference between the groups and the relationship among the severity of comorbid conditions. This study was conducted in 39 OSA patients confirmed by polysomnography and 40 healthy subjects (controls). The OSA group consisted of 10 women and 29 men and the control group consisted of 20 women and 20 men. Polysomnographic revealed mild OSA in two, moderate in 7 and severe in 30 cases. We measured plasma TAS, TOS and nitrite levels from venous blood. The OSI value was obtained by dividing the TOS and TAS values. Values were compared with the control group and between patient groups. A high body mass index (BMI), cardiovasculer diseases (CVD) and the use of medication for co-morbid diseases were more prevalent in the OSA group (p=.001, p=.029 and p=.006, respectively). The median plasma TOS level and OSI in the obstructive sleep apnea syndrome (OUA) group were significantly higher than those in the control group (p=.001 and p=.001, respectively). The plasma median nitrite level and TAS did not show any significant difference between the OSA and the control groups. None of the parameters revealed a significant difference between severe and moderate OSA cases. Our findings in the present study revealed that the oxidant-antioxidant balance shifted toward the oxidant side in OSA cases; however, the NO level did not change. These findings together may point out that some molecules other than NO may have a role in the pathophysiology of endothelial dysfunction and also in the disturbed oxidant-antioxidant balance in OSA.


Obstetrical outcomes of aboriginal pregnancies at a major urban hospital.
While a number of previous papers have documented the poor general health of Australia's Aboriginal population, relatively few have considered the health of Aborigines living in Australia's urban centres. In this latter instance, Aborigines have access to conventional medical services and they live in a physical environment that does not differ greatly from that experienced by the lower-class white population. Of course, racial, familial and economic differences may continue to influence differentially the perceived accessibility of services to Aborigines and their non-Aboriginal neighbours. This paper compares the pregnancy outcomes of Aboriginal women and non-Aboriginal women living in a major urban centre in Australia. The data indicate that urban Aboriginal women have adverse pregnancy outcomes at one and a half to two times the rate experienced by the non-Aboriginal population. Much of the difference can be attributed to lifestyle variations in the groups being compared.


[Operative results in 45 cases of acoustic neurinoma: technical comments on the preservation of the facial nerve and hearing function].
This report deals with the operative results in 45 cases of acoustic neurinoma treated in our service during the past six years. Surgery was performed in a lateral position through a small suboccipital craniectomy. Radical total removal of the tumor was achieved in 37 cases and nearly total resection was performed in 8 cases to preserve the facial nerve. Major complications occurred in 2 patients; one died of acute respiratory distress and the other had persisting ataxia due to damage of AICA. The facial nerve was anatomically preserved in 38 cases. Six patients in whom the facial nerve was not preserved underwent various types of facial nerve reconstruction. Postoperative follow-up showed excellent facial nerve function in 32 cases, good function in 11 and poor function in 3. Hearing was preserved in only one case of 11 cases who had preoperatively retained auditory function. Followings are important points for the preservation of postoperative facial nerve function and useful hearing. FACIAL NERVE: Intraoperative identification of facial nerve is crucial. The facial nerve was in most cases compressed ventrally by the tumor, however, 4 cases showed abnormal course of the facial nerve (dorsal in 1, rostral in 1 and caudal in 2 cases). The facial nerve was extremely thin and adherent at the ventral side of the tumor and invisible under the microscope in 60% of the cases. When the facial nerve is hardly separated from the tumor capsule, nearly total resection (leaving thin tumor capsule with the membranous facial nerve) is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)


A review of mechanics and injury trends among various running styles.
Running related overuse injuries are a significant problem with half of all runners sustaining an injury annually. Many medical providers and coaches question how to advise their running clients to prevent injuries. Alternative running styles with a more anterior footstrike such as barefoot running, POSE running, and Chi running are becoming more popular. Little information, however, has been published comparing the mechanics and injury trends of different running styles. The original purpose of this paper was to examine evidence concerning the biomechanics and injury trends of different running styles. Little to no injury data separated by running style existed. Therefore, we discuss the biomechanics of different running styles and present biomechanical findings associated with different running injuries. English language articles published in peer reviewed journals were identified by searching PubMed, CINAHL, and SPORTDiscus databases. Nearly all of the studies identified by the search were observational studies. A more anterior initial foot contact present in barefoot or other alternative running styles may decrease or eliminate the initial vertical ground reaction peak or "impact transient," possibly reducing knee joint loads and injuries. A more anterior foot strike, however, may increase mechanical work at the ankle and tensile stress within the plantarflexors. Wearing minimal footwear may also increase contact pressure imposed on the metatarsals. More research is needed to determine which individuals with certain morphological or mechanical gait characteristics may benefit from alternative running styles that incorporate a more anterior initial foot contact with or without shoes.


A problem-based learning course in physiology for undergraduate and graduate basic science students.
In small-group problem-based learning (PBL), students work cooperatively to solve complex, real-world problems. The problems lead the students to learn basic concepts rather than being presented as applications of concepts they have already learned. The goals are for students to learn and be able to apply the disciplinary content, develop critical thinking abilities, and acquire skills of life-long learning, communication, and team building. PBL has been widely used in recent years in medical and related areas of professional education. In those settings each small group typically has its own faculty facilitator. PBL can be successfully adapted for teaching undergraduate and graduate basic science students, in part by having multiple groups meet in one room with a roving facilitator. This report describes a two-semester PBL sequence in organ-systems physiology. To keep the interest of a diverse group of seniors and graduate students, several types of problems were used: clinical, laboratory research-based, real-life scenarios, and published research articles. The majority of students have responded enthusiastically.


Intrapleural talc for the prevention of recurrent pneumothorax.
The ipsilateral recurrence rate after the first spontaneous pneumothorax treated with tube thoracostomy is reported to be between 23 percent and 52 percent. The incidence of recurrence after the first recurrence is substantially higher. Chemical pleurodesis has been attempted to decrease the recurrence rate. Tetracycline has been widely utilized, but parenteral tetracycline is no longer available. Therefore, alternative sclerosing agents have been used. Talc has been demonstrated to be effective in preventing recurrences and it has minimal long-term effects. This prospective study was designed to determine the efficacy of talc pleurodesis in patients with recurrent spontaneous pneumothorax. Eighteen patients admitted between May 1985 and March 1993 to the Department of Thoracic Surgery underwent thoracoscopy and were treated by tube thoracostomy with chemical pleurodesis. All the patients had had at least two pneumothoraces and six had had at least six pneumothoraces. Sterile asbestos-free talc, 2g, was aerosolized throughout the pleural surface. One or two chest tubes were inserted, left clamped for 2 h, and unclamped after this time. The tubes were removed when no air had escaped for 24 h. Only one (5.6 percent) patient had recurrence of the pneumothorax, and a second insufflation of talc resulted in no new recurrence after a follow-up of 10 months. The remaining 94.4 percent did not have recurrence of pneumothorax within an observation period of 38.5 +/- 28.1 months. The follow-up was more than 2 years for 66.7 percent with no recurrence and was more than 5 years for 33.3 percent. We conclude from these observations that the insufflation of 2 g of talc into the pleural space is a safe effective treatment for control of recurrent spontaneous pneumothorax.


Development of film-forming gel containing nanoparticles for transdermal drug delivery.
Despite several studies on film-forming systems with the advantages of both the film and the hydrogel, there are still no effective systems for fast film formation with a high level of control over permeability. In this study, a film-forming system for the delivery of nanomedicine, termed a film-forming nanogel (FFN), was produced and investigated for the first time to meet this need. The objective of this research was to study a new generation of film-forming hydrogels (FFHs) loaded with curcumin nanoparticles (CUR-GNPs) for transdermal applications. FFHs were prepared by employing zein and HPMC 4000 as film-forming polymers. Meanwhile, CUR-GNPs were obtained by sonoprecipitation. The film-forming time, particle characteristics and FFN drug release profile were assessed. The optimized FFH had a smooth surface and a fast drying time of 6 min and 4.5 min in vitro and ex vivo, respectively. Additionally, high, sustained drug permeation from the FFN was observed after 24 h. The FFH containing CUR-GNPs showed potential for application in transdermal drug delivery with a fast film-forming time, uniform particle dispersion and high, sustained drug permeation.


[Clinical effect of maternal voice stimulation in alleviating procedural pain in hospitalized neonates].
To study the clinical effect of maternal voice stimulation in alleviating procedural pain in neonates during heel blood collection. A total of 72 neonates who were admitted to the neonate intensive care unit were randomly divided into an intervention group (n=35) and a control group (n=37). Heel blood collection was performed by the routine method in the control group. The intervention group listened to their mothers' voice from 1 minute before heel blood collection to the end of the procedure. Pain score, incidence of crying, and vital signs were recorded before and after heel blood collection. Compared with the control group, the heart rate was significantly reduced, the blood oxygen saturation significantly increased, the incidence of crying and the pain score were significantly reduced in the intervention group during the procedure of heel blood collection (P<0.05). Maternal voice stimulation helps to reduce procedural pain and maintain stable vital signs in neonates.


Detection of alcoholism in three populations by the brief-MAST.
The brief MAST (B-MAST) questionnaire was used to detect alcoholism in three populations, namely, alcoholics in treatment, clinical outpatients, and the general population. Nearly all the alcoholics in treatment tested positive in the B-MAST (99.2%), for lifetime as well as for current (past year) alcohol-related problems. Among the clinical outpatients and general population, 35.6% and 20.2% respectively, tested positive for lifetime alcohol problems, but only 19.6% and 7.6%, respectively, tested positive for past-year alcohol problems. The sensitivity/specificity of the B-MAST (lifetime) was 64.7%/90.0% and 48.3%/96.4% in the clinical outpatients and general population, respectively. Even lower sensitivity (28.2%) was obtained when the B-MAST was used to detect past-year alcohol problems in the general population sample. The poor sensitivity of the B-MAST in the general population was probably because most of the B-MAST questions deal with severe alcohol problems, and they are not sufficiently sensitive to detect those who drank heavily but who had not yet developed these alcohol problems. Anomalous responses to the two questions about "normal drinker" and to the question about "attendance in AA meeting" also contributed (< 3%) to inflated positive B-MAST scores. There were gender differences, and to a lesser extent, racial differences (Whites versus Blacks), in the responses to individual B-MAST questions in the three subject populations, with more males than females in each group reporting more alcohol-related problems. However, there were no gender and racial differences in the average B-MAST scores among those clinical outpatients and general population subjects who tested positive.


How language barriers impact patient care: a commentary.
The population of the United States population is growing more diverse at a rapid rate through the 21st century. Health care providers are interacting more frequently with patients of diverse ethnic affiliations where health beliefs, languages, and life experiences may differ greatly from their own. According to Timmins (2002), "...the U.S. health care system is largely geared toward serving English speakers." This is because language is the most common barrier in any health care setting and has been found to be a risk factor with adverse outcomes. Health care providers and patient communication are positively correlated with improved health outcome. Health outcomes include medication regimen, preventive testing, and patient satisfaction.


NK cells exacerbate the pathology of influenza virus infection in mice.
NK cells offer a first line of defense against viruses and are considered beneficial to the host during infection. Nevertheless, little is understood regarding the phenotype and function of NK cells in the lung during influenza virus infection. We found that the frequency of NK cells in mouse lung increased during influenza infection, with the majority of a mature phenotype. Cell surface CD107a and intracellular IFN-γ were detected in cells expressing multiple NK-cell receptors in infected lung, suggesting that NK cells were activated during infection. The activating receptor NKp46 was predominantly negative on such cells, possibly as a result of encountering influenza HA. Depletion of NK cells in vivo with anti-asialo GM1 or anti-NK1.1 reduced mortality from influenza infection and surviving mice recovered their body weight. Pathology induced by NK cells was only observed with high, not medium or low-dose influenza infection, indicating that the severity of infection influences NK-cell-mediated pathology. Furthermore, adoptive transfer of NK cells from influenza-infected lung, but not uninfected lung, resulted in more rapid weight loss and increased mortality of influenza-infected mice. Our results indicate that during severe influenza infection of the lung, NK cells have a deleterious impact on the host, promoting mortality.


[Second trimester screening for trisomy 21 using ADAM12-S as a maternal serum marker].
To investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol. Serum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR). By comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker. Considering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.


Countdown to 2015: tracking intervention coverage for child survival.
The fourth Millennium Development Goal (MDG) calls for a two-thirds' reduction between 1990 and 2015 in deaths of children younger than five years; achieving this will require widespread use of effective interventions, especially in poor countries. We present the first report of the Child Survival Countdown, a worldwide effort to monitor coverage of key child-survival interventions in 60 countries with the world's highest numbers or rates of child mortality. In 2005, we developed a profile for each of the 60 countries to summarise information on coverage with essential child survival interventions. The profiles also present information on demographics, nutritional status, major causes of death in children under 5 years of age, and the status of selected health policies. Progress toward the fourth MDG is summarised by comparing the average annual rate of reduction in under-5 mortality in each country with that needed to achieve the goal. The profiles also include a comparison of the proportions of children in the poorest and richest quintiles of the population who received six or more essential prevention interventions. Each country's progress (as measured by defined indicators of intervention coverage) was put into one of three groups created on the basis of international targets: "on track"; "watch and act"; and "high alert". For indicators without targets, arbitrary thresholds for high, middle, and low performance across the 60 countries were used as a basis for categorisation. Only seven countries are on track to met MDG-4, 39 countries are making some progress, although they need to accelerate the speed, and 14 countries are cause for serious concern. Coverage of the key child survival interventions remains critically low, although some countries have made substantial improvements in increasing the proportion of mothers and children with access to life saving interventions by as much as ten percentage points in 2 years. Children from the poorest families were less likely than those from wealthier families to have received at least six essential prevention interventions. Our results show that tremendous efforts are urgently needed to achieve the MDG for child survival. Profiles for each country show where efforts need to be intensified, and highlight the extent to which prevention interventions are being delivered equitably and reaching poor families. This first report also shows country-specific improvements in coverage and highlights missed opportunities. The "Countdown to 2015" will report on progress every 2 years as a strategy for increasing accountability worldwide for progress in child survival.


Myasthenia gravis: brief guide to diagnosis and management.
Physicians should consider the possibility of myasthenia gravis in patients complaining of fluctuating muscle weakness and easy fatigability. The disorder may occur in either sex at any age. Repeated measurements of multiple muscle groups and functions to include baseline strength and response to a control as well as anticholinesterase drugs are desirable in reaching a diagnosis. Appropriate doses of anticholinesterase medication reduce weakness and fatigability in most patients. Selected patients may benefit from thymectomy. Patients in crisis failing to respond to anticholinesterase drugs, having difficulty maintaining a patent airway or adequate respiratory exchange are best managed by prompt tracheostomy using a cuffed tube, with adequate tracheobronchial toilet and mechanical respiratory assistance.


Weakness and pain in arms and legs · dark urine · history of vertebral osteomyelitis · Dx?
Rhabdomyolysis is a serious complication of statin treatment. Both higher statin doses and pharmacokinetic factors can raise statin levels, leading to this serious usclerelated syndrome. Co-administration of statins with drugs that are strong inhibitors of cytochrome P450 (CYP) 3A4 (the main cytochrome P450 isoform that metabolizes most statins) can increase statin levels several fold. The trigger for our patient's statin-induced rhabdomyolysis was fluconazole, a known moderate inhibitor of CYP3A4, which is comparatively weaker than certain potent azoles like itraconazole or ketoconazole.


The Use of Particulated Juvenile Allograft Cartilage for the Repair of Porcine Articular Cartilage Defects.
The repair of porcine articular cartilage defects by using particulated juvenile allograft cartilage (PJAC) has demonstrated good short-term clinical efficacy, but the repair process and mechanism have not been fully elucidated. To study the efficacy of PJAC in repairing full-thickness cartilage defects and to provide an experimental basis for its clinical application. Controlled laboratory study. Thirty Guizhou minipigs were randomly divided into an experimental group and control group. An 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of either knee in all minipigs. The experimental group received the PJAC transplantation (PJAC group; n = 15) and the control group received autologous cartilage chips (ACC group; n = 15). Five minipigs were euthanized at 1, 3, and 6 months in each group to obtain samples, which were evaluated by general view of the knee joint and histomorphometry of the chondral defect area (hematoxylin and eosin, safranin O). International Cartilage Repair Society (ICRS) II semiquantitative evaluation and collagen type II staining immunohistochemistry were also performed. All 30 Guizhou minipigs were followed; there was no infection or incision healing disorder after the operation. At 1 month postoperatively, more hyaline cartilage was found in the ACC group (29.4%) compared with the PJAC group (20.1%) (P < .05); there was no statistical difference between the 2 groups at 3 and 6 months after operation. The fibrocartilage content in the ACC group was significantly more than that in the PJAC group at 1 and 3 months postoperatively (27.4% vs 18.2% and 49.9% vs 41.1%, respectively; P < .05); significant differences disappeared at 6 months postoperatively. The PJAC group produced more fibrous tissue than the ACC group at 1 and 3 months postoperatively (60.1% vs 40.6% and 38.8% vs 24.4%, respectively; P < .05) but showed no statistical difference at 6 months postoperatively. Regarding the ICRS II scores, those of the ACC group were significantly better than the scores of the PJAC group in some subclasses at 3 and 6 months postoperatively. The positive rates of immunohistochemical staining in the ACC group were higher at 1 and 3 months postoperatively than those in the PJAC group (54.2% vs 37.8% and 46.4% vs 34.4%, respectively; P < .05). The difference was not statistically significant between the 2 groups at 6 months postoperatively. Both PJAC and ACC can produce a good repair effect on cartilage defects. At 1 and 3 months postoperatively, ACC resulted in better outcomes than PJAC, but there was no statistical difference in the repair effect between the 2 techniques at 6 months postoperatively. Based on this animal experiment, further clinical studies are needed to investigate PJAC as a possible alternative first-line treatment for cartilage defects.


Nonlinear dynamics of a rack-pinion-rack device powered by the Casimir force.
Using the lateral Casimir force-a manifestation of the quantum fluctuations of the electromagnetic field between objects with corrugated surfaces-as the main force transduction mechanism, a nanomechanical device with rich dynamical behaviors is proposed. The device is made of two parallel racks that are moving in the same direction and a pinion in the middle that couples with both racks via the noncontact lateral Casimir force. The built-in frustration in the device causes it to be very sensitive and react dramatically to minute changes in the geometrical parameters and initial conditions of the system. The noncontact nature of the proposed device could help with the ubiquitous wear problem in nanoscale mechanical systems.


A hardware approach for histological and histopathological digital image stain normalization.
Advances in technology made the migration of pathological diagnosis to digital slides possible. As the need for objectivity and automation emerged, new computer software algorithms were proposed. Computer algorithms demand accurate color and intensity values in order to provide reliable results. The tissue samples undergo several processing steps from histological preparation to digitalization, which cannot be completely standardized. Thus, non-standardized input data generates unreliable output data. In this article, we discuss a new computational normalization algorithm for histopathological stained slides that uses a hardware color marker. The marker is added to the glass slide together with the tissue section, exposed to all the processing steps and altered in the same manner as the biological material of interest, thus becoming a solid color marker for image normalization. The results of the proposed method are numerically and perceptually tested in order to prove the advantages of the method. We conclude that our combined hardware-software technique for staining normalization of digital slides is superior to the existing methods based on only software normalization, and that its implementation will tackle not only the acquisition errors but also the technical errors that may occur during the staining process.


Regulation of the cell surface expression and function of angiotensin II type 1 receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac myocytes.
Rab1 GTPase coordinates vesicle-mediated protein transport specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. We recently demonstrated that Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in HEK293 cells and that transgenic mice overexpressing Rab1 in the myocardium develop cardiac hypertrophy. To expand these studies, we determined in this report whether the modification of Rab1-mediated ER-to-Golgi transport can alter the cell surface expression and function of endogenous AT1R and AT1R-mediated hypertrophic growth in primary cultures of neonatal rat ventricular myocytes. Adenovirus-mediated gene transfer of wild-type Rab1 (Rab1WT) significantly increased cell surface expression of endogenous AT1R in neonatal cardiomyocytes, whereas the dominant-negative mutant Rab1N124I had the opposite effect. Brefeldin A treatment blocked the Rab1WT-induced increase in AT1R cell surface expression. Fluorescence analysis of the subcellular localization of AT1R revealed that Rab1 regulated AT1R transport specifically from the ER to the Golgi in HL-1 cardiomyocytes. Consistent with their effects on AT1R export, Rab1WT and Rab1N124I differentially modified the AT1R-mediated activation of ERK1/2 and its upstream kinase MEK1. More importantly, adenovirus-mediated expression of Rab1N124I markedly attenuated the Ang II-stimulated hypertrophic growth as measured by protein synthesis, cell size, and sarcomeric organization in neonatal cardiomyocytes. In contrast, Rab1WT expression augmented the Ang II-mediated hypertrophic response. These data strongly indicate that AT1R function in cardiomyocytes can be modulated through manipulating AT1R traffic from the ER to the Golgi and provide the first evidence implicating the ER-to-Golgi transport as a regulatory site for control of cardiomyocyte growth.


Dietary fibre and cardiovascular health: a review of current evidence and policy.
Dietary fibre comprises many different, mainly plant-based, compounds that are not fully digested in the human gut. Insoluble fibres include cellulose, hemi-celluloses and lignin and soluble fibres include pectins, β-glucan and hydro-colloids. In the UK, the daily recommended amount has increased to 30 g but only 13 % of men and 4 % of women meet this recommendation. Currently the mean intake for adults is 21 g for men and 17 g for women. There is a wealth of epidemiological evidence based on systematic reviews of trials and cohorts to support the higher fibre recommendation. This includes evidence of reductions in the risk for CVD (both heart disease and stroke) and lower risk of type 2 diabetes, lower blood pressure, lower LDL-cholesterol, as well as some cancers. Beneficial effects of fibre operate via a diverse range of mechanisms throughout the digestive system including the mouth, stomach and small and large intestine; some of which are still not completely understood. The updated recommendation for fibre is a long way from a typical British diet and requires several daily portions of fruit and vegetables and wholegrain foods. Improving dietary fibre intakes will require a variety of actions and policies from stakeholders; however, there is currently more of a focus on reducing sugar than increasing fibre. In order to increase the number of adults meeting the fibre recommendation, social marketing and labelling of high-fibre foods are warranted as well as reformulation and wider availability of wholegrain versions of popular foods.


Genetic polymorphisms of flavin monooxygenase 3 in sulindac-induced regression of colorectal adenomas in familial adenomatous polyposis.
Sulindac is a nonsteroidal antiinflammatory drug with a chemopreventive effect in patients with familial adenomatous polyposis (FAP). In vivo, the active form of sulindac is sulindac sulfide, which is inactivated by the hepatic microsomal enzyme, flavin monooxygenase 3 (FMO3). In humans, numerous polymorphisms exist in FMO3, which alter enzymatic activity and subsequent substrate metabolism. We recently showed that certain polymorphic forms of FMO3 with reduced activity were associated with a more favorable response to sulindac in preventing the formation of adenomas in patients with FAP without polyps at baseline. Here, we determined whether these FMO3 polymorphisms correlated with the ability of sulindac to regress polyposis in patients with FAP who had polyps prior to treatment. Nineteen patients were treated with 150 mg sulindac twice a day for 6 months. The size and number of polyps in each patient was assessed at baseline (prior to the administration of sulindac), and at 3 and 6 months. Genotyping was done on seven established FMO3 polymorphisms with functional significance-M66I, E158K, P153L, V257M, E305X, E308G, and R492W. Statistical analyses were done with Wilcoxon rank sum test. Of the loci examined, only E158K and E308G showed polymorphic changes. Six patients exhibited polymorphisms in both E158K and E308G loci and were designated as genotype combination 1. The remaining patients were designated as genotype combination 2. Over the course of treatment, patients with genotype combination 1 had a greater reduction in both the size and number of polyps than those with genotype combination 2. These results suggest that combined polymorphic changes in the E158K and E308G alleles may protect against polyposis in patients with FAP treated with sulindac.


The development of imitation by reinforcing behavioral similarity to a model.
This research demonstrated some of the conditions under which retarded children can be taught to imitate the actions of adults. Before the experiment, the subjects were without spontaneous imitative behavior, either vocal or motor. Each subject was taught, with food as reinforcement, a series of responses identical to responses demonstrated by an experimenter; i.e., each response was reinforced only if it was identical to a prior demonstration by an experimenter. Initially, intensive shaping was required to establish matching responses by the subjects. In the course of acquiring a variety of such responses, the subjects' probability of immediate imitation of each new demonstration, before direct training, greatly increased. Later in the study, certain new imitations, even though perfect, were never reinforced; yet as long as some imitative responses were reinforced, all remained at high strength. This imitativeness was then used to establish initial verbal repertoires in two subjects.


Establishment of specific monoclonal antibodies against recombinant human granulocyte colony-stimulating factor (hG-CSF) and their application for immunoperoxidase staining of paraffin-embedded sections.
Detection of granulocyte colony-stimulating factor (G-CSF), one of the substances responsible for proliferation and differentiation of granulocytes, has been performed up to the present by use of the granulocyte colony-formation assay, because of the lack of a specific anti-G-CSF antibody. This has prevented the advancement of biological investigations of cell dynamics linked to G-CSF, e.g., cell localization of G-CSF and its pathophysiological changes. In the present work, two monoclonal antibodies (MAb), 1E7 and 4A6, against recombinant human G-CSF (rhG-CSF) were developed by cell hybridization between NS-1 myeloma cells and splenocytes from a mouse immunized with rhG-CSF. 1E7 and 4A6 were shown to be reactive with hG-CSF but not with other CSF (hGM-CSF, hIL-3, and mouse GM-CSF) by Western blot analysis. An immunoperoxidase staining method using these MAb was then established. This method was applicable to frozen sections, paraffin-embedded sections, and cells fixed with 4% paraformaldehyde. Positive staining for G-CSF was observed in tumor cells secreting G-CSF and also in Chinese hamster ovary (CHO) cells transfected with hG-CSF cDNA. However, no staining was seen in tumor cells secreting no G-CSF, untransfected CHO cells, lung fibroblasts, or bone marrow stromal cells after short periods of culture. These results confirmed the immunospecificity of MAb 1E7 and 4A6 and the validity of their application to immunohistochemistry using paraffin-embedded sections.


[The effect of castration on bone in prostate cancer patients].
Surgical or chemical castration is widely used for the treatment of advanced prostate cancer. Common side effects of castration are e.g. sweating, increased body fat, decreased muscle mass, impotency and anemia. Castration increases the risk of osteoporosis and fractures in prostate cancer patients via hormonal effects to the bone. Castrated men should be recommended to increase physical activity. Calcium and vitamin-D supplementation is recommended. The European Association of Urology guidelines for prostate cancer recommend bone mineral density measurements before long-lasting castration therapy. Medical therapy should be considered for patients after low-energy fractures, after the diagnosis of osteoporosis based on bone mineral density measurements and for fracture high-risk patients based on clinical decision.


Finite-size effects on the convergence time in continuous-opinion dynamics.
We study finite-size effects on the convergence time in a continuous-opinion dynamics model. In the model, each individual's opinion is represented by a real number on a finite interval, e.g., [0,1], and a uniformly randomly chosen individual updates its opinion by partially mimicking the opinion of a uniformly randomly chosen neighbor. We numerically find that the characteristic time to the convergence increases as the system size increases according to a particular functional form in the case of lattice networks. In contrast, unless the individuals perfectly copy the opinion of their neighbors in each opinion updating, the convergence time is approximately independent of the system size in the case of regular random graphs, uncorrelated scale-free networks, and complete graphs. We also provide a mean-field analysis of the model to understand the case of the complete graph.


Miniaturised medium pressure capillary liquid chromatography system with flexible open platform design using off-the-shelf microfluidic components.
Trends towards portable analytical instrumentation of the last decades have not been equally reflected in developments of portable liquid chromatography (LC) instrumentation for rapid on-site measurements. A miniaturised medium pressure capillary LC (MPLC) system with gradient elution capability has been designed based on a flexible modular microfluidic system using primarily off-the-shelf low cost components to ensure wide accessibility to other analysts. The microfluidic platform was assembled on a breadboard and contained microsyringe pumps and switch valves, complemented with an injection valve and on-capillary detectors, all controlled by a PC. Four miniaturised microsyringe pumps, with 5, 20 and 100 μL syringe volume options, formed the basis of the pumping system. Two pairs of pumps were used for each mobile phase to create gradient elution capability. The two microsyringe pumps in each pairs were linked by two electrically operated microfluidic switching valves and both pairs of pumps were connected through a zero void volume cross-connector, thus providing a low hold-up volume for gradient formation. Sample was injected by a 20 nL nano-LC sampling valve, directly connected to a 18 cm long 100 μm i.d. Chromolith CapRod RP-18 monolithic capillary column. On-capillary LED-based UV-vis photometric detection was conducted through a piece of equal diameter fused silica capillary connected after the column. The performance of the portable LC system was evaluated theoretically and experimentally, including the maximum operating pressure, gradient mixing performance, and the performance of the detectors. The 5 μL microsyringe pump offered the best performance, with typical maximum operating pressures up to 11.4 ± 0.4 MPa (water) and gradient pumping repeatability of between 4 and 9% for gradients between 0.10% s(-1) and 0.33% s(-1). Test analytes of charged and uncharged dyes and pharmaceuticals of varying hydrophobicity showed typical RSD values of 0.7-1.4% and 3.3-4.8% in isocratic mode and 1.2-4.6% and 3.2-6.4% in gradient mode, respectively for retention time and peak area repeatability.