[Grading of diabetic retinopathy from non-stereoscopic color fundus photographs--relationship to fluorescein angiography findings and three-year prognosis].
To evaluate the grading of diabetic retinopathy from non-stereoscopic color fundus photographs, we examined the relation of the photos to fluorescein angiography findings and to the three-year prognosis. Fifty diabetic patients(70 eyes) who had severe non-proliferative diabetic retinopathy or early proliferative retinopathy without photocoagulation treatment were graded regarding 11 items of four-field fundus photographs using a 50-degree mydriatic camera. Fluorescein angiography was performed and the relation of the images to the grades of diabetic retinopathy were analyzed. In 51 eyes, the relation between the grading and the progression and treatment of diabetic retinopathy were evaluated. The grading of microaneurysms and retinal hemorrhages (p < 0.001), soft exudates (p = 0.01), intraretinal microvascular abnormalities (p < 0.001), arteriolar white threads (p = 0.003), venous loops (p = 0.01), and new vessels (p < 0.001) was significantly related to the nonperfused areas on fluorescein angiograms. The grading of diabetic retinopathy was also significantly related to the threeyear prognosis. These results indicated that the grading of diabetic retinopathy from fundus photographs may have a potential advantage over conventional classifications of diabetic retinopathy.


Task and information conflicts in the numerical Stroop task.
Studies of the Stroop color-word task have provided evidence for the existence of two conflicts: (1) an early task conflict between noting the relevant color and reading afforded by the irrelevant word (or word-like stimuli), and (2) a late information conflict between the information provided by the word and the information provided by the color. Measurements of pupil changes, in addition to reaction time (RT), have extended understanding regarding these two conflicts. The current work examines the generalizability of such understanding. We ask whether similar processes work in the comparative judgment of numbers (e.g., in the numerical Stroop task). We present two experiments that support and extend the knowledge gained in the word-color context to numerical processing. Similar to results with the Stroop color-word task, we found a dissociation between RT and pupillometry and an early task conflict followed by an information conflict.


The neuroanatomy of herophilus.
Herophilus (ca. 330 to ca. 260 BC) was one of Hellenistic -Alexandria's renowned scholars, a leading physician, often named the 'Father of Anatomy'. From cadaveric dissections and possibly vivisection Herophilus considered the ventricles to be the seat of the soul, intelligence and mental functions. Herophilus introduced the term rete mirabile found in ungulates but not in man, as opposed to Galen, who erroneously believed it a vital human network. A founder of the principles of observations in science, and an exponent of measurements in medicine, his accurate dissections resulted in original anatomical discoveries. He distinguished nerves that produce voluntary motion from blood vessels, and motor from sensory nerves; the nerves of the spinal cord were directly linked to the brain. He identified at least seven pairs of cranial nerves. Herophilus demonstrated the meninges, and ventricles, regarding the fourth as most important. His name is perpetuated by his accounts of the calamus scriptorius and the confluence of venous sinuses the torcular Herophili.


[Twenty-year History and Future Challenges in Transparency Enhancement of Review Process for Approval: Focus on Public Release of Review Reports regarding New Drugs and Medical Devices].
For 20 years, the Ministry of Health, Labour and Welfare (MHLW, formerly Ministry of Health and Welfare (MHW)) has been trying to increase transparency of the review process for approving reports in order to promote the rational use of newly approved drugs and medical devices. The first Summary Basis of Approval (SBA) was published by MHW in 1994. In 1999, evaluation reports were prepared by MHW and the Pharmaceuticals and Medical Devices Evaluation Center to make them available to the public. In 2005, a notice from the Chief Executive of the Pharmaceuticals and Medical Devices Agency (PMDA) made procedures for public release of information on reviewing applications for new drugs. In 2006, 90 review reports of newly approved drugs and eight medical devices were revealed on PMDA websites. The dissemination of information by the United States Food and Drug Administration (FDA) and that of the European Medicines Agency (EMA) were studied and compared with that of the MHLW and PMDA. While common technical documents (CTD) for new drugs and summary technical documents (STED) for new medical devices have been released by PMDA, such documents are not released by the FDA and EMA. The European Public Assessment Report (EAPR) summary for the public is an interesting questionnaire approach that uses the "What," "How" and "Why" format. Finally, future proposals for the next decade are also outlined.


Metastatic brain tumor manifesting as lacunar syndrome in adults.
Lacunar syndrome can be an initial manifestation of the metastatic brain tumor in young adults. Two patients were encountered with previously undiagnosed lung cancer, one with anaplastic carcinoma and the other with adenocarcinoma. A neurologic syndrome occurred in the morning with unusual headache and stroke-like episodes, presenting an acute ataxic hemiparesis and a pure motor hemiparesis, respectively. Papilloedema was a universal finding. The headache and neurologic deficits responded rapidly to glucocorticoid. A preexisting intracranial mass with an outburst of brain edema is thought to be the mechanism in this situation.


A kindling-like effect induced by repeated exposure to heated water in rats.
Hyperthermia was induced in mature rats by immersing them in 20 cm of 45 degrees C water for 4 min. Rats were made hyperthermic once every 4 days for six exposures. A significant number had at least one convulsion by the third exposure. During the seventh exposure, 2 weeks after the sixth exposure, twice as many rats experienced convulsions. Two weeks later, four rats that had convulsed following exposure to heated water at an earlier time convulsed on exposure to a strobe light flashing at 25 Hz. The percentage of rats having experienced at least one convulsion increased dramatically when tested 2 and then an additional 3 months later. Spontaneous (handling-induced) convulsions also occurred in a few rats that had been exposed to heated water previously. The data indicate that repeated exposure to this type of hyperthermia can result in an increase in convulsive susceptibility in mature rats and may be a useful, noninvasive model for studying kindling, febrile convulsions, and epilepsy in rodents.


3-Carboxybenzoboroxole Functionalized Polyethylenimine Modified Magnetic Graphene Oxide Nanocomposites for Human Plasma Glycoproteins Enrichment under Physiological Conditions.
Boronate affinity materials have been successfully used for the selective recognition of glycoproteins. However, by such materials, the large-scale glycoproteins enrichment from human plasma under physiological conditions is rarely reported. In this work, 3-carboxybenzoboroxole (CBX) functionalized polyethylenimine (PEI) modified magnetic graphene oxide nanocomposites were synthesized. Benefitting from the low pKa value of CBX (∼6.9) and PEI dendrimer-assisted multivalent binding, the Freundlich constant (KF) for the adsorption of horseradish peroxidase (HRP) was 3.0-7.3 times higher than that obtained by previous work, displaying the high enrichment capacity. Moreover, PEI could improve the hydrophilicity of nanocomposites and reduce nonglycoprotein adsorption. Therefore, such nanocomposites were successfully applied to the analysis of human plasma glycoproteome under physiological conditions, and the identified glycoproteins number and recognition selectivity was increased when compared to the results obtained by previous boronic acid-functionalized particles (Sil@Poly(APBA-co-MBAAm)) under common alkaline condition (137 vs 78 and 67.8% vs 57.8%, respectively). In addition, thrombin (F2), an important plasma glycoprotein, labile under alkaline conditions, was specifically identified by our method, demonstrating the great promise of such nanocomposites in the deep-coverage glycoproteome analysis.


Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T cells and macrophages. The clinical characteristics associated with this disease result from overproduction of Th1 cytokines including interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha). In this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was detected in plasma in all patients (mean peak value, 30.0 +/- 5.0 pg/mL), while IFN-gamma was massively produced in nine patients (mean peak value, 79.2 +/- 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma IL-10 levels were elevated in all patients (mean peak value, 2,698.0 +/- 3,535.0 pg/mL). There was a positive correlation between the levels of IFN-gamma and IL-10 (P < .01). The plasma concentrations of these cytokines were initially high, before decreasing after the acute phase. However, the decrease in IL-10 levels was slower than that of IFN-gamma. Although the concentration of IL-12 was high at the acute phase, in some patients, a peak in the level was delayed until the chronic phase. Thus, in HLH, production of cytokines that promote development of Th1 cells appears to be predominant over that for Th2 cell development. Overproduction of IL-10 was also observed indicating that a mechanism suppressing hyperactivation of Th1 cells and monocytes/macrophages functions in patients with this disease.


The Migration, Mental Stress, and Tobacco use of Internal Migrants in China: The Moderating Effect of the Social Context of the Host Society.
Previous studies on the relationship between mental stress and the tobacco use of internal migrants have not fully considered the social context of the host society. This study aims to examine how mental stress influences cigarette smoking in internal migrants in China by considering the social context of the host society. We used the RUMiC data that were collected in 15 cities distributed throughout 9 provinces of China. A total of 8,446 and 5,426 migrant workers were interviewed in 2008 and 2009, respectively. We selected individuals based on the criteria of age, salary, and hukou status. A total of 8,880 observations are valid for this study. This research used the logistic regression method to test the association between mental stress and the tobacco use of internal migrants. The results show that mental stress is not necessarily associated with the tobacco use of internal migrants. However, the effects of mental stress on tobacco use are moderated by the social context of the host society. This article calls for more attention to be paid to the moderate effect of social context in the host society on the association between mental stress and cigarette smoking of internal migrants. Moreover, this article underscores the importance of factors related to local societies in making and enacting tobacco control policies for migrants in developing countries.


The Formation of Nucleobases from the Ultraviolet Photoirradiation of Purine in Simple Astrophysical Ice Analogues.
Nucleobases are the informational subunits of RNA and DNA and are essential to all known forms of life. The nucleobases can be divided into two groups of molecules: the pyrimidine-based compounds that include uracil, cytosine, and thymine, and the purine-based compounds that include adenine and guanine. Previous work in our laboratory has demonstrated that uracil, cytosine, thymine, and other nonbiological, less common nucleobases can form abiotically from the UV photoirradiation of pyrimidine in simple astrophysical ice analogues containing combinations of H2O, NH3, and CH4. In this work, we focused on the UV photoirradiation of purine mixed with combinations of H2O and NH3 ices to determine whether or not the full complement of biological nucleobases can be formed abiotically under astrophysical conditions. Room-temperature analyses of the resulting photoproducts resulted in the detection of adenine, guanine, and numerous other functionalized purine derivatives. Key Words: Pyrimidine-Nucleobases-Interstellar; Ices-Cometary; Ices-Molecular processes-Prebiotic chemistry. Astrobiology 17, 761-770.


Coarse-Grained Model for Prediction of Hole Mobility in Polyethylene.
Electrical conductivity measurements of polyethylene indicate that the semicrystalline structure and morphology influence the conductivity. To include this effect in atomistic charge transport simulations, models that explicitly or implicitly take morphology into account are required. In the literature, charge transport simulations of amorphous polyethylene have been successfully performed using short oligomers to represent the polymer. However, a more realistic representation of the polymer structure is desired, requiring the development of fast and efficient charge transport algorithms that can handle large molecular systems through coarse-graining. Here, such a model for charge transport simulations in polyethylene is presented. Quantum chemistry calculations were used to define six segmentation rules on how to divide a polymer chain into shorter segments representing localized molecular orbitals. Applying the rules to amorphous systems yields distributions of segments with mode and median segment lengths relatively close to the persistence length of polyethylene. In an initial test, the segments of an amorphous polyethylene were used as hopping sites in kinetic Monte Carlo (KMC) simulations, which yielded simulated hole mobilities that were within the experimental range. The activation energy of the simulated system was lower compared to the experimental values reported in the literature. A conclusion may be that the experimental result can only be explained by a model containing chemical defects that generate deep traps.


Hemorrhagic Rathke's cleft cyst presenting as diplopia.
To report a case of uncommon presentation of hemorrhagic Rathke's cleft cyst (RCC) extending into the cavernous sinus, causing diplopia. We present clinical, radiologic, and histologic findings on this patient, and review related medical literature. A 34-year-old man presented with a 4-month duration of worsening left-sided headache with acute development of diplopia which worsened upon looking to the left. Magnetic resonance imaging identified a left pituitary mass with posterior extension and involvement of the cavernous sinus. Hormone level evaluation revealed a low free thyroxine index and elevated prolactin levels, and normal levels of thyroid stimulating hormone, growth hormone, insulin-like growth factor type 1, and cortisol. The patient underwent transsphenoidal resection of a yellow fibrous mass from the left side of the sella. Tumor tissue pathology was consistent with a RCC that may have undergone secondary hemorrhage and rupture. Postoperatively, this patient developed transient diabetes insipidus, and required levothyroxine therapy for hypothyroidism. The diplopia improved, though he continues to complain of episodic headaches. RCCs are challenging to diagnose, as they can cause symptoms related to enlargement and hemorrhage. Imaging studies and other diagnostic measures may, therefore, describe heterogeneous features. The most common clinical presentation of this disorder is a manifestation of pituitary dysfunction, such as hyperprolactinemia, diabetes insipidus, and, occasionally, apoplexy. These symptoms may be accompanied by headache. Visual disturbances often appear, usually as visual field defects and decreased visual acuity. This case demonstrates that nonpituitary masses such as RCC can hemorrhage and extend into the cavernous sinus, causing acute ophthalmoplegia.


Strategic design and refinement of Lewis acid-base catalysis by rare-earth-metal-containing polyoxometalates.
Efficient polyoxometalate (POM)-based Lewis acid-base catalysts of the rare-earth-metal-containing POMs (TBA(6)RE-POM, RE = Y(3+), Nd(3+), Eu(3+), Gd(3+), Tb(3+), or Dy(3+)) were designed and synthesized by reactions of TBA(4)H(4)[γ-SiW(10)O(36)] (TBA = tetra-n-butylammonium) with RE(acac)(3) (acac = acetylacetonato). TBA(6)RE-POM consisted of two silicotungstate units pillared by two rare-earth-metal cations. Nucleophilic oxygen-enriched surfaces of negatively charged POMs and the incorporated rare-earth-metal cations could work as Lewis bases and Lewis acids, respectively. Consequently, cyanosilylation of carbonyl compounds with trimethylsilyl cyanide ((TMS)CN) was efficiently promoted in the presence of the rare-earth-metal-containing POMs via the simultaneous activation of coupling partners on the same POM molecules. POMs with larger metal cations showed higher catalytic activities for cyanosilylation because of the higher activation ability of C═O bonds (higher Lewis acidities) and sterically less hindered Lewis acid sites. Among the POM catalysts examined, the neodymium-containing POM showed remarkable catalytic performance for cyanosilylation of various kinds of structurally diverse ketones and aldehydes, giving the corresponding cyanohydrin trimethylsilyl ethers in high yields (13 substrates, 94-99%). In particular, the turnover frequency (714,000 h(-1)) and the turnover number (23,800) for the cyanosilylation of n-hexanal were of the highest level among those of previously reported catalysts.


High performance testbed for four-beam infrared interferometric nulling and exoplanet detection.
Technology development for a space-based infrared nulling interferometer capable of earthlike exoplanet detection and characterization started in earnest in the last 10 years. At the Jet Propulsion Laboratory, the planet detection testbed was developed to demonstrate the principal components of the beam combiner train for a high performance four-beam nulling interferometer. Early in the development of the testbed, the importance of "instability noise" for nulling interferometer sensitivity was recognized, and the four-beam testbed would produce this noise, allowing investigation of methods for mitigating this noise source. The testbed contains the required features of a four-beam combiner for a space interferometer and performs at a level matching that needed for the space mission. This paper describes in detail the design, functions, and controls of the testbed.


Finding reality: the use of objective structured clinical examination (OSCE) in the assessment of mental health nursing students interpersonal skills.
This paper presents the implementation of an objective structured clinical examination (OSCE) in the assessment of mental health nursing students' interpersonal skills. It begins by providing a rationale for the use of this instrument to assess such ski lls and offers a brief discussion of the development of OSCEs. The preparation and implementation of the OSCE is explored and both students' and tutors' reflections of the process are highlighted. The strengths and problems, particularly the use of an ac tor and video tape recordings are examined, in the light of other studies. The paper concludes by advocating the use of such an assessment tool as a formative exercise.


Mapping cross-species connectome atlas of human and macaque striatum.
Cross-species connectome atlas (CCA) that can provide connectionally homogeneous and homologous brain nodes is essential and customized for cross-species neuroscience. However, existing CCAs were flawed in design and coarse-grained in results. In this study, a normative mapping framework of CCA was proposed and applied on human and macaque striatum. Specifically, all striatal voxels in the 2 species were mixed together and classified based on their represented and characterized feature of within-striatum resting-state functional connectivity, which was shared between the species. Six pairs of striatal parcels in these species were delineated in both hemispheres. Furthermore, this striatal parcellation was demonstrated by the best-matched whole-brain functional and structural connectivity between interspecies corresponding subregions. Besides, detailed interspecies differences in whole-brain multimodal connectivities and involved brain functions of these subregions were described to flesh out this CCA of striatum. In particular, this flexible and scalable mapping framework enables reliable construction of CCA of the whole brain, which would enable reliable findings in future cross-species research and advance our understandings into how the human brain works.


Risk factors for acute renal failure in nephrectomized patients treated in a university hospital.
New surgical techniques for nephrectomy mainly related to early diagnosis made possible by advances in imaging studies have been developed in recent decades. However, postoperative renal dysfunction is a constant concern because of the major problems faced by healthcare services and by the patients themselves. To assess risk factors for developing acute renal failure (ARF) in patients submitted to nephrectomy in a university hospital. Seventy-seven patients submitted to nephrectomy for benign and malignant diseases in a university hospital were evaluated in respect to preoperative and postoperative creatinine clearance. Demographic (gender, age), clinical (cancer, diabetes, high blood pressure, chronic kidney disease) and surgical (anesthesia time, open or laparoscopic surgery) variables were also analyzed. Of the 77 patients, 72 met the inclusion criteria. Of these, ten (13.8%) had a diagnosis of chronic renal failure (CRF), 30 (48%) had stage I ARF and one (16.1%) had stage II ARF. The anesthesia time, type of surgery (open or laparoscopy), total or partial nephrectomy, the side of the procedure, hypertension, diabetes, CRF, renal cancer, preoperative and postoperative creatinine concentrations were analyzed. Only the difference between preoperative and postoperative creatinine clearance was clinically significant (P<0.001). An altered preoperative renal function is a risk factor for the development of ARF in nephrectomized patients.


Integrated phenotypic-genotypic approach to understand the influence of ultrasound on metabolic response of Lactobacillus sakei.
The lethal effects of soundwaves on a range of microorganisms have been known for almost a century whereas, the use of ultrasound to promote or control their activity is much more recent. Moreover, the fundamental molecular mechanism influencing the behaviour of microorganisms subjected to ultrasonic waves is not well established. In this study, we investigated the influence of ultrasonic frequencies of 20, 45, 130 and 950 kHz on growth kinetics of Lactobacillus sakei. A significant increase in the growth rate of L. sakei was observed following ultrasound treatment at 20 kHz despite the treatment yielding a significant reduction of ca. 3 log cfu/mL in cells count. Scanning electron microscopy showed that ultrasound caused significant changes on the cell surface of L. sakei culture with the formation of pores "sonoporation". Phenotypic microarrays showed that all ultrasound treated L. sakei after exposure to various carbon, nitrogen, phosphorus and sulphur sources had significant variations in nutrient utilisation. Integration of this phenotypic data with the genome of L. sakei revealed that various metabolic pathways were being influenced by the ultrasound treatments. Results presented in this study showed that the physiological response of L. sakei in response to US is frequency dependent and that it can influence metabolic pathways. Hence, ultrasound treatments can be employed to modulate microbial activity for specialised applications.


Apolipoprotein ɛ4 Allele and Subjective Cognitive Functioning in Parents of Adults With Disabilities.
Parents of individuals with disabilities face ongoing responsibilities of providing care and support for their children, even during the child's adulthood. Past research has shown that this caregiving role is linked to chronic stress and subsequent adverse health outcomes for parents, including impaired cognition. This study examines the impacts of genetic risk for cognitive impairment (apolipoprotein [APOE] ɛ4 allele) among parents of adults with disabilities and comparison parents whose adult children do not have disabilities. We performed rank order regression analysis of data from the Wisconsin Longitudinal Study (2004-2006 and 2010-2012 surveys and DNA samples). Participants included parents of adults with disabilities (247 mothers and 159 fathers) and comparison parents whose adult children were not disabled (1,482 mothers and 954 fathers). Mothers who had adult children with disabilities and who were APOE ɛ4 carriers reported significantly declining levels of subjective cognitive functioning over time, but mothers of adults with disabilities who did not have the APOE ɛ4 allele did not manifest this change. Among comparison group mothers, cognitive change over time was not a function of their APOE ɛ4 carrier status. Fathers' cognitive function did not differ significantly by either parental status or APOE ɛ4 carrier status. The results show that older mothers of adults with disabilities are more susceptible to cognitive impairment than their age peers if they have the genetic risk factor of APOE ɛ4 allele.


Body dysmorphic disorder in a Nigerian boy presenting as depression: a case report and literature review.
Body dysmorphic disorder (BDD) has been described widely in the Western world as relatively common yet under-recognized, but rarely in Africans and none in Nigeria to the best of our knowledge. To report a case of BDD in a Nigerian boy presenting with depression to the psychiatric unit of a teaching hospital. A 17-year-old secondary school boy with BDD presenting with depression is reported and relevant literature is reviewed. BDD is rare and hardly reported in this environment and high index of suspicion is necessary in patient presenting with medically unexplained physical complaints and depression.


MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3.
Neuraminidase (NA), a structural protein of the H9N2 avian influenza virus (H9N2 AIV), can facilitate viral invasion of the upper airway by cleaving the sialic acid moieties on mucin. Dendritic cells (DCs) are major antigen-presenting cells whose immune functions, such as presenting antigens and activating lymphocytes, can be regulated by microRNAs. Here, we studied the molecular mechanism of miRNA-induced repression of immune responses in mouse DCs. First, we screened for and verified the miRNAs induced by NA. Then, we showed that, consistent with the H9N2 virus treatment, the viral NA up-regulated the expression of miR-155, miR-674, and miR-499 in DCs; however, unlike H9N2 virus treatment, the presence of NA was associated with reduced expression of miR-181b1. Our results suggest that NA significantly increased DC surface markers CD80 and MHCII and enhanced the ability of activating lymphocytes and secreting cytokines compared with HA, NP and M2. Meanwhile, we found that miR-674 and miR-155 over-expression increased all surface markers of DC. Nevertheless, by inhibiting the expression of miR-674 and miR-155, NA lost the ability to promote DC maturation. Furthermore, we predicted and demonstrated that Pgm2l1, Aldh18a1, Camk1d, and Mbnl3 were the target genes of miR-674. Among them, Mbnl3 interference strongly blocked the mature DCs. Collectively, our data shed new light on the roles of and mechanisms involved in the repression of DCs by miRNAs, which may contribute to efforts to develop a prophylaxis for the influenza virus.


Validation of Esaso Classification of Diabetic Maculopathy.
To test reliability and reproducibility of ESASO morphologic OCT-based classification of diabetic maculopathy (DM). This is a multi-center cross-sectional study including a coordination center (CC) and 18 participating centers (PCs). After instruction on the correct use of ESASO Classification, the validation process was carried out in two consecutive stages. In the first retrospective phase, we evaluated the concordance between PCs and CC in the staging of OCT images collected during PCs' daily activity (608 images). In a second prospective phase, we analyzed the inter-observer agreement of staging assigned by each PCs to OCT images selected by the CC (22 images). The overall concordance achieved in the retrospective phase was 89.8% (Kappa = 0.83 (95% CI: 0.78-0.87); p<0.0001). In 99.5% of cases, concordance did not differ by more than one stage. In the prospective phase, PCs reached an inter-operator agreement of 93.0% (Krippendorff's Alpha = 0.953, 95% CI: 0.929-0.977, p<0.0001). Any discrepancy among the 22 images was within one stage. The results achieved in this study confirm that ESASO OCT-based Classification can be considered as an easy and reproducible method to stage DM during clinical practice. A diffused use of a common and validated method to describe the progression of retinal damage in DM may offer several clinical and scientific advantages.


[Efficacy and safety of early use of urokinase for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths].
To explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths. Thirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were randomly divided into experimental group and control group. Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group. The catheter function, mean blood flow and venous pressure of dialysis, coagulation, and side effects in the two groups were observed for 6 months. The rates of catheter dysfunction on the arterial side were 0.65% and 2.71% in the experimental group and control group, respectively (P<0.05), with catheter dysfunction rates on the vein side of 0.92% and 2.41%, respectively (P<0.05). Catheter dysfunction occurred for the first time at 87.9 ± 24.1 days in the experimental group, and at 31.3 ± 11.5 days in the control group (P<0.05). The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion (P>0.05), but was higher in the experimental group at 3 and 6 months after the tube insertion (P<0.05). The mean venous pressure in two groups was similar 1 and 3 months after tube insertion (P>0.05), but was significantly lower in the experimental group at 6 months (P<0.05). Compared with control group, the experimental group showed significantly prolonged prothrombin time (P<0.05) but similar rest coagulation parameters. No serious drug-related side effects occurred in these two groups. Early use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects.


Landscape Demography: Population Change and its Drivers Across Spatial Scales.
Demographic studies of plants and animals have a rich history and literature in ecology, and are important for both fundamental and applied ecology and conservation biology. Almost all demographic work has focused on intensive studies in which births, deaths, growth of individuals, and related measures are quantified in a single population or a few populations. This has been for practical reasons due to the high demands of labor required for this work, and because the questions addressed in these studies have been asked at the level of individual populations, with implicit assumptions about generalizing from the results. We introduce the concept of landscape demography, the study of the demographic properties of populations and their drivers at multiple spatial scales, and of how the relationships among populations and their drivers at any one scale influence demographic outcomes at other scales. We explore the ways in which considering the dynamics of ensembles of populations at different spatial scales can advance progress in thinking about ecological issues of high current interest such as biological invasions, range expansions and contractions due to climate change, and the decline of threatened species, as well as fundamental ecological and evolutionary questions.


Long-term results of abrasion arthroplasty for full-thickness cartilage lesions of the medial femoral condyle.
To evaluate the long-term functional results of arthroscopic abrasion arthroplasty for the treatment of full-thickness cartilage lesions of the medial femoral condyle. Between 1990 and 1996, 75 consecutive patients with isolated chondral lesions of the medial femoral condyle were treated with arthroscopic chondral abrasion. A retrospective analysis of the clinical results of this cohort was performed. The patients were evaluated according to the Knee Society Score questionnaire preoperatively, at 10 years postoperatively, and at final long-term follow-up at a mean of 20 years. At final follow-up, they were also assessed according to the Western Ontario and McMaster Universities Osteoarthritis Index. Patients were divided according to the lesion size and by age, and the Kaplan-Meier survivorship function (with second operation taken as an endpoint) for the various groups was calculated. At a mean of final follow-up of 20 years (range, 16.94 to 23.94 years), a positive functional outcome (Knee Society Score ≥70 points or no reoperation) was recorded in 67.9% of the patients. Twenty-year survivorship in this cohort was 71.4% (95% confidence interval, 0.5690 to 0.8590). The survivorship was 89.5% for patients younger than 50 years and 55.7% for patients aged 50 years or older. The functional results for patients with lesions smaller than 4 cm(2) were significantly better than those for patients with lesions of 4 cm(2) or greater (P = .031). There were no statistical differences between patients with and without associated lesions at the time of surgery. Our hypothesis that there would be survivorship greater than 86% was disproved. However, arthroscopic abrasion arthroplasty can be a valid treatment for medial femoral condylar full-thickness defects of the knee, even in the long-term, particularly for younger patients and those with smaller lesions. Level IV, therapeutic case series.


[Verbal reflection in therapeutic discourse. On vertical co-occurrence analysis of a 28 session behavior therapy].
The purpose of computer-aided individual case analysis the examination of the frequency of mutual verbal referencing by the interlocutors during a series of 28 therapeutical conversations. The question is studied whether the number of transfers of identical words or words of the same family from one speechcontribution to the next (vertical text co-occurrences) corresponds with the evaluations of the sessions. Significant correlations have been established between single lexical units (in the emotional sphere) and single item groups (differentiated by cluster analysis) as determined in the Bernese hour sheets for clients.


Two algorithms for biospecimen comparison and differentiation using SNP genotypes.
Biobanks are frequently required to verify specimen relationships. We present two algorithms to compare SNP genotype patterns that provide an objective, high-throughput tool for verification. The first algorithm allows for comparison of all holdings within a biobank, and is well suited to construct sample relationships de novo for comparison with assumed relationships. The second algorithm is tailored to oncology, and allows one to confirm that paired DNAs from malignant and normal tissues are from the same individual in the presence of copy number variations. To evaluate both algorithms, we used an internal training data set (n = 1504) and an external validation data set (n = 1457). In comparison with the results from manual review and a priori knowledge of patient relationships, we identified no errors in interpreting sample relationships within our validation data set. We provide an efficient and objective method of automated data analysis that is currently lacking for establishing and verifying specimen relationships in biobanks.


Young onset demented patients in French cognitive-behavioral specialized units.
The number of patients with young onset dementia (YOD) (first symptoms beginning before the age of 60 years) is estimated around 5,000 in France. On account of the usual severity of behavioral symptoms in these patients, the need for cognitive-behavioral specialized unit (UCC) is expected. To determine the number and characteristics of YOD patients cared for in UCC in France during the year 2013. A specific questionnaire was sent to the 84 French UCC. The questionnaire was completed by 55 UCC (65%), whose 33 received 179 YOD patients. The diagnosis was Alzheimer's disease in 50% of the cases and frontotemporal dementia in 30%. The main reasons for the hospitalization in UCC were the severity of behavioral symptoms in 86% of cases, the need to alleviate the caregiver burden in 31% and the waiting for a place in a nursing home in 23%. Mean duration of hospitalization was 40.4 ± 20.5 days. At the end of hospitalization 51% of the patients returned to their original living accomodation and 39% entered into a nursing home. The main reason of YOD patients hospitalization reject was the care team's fear in the UCC without experience. The severity of the behavioral troubles was the major issue while the necessary ethical reflection raised by the YOD patients management was a positive aspect. The teams rated how ready do they feel about taking care of YOD patients on a scale from 0 to 100, the median was 35. The welcoming of YOD patients in UCC is necessary, however the severity of the behavioral troubles and the care teams fear prompt to set up specific education and to increase of the number of staff for YOD patients management.


Complications and re-operations after tension-free vaginal tape operation in women with stress urinary incontinence.
We evaluate intraoperative and short-term postoperative (≤ 3 months) complications and long-term re-operations (up to 6 years) after tension-free vaginal tape (TVT) operation in women with stress urinary incontinence (SUI). Data from 446 women undergoing TVT operation between 2012 and 2016 at a tertiary referral center was retrospectively collected. Data included patient baseline demographics, information from the TVT operation and the following postoperative period, and scores from patient questionnaires [the International Consultation of Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and Patient Global Impression of Improvement (PGI-I)]. Collected data were investigated for incidence of complications and re-operations, postoperative improvement in patient questionnaires, and association between complications and baseline patient demographics. The only intraoperative complication was bladder perforation (2.0%). Postoperative complications included: infection (0.7%), hematoma (0.9%), bleeding (0.2%), pain (0.9%), erosion of the vaginal mucosa (1.1%), persistent SUI (0.7%), and voiding dysfunction > 24 h (10.3%). Re-operations included: operation due to infections (0.4%), incontinence surgery for persistent SUI (0.4%), revision for tape erosion (1.1%), tape mobilization (3.6%), and tape division (0.2%). A significant reduction in urinary incontinence symptoms was observed in the ICIQ-UI SF and PGI-I. The reduction in ICIQ-UI SF did not vary significantly between patients with and without complications. No association between complications and baseline patient demographics was found. This study demonstrated high safety and efficacy of the TVT operation with only minor short-term complications and few long-term re-operations. The ICIQ-UI SF improved significantly postoperatively and was not statistically significantly affected by the occurrence of complications.


Stimuli-responsive epoxy coatings.
The design, formulation, and characterization of new epoxy coatings with built-in chemical and threshold temperature sensors are reported. The materials were prepared by dissolving a chromogenic, fluorescent oligo(p-phenylenevinylene) dye into a cross-linked epoxy resin by reacting monomer/cross-linker/dye mixtures at 180-200 degrees C and quenching the cured polymer to below its glass transition temperature (T(g)). Subjecting these kinetically trapped, thermodynamically unstable molecularly mixed epoxy/dye blends to temperatures above T(g) leads to aggregation of the dye molecules and causes permanent and pronounced changes of their optical absorption and fluorescence properties. Exposure of the materials to selected chemical stimuli, e.g., water, acid, base, and several organic compounds, also causes plasticization of the polymer matrix and leads to irreversible aggregation of dye molecules, concomitant with the pronounced fluorescence and absorption color change. This response is well described by standard kinetic models and can be controlled via the chemical structure and cross-link density of the resin and the dye content.


Renal allograft eosinophilia: An unusual presentation of sudden graft dysfunction.
We present a case of sudden allograft dysfunction 11 months after renal transplantation which presented as severe peripheral and allograft eosinophilia and was managed as a case of an acute cellular rejection with significant interstitial graft eosinophilic infiltration. Patient had partial response to antirejection therapy and eventually ended up in a chronic allograft dysfunction.


Structurally and Functionally Optimized Silk-Fibroin-Gelatin Scaffold Using 3D Printing to Repair Cartilage Injury In Vitro and In Vivo.
Articular cartilage repair remains a great challenge for clinicians and researchers. Recently, there emerges a promising way to achieve one-step cartilage repair in situ by combining endogenic bone marrow stem cells (BMSCs) with suitable biomaterials using a tissue engineering technique. To meet the increasing demand for cartilage tissue engineering, a structurally and functionally optimized scaffold is designed, by integrating silk fibroin with gelatin in combination with BMSC-specific-affinity peptide using 3D printing (3DP) technology. The combination ratio of silk fibroin and gelatin greatly balances the mechanical properties and degradation rate to match the newly formed cartilage. This dually optimized scaffold has shown superior performance for cartilage repair in a knee joint because it not only retains adequate BMSCs, due to efficient recruiting ability, and acts as a physical barrier for blood clots, but also provides a mechanical protection before neocartilage formation and a suitable 3D microenvironment for BMSC proliferation, differentiation, and extracellular matrix production. It appears to be a promising biomaterial for knee cartilage repair and is worthy of further investigation in large animal studies and preclinical applications. Beyond knee cartilage, this dually optimized scaffold may also serve as an ideal biomaterial for the regeneration of other joint cartilages.


[Traditional Chinese medicine combined with Western medicine in the treatment of severe renal failure in patients with epidemic hemorrhagic fever].
This article reports the treatment of 23 cases (with the control group 20 cases) of severe renal failure in patients with epidemic hemorrhagic fever (EHF) by integrated traditional Chinese medicine and western medicine (TCM-WM), i.e., the renal protective decoction and modern medical treatment during the period of 1988-1989. The effects were as follows: (1) The curative rate was elevated and the morbidity was dropped (P less than 0.01-0.05). (2) Both the period of oliguria and albuminuria were shortened (P less than 0.01-0.05). (3) The severity of the complication, e.g., massive gastro-intestinal hemorrhage, etc., was much reduced (P less than 0.05). (4) The degree of azotemia was getting milder. And the renal function was much improved (P less than 0.05). The mode of action of the renal protective decoction is based on the point of view of the TCM in the treatment of infectious disease.


Free volume under shear.
Using an athermal quasistatic simulation protocol, we study the distribution of free volumes in sheared hard-particle packings close to, but below, the random-close packing threshold. We show that under shear, and independent of volume fraction, the free volumes develop features similar to close-packed systems - particles self-organize in a manner as to mimick the isotropically jammed state. We compare athermally sheared packings with thermalized packings and show that thermalization leads to an erasure of these structural features. The temporal evolution in particular the opening-up and the closing of free-volume patches is associated with the single-particle dynamics, showing a crossover from ballistic to diffusive behavior.


Cost-effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma.
We conducted an economic evaluation in a UK setting based on a 12-week prospective randomized open-label parallel-group comparison of eformoterol Turbohaler 12 microg b. i.d. with salmeterol Accuhaler 50 microg b. i.d. in children aged 6-17 with symptomatic asthma receiving inhaled corticosteroids and short-acting beta2-agonists. The principal effectiveness measure was percentage of symptom-free days with no short-acting beta2-agonist use during the study period. Asthma-related medication, unscheduled physician contacts and hospitalizations were collected prospectively and cost to the UK NHS calculated using year 2,000 prices. The economic evaluation included 73 patients in the eformoterol group and 72 patients in the salmeterol group. The mean age of patients was 11.6 years (eformoterol) and 11.8 years (salmeterol). The mean percentage of symptom-free days with no short-acting beta2-agonist use was 39% in the eformoterol group and 30% in the salmeterol group. Mean per patient daily cost was 1.15 pounds in the eformoterol group and 1.39 pounds in the salmeterol group. Both cost and effectiveness differences favoured eformoterol (P < 0.05; one-sided). Sensitivity analysis confirmed the results to be robust to changes in effectiveness, price and resource utilisation parameters. Eformoterol delivered by Turbohaler was found to be significantly more effective and less expensive than salmeterol Accuhaler in this study.


[The variability of respiratory pattern and gas exchange].
It is known, that spectral analysis of heart rate and respiratory variability allows to find out the very low frequency (VLF) rhythm. However it is not known, it is necessary to carry this rhythm to what type of wave processes. The purpose of the present researches was to study the respiratory variability and the variability of gas exchange parameters. 10 healthy subjects have been surveyed. The pneumogramms within 30 minutes spent record, and then a method "breath-by-breath" within 30 minutes registered gas exchange parameters (Ve--lung ventilation, V(O2) -O2 consumption and other parameters). Fast Fourier transform method has found out two groups of the basic peaks. The first--in a range 0.2-0.3 Hz (a time cycle--3-5 s), that corresponds respiratory frequency which size at subjects varied from 12 to 20 per minute. The second--in a range 0.002-0.0075 Hz, that corresponds VLF diapason (a time cycle--1-3.5 minutes). At the analysis pneumogramms rhythms in the same ranges have been established. The carried out researches allow to draw a conclusion on steady character of wave process in a VLF-range. It can be carried to quasi-periodic oscillations type. First oscillator or respiratory frequency it is formed by means of mechanisms of chemoreception. Considering, that V(O2) and V(CO2) are function energy exchange, it is possible to believe, what exactly energy demand define the second oscillator.


Chlamydia trachomatis infection in late pregnancy: a prospective study.
During a 1-year period, 3309 women were screened in pregnancy for Chlamydia trachomatis infection. A cervical swab was taken and chlamydial antigen was detected, using a monoclonal antibody ELISA technique, in 198 women (6%). The prevalence of chlamydial infection was high in women under 20 years (14.5%), single women (14.2%) and black women (16.8%). Binomial regression of these data estimates a relative risk of 2.9 for women under 20 years compared with women aged 25 and over. There was an interaction between race and marital status with a high risk in single white and single asian women (2.3, 4.5 respectively) but a similar risk in black single and black married women (3.0, 4.0 respectively). Parity and social class did not effect the prevalence of antigen carriage. There was no demonstrable effect of maternal antigen carriage on outcome of pregnancy, gestation or admission to neonatal unit. Infants of 174 antigen-positive mothers were followed-up. Tissue culture for Chlamydia trachomatis was positive in 43 (24%) infants. Complications occurred in 23 (53%): 17 had conjunctivitis, three had lower respiratory tract infection and three both complications. Amongst 131 chlamydia-negative infants, complications occurred in 21 (16%). Since this infection, in infants, responds promptly to erythromycin therapy, screening and treatment in pregnancy will convey little benefit in prevention of perinatal morbidity or perinatal mortality.


Mandatory vaccination of infants in France: Is that the way forward?
In this opinion paper, the authors argue that the extension of mandatory immunization of infants up to two years of age from three diseases (diphtheria, tetanus, poliomyelitis) to 11 diseases, introduced in France in January 2018, is not a sustainable response to the challenge of controlling vaccine-preventable diseases. In France in 2017, infant immunization coverage (IC) rates were sufficiently high or increasing (hepatitis B), except for measles, mumps and rubella (MMR) and meningococcus C disease. Even if vaccination obligation makes it possible to achieve the MMR IC objectives among infants, communication programmes and supported advice from GPs are essential for the catch-up of susceptible adults to obtain herd immunity. The impact of mandatory immunization on hesitancy remains uncertain, and it contradicts the evolution of the patient's role in the governance of his own health and the principle of autonomy. Numerous studies have shown that interventions and advice from health professionals improve vaccine acceptance. To correct the poor implementation of some vaccination programmes by health professionals, strong communication and resources from health authorities are needed, rather than a retreat towards obligation. Reducing missed opportunities and increasing access to immunization are essential objectives. Finally, an immunization policy based on primary care and a patient-centred approach to each vaccination are more likely to reduce vaccine hesitancy, sustainably.


L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH.
The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D-R- or L-S- enantiomer, each of which inhibits α-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase (IDH) produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via 'promiscuous' reduction of the alternative substrate αKG. Acidic pH enhances production of L-2HG by promoting a protonated form of αKG that binds to a key residue in the substrate-binding pocket of LDHA. Acid-enhanced production of L-2HG leads to stabilization of hypoxia-inducible factor 1 alpha (HIF-1α) in normoxia. These findings offer insights into mechanisms whereby microenvironmental factors influence production of metabolites that alter cell fate and function.


[Connotation of Baimai disease and analysis of compatibility and usage of Baimai Ointment: based on Tibetan medicine theory].
Baimai is a complex of structure and function with the characteristics of wide distribution, complex structure, and multi-dimensional functions. Baimai, consisting of the channels in brain, the internal hidden channels connecting the viscera, and the external channels linking the limbs, governs the sensory, motor, and information transmission functions of human. According to Tibetan medicine, Baimai functions via "Long"(Qi) which moves in Baimai. "Long" is rough, light, cold, tiny, hard, and dynamic. The dysfunction of Baimai is manifested as numbness, swelling and pain, stiffness, atrophy, contracture, disability, hyperactivity, etc. The clinical manifestations of Baimai disease are facial paralysis, limb numbness, hemiplegia, contracture and rigidity, pain, opistho-tonos, paralysis, unconsciousness, head tremor, aphasia and tongue stiffness, and other abnormalities in facial consciousness, limb movement, and tactile sensation. Baimai Ointment for external use is used for the treatment of Baimai disease. It is mainly composed of medicinals which are spicy and bitter, warm, soft, mild, heavy, moist, and stable, and thus it is effective for the rough, light, cold, tiny, hard, and dynamic "Long" of Baimai disease. In clinical practice, it is mainly used for musculoskeletal diseases, such as osteoarthritis, scapulohumeral periarthritis, cervical spondylosis, low back pain, myofascitis, and tenosynovitis, nervous system diseases, such as paralysis and shoulder-hand syndrome, and limb stiffness caused by stroke, spastic cerebral palsy, trigeminal neuralgia, and facial neuritis, and limb motor and sensory dysfunction caused by trauma. According to the main symptoms of Baimai disease such as stiffness, rigidity, contraction, numbness, sensory disturbance and pain, clinicians should apply the Baimai Ointment via the inunction treatment of Tibetan medicine and in combination with Huo'ermai therapy and physiotherapy.


[Bronchiolitis treated with mechanical ventilation: prognosis factors and outcome in a series of 135 children].
Viral bronchiolitis is usually associated with favorable outcome as regard to mortality. Only few studies reported severe bronchiolitis requiring mechanical ventilation, and respiratory outcome is not well described. Therefore, we conducted a retrospective study in a series of 135 children admitted in a single Pediatric Intensive Care Unit (PICU) over a four year period (1994-1998). All of them were admitted for viral bronchiolitis requiring mechanical ventilation. At admission, 83% of them were less than three months old. Prematurity at birth was present in 33,3%. Mortality was observed in four cases (2,9%), all premature babies with mechanical ventilation at birth. Univariate analysis showed as main factors associated to mortality: prematurity (P =0,056) and acute respiratory distress syndrome (P =0,017). Childhood asthma was observed in 40,4% of children without any associated factor wether at birth or in PICU related to such outcome. Bronchiolitis associated with mechanical ventilation is particularly observed in very young babies and prematurity is the main factor associated to mortality. Mechanical ventilation seems not to be associated with unfavorable respiratory outcome. Considering physiology and population, non invasive ventilation could be an effective alternative of mechanical ventilation.


[Monkeypox: Proposals for care in pregnancy].
Although the 2022 Monkeypox virus epidemic mostly affects males, particularly men having sex with men, transmission to women may also occur. In case of MPXV infection in pregnancy, transmission to the fetus can result in very severe disease. Thus, caregivers should be aware of the measures to be taken according to the available evidence, in case of exposure or in case of symptoms particularly skin rash compatible with this diagnosis in a pregnant woman. Pregnant women should have access to vaccination, vaccinia immunoglobulin or antiviral medications as required.


New Therapy for Spinal Muscular Atrophy Offers Modest Bang for Pharamaceutical Buck.
Spinraza is a breakthrough, no doubt. It is a survival SMN-2-directed antisense oligonucleotide indicated for the treatment of SMA in pediatric and adult patients and is administered by injections into the spinal fluid (intrathecally). But it is another ultraexpensive drug, and the evidence so far points to a modest improvement in motor milestones.


Theranostic Fibers for Simultaneous Imaging and Drug Delivery.
New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core-shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core-shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79-9.75 s(-1) mM(-1); r2 = 7.98-14.22 s(-1) mM(-1)) compared with fresh Gd(DTPA) (r1 = 4.13 s(-1) mM(-1) and r2 = 4.40 s(-1) mM(-1)), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon.


The value of sonography in the diagnosis and follow-up of patients with blunt renal trauma.
Eighty-eight patients with blunt renal trauma were examined sonographically. Rupture of the kidney was diagnosed in 41 patients and contusion of the kidney in 45. The correlation between operative findings, sonography and urography showed positive sonographic findings to be correct in all patients with rupture of the kidney. In 4 patients with normal sonograms, the diagnosis of a contusion was based on the urographic results. Three patients underwent angiography. An intimal lesion was seen in 2 and a tear of the renal artery in 1. The results of our investigation suggest that sonography should be applied in the first place in the evaluation of blunt renal trauma. It is the investigation of choice during follow-up after surgical as well as conservative therapy.


Aneuploidy in Early Miscarriage and its Related Factors.
Genetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH) using probes for 13, 16, 18, 21, 22, X and Y chromosomes. A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion. A total of 832 samples were finally analyzed. 368 (44.23%) were abnormal, in which 84.24% (310/368) were aneuploidies and 15.76% (58/368) were polyploidies. The first was trisomy 16 (121/310), followed by trisomy 22, and X monosomy. There was no significant difference in the rate of aneuploidy in the advanced maternal age group (≥ 35 years old) and young maternal age group (<35 years old). However, the rate of trisomy 22 and the total rate of trisomies 21, 13, and 18 (the number of trisomy 21 plus trisomy 13 and trisomy 18 together) showed significantly different in two groups. We found no skewed sex ratio. There was no significant difference in the rate of aneuploidy between recurrent miscarriage and sporadic abortion or between the samples from previous artificial abortion and those from no previous artificial abortion. Aneuploidy is a principal factor of miscarriage and total parental age is a risk factor. There is no skewed sex ratio in spontaneous abortion. There is also no difference in the rate of aneuploidy between recurrent abortion and sporadic abortion or between previous artificial abortion and no previous induced abortion.


Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus (HCV): influence on the characteristics of the infection and responses to interferon alfa therapy in patients with chronic hepatitis C.
HCV exists within its host as pools of related genetic variants referred to as quasispecies. The hypervariable region 1 (HVR1) of the E2 envelope gene is subjected to strong selective pressure from neutralizing antibodies. The genetic complexity of this region is defined as the total number of genetic variants within the quasispecies population. The genetic complexity of the HVR1 region was examined in patients with chronic hepatitis C and its relationship with the epidemiology of HCV infection, and its influence on liver disease and the response to interferon treatment were determined in 114 patients with chronic hepatitis C. The genetic complexity of the HVR1 major variants was measured before treatment by using a polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) technique, and was compared with epidemiological, clinical, virological and histological features. The patients were treated with 3 megaunits of interferon (IFN) alfa for 3 to 6 months and the response to treatment was assessed at 3, 6 and 12 months. The HVR1 could be studied in 101 of the 114 patients (89%). Genetic complexity was significantly higher in patients infected through blood transfusion than intravenous drug use (mean complexity index: 5.7 +/- 2.3 vs. 4.7 +/- 1.5, respectively; P = 0.04). This relationship was independent of age and the estimated time since infection. No significant relationship was found with other parameters of infection or liver disease. In univariate analysis, the genetic complexity of HVR1 major variants did not affect the rates of ALT normalization at months 3 and 6 of IFN treatment. HVR1 genetic complexity was lower in patients with a sustained virological response than in non-responders (4.0 +/- 1.7 vs. 5.4 +/- 2.0, respectively; P = 0.07). In multivariate analysis of pretreatment parameters associated with a sustained virological response to treatment, three parameters appeared to be independent predictors of such a response: a low viral load (P < 0.04), a low anti-HCV core IgM titer (P = 0.03) and a low genetic complexity of HVR1 major variants (P < 0.04). In conclusion, the HVR1 of HCV has a quasispecies distribution in infected individuals. Its genetic complexity is significantly higher in transfusion recipients than in intravenous drug users, suggesting that the size of the initial inoculum affects the later emergence and development of viral quasispecies. The genetic complexity of HVR1, together with viral load and the anti-HCV IgM titer, are independent predictors of a sustained virological response to IFN alfa in patients with chronic hepatitis.


Action of staphylococcal exfoliative toxins on epidermal cell cultures and organotypic skin.
In the staphylococcal scalded skin syndrome, spontaneous intraepithelial cleavages are due to the exfoliative toxins A or B (ETA or ETB). Until now, these toxins have been studied either on epidermis or on organotypic skin cultures. In the present study, we compare the effects of these toxins on human keratinocyte cell cultures to those on human and mouse organotypic skin cultures. With concentrations of ETA or ETB of 1 mg/ml for 3 hours, spontaneous intraepithelial cleavages were noted in both cell and organotypic cultures. Keratinocyte cell cultures were as sensitive as organotypic skin cultures to these toxins. Since keratohyaline granules may represent a possible binding site for ETA or ETB, we tried to correlate the expression of keratohyaline granules with the appearance of intraepithelial clefts due to the toxins. However, when cultured in liquid medium, epithelia were not differentiated enough to allow the detection of the binding site of ETA-ETB.


A synthesis of trisubstituted alkenes by a Ru-catalyzed addition.
Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.


Activation mechanism for CRAC current and store-operated Ca2+ entry: calcium influx factor and Ca2+-independent phospholipase A2beta-mediated pathway.
Here we tested the role of calcium influx factor (CIF) and calcium-independent phospholipase A2 (iPLA2) in activation of Ca2+ release-activated Ca2+ (CRAC) channels and store-operated Ca2+ entry in rat basophilic leukemia (RBL-2H3) cells. We demonstrate that 1) endogenous CIF production may be triggered by Ca2+ release (net loss) as well as by simple buffering of free Ca2+ within the stores, 2) a specific 82-kDa variant of iPLA2beta and its corresponding activity are present in membrane fraction of RBL cells, 3) exogenous CIF (extracted from other species) mimics the effects of endogenous CIF and activates iPLA2beta when applied to cell homogenates but not intact cells, 4) activation of ICRAC can be triggered in resting RBL cells by dialysis with exogenous CIF, 5) molecular or functional inhibition of iPLA2beta prevents activation of ICRAC, which could be rescued by cell dialysis with a human recombinant iPLA2beta, 6) dependence of ICRAC on intracellular pH strictly follows pH dependence of iPLA2beta activity, and 7) (S)-BEL, a chiral enantiomer of suicidal substrate specific for iPLA2beta, could be effectively used for pharmacological inhibition of ICRAC and store-operated Ca2+ entry. These findings validate and significantly advance our understanding of the CIF-iPLA2-dependent mechanism of activation of ICRAC and store-operated Ca2+ entry.


Environmentally benign in situ synthesis of gold nanotapes using carboxymethyl cellulose.
An environmentally friendly one-step wet-chemical approach has been described for controlling the shape of gold nanocrystals at ambient temperature. In this approach, sodium salt of carboxymethyl cellulose (NaCMC) has been used as a reducing-cum-stabilizing agent for the in situ generation of gold nanotapes from an aqueous chloroaurate ion. Transmission electron microscopy confirmed the formation of tape-shaped gold nanostructures. These gold nanotapes exhibited interesting optical properties. The nature of crystallinity of the nanotapes has been studied by X-ray diffractometry. Control experiments with other cellulose derivatives resulted in the formation of only spherical gold nanoparticles.


Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children.
The level of fecal calprotectin (FC) can predict the onset of inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated the cost-effectiveness of using measurements of FC to identify adults and children who require endoscopic confirmation of IBD. We constructed a decision analytic tree to compare the cost-effectiveness of measuring FC before endoscopy examination with that of direct endoscopic evaluation alone. A second decision analytic tree was constructed to evaluate the cost-effectiveness of FC cutoff levels of 100 μg/g vs 50 μg/g (typically used to screen for intestinal inflammation). The primary outcome measure was the incremental cost required to avoid 1 false-negative result by using FC level to diagnose new-onset IBD. In adults, FC screening saved $417/patient but delayed diagnosis for 2.2/32 patients with IBD among 100 screened patients. In children, FC screening saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100 screened patients. If endoscopic biopsy analysis remained the standard for diagnosis, direct endoscopic evaluation would cost an additional $18,955 in adults and $6250 in children to avoid 1 false-negative result from FC screening. Sensitivity analyses showed that cost-effectiveness of FC screening varied with the sensitivity of the test and the pre-test probability of IBD in adults and children. Pre-test probabilities for IBD of ≤75% in adults and ≤65% in children made FC screening cost-effective, but it was cost-ineffective if the probabilities were ≥85% and ≥78% in adults and children, respectively. Compared with the FC cutoff level of 100 μg/g, the cutoff level of 50 μg/g cost an additional $55 and $43 for adults and children, respectively, but it yielded 2.4 and 6.1 additional accurate diagnoses of IBD per 100 screened adults and children, respectively. Screening adults and children to measure fecal levels of calprotectin is effective and cost-effective in identifying those with IBD on a per-case basis when the pre-test probability is ≤75% for adults and ≤65% for children. The utility of the test is greater for adults than children. Increasing the FC cutoff level to ≥50 μg/g increases diagnostic accuracy without substantially increasing total cost.


The Critical Role of Calpain in Cell Proliferation.
Calpain is a conserved family of calcium-dependent, cytosolic, neutral cysteine proteases. The best characterized members of the family are the ubiquitously expressed calpain 1 and calpain 2. They perform controlled proteolysis of their target proteins. The regulation of these enzymes includes autolysis, calcium, phosphorylation as a posttranslational modification, and binding of calpastatin, phospholipids or activator proteins, respectively. Calpain are implicated in many physiological and pathological processes. They have significant role in the cell proliferation, differentiation and migration in a variety of mammalian cell types, contributing to the development of angiogenesis, vascular remodeling, and cancer. Therefore the knowledge of the precise mechanism of calpain signaling could provide therapeutic approaches in these processes.


Spontaneous cervical epidural hematomas with acute hemiparesis should be considered a contraindication for intravenous thrombolysis: a case report with a literature review of 50 cases.
We herein report the case of a 63-year-old woman with an acute spontaneous cervical epidural hematoma who presented with acute hemiparesis and was successfully managed with surgery. Based on a literature review of 50 cases of spontaneous cervical epidural hematomas, we concluded that the relatively high frequency of hemiparesis (12 of 50 cases, 24%) is the result of the fact that epidural hematomas are predominantly distributed dorsolaterally in the region of the mid and lower cervical spine, leading to unilateral cervical cord compression. Clinicians should keep in mind that acute hemiparesis can be caused by spontaneous cervical epidural hematomas for which intravenous thrombolysis is contraindicated.


Vascular endothelial growth factor-induced osteopontin expression mediates vascular inflammation and neointima formation via Flt-1 in adventitial fibroblasts.
Adventitia acts as an active participant in vascular inflammation but the precise mechanism underlying adventitia-mediated vascular inflammation is not fully understood. In this study, we sought to determine whether vascular endothelial growth factor (VEGF) regulates osteopontin (OPN) expression through Flt-1 in adventitial fibroblasts (AFs) to mediate vascular inflammation and neointima formation. In primary cultured AFs, VEGF increased intracellular and secreted OPN expression in a time- and dose-dependent manner, which was effectively suppressed by a specific anti-Flt-1 hexapeptide. Interestingly, VEGF treatment of AFs enhanced the capability of AF-conditioned medium to stimulate macrophages chemotaxis, and this effect was attenuated after blockade of OPN from AF-conditioned medium. Furthermore, perivascular delivery of anti-Flt-1 peptide preferentially concentrated in the adventitia resulted in a decrease of neointima formation after balloon injury in carotid arteries. The inhibition of neointima formation was preceded by significant reduction of VEGF and OPN expression with concurrent macrophage infiltration into adventitia after injury. Activation of extracellular signal-regulated kinase 1/2 pathway was involved in OPN upregulation and macrophage chemotaxis. These results demonstrate that VEGF/Flt-1 signaling plays a significant role in vascular inflammation and neointima formation by regulating OPN expression in AFs and provide insight into Flt-1 as a potential therapeutic target for vascular diseases.


The cell coat of the sensory and supporting cells of the rainbow trout saccular macula as demonstrated by reaction with ruthenium red and tannic acid.
The surface of most cells is covered by glycoconjugates. The composition and thickness of the surface coat varies among different cell types. The purpose of the present study was to demonstrate the presence of and to characterize the cell coat surrounding the cells in the saccular macula of the rainbow trout. Tissues were fixed in Karnovsky's fixative containing either ruthenium red (0.5, 1, or 2%) or tannic acid (1, 2, or 4%). The apical surface of the sensory and supporting cells reacted with both agents. Varying the concentration of the compounds within a certain range did not significantly affect the degree of tissue staining. Whereas ruthenium red staining was distributed evenly along the luminal surface of the epithelium and along the length of the stereocilia, tannic acid formed electron-dense clumps on the luminal surface of sensory and non-sensory cells and in the basal region of the macular epithelium. The stereocilia of the sensory cells also exhibited tannic acid-positive, electrondense precipitate, particularly near the distal ends of these processes, while uniform staining of the plasma membrane was seen along their lengths. The results of this study suggest that the trout saccular macula is provided with extracellular microenvironments which may be necessary for functional integrity.


Age- and sex-associated differences in hematology and biochemistry parameters of Dunkin Hartley guinea pigs (Cavia porcellus).
The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.


[Probable post-traumatic aneurism of ascending thoracic aorta: about a case].
Thoracic aortic aneurysms are relatively rare. Etiologies are dominated by atherosclerosis, elastic tissue dystrophies and trauma. We report the case of a 50-year old patient with a personal history of severe chest trauma occurring at age 25 years during parachute training. He presented with neurosensory signs of arterial hypertension. Chest X-ray showed aneurysmal dilatation of the thoracic aorta. Transthoracic echocardiography, CT angiography and MRI objectified ascending aortic aneurysm. The assessment of extent and etiological research were negative. The anatomopathological examination of surgical specimen showed nonspecific lesions.


Health of the Elderly Migration Population in China: Benefit from Individual and Local Socioeconomic Status?
The study aims to estimate the relationship between the individual/local socioeconomic status and the health of internal elderly migrants in China. A multilevel logistic model was used to estimate this association. The estimations were undertaken for 11,111 migrants aged over 60 years, using nationally representative data: the 2015 Migrant Dynamics Monitoring Survey (MDMS), which was carried out in China. Odds ratios with 95% confidence intervals were reported. Both the household income per capita and the area-level average wage were positively associated with migrants' self-reported health; however, public service supply was not significantly related to their health. In addition, given the household income, migrants living in communities with a higher average wage were more likely to report poor health. Migrants' health benefited from individual socioeconomic status, but not from the local socioeconomic status, which the migrants cannot enjoy. This study highlights the importance of multilevel and non-discriminatory policies between migrants and local residents.


Use of the ShangRing circumcision device in boys below 18 years old in Kenya: results from a pilot study.
Male circumcision is a proven prevention strategy against the spread of HIV. The World Health Organization's new 2016-2021 strategic framework on voluntary medical male circumcision (VMMC) targets 90% of males aged 10-29 years to receive circumcision by 2021 in 14 priority sub-Saharan countries while anticipating an increase in the demand for infant circumcision. It also states that the use of circumcision devices is a safe and efficient innovation to accelerate attainment of these goals. The primary objective of this pilot study was to evaluate the safety and acceptability of the ShangRing, a novel circumcision device, in boys below 18 years of age. A total of 80 boys, 3 months to 17 years old, were circumcised using the no-flip ShangRing technique. All rings were removed 5-7 days later. Participants were evaluated weekly until the wound was completely healed. Data on procedure times, adverse events (AEs), time to clinical wound healing and satisfaction were recorded and analysed. Nearly all (79/80, 98.8%) circumcisions were successfully completed using the no-flip ShangRing technique without complications. In one (1.2%) case, the outer ring slipped off after the foreskin was removed and the procedure was completed by stitching. The mean circumcision and ring removal times were 7.4 ± 3.2 and 4.4 ± 4.2 min, respectively. There were four (5%) moderate AEs, which were managed conservatively. No severe AEs occurred. The mean time to complete clinical healing was 29.8 ± 7.3 days. Participants or their parents liked ShangRing circumcision because it improved hygiene, was quick and possessed an excellent cosmetic appearance. Most (72/80, 94.7%) were very satisfied with the appearance of the circumcised penis, and all (100%) said they would recommend circumcision to others. Our results suggest that no-flip ShangRing VMMC is safe and acceptable in boys below 18 years of age. Our results are to be compared those seen following ShangRing VMMC in African men. Further study with larger sample sizes are needed to explore the scalability of the ShangRing in larger paediatric cohorts in Africa. We believe that the ShangRing has great potential for use in all age groups from neonates to adults, which would simplify device implementation.


Enriched environment attenuates cell genesis in subventricular zone after focal ischemia in mice and decreases migration of newborn cells to the striatum.
Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdU+/S-100beta+ cells), neuroblasts (dcx+ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdU+/NeuN+) were not found. The enriched environment did not affect infarct size or mortality. An enriched environment after experimental stroke increased neurogenesis in the hippocampus, whereas there was a decreased cell genesis and migration of neuroblasts and newborn astrocytes in the striatum.


Tuberculosis outbreak in an immigrant reception center in Israel: a clinical and epidemiologic perspective.
Tuberculosis (TB) outbreaks in congregate settings pose a public health concern and a clinical challenge. We report a TB outbreak involving 6 cases of active TB among 28 recent Ethiopian immigrants (EIs) in an immigrant reception center in Israel. The outbreak erupted several weeks after a meticulous pre-immigration TB screening of this group. All five culture-positive TB patients were infected with the CAS1_DELHI family, SIT 25 strain. Pulmonary involvement manifested as only a persistent cough without systemic symptoms. This outbreak occurred because of miscommunication among healthcare staff and between healthcare staff and the EI index case. It was fuelled by the staff ignorance of the social bonds within the group, and the sluggish once-monthly schedule of the on-site TB clinic operated at the reception center, which further lacked radiography facilities. This outbreak highlights the challenges of screening for active TB among immigrants and hard to reach groups.


GM13133 is a negative regulator in mouse white adipocytes differentiation and drives the characteristics of brown adipocytes.
Obesity is tightly associated with the disturbance of white adipose tissue storing excess energy. Thermogenic adipocytes (brown and beige) exert a critical role of oxidizing nutrients at the high rates through non-shivering thermogenesis. The recruitment of brown characteristics in white adipocytes, termed browning, has been considered as a promising strategy for treating obesity and associated metabolic complications. Recently, long noncoding RNAs play a crucial role in regulating tissue development and participating in disease pathogenesis, yet their effects on the conversion of white into brown-like adipocytes and thermogenic function were not totally understood. Here, we identified a mouse brown adipose specific expressed lncRNA, termed GM13133. Moreover, a considerable amount of GM13133 is expressed in adipocytes and actively modulated by cold, β3 -adrenergic agonist and cAMP stimuli, implying a potential role in the conversion from white to brown adipocytes. Overexpression of GM13133 did not affect the proliferation of mouse white pre-adipocytes, but inhibited white adipocyte differentiation by decreasing lipid accumulation. The forced expression of GM13133 also significantly drove the conversion of white into brown-like adipocytes with the enhanced mitochondrial biogenesis and the induced expression of brown adipocytes specific markers. A global mRNA analysis further indicated the possible regulatory role of cAMP signaling pathway in GM13133 mediated white-to-brown adipocytes conversion. Our results identified a lncRNA-mediated modulation in primary mouse white adipocyte differentiation and indicate the functional significance of GM13133 in promoting browning of white adipocytes and maintenance of thermogenesis, further providing a potential strategy to treating obesity.


Oskar Minkowski (1858-1931). An outstanding master of diabetes research.
Oskar Minkowski, a physician of many talents, was an outstanding clinical scientist, a brilliant experimental investigator and a prolific medical writer. His name is connected with highly important clinical studies and experimental probes, all of which significantly contributed to our understanding of the pathogenesis of diabetes mellitus after removal of the pancreas (experimental pancreatectomy).


Effects of dietary lysozyme levels on growth performance, intestinal morphology, non-specific immunity and mRNA expression in weanling piglets.
The aim of the present study was to determine the effect of dietary lysozyme levels on growth performance, gut health and non-specific immunity of weanling piglets. A total of 150 weanling piglets were allocated to six treatments. The piglets were fed the same basel diet supplemented with 0, 30, 60, 90 and 120 mg/kg lysozyme as well as antibiotics for 28 days. From day 14 to day 28 of dietary treatment, piglets fed 90 mg/kg lysozyme had greater average daily gain than piglets fed control diet. During the whole experimental period, piglets fed 120 mg/kg lysozyme tended to have greater average daily gain than piglets fed control diet. Compared with piglets fed control diet, piglets fed diets containing antibiotics and 90 mg/kg lysozyme had greater villus height to crypt depth ratio in duodenum and jejunum. Additionally, dietary supplementation of 60 and 90 mg/kg lysozyme as well as antibiotics enhanced the phagocytic activity of peritoneal macrophages in piglets. In conclusion, dietary lysozyme can accelerate the growth of weanling piglets by improving gut health and non-specific immunity and supplementing 90 mg/kg lysozyme is as effective as antibiotics (20 mg/kg colistin sulphate + 50 mg/kg kitasamycin) in improving the growth performance of weanling piglets.


Nonconventional medicine in Israel: consultation patterns of the Israeli population and attitudes of primary care physicians.
This paper reports the findings of a study of nonconventional medicine in Israel. Data regarding patterns and correlates of consultations with alternative medicine practitioners were obtained from structured face-to-face interviews with a representative sample of 2030 Jewish adults aged 45 to 75. In addition, in-depth open-ended interviews were conducted with a convenience sample of 20 primary care physicians in order to explore their beliefs, attitudes and behaviors regarding nonconventional medicine. Six percent of the respondents interviewed in the population study visited an alternative practitioner in the year prior to the interview. For most of them, the consultation was a consequence of disappointment with the lack of success of conventional medical treatment. Most felt that the alternative medicine treatment had helped. Nearly 40% were seeing their regular primary care physician at the same time as they were seeing an alternative medical practitioner. Women were more likely than mean to consult an alternative medicine practitioner; consulters rated their health status more negatively than non-consulters. Consulters had a higher level of education than non-consulters, but the two groups did not differ in terms of age or economic status. Nearly all of the physicians stated that they refer patients to alternative practitioners; in most cases, the referrals are in response to patients' requests. Although skeptical of the scientific basis of alternative medicine therapies, most of the physicians believed that some therapies, even if only because of the "placebo effect", were effective in some cases. Almost all felt that the Ministry of Health, which today does not recognize any form of alternative medicine, should establish control over the training and practice of alternative medical practitioners. The findings from both parts of the study suggest that patients and primary care physicians in Israel do not view nonconventional medicine as a threat to conventional medicine, but rather as complementary to it.


Dual role of heat shock proteins as regulators of apoptosis and innate immunity.
Stress or heat shock proteins (HSPs) 70 and 90 are powerful chaperones whose expression is induced in response to a wide variety of physiological and environmental insults. These proteins have different functions depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive potentially lethal conditions. The cytoprotective functions of HSPs can largely be explained by their anti-apoptotic properties. HSP70 and HSP90 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of HSP70 and/or HSP90 is frequently abnormally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of HSPs has become an interesting strategy in cancer therapy. In contrast to intracellular HSPs, extracellularly located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response providing a link between innate and adaptive immune systems. In cancer, most immunotherapeutical approaches based on extracellular HSPs exploit their carrier function for immunogenic peptides. This review will focus on the roles of HSP70 and HSP90 in apoptosis and in innate immunity and how these functions are being exploited in cancer therapy.


Helicobacter pylori lipopolysaccharide: biological activities in vitro and in vivo, pathological correlation to human chronic gastritis and peptic ulcer.
To determine the biological activity of Helicobacter pylori (H. pylori) lipopolysaccharide (H-LPS) and understand pathological correlation between H-LPS and human chronic gastritis and peptic ulcer. H-LPS of a clinical H. pylori strain and LPS of Escherichia coli strain O55:B5 (E-LPS) were extracted by phenol-water method. Biological activities of H-LPS and E-LPS were detected by limulus lysate assay, pyrogen assay, blood pressure test and PBMC induction test in rabbits, cytotoxicity test in NIH 3T3 fibroblast cells and lethality test in NIH mice. By using self-prepared rabbit anti-H-LPS serum as the first antibody and commercial HRP-labeled sheep anti-rabbit sera as the second antibody, H-LPS in biopsy specimens from 126 patients with chronic gastritis (68 cases) or gastric ulcer (58 cases) were examined by immunohistochemistry. Fibroblast cytotoxicity and mouse lethality of H-LPS were weaker than those of E-LPS. But the ability of coagulating limulus lysate of the two LPSs was similar (+/0.5 ng/mL). At 0.5 h after H-LPS injection, the blood pressures of the 3 rabbits rapidly declined. At 1.0 h after H-LPS injection, the blood pressures in 2 of the 3 rabbits fell to zero causing death of the 2 animals. For the other one rabbit in the same group, its blood pressure gradually elevated. At 0.5 h after E-LPS injection, the blood pressures of the three rabbits also quickly declined and then maintained at low level for approximately 1.0 h. At 0.5 h after injection with H-LPS or E-LPS, PBMC numbers of the rabbits showed a remarkable increase. The total positivity rate of H-LPS from 126 biopsy specimens was 60.3%(76/126). H-LPS positivity rate in the biopsy specimens from chronic gastritis (50/68, 73.5%) was significantly higher than that from gastric ulcer (26/58, 44.8%) (chi(2)=10.77, P<0.01). H-LPS positivity rates in biopsy specimens from chronic superficial gastritis (38/48, 79.2%) and chronic active gastritis (9/10, 90.0%) were significantly higher than that of the patients with atrophic gastritis (3/10, 30.0%) (chi(2)=7.50-9.66, P<0.01). The biological activities of H-LPS were weaker than those of E-LPS, the activities of H-LPS of lowering rabbit blood pressure and inducing rabbit PBMC were relatively stronger. H-LPS may play a critical role in inducing inflammatory reaction in human gastritis.


Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process.
According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.


Diversity of cultivable protease-producing bacteria in sediments of Jiaozhou Bay, China.
Although protease-producing bacteria are key players in the degradation of organic nitrogen and essential for the nitrogen recycling in marine sediments, diversity of both these bacteria and their extracellular proteases is still largely unknown. This study investigated the diversity of the cultivable protease-producing bacteria and their extracellular proteases in the sediments of the eutrophied Jiaozhou Bay, China through phylogenetic analysis and protease inhibitor tests. The abundance of the cultivable protease-producing bacteria was up to 10(4) cells/g in all six sediment samples. The cultivated protease-producing bacteria mostly belonged to the phyla Proteobacteria and Firmicutes with the predominant genera being Photobacterium (39.4%), Bacillus (25.8%), and Vibrio (19.7%). Protease inhibitor tests revealed that extracellular proteases secreted by the bacteria were mainly serine proteases and/or metalloproteases with relatively low proportions of cysteine proteases. This study represents the first comprehensive analysis on the diversity of protease-producing bacteria and their extracellular proteases in sediments of a eutrophic bay.