Azadipyrromethene cyclometalation in neutral Ru(II) complexes: photosensitizers with extended near-infrared absorption for solar energy conversion applications.
In the on-going quest to harvest near-infrared (NIR) photons for energy conversion applications, a novel family of neutral ruthenium(ii) sensitizers has been developed by cyclometalation of an azadipyrromethene chromophore. These rare examples of neutral ruthenium complexes based on polypyridine ligands exhibit an impressive panchromaticity achieved by the cyclometalation strategy, with strong light absorption in the 600-800 nm range that tails beyond 1100 nm in the terpyridine-based adducts. Evaluation of the potential for Dye-Sensitized Solar Cells (DSSC) and Organic Photovoltaic (OPV) applications is made through rationalization of the structure-property relationship by spectroscopic, electrochemical, X-ray structural and computational modelization investigations. Spectroscopic evidence for photo-induced charge injection into the conduction band of TiO2 is also provided.


Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.
-Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.


Gingival matrix collagen in chronic periodontitis.
The isolation and characterization of cyanogen bromide peptides derived from the human gingival collagen of patients with chronic periodontitis revealed the presence of both Type I and Type III collagens in this tissue. The amount of TYPE III collagen, however, was found to be lower than that in normal gingival tissue. In addition, a non-collagenous protein fraction, accounting for approximately 20% of the insoluble matrix, was relatively rich in acidic, hydrophobic, and hydroxy-containing amino acids. Amino acid analysis, likewise, revealed qualitative and quantitative differences between the normal and diseased tissues.


The alpha and beta subunits of the metalloprotease meprin are expressed in separate layers of human epidermis, revealing different functions in keratinocyte proliferation and differentiation.
The zinc endopeptidase meprin (EC 22.214.171.124) is expressed in brush border membranes of intestine and kidney tubules, intestinal leukocytes, and certain cancer cells, suggesting a role in epithelial differentiation and cell migration. Here we show by RT-PCR and immunoblotting that meprin is also expressed in human skin. As visualized by immunohistochemistry, the two meprin subunits are localized in separate cell layers of the human epidermis. Meprin alpha is expressed in the stratum basale, whereas meprin beta is found in cells of the stratum granulosum just beneath the stratum corneum. In hyperproliferative epidermis such as in psoriasis vulgaris, meprin alpha showed a marked shift of expression from the basal to the uppermost layers of the epidermis. The expression patterns suggest distinct functions for the two subunits in skin. This assumption is supported by diverse effects of recombinant meprin alpha and beta on human adult low-calcium high-temperature keratinocytes. Here, beta induced a dramatic change in cell morphology and reduced the cell number, indicating a function in terminal differentiation, whereas meprin alpha did not affect cell viability, and may play a role in basal keratinocyte proliferation.


Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux.
The residual risk for arteriosclerotic cardiovascular disease after optimal statin treatment may amount to 50% and is the consequence of both immunological and lipid disturbances. Regarding the lipid disturbances, the role of triglyceride-rich lipoproteins (TRLs) and their remnants has come to the forefront in the past decade. Triglycerides (TGs) stand as markers of the remnants of the catabolism of TRLs that tend to contain twice as much cholesterol as compared to LDL. The accumulation of circulating TRLs and their partially lipolyzed derivatives, known as "remnants", is caused mainly by ineffective triglyceride catabolism. These cholesterol-enriched remnant particles are hypothesized to contribute to atherogenesis. The aim of the present narrative review is to briefly summarize the main pathways of TRL metabolism, bringing to the forefront the newly discovered role of apolipoproteins, the key physiological function of lipoprotein lipase and its main regulators, the importance of the fluxes of these particles in the post-prandial period, their catabolic rates and the role of apo CIII and angiopoietin-like proteins in the partition of TRLs during the fast-fed cycle. Finally, we provide a succinct summary of the new and old therapeutic armamentarium and the outcomes of key current trials with a final outlook on the different methodological approaches to measuring TRL remnants, still in search of the gold standard.


The role of gut microbiota in hepatitis B disease progression and treatment.
Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the 'Gut-Liver Axis', where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.


DROUGHT STRESS AND INBREEDING DEPRESSION IN LYCHNIS FLOS-CUCULI (CARYOPHYLLACEAE).
Interactions between drought stress and inbreeding depression were studied in Lychnis flos-cuculi. Four inbreeding levels (F = 0, 0.25, 0.50 and 0.75), and three watering treatments were used. Performance was scored for germination rate and proportion, survival, plant size, proportion of plants flowering, flowering date, stem height, number of flowers, flower size, anther weight, fruiting proportion and number of capsules. Multiplicative fitness values were estimated from these traits. Inbreeding affected most of the traits studied, and a severe inbreeding depression was found for the combined fitness estimates. The higher inbreeding depression found here relative to the same family groups in a former experiment may reflect greater dominance and suppression in the present experiment at higher density.


Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study.
This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of expression of either antigen and traditional clinical risk factors, ploidy, or t(9;22) or t(1;19). All patients with t(4;11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its prognostic significance after adjusting for t(4;11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and 10, and adverse translocations including t(1;19), t(9;22), and t(4;11). We conclude that in childhood B-precursor ALL, the intensity of expression of CD20 and CD45 provides prognostic information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.


Risk of cancer after lumbar fusion surgery with recombinant human bone morphogenic protein-2 (rh-BMP-2).
Retrospective cohort study among Medicare beneficiaries with lumbar spinal fusion surgery. To determine the risk of subsequent cancer among patients who received recombinant human bone morphogenic protein (rhBMP) at surgery compared with those who did not. rhBMP is commonly used to promote bone union after spinal surgery. BMP receptors are present on multiple cancer types, but the risk of cancer after receiving rhBMP has not been well studied. We identified 146,278 subjects aged 67 years and older who underwent surgery in 2003 to 2008 and were followed through 2010 for a new diagnosis of 1 of 26 cancers. Proportional hazards models were used to determine cancer risk associated with rhBMP use. rhBMP was administered in 15.1% of the cohort. After an overall average follow-up of 4.7 years, 15.4% of rhBMP-treated and 17.0% of untreated patients had a new cancer diagnosis, with most commonly recorded types as prostate, breast, lung, and colorectal. In a multivariate proportional hazards model, there was no association of rhBMP with cancer risk (hazard ratio: 0.99, 95% confidence interval: 0.95-1.02). There was also no association of rhBMP with the risk of any individual cancer types. The results were consistent in analyses using 2 secondary definitions of incident cancer. In this large population-based analysis of Medicare beneficiaries, we found no evidence that administration of rhBMP at the time of lumbar fusion surgery was associated with cancer risk. 4.


CD74 in Kidney Disease.
CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.


Self-organization of metallo-supramolecular polymer networks by free formation of pyridine-phenanthroline heteroleptic complexes.
Nature employs spontaneous self-organization of supramolecular bonds to create complex matter capable of adaptation and self-healing. Accordingly, the self-sorting of unlike ligands towards a cooperative heteroleptic complex or narcistic homoleptic association in a mixed ligand system is frequently employed to form interchangeable stimuli-responsive complex geometries with a wide range of applications. This notion is however just rarely employed in the organization of polymer networks. In this paper, we report the free-formation of heteroleptic complexes between tetra-am poly(ethylene glycol) (tetraPEG) precursors functionalized either with pyridine (tetraPy) or phenanthroline (tetraEPhen). Among a wide range of studied metal ions, tetraPy could form a network only in combination with Pd2+, presumably with a square-planar geometry, highlighting the importance of complex strength and stability in forming gels with monodentate ligands. Also, mixed networks with tetraEPhen form only in combination with Pd2+ and Fe2+, with strengths surpassing those of individual components and stabilities incomparable to those of parent networks, indicative of heteroleptic complexation. Extensive rheological, UV-vis, and DFT simulation studies revealed the coexistence of different coordination geometries, with an octahedral arrangement prevailing in the presence of Fe2+ and a square-planar geometry in the presence of Pd2+. Therefore, this study offers new opportunities for the development of stimuli-responsive topology-switching polymer networks.


Quantifying the dilution effect for models in ecological epidemiology.
The dilution effect, where an increase in biodiversity results in a reduction in the prevalence of an infectious disease, has been the subject of speculation and controversy. Conversely, an amplification effect occurs when increased biodiversity is related to an increase in prevalence. We explore the conditions under which these effects arise, using multi species compartmental models that integrate ecological and epidemiological interactions. We introduce three potential metrics for quantifying dilution and amplification, one based on infection prevalence in a focal host species, one based on the size of the infected subpopulation of that species and one based on the basic reproduction number. We introduce our approach in the simplest epidemiological setting with two species, and show that the existence and strength of a dilution effect is influenced strongly by the choices made to describe the system and the metric used to gauge the effect. We show that our method can be generalized to any number of species and to more complicated ecological and epidemiological dynamics. Our method allows a rigorous analysis of ecological systems where dilution effects have been postulated, and contributes to future progress in understanding the phenomenon of dilution in the context of infectious disease dynamics and infection risk.


Acne and diet: a review.
Acne is one of the most frequent dermatological afflictions especially for people in their first 30 years of age. Several studies have shown that nutrition is one of the key factors involved in acne pathogenesis. Data show that a high glycemic index diet may be a trigger in acne pathogenesis, while patients with a low glycemic index diet have fewer acne lesions. Milk and chocolate are also involved in the exacerbation of acne. However, foods rich in omega-3 fatty acids suppress the production of inflammatory cytokines with therapeutic effect. Additionally, docosapentaenoic acid and γ-linolenic acid have demonstrated improved acne lesions. The aim of this review was to summarize current knowledge on the association between acne and diet with special attention to the most frequently discussed factors involved in its pathogenesis: milk, chocolate, omega-3 fatty acids, hyperglycemia, hyperinsulinism, and IGF-1.


On the trail of potassium in heat injury.
In both classical and exertional heatstroke and in various animal models of human heat injury, clinical manifestations have included observations of normokalemia, hyperkalemia, and hypokalemia. This review attempts to address these observations as well as the role of potassium and potassium depletion in heat injury with an emphasis on the integration of information from the level of transmembrane potassium transport mechanisms to systems physiology. Under moderate conditions of passive heat exposure or exercise in the heat, the adaptive capacity of the Na-K pump (Na+-K+ ATPase activity) and cotransport mechanisms can ordinarily accommodate the attendant increased efflux of intracellular K+ and influx of extracellular Na+ to maintain ionic equilibrium. Several factors affecting transmembrane K+ kinetics include protracted K+ deficiency, extreme hyperthermia, dehydration, and excessive exertion. These could elicit reduced membrane potentials and conductance, futile cycling of the Na-K pump with concomitant energy depletion and greatly increased metabolic heat production, reduced arteriolar vasodilation, altered neurotransmitter release, or cell swelling, each of which could contribute to the pathophysiology of heat injury. This review represents a preliminary attempt to link transmembrane K+ pathophysiology with clinical heat injury.


Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases.
The potential of proton therapy to improve the sparing of the healthy tissue has been demonstrated in several studies. However, even small doses delivered to the organs at risk (OAR) may induce long-term detriments after radiotherapy. In this study, we investigated the possibility to reduce the risk of radiation-induced secondary cancers with intensity modulated proton therapy (IMPT), when used for radiosurgery of liver metastases. Ten patients, previously treated for liver metastases with photon-beam based stereotactic body radiation therapy (SBRT) were retrospectively planned for radiosurgery with IMPT. A treatment plan comparison was then performed in terms of calculated risk of radiation-induced secondary cancer. The risks were estimated using two distinct models (Dasu et al., 2005; Schneider et al., 2005, 2009). The plans were compared pairwise with a two-sided Wilcoxon signed-rank test with a significance level of 0.05. Reduced risks for induction of fatal and other types of cancers were estimated for the IMPT plans (p<0.05) with the Dasu et al. Using the Schneider et al. model, lower risks for carcinoma-induction with IMPT were estimated for the skin, lungs, healthy part of the liver, esophagus and the remaining part of the body (p<0.05). The risk of observing sarcomas in the bone was also reduced with IMPT (p<0.05). The findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT.


Occurrence of hemolytic anemia in patients with GBS treated with high-dose IVIg.
We describe an underrecognized side effect of high-dose IV immunoglobulin (IVIg), hemolytic anemia. There are no established guidelines on treating patients with Guillain-Barré syndrome (GBS) who relapse or do not improve after a standard course of treatment (IVIg or plasma exchange). Some centers will opt for a second course of the initial treatment. There is an ongoing trial of a second course of IVIg in patients with severe GBS. We retrospectively reviewed 4 patients with severe GBS who received high-dose IVIg. One patient inadvertently received a high dose of IVIg for Miller Fisher syndrome. All patients received a total of at least 2 courses of the standard dose of IVIg (total >4 g/kg). We review their clinical course and side effects. All patients with non-O blood types developed clinically significant hemolytic anemia requiring blood transfusion. Hemolytic anemia may limit doses of IVIg for treatment of severe GBS in patients with non-O blood types.


[Itinerant medicine in Fujian-Taiwan in early Qing dynasty and Zou Jie Hui Xin Lu].
By itinerant (zou jie), it refers to the physicians from southern Fujian and Taiwan who possess some special medical characteristics. They are TCM physicians. By chance, this author found a book, Zou Jie Hui Xin Lu, and explored its author and his native place, analyzed the historical background of the appearance of such physicians and their lofty medical morality during the Ming-Qing dynasties. Conclusion has been reached that the so-called itinerant medicine accumulated rich experience, emphasized an overall idea. However, it was also restricted by geographical area and the divorce of theory with practice.


Copper-Catalyzed Selective ortho-C-H/N-H Annulation of Benzamides with Arynes: Synthesis of Phenanthridinone Alkaloids.
An efficient and convenient copper-catalyzed method has been developed to achieve direct ortho-C-H/N-H annulation to synthesize phenanthridinones with arynes. This method highlights an emerging strategy to transform inert C-H bonds into versatile functional groups in organic synthesis and provides a new way to synthesize phenanthridinone alkaloids efficiently.


Neural spatio-temporal patterns of information processing related to cognitive conflict and correct or false recognitions.
Using a visual short-term memory task and employing a new methodological approach, we analyzed neural responses from the perspective of the conflict level and correctness/erroneous over a longer time window. Sixty-five participants performed the short-term memory task in the fMRI scanner. We explore neural spatio-temporal patterns of information processing in the context of correct or erroneous response and high or low level of cognitive conflict using classical fMRI analysis, surface-based cortical data, temporal analysis of interpolated mean activations, and machine learning classifiers. Our results provide evidence that information processing dynamics during the retrieval process vary depending on the correct or false recognition-for stimuli inducing a high level of cognitive conflict and erroneous response, information processing is prolonged. The observed phenomenon may be interpreted as the manifestation of the brain's preparation for future goal-directed action.


[Analysis of recurrence pattern and prognosis of patients with cervical carcinoma and pelvic lymph node metastasis].
To investigate the pattern of disease relapse and prognostic risk factor of patients with cervical carcinoma and pelvic lymph node metastasis. A total of 124 cases of International Federation of Gynecology and Obstetrics (FIGO) Ib1-IIa cervical carcinoma with pelvic node metastasis who were treated at the Cancer Center of Sun Yat-sen University during January 1994 to December 2001 were selected for this study. Prognosis and recurrence were retrospectively analyzed using the clinico-pathological data The overall 5 year survival and 5 year disease-free survival were 63.3% and 61.4%, respectively. Overall recurrence rate was 39.5% (49/124), among which intra-pelvic relapse (61.0%, 25/41) was significantly more common than extra-pelvic relapse (31.7%,13/41; P=0.008). Multivariate analysis identified involvement of common iliac node as an independent prognostic factor (P=0.035). According to this factor, node-positive patients could be divided into low risk group (without common iliac node involvement, 104 cases) and high risk group (with common iliac node involvement, 20 cases). The 5 year disease-free survival were 69.4% and 24.5% respectively, with a significant difference (P=0.003). Intra-pelvic relapse was observed in 22.1% (23/104) of low risk and 25.0% (5/20) of high risk group respectively, with no significant difference (P>0.05). However extra-pelvic relapse was seen in 7.7% (8/104) of low risk and 40.0% (8/20) of high risk group, with a significant difference (P<0.01). Common iliac node involvement is a significant factor influencing the prognosis of patients with cervical carcinoma and pelvic lymph node metastasis. Patients with positive common iliac nodes have significantly decreased 5 year disease-free survival and higher extra-pelvic disease recurrence rates compared with those whose common iliac nodes are negative. These findings provide important data for design of individualized treatment mode.


Rapid and sustained contact tracing training for COVID-19 in San Francisco: a training model for developing an emergency public health workforce.
The City and County of San Francisco was the first municipality in the United States to institute a COVID-19 contact tracing program. The San Francisco Department of Public Health (SFDPH) and the University of California, San Francisco (UCSF) created an outcome-based fully remote contact tracing curriculum using participatory learning methods to train non-public health emergency workers as contact tracers. Between April and December 2020, we trained over 300 individuals in contact tracing skills and procedures over three training phases. Using iterative curriculum design and Kirkpatrick's evaluation methodology, we aimed to ensure high quality and successful person-centered contact tracing. The resulting curriculum consisted of 24 learning outcomes taught with six participatory skills development activities, asynchronous materials, and one-on-one contact tracer support. We collected more than 700 responses from trainees using various evaluation tools across the training phases, and contact tracers interviewed more than 24,000 contacts after training in our program. Our evaluations showed that knowledge and skills improved for most trainees and demonstrated the utility of the training program in preparing trainees to perform person-centered contact tracing in San Francisco. Local health jurisdictions and state health agencies can use this model of curriculum development and evaluation to rapidly train a non-public health workforce to respond to future public health emergencies.


Influence of cartilage interstitial fluid on gene expression in cruciate ligament fibroblasts.
Loading of articular cartilage during motion squeezes the fluid from the cartilage, termed cartilage interstitial fluid (CIF), which was found to influence gene expression in synovial membrane cells. After crucial ligaments damage, these cells are exposed to synovial fluid containing factors released from articular cartilage; the aim of the present study was to establish the influence of CIF and factors present in CIF (CIF-like cocktails) on crucial ligament fibroblasts. CIF was squeezed from articular-epiphyseal cartilage complexes of newborn rats. Fibroblasts were obtained from crucial ligaments of adult rat knee joints. Cells were cultured in control medium, CIF and CIF-like cocktails, and the expression of selected genes was evaluated using quantitative PCR. CIF stimulated the expression of HAS1, HAS2, aggrecan, lubricin, MMP3, TIMP3 and TGFβ1. Expression of collagen type I, versican, MMP2, TIMP2, TNF and IL1β was inhibited. The CIF-like cocktail stimulated HAS1, HAS2, collagen type I, versican, aggrecan, lubricin, TIMP1, TGFβ1, IL1β, IL6 and inhibited of MMP3 and TNF expression. Both agents exerted similar effects on the expression of HAS2, aggrecan, lubricin, TGFβ1 and TNF. CIF contains inhibitory and stimulatory factors affecting gene expression in crucial ligament fibroblasts and some of them were not included in the CIF-like cocktail. Due to the powerful influence of CIF on crucial ligament fibroblasts and the synovial membrane, further studies on its composition are needed. An improved CIF like-cocktail could be applied in the treatment of various joint or tendon ailments.


Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based study.
Infectious diseases are the leading cause of deaths in adults aged 65 years or older. Studies of adverse infection outcomes have been limited to specific infections and acute episodes and have not investigated longitudinal trends of cumulative infections. We aimed to identify distinct trajectories of longitudinal infection episodes in older adults and to assess their corresponding risk of all-cause mortality. In this retrospective cohort study, we included people aged 65 years or older who were admitted to hospital between Jan 1 and Dec 31, 2011, with one of the following infections: urinary tract, pneumonia, sepsis, cellulitis, cholecystitis, peritonitis, endocarditis, and meningitis. Participants were identified from Taiwan's National Health Insurance Research Database. We analysed infection episodes on a quarterly basis during a 5-year period (2011-15) and used group-based trajectory modelling to identify distinct trajectories. We examined the associations between infection trajectories and all-cause mortality using Kaplan-Meier curves and the Cox proportional hazard model. Among 79 666 eligible older adults, we identified four distinct infection trajectories over the 5-year follow-up: infrequent (58 619 [73·6%]), increasing (9746 [12·2%]), decreasing (9069 [11·4%]), and frequent (2232 [2·8%]). Compared with people with infrequent infections, the adjusted hazard ratios for all-cause mortality were 2·96 (95% CI 2·82-3·11) in participants with frequent infections, 2·15 (2·09-2·22) in those with increasing infections, and 1·85 (1·80-1·91) in those with decreasing infections. Older adults with multiple infection episodes, irrespective of type, pathogens, and distinct infection pattern, had greater risk of all-cause mortality compared with those with infrequent infections. Further research to define the overall infection burden in older adults is needed for risk stratification and to inform prevention strategies. The Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education, the National Science and Technology Council, and the Ministry of Science and Technology in Taiwan.


Heterogeneity of alpha 1-adrenoceptor subtypes mediating noradrenaline-induced contractions of the rat superior mesenteric artery.
The effects of subtype-selective alpha 1-adrenoceptor antagonists on noradrenaline-induced contractions of ring segments of rat superior mesenteric artery were investigated to determine the subtype(s) of alpha 1-adrenoceptors mediating contractions in this preparation. Noradrenaline-induced contractions of rat mesenteric artery ring segments were potently and surmountably antagonized by prazosin, WB 4101 and BMY 7378. Judging from the slopes of the Schild regression lines, which were significantly different from 1, WB 4101 and BMY 7378 behaved as noncompetitive antagonists. Spiperone and 5-methylurapidil were only effective at high concentrations. Chloroethylclonidine (CEC, 100 mumol/l) displaced the noradrenaline concentration-response curve to the right reducing its potency approximately 100-fold. Noradrenaline-induced contractions post-CEC were also antagonized by prazosin. However, prazosin was less potent against these contractions. A 61,603, a selective alpha 1A-adrenoceptor agonist, contracted ring segments of the mesenteric artery. These contractions were antagonized by prazosin, however with a low affinity, indicating interaction with a low-affinity receptor subtype. It was therefore concluded that alpha 1D- and, possibly, alpha 1L-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat superior mesenteric artery.


Standardized range of conformers and symblepharon rings.
Conformers and symblepharon rings are routinely used to keep fornices formed after socket surgery or in the presence of conjunctival cicatricial disease. However, there is no accepted standard size or shape of conformers or symblepharon rings. We measured the ideal conformer and symblepharon sizes in patients undergoing socket surgery and designed six conformer and symblepharon sizes. The full set of six conformers and symblepharon rings is available to the surgeon at the end of surgery. We have successfully used these conformers and symblepharon rings in over 600 cases during the last 7 years. These standardized sizes allow more accurate fitting of conformers and symblepharon rings.


Vibrational studies and properties of hybrid inorganic-organic proton conducting membranes based on Nafion and hafnium oxide nanoparticles.
In this report, we will describe the effect of different concentrations of HfO2 nanopowders on the structure and properties of [Nafion/(HfO2)n] membranes with n = 0, 3, 5, 9, 11, 13, and 15 wt %, respectively. Films were prepared by a solvent casting procedure using HfO2 oxoclusters and Nafion. Seven new homogeneous membranes were obtained with thicknesses ranging from 200 to 350 microm. Each membrane is characterized by a rough HfO2-rich surface and a smooth Nafion-rich surface, with different physical-chemical properties. Membrane characterization was accomplished by means of thermogravimetric analysis (TGA), morphological measurements (environmental scanning electron microscopy) and vibrational spectroscopy (Fourier transform infrared attenuated total reflectance spectroscopy and Fourier transform Raman spectroscopy). These systems can be described in terms of five types of water domains, Nafion-HfO2 species with well-defined stoichiometry surrounded by Nafion and hydrated hafnia. The highest conductivity at 125 degrees C (3.2 x 10-2 S x cm(-1)) was measured on the [Nafion/(HfO2)5] film by electrical spectroscopy, with a stability range of conductivity between 5 and 115 degrees C.


Is the circulating urokinase plasminogen activator upregulated by the circulating p105 fraction of the HER-2/neu proto-oncogene in patients with cervical cancer?
It has been suggested that urokinase plasminogen activator (uPA) in cancer cells is upregulated by the p185 kD form of the HER-2/neu oncogene. This study was performed to see if the extracellular domain of HER-2/neu, the p105 fraction, which is found in the circulation, has any regulatory influence on uPA in patients with cervical cancer. Levels of uPA and p105 HER-2/neu were determined in blood from age-matched controls and patients with early and advanced cervical cancer. In the patients with cervical cancer, samples were obtained before treatment only. No significant increase in either uPA or HER-2/neu was seen in the patients before their treatment for cervical cancer. Additionally, correlation analysis of circulating uPA and HER-2/neu against each other in both the controls and cervical cancer indicated no relationship except in early stage disease. It appears that circulating uPA and HER-2/neu are not altered in patients with cervical cancer, either early or advanced stages. The upregulation of uPA by HER-2/neu seen in cancer cells in vitro appears to occur in vivo in early stage cervical cancer.


Cytokeratin 20 and guanylyl cyclase C mRNA is largely present in lymph node and liver specimens of colorectal cancer patients.
The aim of our prospective study was to detect circulating epithelial cells (CEC) indicating the presence of disseminated tumor cells (DTC) in tissues affected by lymphatic and hematogenic colorectal cancer metastasis. DTC were tracked in lymph node, liver or bone marrow samples of 245 colorectal cancer patients using 2 independent RT-PCR assays for cytokeratin 20 (CK20) and guanylylcyclase C (GCC) that demonstrated a sensitivity of 1 colorectal cancer cell in 10(6) nucleated hematopoietic cells. CK20 mRNA was detected in 79% of lymph nodes, 35% of both liver lobes and 11% of bone marrow samples. GCC mRNA was found in 68% of lymph nodes, 60% of both liver lobes and 6% of bone marrow specimens. Both markers were recorded in 63% of lymph nodes, 45% of at least 1 liver lobe and 1% of bone marrow samples. There was no significant difference when comparing lymph node samples tested positive for both markers in patients with (N1/2; 65%) and without (N0; 56%) nodal involvement. The same was true when comparing the percentages of patients with and without clinically overt distant metastasis who were positive for both markers in at least 1 liver lobe (62% vs. 41%) or in bone marrow (4% vs. 0%). A score denoting the cumulative sum of tests indicating presence of CK20 and GCC mRNA in the liver was significantly related with UICC classification (p = 0.039). However, addition of lymph node results to this score decreased the correlation. The high incidence of clinically inconspicuous lymph node and liver samples tested positive for both markers emphasizes the function of these organs as primary filters for epithelial cells possibly shed from colorectal carcinomas. The potential prognostic significance of these findings warrants verification, especially regarding the importance of CEC or DTC resident in the liver of colorectal cancer patients.


Room-temperature direct arylation of polyfluorinated arenes under biphasic conditions.
New biphasic conditions for the palladium-catalyzed direct arylation of electron-poor fluorinated arenes have been developed. Taking advantage of biphasic chemistry, the use of an immiscible mixture of water and an organic solvent allows complete solubilization of all components of the system, enabling the reaction to proceed at room temperature in yields up to 99%.


KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells.
Lipid synthesis is required for cell growth and is subject to pharmacologic regulation. Keratinocyte growth factor (KGF) stimulates proliferation and lipogenesis in H292 cells, a pulmonary epithelial cancer cell line, but the signaling pathways are not known. KGF stimulated the expression of the transcription factors sterol-regulatory element binding protein-1 (SREBP-1), CCAAT/enhancer binding protein alpha (C/EBPalpha), and C/EBPdelta and two key enzymes involved in lipogenesis, FAS and stearoyl coenzyme A desaturase-1 (SCD-1). We found that KGF induced rapid activation of Akt, p70 S6K, JNK, and extracellular signal-regulated (ERK). Induction of SREBP-1, SCD-1, and FAS by KGF was inhibited by the JNK inhibitor SP600125 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the ERK inhibitor PD98059. Using FAS and SCD-1-luciferase promoter constructs, we observed that KGF stimulated the transcription of these promoters and that exogenous cholesterol inhibited the induction. Mutation of the SREBP-1 binding site in the SCD-1 promoter abolished the effect of KGF on SCD-1 transcription. In addition, overexpression of active SREBP-1 directly stimulated SCD-1 and FAS. Conversely, adenovirus-mediated overexpression of a dominant negative form of SREBP-1 inhibited the KGF effect on FAS and SCD-1 expression. In summary, we conclude that KGF requires both PI3K and JNK signaling pathways to induce SREBP-1, which in turn induces SCD-1 and FAS expression in H292 cells.


Understanding care coordination for Veterans with complex care needs: protocol of a multiple-methods study to build evidence for an effectiveness and implementation study.
For patients with complex health and social needs, care coordination is crucial for improving their access to care, clinical outcomes, care experiences, and controlling their healthcare costs. However, evidence is inconsistent regarding the core elements of care coordination interventions, and lack of standardized processes for assessing patients' needs has made it challenging for providers to optimize care coordination based on patient needs and preferences. Further, ensuring providers have reliable and timely means of communicating about care plans, patients' full spectrum of needs, and transitions in care is important for overcoming potential care fragmentation. In the Veterans Health Administration (VA), several initiatives are underway to implement care coordination processes and services. In this paper, we describe our study underway in the VA aimed at building evidence for designing and implementing care coordination practices that enhance care integration and improve health and care outcomes for Veterans with complex care needs. In a prospective observational multiple methods study, for Aim 1 we will use existing data to identify Veterans with complex care needs who have and have not received care coordination services. We will examine the relationship between receipt of care coordination services and their health outcomes. In Aim 2, we will adapt the Patient Perceptions of Integrated Veteran Care questionnaire to survey a sample of Veterans about their experiences regarding coordination, integration, and the extent to which their care needs are being met. For Aim 3, we will interview providers and care teams about their perceptions of the innovation attributes of current care coordination needs assessment tools and processes, including their improvement over other approaches (relative advantage), fit with current practices (compatibility and innovation fit), complexity, and ability to visualize how the steps proceed to impact the right care at the right time (observability). The provider interviews will inform design and deployment of a widescale provider survey. Taken together, our study will inform development of an enhanced care coordination intervention that seeks to improve care and outcomes for Veterans with complex care needs.


Reassurance therapy: what to say to symptomatic patients with benign or non-existent medical disease.
Reassurance is one of the most important therapies that primary care physicians give; however, little has been written about it in the literature. This article suggests six steps needed for effective reassurance in patients with benign disease or symptoms not explained by disease. These include; 1) question and examine the patient, 2) assure the patient that serious illness is not present, 3) suggest the symptom will resolve, 4) tell the patient to return to normal activity, 5) consider non-specific treatment, and 6) follow the patient Only if these systematic steps are followed will reassurance consistently work. Since examination of the patient is a critical component of reassurance therapy, it can most effectively be administered by individuals who include a physical assessment as a part of the clinical evaluation.


Stress testing in patients with hypertrophic cardiomyopathy.
Exercise echocardiography is an important and useful tool for the evaluation of symptoms and monitoring the response to therapy in patients with hypertrophic cardiomyopathy (HCM). A significant number of patients without resting left ventricular outflow tract gradients develop dynamic obstruction with exercise. Detection of an exercise-induced gradient provides a therapeutic target for the relief of symptoms. Abnormal blood pressure response to exercise is an important, although nonspecific, risk factor for cardiovascular death in patients with HCM. Stress testing such as myocardial perfusion imaging lacks specificity in diagnosing coronary artery disease in patients with HCM but has a good negative predictive value. Exercise stress test in controlled environment seems to be safe in properly selected patients with HCM, and benefits of the diagnostic and prognostic information obtained outweigh the small risks.


Maximizing hydrogen production and substrate consumption by Escherichia coli WDHL in cheese whey fermentation.
Fermentative hydrogen production is strongly affected by pH. In order to maximize hydrogen production and substrate consumption in Escherichia coli ΔhycA, ΔlacI (WDHL) cheese whey fermentation, the influence of pH control at values of 5.5, 6, and 6.5 was studied in batch stirred-tank bioreactors. From the conditions evaluated, pH 6.5 was the best condition, at which the highest cumulative hydrogen production and yield (1.78 mol H2/mol lactose) were obtained. Moreover, at this pH, all carbohydrates from the cheese whey were consumed, and a mix of ethanol and organic acids, mainly lactate, were produced from glucose, whereas galactose yielded acetate, ethanol, and succinate. Operating the reactor at pH 5.5 resulted in the highest maximum specific production rate, but smaller hydrogen yield because only glucose was metabolized and galactose was accumulated. At pH 6, not all cheese whey carbohydrates were consumed, and it was not favorable for hydrogen production. Lactose consumption and growth kinetics were not affected by the pH. The results show the importance of controlling pH to maximize hydrogen production and substrate consumption using cheese whey as substrate.


Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway.
Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.


Hyperglycemia presenting as left middle cerebral artery stroke: a case report.
Hyperglycemia is an important diagnostic differential and has been reported to cause focal neurological deficits masquerading as stroke. Discussion of hyperglycemia as a stroke mimic has been sparse in the era of diffusion weighted imaging, but remains an important mimic. A 67 year-old right-handed woman with presented with lethargy, global aphasia, left eye deviation and right hemiparesis. She received IV t-PA for left MCA syndrome and transferred for possible intervention. Initial labs showed a glucose 825mg/dL. MRI/MRA brain was negative for acute stroke with patent vessels, but abnormalities on MRperfusion. The patient was admitted and treated with medical resuscitation including IV fluids and an insulin drip. After normoglycemia was achieved the patient's neurological deficits resolved. EEG on day one of hospitalization showed left hemispheric slowing that subsequently normalized on continuous recording. We report a case of hyperglycemia clinically mimicking a left MCA syndrome reversed with medical management possibly explained by metabolic demand-blood flow coupling of inactive tissue rather than hypoperfused tissue at risk of infarction.


The collateral arterial network of the spleen following ligation of the splenic artery in traumatic rupture of the spleen; an arteriographic study.
Ligation of the splenic artery, combined with splenorrhaphy, was used successfully on eight children with splenic trauma involving major segmental vessels. Evaluation of the collateral arterial network and of its adequacy was done by means of arteriography on four out of the eight patients. Aortographies were carried out on the twentieth day, the first month, the third month, and the fourth month following the ligation. A collateral arterial network, deriving mainly from the short gastric arteries was detected, dyestream disruption and retrograde filling of the artery. No complications after aortography were noted. Findings demonstrate that collateral blood supply develops rapidly and its pattern is rather uniform.


Sexual Self-Concept in Women with Disorders/Differences of Sex Development.
Many women born with disorders or differences of sex development (DSD) report sexual problems, in particular women who have undergone extensive genital reconstruction. Examining cognitions and emotions that hinder or promote sexuality may facilitate understanding these sexual problems and may contribute to the development of specific interventions. In this study, sexual self-concept, body image, and sexual functioning were investigated in relation to genital surgery. To conduct the study, the women's Sexual Self-Concept Scale was translated to Dutch. Evaluation of psychometric properties was conducted in a sample of healthy Belgian and Dutch women participating in an anonymous web-based survey (N = 589, Mdn age, 23 years). The resulting three-factor structure corresponded largely to that of the original version. Compared to control women, women born with a DSD who were included in the Dutch DSD study (N = 99, Mdn age, 26 years) described themselves as being less interested in sex and less sexually active. These women also harbored more negative emotions and cognitions regarding their sexuality and were less satisfied with their external genitalia. In women with a DSD, sexual self-concept was associated with compromised outcomes on sexual functioning and distress. Women who were in a steady relationship, and/or had been sexually active in the past 4 weeks had a more positive sexual self-concept, took a more active role in their sexual relationship, experienced more sexual desire and arousal and less sexual distress than women who were not involved in a partner relationship. Findings in this study indicate that cognitions and emotions related to sexual self-concept play a role in sexual functioning of women with a DSD. A cognitive behavioral counseling approach with focus on coping and exploration of their own sexual needs could prove useful in this group.


Note: a 3-stage stacked Blumlein using ceramic for energy storage.
We have developed a novel stacked Blumlein with high compactness by using ceramic for energy storage. The total volume of this stacked Blumlein is only 320 × 100 × 185 mm(3). By triggering 3 spark gaps simultaneously, the developed stacked Blumlein is capable of producing a rectangular pulse with a voltage multiplication. A 32 ns quasi-rectangular pulse of 11.4 kV is measured across a 10 Ω dummy load when the 3-stage stacked Blumlein is DC charged up to 4 kV. The voltage multiplication is about 2.9, and the energy efficiency is about 96%. Simulation results indicate that vacuum or transformer oil is appropriate to be the insulation medium for the stacked Blumlein.


Personal continuity of GP care and outpatient specialist visits in people with type 2 diabetes: A cross-sectional survey.
Continuity of care is particularly important for patients with chronic conditions, such as type 2 diabetes (T2D). Continuity is shown to reduce overall health service utilization among people with diabetes, however, evidence about how it relates to the utilization of outpatient specialist services in Norway is lacking. The aim of this study was to investigate continuity of GP care for people with T2D, and its association with the use of outpatient specialist health care services. We used e-mail questionnaire data obtained from members of The Norwegian Diabetes Association in 2018. Eligible for analyses were 494 respondents with T2D and at least one GP visit during the previous year. By descriptive statistics and logistic regressions, we studied usual provider continuity (UPC) and duration of the patient-GP relationship and associations of these measures with somatic outpatient specialist visits. Analyses were adjusted for gender, age, education, self-rated health, and diabetes duration. Mean age was 62.6 years and mean UPC was 0.85 (CI 0.83-0.87). Two thirds of the sample (66.0%) had made all visits to the regular GP during the previous year (full continuity). Among these, 48.1% had made one or more specialist visits during the previous year, compared to 65.2% among those without full continuity. The probability of outpatient specialist visits was significantly lower among participants with full continuity, compared to those without full continuity (Odds Ratio 0.53, Confidence Interval 0.35-0.80). The probability of visiting outpatient specialist services was not associated with duration of the patient-GP relationship. We conclude that continuity of care, as measured by Usual Provider Continuity, is high and associated with reduced use of somatic outpatient specialist services in people with T2D in Norway. Continuity and its benefits will become increasingly important as the number of older people with diabetes and other chronic diseases increases.


[Clinical and performance results of functional endoscopic sinus surgery].
Our aim was to know the clinical performance and management results of Functional Endoscopic Sinus Surgery (FESS) in Spanish hospitals. We sent a survey on the use and results of FESS to 160 Spanish public hospitals in June of 2002, obtaining a response rate of 69%. 82.9% of the interviewed hospitals carried out FESS and 17.1% of the remaining used the classic techniques of approaching the paranasal sinuses. The reported length of stay in hospital was 1.4 days for the FESS and 2.4 for the traditional surgery. The surgical time was 15 minutes shorter for the CENS, and the rate of recurrence was 16% less than for the classic surgery. As years of experience in the practice of the CENS go by, the surgical times tend to decrease, that didn't happen with the rate of recurrence. In conclusion, we consider that FESS seems to improve the analyzed clinical performance and assistential results.


Manganese superoxide dismutase gene polymorphisms in psoriatic arthritis.
The purpose of the present study is to investigate the role of manganese superoxide dismutase (MnSOD) gene polymorphisms in the susceptibility to psoriatic arthritis. MnSOD gene polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphisms method in fifty-two patients with psoriatic arthritis and 90 healthy controls.The genotype frequency of MnSOD 1183C/T was significantly higher in patients with psoriatic arthritis than in controls. In contrast, the frequency of MnSOD 1183T/T was significantly decreased in patients with psoriatic arthritis. The phenotype frequency of MnSOD 1183C was significantly increased in patients with psoriatics arthritis in comparison to healthy controls.Therefore, MnSOD 1183C polymorphisms may be a precipitating factor for the development of psoriatic arthritis.


LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer.
Increasing evidence suggests that the long non-coding RNA, HOX transcript antisense intergenic RNA (HOTAIR) is widely involved in the progression and metastasis of cancer. However, the specific role of HOTAIR in ovarian carcinogenesis remains to be fully elucidated. In the present study, the levels of HOTAIR were detected in 30 paired cancer and noncancer tissues using reverse transcription-quantitative polymerase chain reaction analysis. The effect of HOTAIR on the ovarian cancer cells was examined by overexpression or small interfering RNA interference experiments. To examine the competitive endogenous RNA (ceRNAs) mechanism, a luciferase reporter assay was used. In patients with ovarian cancer, HOTAIR was significantly upregulated. Furthermore, the upregulation of HOTAIR increased the proliferation, migration and invasion of ovarian cancer cells. By contrast, the knockdown of HOTAIR repressed cell invasion and viability. HOTAIR functioned as a ceRNA, and acted as a sink for microRNA (miR)‑373, thereby regulating the expression of Rab22a. The upregulation of HOTAIR contributed to the malignant progression of ovarian cancer cells. Therefore, the positive regulation between HOTAIR and Rab22a can be partially attributed to the ceRNA regulatory network through miR-373.


Towards a virtual lung: multi-scale, multi-physics modelling of the pulmonary system.
The essential function of the lung, gas exchange, is dependent on adequate matching of ventilation and perfusion, where air and blood are delivered through complex branching systems exposed to regionally varying transpulmonary and transmural pressures. Structure and function in the lung are intimately related, yet computational models in pulmonary physiology usually simplify or neglect structure. The geometries of the airway and vascular systems and their interaction with parenchymal tissue have an important bearing on regional distributions of air and blood, and therefore on whole lung gas exchange, but this has not yet been addressed by modelling studies. Models for gas exchange have typically incorporated considerable detail at the level of chemical reactions, with little thought for the influence of structure. To date, relatively little attention has been paid to modelling at the cellular or subcellular level in the lung, or to linking information from the protein structure/interaction and cellular levels to the operation of the whole lung. We review previous work in developing anatomically based models of the lung, airways, parenchyma and pulmonary vasculature, and some functional studies in which these models have been used. Models for gas exchange at several spatial scales are briefly reviewed, and the challenges and benefits from modelling cellular function in the lung are discussed.


Differential regulation of endogenous and transduced beta-globin genes during infection of erythroid cells with a herpes simplex virus type 1 recombinant.
We infected murine erythroleukemia cells with a nondefective herpes simplex virus (HSV) type 1 recombinant bearing the rabbit beta-globin gene under the control of its own promoter, in order to compare the regulation of a cellular gene residing in the viral genome to that of its active endogenous counterpart. We found that the viral globin gene was activated by HSV immediate-early polypeptides, whereas expression of the endogenous beta-globin gene was strongly suppressed: transcription was greatly inhibited, and beta-globin mRNA was rapidly degraded. Degradation of globin mRNA was induced by a component of the infecting virion and required a functional UL41 gene product. These results demonstrate that HSV products can have opposing effects on the expression of homologous genes located in the cellular and viral genomes and suggest that the preferential expression of HSV genes that occurs during infection is not achieved solely through sequence-specific differentiation between viral and cellular promoters or mRNAs.


The Nucleoshuttling of the ATM Protein: A Unified Model to Describe the Individual Response to High- and Low-Dose of Radiation?
The evaluation of radiation-induced (RI) risks is of medical, scientific, and societal interest. However, despite considerable efforts, there is neither consensual mechanistic models nor predictive assays for describing the three major RI effects, namely radiosensitivity, radiosusceptibility, and radiodegeneration. Interestingly, the ataxia telangiectasia mutated (ATM) protein is a major stress response factor involved in the DNA repair and signaling that appears upstream most of pathways involved in the three precited RI effects. The rate of the RI ATM nucleoshuttling (RIANS) was shown to be a good predictor of radiosensitivity. In the frame of the RIANS model, irradiation triggers the monomerization of cytoplasmic ATM dimers, which allows ATM monomers to diffuse in nucleus. The nuclear ATM monomers phosphorylate the H2AX histones, which triggers the recognition of DNA double-strand breaks and their repair. The RIANS model has made it possible to define three subgroups of radiosensitivity and provided a relevant explanation for the radiosensitivity observed in syndromes caused by mutated cytoplasmic proteins. Interestingly, hyper-radiosensitivity to a low dose and adaptive response phenomena may be also explained by the RIANS model. In this review, the relevance of the RIANS model to describe several features of the individual response to radiation was discussed.


Going back into the wild: the behavioural effects of raising sea urchins in captivity.
Sea urchin harvesting has rapidly expanded in the last decades. Since many sea urchin species play important ecological role, large-scale commercial sea urchin fisheries can have complex effects on benthic communities. In many temperate regions, overharvesting has compromised marine ecosystems to such an extent that reintroduction of sea urchins raised in captivity may be a valid solution for the enhancement of depleted marine wild populations. In some regions of the Mediterranean Sea, improving the growth efficiency of captive sea urchin Paracentrotus lividus to be reintroduced has become a widespread practice. However, no study has yet considered the potential behavioural effects of raising sea urchins in captivity when they are introduced in the natural environment. This study provides information about the behavioural effects of captivity on P. lividus in terms of locomotion performance, a trait that can be fundamental for responding to predators and for relocation after environmental disturbances such as currents and waves. Movements of captive-born and wild sea urchins were video-recorded and compared in (i) total exposure to external cues, (ii) partial exposure to external cues and (iii) absence of external cues. Latency of locomotion, average speed and average velocity of sea urchins showed significant differences with respect to the level of exposure and their origin (i.e. wild vs. captive-born). Our results demonstrate that captive-born sea urchins in the wild showed long latency and slower locomotor performance when compared to wild sea urchins. Conversely, the straightness-of-path and locomotion direction of captive-born and wild sea urchins were similar in natural settings. Our results therefore suggest that captive-born sea urchins suffer the negative effects of captivity when introduced in a natural environment. Understanding the factors that decrease the performance of sea urchin will be important for developing procedures aimed at minimizing the negative effect of captivity before release into the wild.


Advances in proton-exchange membranes for fuel cells: an overview on proton conductive channels (PCCs).
Proton-exchange membranes (PEM) display unique ion-selective transport that has enabled a breakthrough in high-performance proton-exchange membrane fuel cells (PEMFCs). Elemental understanding of the morphology and proton transport mechanisms of the commercially available Nafion® has promoted a majority of researchers to tune proton conductive channels (PCCs). Specifically, knowledge of the morphology-property relationship gained from statistical and segmented copolymer PEMs has highlighted the importance of the alignment of PCCs. Furthermore, increasing efforts in fabricating and aligning artificial PCCs in field-aligned copolymer PEMs, nanofiber composite PEMs and mesoporous PEMs have set new paradigms for improvement of membrane performances. This perspective profiles the recent development of the channels, from the self-assembled to the artificial, with a particular emphasis on their formation and alignment. It concludes with an outlook on benefits of highly aligned PCCs for fuel cell operation, and gives further direction to develop new PEMs from a practical point of view.


[Great master of TCM CHENG Xin-nong 's three key points of acupuncture clinical experience].
Professor CHENG Xin-nong has practiced in medicine for over 70 years and gained profound clinical experience. He points out that these rules below should be obeyed to improve the efficacy of acupuncture. Firstly, the diseases should be diagnosed basing on meridians order and meridian syndrome differentiation while acupoints should be chosen and adjuncted according to their main medical functions. Secondly, the three Cai inserting method should be flexibly applied on different patients, by adjusting the needling depth and manipulation to reinforce the deficiency and reduce the excess. Thirdly, the arrival of qi is a key point and such methods as the retaining of needles, electroacupuncture and moxibustion should be cointegrated used.


Middle Ear Function and Pathophysiology in Andean Children Living at High Altitudes.
Counter, S. Allen, Leo H. Buchanan, Fernando Ortega, Anthony B. Jacobs, and Göran Laurell. Middle ear function and pathophysiology in Andean children living at high altitudes. High Alt Med Biol. 18:163-170, 2017.-The extent of altitude-related middle ear disorders in children native to high altitudes is unclear. This study examined middle ear pathophysiology in two groups of children living in high-altitude Ecuadorian Andean communities by investigating middle ear pressure (MEP), tympanic membrane compliance (TMC), and ear canal volume (ECV) using tympanometry, and by otological examination. Altitude I Group lived at 2850 m, and Altitude II Group resided at around 4000 m. The two high-altitude groups were compared with a reference group of children residing at sea level. Mean MEP was -3.6 daPa (SD: 39.2), 3.5 daPa (SD: 28.7), and 1.3 daPa (SD: 13.6) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The MEP was not significantly different among the three groups. Mean TMC was 0.63 cm3 (SD: 0.51), 0.60 cm3 (SD: 0.43), and 0.60 cm3 (SD: 0.24) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The TMC was not significantly different among the three groups. Mean ECV was 1.1 (SD: 0.26), 1.2 (SD: 0.26), and 1.0 (SD: 0.23) for Altitude I Group, Altitude II Group, and the Sea Level Group, respectively. The difference in ECV between Altitude I Group and Altitude II Group was significant (p = 0.043), as was the difference between Altitude II Group and the Sea Level Group (p = 0.001). ECV did not differ significantly between Altitude I Group and the Sea Level Group. Otological examination revealed a low incidence of ear canal and middle ear pathology. In conclusion, tympanometric and otological findings did not reveal a high incidence of middle ear pathophysiology in children living at altitudes as high as around 4000 m.


Synthesis, characterization and removal of Cd(II) using Cd(II)-ion imprinted polymer.
A novel ion imprinted polymer (IIP), phenol-formaldehyde-Cd(II)-2-(p-sulphophenylazo)-1,8-dihydroxynaphthalene-3,6-disulphonate (PF-Cd(II)-SPANDS) has been synthesized for selective solid phase extraction (SPE) of Cd(II) from aqueous solutions. IIP was prepared by the copolymerization of phenol and formaldehyde in the presence of Cd(II)-SPANDS complex in acidic medium. This polymer has been characterized on the basis of FTIR, elemental analysis and surface area measurement. Subsequently, the imprinted Cd(II) was completely removed by leaching the dried and powdered imprinted polymer with 1M HNO(3) or 0.01 M EDTA in 0.5M HNO(3). Adsorption capacity was determined by batch experiments for Cd(II), Zn(II), Cu(II) and Hg(II) ions. The effect of pH, flow rate and equilibrium adsorption time was also studied for Cd(II). Adsorption equilibrium time was 50 min. The maximum adsorption of Cd(II) ions on to the imprinted polymer was 270 microg g(-1). For comparison, the adsorption of metal ions was also studied on non-imprinted polymer (NIP). The adsorption capacity of IIP was found 59.2% higher than that of NIP for Cd(II) ion. However, for other investigated transition metal ions the capacity difference was not significant. The relative selectivity factor (alpha(r)) values of Cd(II)/Zn(II), Cd(II)/Cu(II) and Cd(II)/Hg(II) are 7.4, 6.6 and 6.7, respectively which are greater than 1.


The modulation of the human sodium iodide symporter activity by Graves' disease sera.
The transport of iodide into the thyroid, catalyzed by the Na+/I- symporter (NIS), is the initial and rate-limiting step in the formation of thyroid hormones. To study the basic characteristics of the human (h) NIS, we have established a Chinese hamster ovary cell line stably expressing the hNIS (CHO-NIS9). In agreement with previous work on the rat NIS, iodide uptake in these cells was initiated within 2 min of the addition of 131I, reaching a plateau after 30 min. Both perchlorate and thiocyanate inhibited iodide uptake in a dose-dependent manner, with inhibition evident at concentrations of 0.01 and 0.1 micromol/L, respectively, and reaching complete inhibition at 20 micromol/L and 500 micromol/L, respectively. Ouabain, which blocks the activity of the Na+/K+ adenosine triphosphatase, also inhibited iodide uptake in a dose-dependent manner, starting at concentrations of 100 micromol/L and reaching maximum inhibition at 1600 micromol/L, indicating that iodide uptake in these cells is sodium dependent. CHO-NIS9 cells were further used to study 88 sera from patients with Graves' disease, for iodide uptake inhibitory activity, which were compared with sera from 31 controls. Significant iodide uptake inhibition was taken as any inhibition in excess of the mean + 3 SD of the results with the control sera. On this basis, 27 (30.7%) of the Graves' sera, but none of the controls, inhibited iodide uptake in CHO-NIS9. IgGs from these patients also inhibited iodide uptake, indicating that this inhibitory activity was antibody mediated. In summary, we have established a CHO cell line stably expressing the hNIS and shown that antibodies in GD sera can inhibit iodide uptake in these cells. This further emphasizes the role of NIS as a novel autoantigen in thyroid immunity.


Sex differences in prevalence and risk factors of asymptomatic cholelithiasis in Korean health screening examinee: A retrospective analysis of a multicenter study.
The aim of this study was to evaluate sex difference in the prevalence and risk factors for asymptomatic cholelithiasis in Korean health screening examinees.Examinees who underwent examination through health promotion center at 5 hospitals of Daegu-Gyeongbuk province in 2014 were analyzed retrospectively. All examinees were checked for height, weight, waist circumference, and blood pressure, and underwent laboratory tests and abdominal ultrasound. Diagnosis of cholelithiasis was made by ultrasound.Of the total of 30,544 examinees, mean age was 47.3 ± 10.9 years and male to female ratio was 1.4:1. Asymptomatic cholelithiasis was diagnosed in 1268 examinees with overall prevalence of 4.2%. In age below 40 years, females showed higher prevalence of asymptomatic cholelithiasis than males (2.7% vs. 1.9%, P = 0.020), whereas prevalence of asymptomatic cholelithiasis was higher in males than females older than 50 years (6.2% vs. 5.1%, P = 0.012). Multiple logistic regression analysis revealed age (≥50 years), obesity, and high blood pressure as risk factors for asymptomatic cholelithiasis in males and age, obesity, hypertriglyceridemia, and chronic hepatitis B infection in females (P < 0.05).Overall prevalence of asymptomatic cholelithiasis was 4.2% in Korean health screening examinees. Females showed higher prevalence of asymptomatic cholelithiasis than males younger than 40 years, whereas it was higher in males older than 50 years. Age and obesity were risk factors for asymptomatic cholelithiasis in both sexes. Males had additional risk factors of high blood pressure and females had hypertriglyceridemia and chronic hepatitis B infection.


Hindlimb claudication reflects impaired nitric oxide-dependent revascularization after ischemia.
Although vascular remodeling is important in preventing tissue damage and restoring muscle function, there is no evidence of a relationship between vascular remodeling and muscle function after peripheral vascular occlusion. Nitric oxide (NO) has been implicated in the process of vascular remodeling in hindlimb ischemia. Thus, development of alterations in hindlimb gait after ischemia may be associated with impaired nitric oxide-dependent, vascular blood flow recovery. We evaluated hindlimb gait as an index of ischemia-induced revascularization and tested the effects of NO synthase inhibition on both hindlimb blood flow and hindlimb gait locomotion. After 14 days of ischemia, the ischemic hindlimb showed no significant differences in gait locomotion compared to the sham-operated hindlimb. However, hindlimb ischemia drastically reduced hindlimb blood flow from 46+/-3 mL/min/100 g to 12+/-2 mL/min/100 g which reverted to 33+/-5 mL/min/100 g after 14 days of ischemia. eNOS mRNA expression levels at 3, 7, 14, and 28 days after initiation of ischemia, were increased by 50+/-5%, 100+/-10%, 140+/-8% and 270+/-12% respectively and eNOS protein expression levels at 7, 14, and 28 days, were increased by 28+/-3%, 62+/-6% and 80+/-16% respectively. However, eNOS inhibition caused by l-NAME treatment prevented blood flow recovery and correction of abnormal gait locomotion in rats. Thus, the duration of the stride-swing phase increased and the stride length decreased. The knee joint angle decreased during flexion and extension with eNOS inhibition. In conclusion, ischemia-induced revascularization is associated with recovery of both hindlimb blood flow and normal gait locomotion. Moreover, prevention of NO synthesis, a key messenger in ischemia-induced revascularization, is associated with impairment in hindlimb locomotion. Thus, gait locomotion represents a functional model that could be used to evaluate the degree of ischemia-induced revascularization.


Recent advances in audiologic assessment.
Hearing impairment in the developing child can have far reaching and long lasting consequences. In addition to communicative difficulties, children with undetected or misdiagnosed hearing impairment can suffer intellectually, socially, emotionally and/or behaviorally. There is little reason, however, for infants or children with hearing impairment to go without accurate assessment because the pediatric audiologist is now armed with reliable test techniques for virtually every child. This paper is a review of some of the behavioral and physiological methods used by the audiologist to identify and describe the hearing of infants and children. Also included are suggestions for the pediatrician about when it is appropriate to request the help of the audiologist in evaluating an infant or child at risk for or with suspected hearing loss.


Side-by-side viewing of anatomically aligned left ventricular segments in three-dimensional stress echocardiography.
Dobutamine stress echocardiography (DSE) suffers from high interobserver and inter-institution variability in the diagnosis of myocardial ischemia. Therefore, we developed a three-dimensional (3D) analysis tool that makes it possible to anatomically align 3D rest and stress data systematically, to generate optimal, nonforeshortened standard anatomical cross sections and to analyse the images synchronized and side-by-side. To investigate whether this 3D analysis tool could improve interobserver agreement on myocardial ischemia during 3D DSE. The study comprised 34 consecutive patients with stable chest pain who underwent both noncontrast and contrast 3D DSE. Two observers scored segmental wall motion using a conventional analysis and the novel analysis with the new 3D tool. The two observers agreed on the presence or absence of myocardial ischemia in 81 of 102 coronary territories (agreement 79%, kappa (kappa) 0.28) during noncontrast 3D imaging and 92 of 102 coronary territories (agreement 90%, kappa 0.65) during contrast-enhanced 3D imaging. With the new 3D analysis software these numbers improved to 98 of 102 coronary territories (agreement 96%, kappa 0.69) during noncontrast 3D imaging and 98 of 102 coronary territories (agreement 96%, kappa 0.82) during contrast-enhanced 3D imaging. The use of a 3D DSE analysis tool improves interobserver agreement for myocardial ischemia both for noncontrast and contrast images.


Dose area product reference levels in dental panoramic radiology.
The purpose of this study was to measure DAP (Dose Area Product) values in panoramic radiology with the use of a DAP meter, to determine corresponding reference levels, and to compare DAP between panoramic and intraoral radiology. DAP was measured in 62 panoramic X-ray units for 3 types of exposure (male, female and child) and in 20 intraoral X-ray units of 50, 60 and 70 kVp. DAP reference levels were 117 mGy cm2, 97 mGy cm2 and 77 mGy cm2 for exposure of a male, female and child respectively. Results showed that DAP from a panoramic dental examination is approximately twice that from a single intraoral examination. DAP meter is a very convenient and easy to use tool for patient dosimetry and for the establishment of reference levels in dental panoramic radiology.


Alcohol use after liver transplantation in alcoholics: a clinical cohort follow-up study.
The purposes of this study were to determine among a cohort of long-term alcoholic survivors after liver transplantation (1) the incidence of alcohol use, (2) its effect on allograft integrity and extrahepatic health, and (3) the validity of the pretransplant alcohol prognosis screening process. Retrospective clinical cohort study of all alcoholic patients undergoing orthotopic liver transplantation at a single center from February 1987 until January 1991 with follow-up through December 1994, giving a median duration of follow-up of 63 months (range, 6-89 months). Multidisciplinary liver transplantation program at a tertiary-care academic medical center. Fifty alcoholic, long-term liver transplant recipients. The frequency of alcohol relapse, defined as any alcohol use in the period after transplantation, was determined by two questionnaire studies and by clinical follow-up. Allograft integrity was assessed by coded review of serial percutaneous allograft biopsies. Potential systemic effects of alcohol relapse were assessed by chart review. The alcohol prognosis screening process was evaluated by retrospectively comparing pretransplant estimates of putative indicators of alcoholism prognosis in posttransplant alcohol users and abstainers. Thirty-three recipients (66%) consistently denied any alcohol use throughout the duration of posttransplant follow-up, whereas 17 (34%) were identified as having consumed alcohol at least once since the transplant. There were no significant differences at the time of evaluation between abstainers and alcohol users in age, sex distribution, severity of liver dysfunction, median duration of abstinence, or University of Michigan alcoholism prognosis score. The median interval from transplantation to alcohol relapse was 17 months, with a range of 3 to 45 months. Recurrent alcohol use was associated with significant medical complications sufficient to require admission to the hospital in 6 patients. One patient died of graft dysfunction, noncompliance with immunosuppressant medications, and presumed graft rejection while drinking. Mild or progressive hepatitis, which was the most common abnormality in posttransplant liver biopsy findings, was equally distributed between both alcohol users and abstainers and sometimes occurred in the absence of antibody to hepatitis C virus antibodies. There was a similar frequency of biopsy-proven acute cellular rejection in alcohol users and abstainers. Typical histological features of alcoholic liver injury were present in posttransplant biopsies from 1 alcohol user only. Alcohol use by alcoholics is uncommon in the first 5 years after liver transplantation, and alcohol-associated liver injury is unusual. Mild nonspecific hepatitis is common in both alcohol users and nonusers alike. Among a small subset of alcoholic transplant recipients, drinking behavior after liver transplantation is associated with considerable morbidity, requiring hospital admissions and occasionally leading to graft loss and death.


Systemic lupus erythematosus as the concomitant manifestation of angioimmunoblastic T-cell lymphoma.
Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.


Encapsulation of sulfur in MoS2-modified metal-organic framework-derived N, O-codoped carbon host for sodium-sulfur batteries.
Room-temperature sodium-sulfur batteries (RT Na-S) are promising energy storage systems with high energy densities and low costs. Nevertheless, drawbacks, including the limited cycle life and sluggish redox kinetics of sodium polysulfides, hinder their implementation. Herein, a heterostructure of MoS2 nanosheets coated on a metal-organic framework (MOF)-derived N, O-codoped flower-like carbon matrix (NOC) was designed as a sulfur host for advanced RT Na-S batteries. The NOC@MoS2 hierarchical host provided a sufficient space to guarantee a high sulfur loading and confinement for the volume expansion of sulfur during the charge/discharge process. According to first-principle calculations, the NOC@MoS2 composite exhibited metallic conductivity because electronic states crossed the Fermi level, which indicates that the introduction of NOC significantly improved the electronic conductivity of MoS2. Furthermore, electron transfer from MoS2 to the O-doped carbon sites was observed owing to the strong electronegativity of O, which can effectively increase the Lewis acidity of MoS2 and weaken the sodium-sulfur bonds in sodium polysulfides after adsorption on the cathode, leading to reductions in the Na2S dissociation energy barrier and Gibbs free energy for the rate-limiting step of the sulfur reduction process. Therefore, with the synthetic effects of MoS2 and N, O-codoped carbon, the obtained cathode exhibited a superior electrochemical performance.


Organization and hierarchy of the human functional brain network lead to a chain-like core.
The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.


Assessing conversational disability.
In spite of current interest in conversational disability, and the growing number of children who are being diagnosed as exhibiting this disorder, there are few satisfactory procedures that can be used to assess their conversation. In the following paper, data from the naturally occurring conversations of two children, who were identified as having difficulties in participating in conversation, are presented. The data were scanned for the following conversational skills: securing the attention of the addressee before speaking, initiating new topics of conversation effectively, using the grammatical forms that are most frequently associated with particular linguistic functions, filling response slots effectively, maintaining cohesion within the discourse, and taking steps to repair mishearings or misunderstandings. This kind of assessment, based on the principles of conversational analysis, provided an objective appraisal of the conversational skills of the children, and also highlighted potential areas for therapeutic intervention. Many of the conversational behaviours exhibited by the two subjects corresponded with those that have been observed in very young children who are developing language normally. It is suggested that the subjects studied here presented with a severe delay in their conversational development rather than a disorder.


Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1.
Loss of CD4+ T helper lymphocytes is central to the development of immunodeficiency after infection with HIV. In this study, we demonstrate that contact of primary uninfected CD4+ T lymphocytes with HIV-infected or HIV envelope glycoprotein-expressing cells results in apoptotic cell death of both uninfected and infected cells. Apoptosis was blocked by inhibitors of caspases/IL-1beta-converting enzyme-like proteases. This finding provides conclusive evidence that cytotoxicity upon contact of HIV-infected and uninfected primary cells is an active process and represents another example for the role of caspases in the induction of apoptosis. Prevention of apoptosis by inhibition of caspases did not block the formation of syncytia, indicating that apoptosis occurs either in a subpopulation of cells or in syncytia. Cell death was not mediated by the CD95 (Fas/Apo-1) or TNF receptor 1 molecules, which indicates a different pathway of apoptosis induction. The data indicate that initiation of apoptosis significantly shortens the life span of uninfected CD4+ T cells upon contact with HIV-infected cells and may represent a factor that contributes to the destruction of CD4+ T lymphocytes in vitro. Elucidation of the mechanism that initiates apoptosis in this situation will add to our understanding of both HIV pathogenesis and apoptotic signaling.


Urinary albumin, immunoglobulin G and Beta-microglobulin in the diagnosis of diabetes in the elderly.
Diabetes shows no obvious clinical symptoms in the early stage, which makes it difficult to be detected; however, as a common and frequently occurring disease, its morbidity increases with the improvement in the standard of living. Therefore, early detection, diagnosis and treatment of diabetes are of great importance. This study investigated the application values of urinary albumin (Alb), immunoglobulin G (IgG) and Beta-microglobulin (β2mG) in the diagnosis of diabetes. Seventy-four elderly patients with confirmed diabetes who were admitted to the Central Hospital of Zibo from May 2014 to May 2015 were taken as an observation group, and fifty normal healthy people were taken as a control group. Levels and positive detection rates of Alb, IgG and β2mG in the two groups were compared. The results showed that the levels of Alb, IgG and β2mG of the observation group were higher than those of the control group, and the positive detection rates of Alb, IgG and β2mG were 74.3%, 62.2% and 67.6%, respectively, which were higher than 6%, 16% and 12% in the control group; the differences were all statistically significant (P less than 0.05). The difference of the content of Alb, IgG and β2mG between patients with different disease courses was statistically significant (P less than 0.05). Therefore, Alb, IgG and β2mG levels are closely related to severity of diabetes, which provides a medical reference to the diagnosis and examination of diabetes and has important clinical values.


Socioeconomic variations in female fertility impairment: a study in a cohort of Portuguese mothers.
This study aimed to assess the association of socioeconomic conditions with female fertility impairment among women who delivered a live birth. Cross-sectional analysis. Population-based birth cohort (Generation XXI) assembled in 2005/2006 from five public maternity units in Porto Metropolitan Region, Northern Portugal. 7472 women aged 18 or more with spontaneous conception and no male diagnosis of infertility were recruited and interviewed immediately after birth with structured questionnaires. Maternal education, occupation and income were recorded as proxy indicators of social conditions. Impaired female fertility, defined as women who had unsuccessfully tried to conceive for over a year. Multivariate logistic regression models were fitted to estimate the association between each socioeconomic indicator and impaired female fertility, stratified by previous pregnancy experience and adjusted for age, pregnancy planning and behavioural characteristics. Among primigravidae, 7.7% (95% CI 6.8% to 8.6%) presented impaired fertility and the prevalence was 9.6% (95% CI 8.7% to 10.6%) in multigravidae. In crude analysis, we found women with impaired fertility to be older, less educated, more likely to have planned the current pregnancy and to be overweight/obese; they had similar levels of income or occupation. In multivariate models, a significant independent association between educational level and female fertility impairment remained among primigravidae (OR (95% CI) vs ≤6 schooling years: 7-9: 0.85 (0.54 to 1.34); 10-12: 0.34 (0.21 to 0.54); >12: 0.24 (0.14 to 0.40), ptrend<0.001) but not in multigravidae. This study shows that education might be important in understanding female fertility impairment, particularly among first-time pregnant women. It also points out that the association is not totally explained by other sociodemographic and lifestyle characteristics that have been previously found to be important to disclose this relation.


Enhanced levels of biochemical markers for cobalamin deficiency in totally gastrectomized rats: uncoupling of the enhancement from the severity of spongy vacuolation in spinal cord.
The totally gastrectomized (TGX) rat is a new experimental model for studying the pathogenesis of cobalamin (Cbl)-deficient myelopathy, i.e., subacute combined degeneration, total gastrectomy (TG) serving as a surgical paradigm of human pernicious anemia. We determined the serum levels of some biochemical indicators of Cbl deficiency in TGX rats at 2 to 10 months after TG. Methylmalonic acid (MMA) rose within 2 months and progressively increased thereafter until the end of the investigation period. 2-Methylcitric acid (MCA) rose significantly by 6 months and showed a further increment 4 months later. Homocysteine was only clearly elevated much later than the serum MMA, i.e., 10 months after the operation. The concentrations of MMA, MCA, and cystathionine were increased in kidney, liver, and spinal cord (SC) of TGX rats at 10 months. Chronic treatment of TGX rats with Cbl greatly decreased the serum levels of all the metabolic indicators of Cbl deficiency. Chronic peroral administration of the antibiotic lincomycin to TGX rats in an attempt to suppress the enteric flora markedly decreased serum MMA levels. Only Cbl, however, given either for the first 2 months after TG or for the third and fourth postoperative months (i.e., after SC abnormalities had already appeared) significantly decreased the severity of spongy vacuolation in SC white matter, although not completely preventing or repairing the neuropathological damage. Therefore, neither the early impairment in TGX rats of the Cbl-dependent methylmalonyl-coenzyme A mutase reaction nor the more delayed impairment of the Cbl-dependent methionine synthase step, as reflected by changes in serum metabolite levels, seems to be causally related to the TG-induced spongy vacuolation in SC white matter.


Pharmacogenomics: the importance of accurate phenotypes.
Lack of knowledge regarding genotype-phenotype correlations is often cited as the major barrier delaying the uptake of pharmacogenomics into routine medical practice. When we look forward to genome-wide association studies as one of the most promising tools for overcoming the pharmacogenomics knowledge barrier, we must keep in mind that having large patient cohorts may not help improve our understanding of alleles implicated in drug-response phenotypes, unless we ensure that such phenotypes are precise and pertinent. It may be wiser, and far more cost effective, to invest scarce research funding in accurate patient drug-response phenotyping than to genotype (or fully sequence) hundreds to thousands of study participants. Biobanks created with personalized medicine research in mind should, when possible, have access to donors' clinical data, including detailed disease- and drug-response phenotypes.


Vector competence of Culex neavei (Diptera: Culicidae) for Usutu virus.
Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was isolated for the first time from a Culex neavei mosquito in 1959 in South Africa. Despite multiple isolations of USUV from Cx. neavei in Africa, its vector competence remains unproven. Therefore, we infected Cx. neavei orally with the USUV reference strain and used reverse transcription-polymerase chain reaction and an indirect immunofluorescence assay to detect virus in bodies, legs, wings, and saliva of mosquitoes. We demonstrated the susceptibility of Cx. neavei mosquitoes for the USUV reference strain, its potential to be transmitted, and infection, dissemination, and transmission rates of 90.9%, 40.0%, and 81.3%, respectively. Also, we showed that infection rates are dependent on the virus titer of the blood meal. Given the bionomics of Cx. neavei, its role as enzootic vector for USUV in Africa in a mosquito-bird transmission cycle or as bridge vector for USUV transmission to humans is discussed.


Functional studies of chronic lymphocytic leukemia B cells expressing β2-integrin type complement receptors CR3 and CR4.
The expression and role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in B cells are not yet explored in contrast to myeloid cells, where these β2-integrin type receptors are known to participate in various cellular functions, including phagocytosis, adherence and migration. Here we aimed to reveal the expression and role of CR3 and CR4 in human B cells. In B cells of healthy donors CR3 and CR4 are scarcely expressed. However, two patients with chronic lymphocytic leukemia (CLL) characterized by a peculiar immune-phenotype containing both CD5-positive and CD5-negative B cell populations made possible to study these molecules in distinct B cell subsets. We found that CD11b and CD11c were expressed on both CD5-positive and CD5-negative B cells, albeit to different extents. Our data suggest that these receptors are involved in spreading, since this activity of CpG-activated B cells on fibrinogen could be partially blocked by monoclonal antibodies specific for CD11b or CD11c. CpG-stimulation lead to proliferation of both CD5-positive and CD5-negative B cells of the patients with a less pronounced effect on the CD5-positive cells. In contrast to normal B cells, CLL B cells of both patients reacted to CpG-stimulation with robust IL-10 production. The concomitant, suboptimal stimulus via the BCR and TLR9 exerted either a synergistic enhancing effect or resulted in inhibition of proliferation and IL-10 production of patients' B cells. Our data obtained studying B cells of leukemic patients point to the role of CR3 and probably CR4 in the interaction of tumor cells with the microenvironment and suggest the involvement of IL-10 producing B cells in the pathologic process.