A new tracking algorithm for multiple colloidal particles close to contact.
In this paper, we propose a new algorithm based on radial symmetry center method to track colloidal particles close to contact, where the optical images of the particles start to overlap in digital video microscopy. This overlapping effect is important to observe the pair interaction potential in colloidal studies and it appears as additional interaction in the measurement of the interaction with conventional tracking analysis. The proposed algorithm in this work is simple, fast and applicable for not only two particles but also three and more particles without any modification. The algorithm uses gradient vectors of the particle intensity distribution, which allows us to use a part of the symmetric intensity distribution in the calculation of the actual particle position. In this study, simulations are performed to see the performance of the proposed algorithm for two and three particles, where the simulation images are generated by using fitted curve to experimental particle image for different sized particles. As a result, the algorithm yields the maximum error smaller than 2 nm for [Formula: see text] μm silica particles in contact condition.


Localization of soluble guanylate cyclase activity in the guinea pig inner ear.
The aim of this study was to characterize the nitric oxide (NO) receptor soluble guanylate cyclase (sGC), to determine the cells targeted by NO and to elucidate the function of the NO/cGMP pathway in the inner ear. sGC activity in the inner ear was localized by immunohistochemical detection of NO-stimulated cGMP. Soluble guanylate cyclase activity in the cochlea was detected in the nerve endings underneath the outer and inner hair cells, supporting cells, stria vascularis and vessels. In the vestibular organs, sGC activity was detected in the cytoplasm of sensory cells, nerve fibres, dark cells and transitional cells and vessels. These findings suggest that the NO/cGMP pathway may be involved in regulatory processes in neurotransmission, blood flow and inner ear fluid homeostasis.


Characterizing Retinal Ganglion Cell Responses to Electrical Stimulation Using Generalized Linear Models.
The ability to preferentially stimulate different retinal pathways is an important area of research for improving visual prosthetics. Recent work has shown that different classes of retinal ganglion cells (RGCs) have distinct linear electrical input filters for low-amplitude white noise stimulation. The aim of this study is to provide a statistical framework for characterizing how RGCs respond to white-noise electrical stimulation. We used a nested family of Generalized Linear Models (GLMs) to partition neural responses into different components-progressively adding covariates to the GLM which captured non-stationarity in neural activity, a linear dependence on the stimulus, and any remaining non-linear interactions. We found that each of these components resulted in increased model performance, but that even the non-linear model left a substantial fraction of neural variability unexplained. The broad goal of this paper is to provide a much-needed theoretical framework to objectively quantify stimulus paradigms in terms of the types of neural responses that they elicit (linear vs. non-linear vs. stimulus-independent variability). In turn, this aids the prosthetic community in the search for optimal stimulus parameters that avoid indiscriminate retinal activation and adaptation caused by excessively large stimulus pulses, and avoid low fidelity responses (low signal-to-noise ratio) caused by excessively weak stimulus pulses.


Impact of a hand hygiene educational programme on hospital-acquired infections in medical wards.
Improvement in hand hygiene (HH) compliance has been associated with a decrease in the incidence of hospital-acquired infection (HAI) and hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) infection/colonization. We aimed to evaluate the impact of a multimodal intervention in medical wards on HH compliance, alcohol-based hand rub (AHR) consumption and incidence of HAI and HA-MRSA. A before-after intervention study and an assessment 1 year later were conducted in three internal medicine wards. HH compliance during routine patient care was monitored using the WHO HH observation method. AHR consumption was registered. HAI incidence was actively sought during the PRE and POST periods. HAI risk factors were prospectively recorded and incidence density was calculated. A total of 825 patients were prospectively followed in the PRE period and 868 patients in the POST period. We observed 1531 opportunities for HH in PRE and POST periods and 450 1 year later. HH compliance improved from 54.3% to 75.8% (p 0.005) and remained 75.8% at follow-up. AHR consumption increased from 10.5 to 27.2 L/1000 hospital-days and 31.5 L/1000 hospital-days at follow-up. Incidence density of HAI was 6.93 and 6.96/1000 hospital-days in the PRE and POST intervention periods, respectively. HA-MRSA incidence density was 0.92 in the PRE period vs. 0.25/1000 hospital-days in the POST period (p 0.2) and 0.15/1000 hospital-days (p 0.1) 1 year later. A sustained increase in AHR consumption was followed by an improvement in HH compliance after a multimodal campaign. A trend for lower incidence density of new hospital-acquired MRSA was detected in the POST intervention and follow-up periods.


Doctors' preferences in de-escalating DMARDs in rheumatoid arthritis: a discrete choice experiment.
Current guidelines suggest reduction of DMARDs can be considered in RA patients in remission. Objectives were (1) to estimate the relative importance of patient characteristics rheumatologists consider in their decision to de-escalate (2) to assess whether heterogeneity exists among rheumatologists with respect to de-escalation and (3) to identify the preferred de-escalation strategy. A discrete choice experiment (DCE) was conducted. All rheumatologists and trainees in The Netherlands were invited to participate. A conditional logit model was estimated to assess overall preference for de-escalation and its determinants. Heterogeneity was estimated by latent class analysis. The DCE questionnaire was completed by 156 doctors. This questionnaire was constructed using the results of semi-structured interviews with 12 rheumatologists that identified five patient characteristics relevant for de-escalation: number of swollen joints (SJC), presence of DAS remission/low disease activity (LDA), patient history, duration of remission/LDA and patient willingness to de-escalate DMARDs. Overall SJC and patient history were most important. Latent class analysis revealed five subgroups of doctors, showing differences regarding willingness to de-escalate and relative importance of patient characteristics. De-escalation of the TNF inhibitor rather than methotrexate first was the most preferred strategy. Rheumatologists are not uniform in their decision on whom to de-escalate. Differences emerged in which characteristics they traded off resulting in five subgroups: those that taper (1) always, (2) in absence of swollen joints, (3) in absence of swollen joints and presence of favorable patient history, (4) in DAS remission and favorable patient history, and (5) taking into account all factors.


Endogenous read-through of a UGA termination codon in a Saccharomyces cerevisiae cell-free system: evidence for involvement of both a mitochondrial and a nuclear tRNA.
Globin mRNA, translated in a Saccharomyces cerevisiae cell-free protein synthesizing system prepared from a [psi+ rho+] strain, primarily directed the synthesis of alpha- and beta-globin. A third globin mRNA-specific polypeptide was also synthesized, representing approximately 10% of the total translation products. This polypeptide (beta') was synthesized by translational read-through of the beta- globin mRNA UGA terminator and was mediated primarily by an endogenous tRNA coded for by the mitochondria. This mitochondrial tRNA, when charged, could be preferentially bound, in high salt, to benzoylated DEAE-cellulose, a characteristic of a tRNATrp. The synthesis of beta- mediated by this mitochondrial tRNATrp was significantly reduced when the translation system was prepared from an isogenic [psi-] strain. Evidence for a nuclear-coded tRNA, also able to suppress the beta-globin mRNA UGA terminator in [psi+] but not [psi-] lysates, was also obtained. The presence of these endogenous UGA suppressor activities in the yeast cell-free system should allow successful in vitro translation of mitochondrial mRNAs.


Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.
Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery.


Late complications of immune deviation therapy in a nonhuman primate.
The administration of antigens in soluble form can induce antigen-specific immune tolerance and suppress experimental autoimmune diseases. In a marmoset model of multiple sclerosis induced by myelin oligodendrocyte glycoprotein (MOG), marmosets tolerized to MOG were protected against acute disease, but after tolerization treatment a lethal demyelinating disorder emerged. In these animals, MOG-specific T cell proliferative responses were transiently suppressed, cytokine production was shifted from a T helper type 1 (TH1) to a TH2 pattern, and titers of autoantibodies to MOG were enhanced. Thus, immune deviation can increase concentrations of pathogenic autoantibodies and in some circumstances exacerbate autoimmune disease.


The Longitudinal Associations between Physical Health and Mental Health among Older Adults.
This study examines the lead-lag relationship between physical and mental health among older adults. Data are collected from 16,417 older adults aged 50 years and older participating in the biannual Health and Retirement Study (HRS). Participants were assessed on up to 11 measurement points over a 21-year period from 1994 to 2014. Physical health was measured as a composite of chronic diseases, functional limitations, and difficulties in basic and instrumental activities of daily living. Mental health was measured with the modified CES-D. Bivariate latent change score models (BLCSM) were estimated. Both physical and mental health declined in the observed years, with slower declining rates over time. A reciprocal relationship emerged, with the prior level of physical health acting as the leading indicator of subsequent change in mental health, and the prior mental health state acting as the leading indicator of subsequent changes in physical health. Additionally, the influence of physical health on mental health changes was larger than the corresponding effect of mental health on subsequent physical health. This study demonstrates the reciprocal relationship between physical and mental health in later adulthood and highlights the need to pay attention to the mental health of older people with physical health problems.


Importation of CyHV-2-infected goldfish into the Netherlands.
Cyprinid herpesvirus 2 (CyHV-2) is known as the causative agent of herpesviral haematopoietic necrosis in goldfish Carassius auratus auratus. However, the virus has also been detected in Prussian carp C. gibelio and crucian carp C. carassius from European and Asian countries. To prevent spread of the causative virus to other areas, investigation of the risk factors of spread of this virus is important. In this study, 8 batches of goldfish imported into the Netherlands by airfreight from Asia and the Middle East were investigated for the presence of the virus. CyHV-2 DNA was detected by PCR in the pooled kidneys of 4 of the 8 imported goldfish batches, of which 1 was from a CyHV-2 disease case at a Dutch importer's quarantine facility. Sequence analysis of the CyHV-2 strains from this study and from previous reports showed that there were at least 6 different lengths in the mA region, resulting in tentatively at least 4 genotypes. Virus isolation was positive for only 1 (Amsterdam Schiphol-1 [AMS-1]) of the 8 samples. It was shown that the AMS-1 isolate was highly virulent to Ryukin goldfish after 100.3 TCID50 fish-1 intraperitoneal injection. The viral titre of the AMS-1 isolate for goldfish fin cells at several temperatures was similar to that of a Japanese CyHV-2 isolate. Our results prove that one of the routes of spread of various CyHV-2 strains is through the global trade of apparently healthy infected goldfish.


225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins.
Prostate-specific membrane antigens (PSMAs) are frequently overexpressed in both tumor stromal endothelial cells and malignant cells (stromal/tumor cells) of various cancers. The RGD (Arg-Gly-Asp) peptide sequence can specifically detect integrins involved in tumor angiogenesis. This study aimed to preclinically evaluate the cytotoxicity, biokinetics, dosimetry, and therapeutic efficacy of 225Ac-iPSMA-RGD to determine its potential as an improved radiopharmaceutical for alpha therapy compared with the 225Ac-iPSMA and 225Ac-RGD monomers. HEHA-HYNIC-iPSMA-RGD (iPSMA-RGD) was synthesized and characterized by FT-IR, UV-vis, and UPLC mass spectroscopy. The cytotoxicity of 225Ac-iPSMA-RGD was assessed in HCT116 colorectal cancer cells. Biodistribution, biokinetics, and therapeutic efficacy were evaluated in nude mice with induced HCT116 tumors. In vitro results showed increased DNA double-strand breaks through ROS generation, cell apoptosis, and death in HCT116 cells treated with 225Ac-iPSMA-RGD. The results also demonstrated in vivo cytotoxicity in cancer cells after treatment with 225Ac-iPSMA-RGD and biokinetic and dosimetric properties suitable for alpha therapy, delivering ablative radiation doses up to 237 Gy/3.7 kBq to HCT116 tumors in mice. Given the phenotype of HCT116 cancer cells, the results of this study warrant further dosimetric and clinical studies to determine the potential of 225Ac-iPSMA-RGD in the treatment of colorectal cancer.


Depigmentation of the skin induced by 4-(4-hydroxyphenyl)-2-butanol is spontaneously re-pigmented in brown and black guinea pigs.
Chemically induced depigmentation of the skin, which occurs following exposure (application or inhalation) to a depigmenting agent, is a disease with clinical findings similar to vitiligo. Recently, skin depigmentation possibly resulting from exposure to 4-(4-hydroxyphenyl)-2-butanol (HPB) was reported in humans. However, the role of HPB as the causative material of this skin depigmentation was not clear. To evaluate whether HPB has the potential for skin depigmentation, we characterized its effects on the skin of pigmented guinea pigs. Following exposure to 30% HPB 3 times/day for about 20 days, we found that obvious skin depigmentation was induced in brown and black guinea pigs. In the depigmented skin, there was a marked reduction in melanin pigment, and decreased numbers of DOPA and S-100 positive epidermal melanocytes were observed histologically. In addition, the depigmentation gradually recovered spontaneously and the number of melanocytes in the skin also increased after terminating the application of HPB. Complete re-pigmentation needed 31 to 70 days to return to the original baseline level. These data indicate that skin depigmentation is induced by the toxicity of HPB to epidermal melanocytes, and that the induced skin depigmentation can recover by terminating the application of HPB.


The histone H3-K27 demethylase Utx regulates HOX gene expression in Drosophila in a temporally restricted manner.
Trimethylation of histone H3 at lysine 27 (H3-K27me3) by Polycomb repressive complex 2 (PRC2) is a key step for transcriptional repression by the Polycomb system. Demethylation of H3-K27me3 by Utx and/or its paralogs has consequently been proposed to be important for counteracting Polycomb repression. To study the phenotype of Drosophila mutants that lack H3-K27me3 demethylase activity, we created Utx(Δ), a deletion allele of the single Drosophila Utx gene. Utx(Δ) homozygotes that contain maternally deposited wild-type Utx protein develop into adults with normal epidermal morphology but die shortly after hatching. By contrast, Utx(Δ) homozygotes that are derived from Utx mutant germ cells and therefore lack both maternal and zygotic Utx protein, die as larvae and show partial loss of expression of HOX genes in tissues in which these genes are normally active. This phenotype classifies Utx as a trithorax group regulator. We propose that Utx is needed in the early embryo to prevent inappropriate instalment of long-term Polycomb repression at HOX genes in cells in which these genes must be kept active. In contrast to PRC2, which is essential for, and continuously required during, germ cell, embryonic and larval development, Utx therefore appears to have a more limited and specific function during development. This argues against a continuous interplay between H3-K27me3 methylation and demethylation in the control of gene transcription in Drosophila. Furthermore, our analyses do not support the recent proposal that Utx would regulate cell proliferation in Drosophila as Utx mutant cells generated in wild-type animals proliferate like wild-type cells.


Acquired immunodeficiency syndrome-associated psoriasis and Reiter's syndrome.
Human immunodeficiency virus (HIV) causes a spectrum of immunodysfunction, the most severe of which is the acquired immunodeficiency syndrome (AIDS). We have followed the course of psoriasis in 13 patients over 2 1/2 years in a population of more than 1000 HIV-positive individuals. Four patients had a history of mild psoriasis that became severe and uncontrollable as symptoms of immunodeficiency developed. Psoriasis and HIV positivity, AIDS-related complex, or AIDS simultaneously developed in nine patients. In addition to psoriasis, Reiter's syndrome (arthritis, urethritis, and conjunctivitis) developed in one patient in the first group and three patients in the second group. Opportunistic infections, especially candidiasis and Staphylococcus, drugs, and an altered immune system may contribute to the development or flare of psoriasis in these patients. The appearance of severe psoriasis (especially in a patient with other risk factors for HIV) should prompt evaluation for HIV, and may be a poor prognostic indicator in HIV-positive patients, since nine of our 13 patients have died. Immunosuppressive therapy with methotrexate is contraindicated in this group of patients. Newer forms of drug therapy including etretinate show promising results for the management of AIDS-associated psoriasis.


Silica exposure increases expression of pulmonary intercellular adhesion molecule-1 (ICAM-1) in C57Bl/6 mice.
Although the pathogenic mechanisms underlying silica-induced lung damage are well described, few studies have examined the expression and role of adhesion molecules in lung injury induced by this particle. Here we report that intratracheal instillation of silica crystals (alpha quartz) (SI) into the lungs of C57Bl/6 mice results in a significant increase in levels of intercellular adhesion molecule-1 (ICAM-1) in lung tissue and in lung lavage fluid. This increased expression of ICAM-1 appeared to be associated with later (> or = 24 h) cell influx and lung injury rather than in the initiation of these events. Exposure of mice to the nontoxic particle titanium dioxide did not elicit increased expression of ICAM-1 in lung tissue or lavage fluid. Passive administration of rat anti-mouse ICAM-1 monoclonal antibody significantly decreased the influx of neutrophils (PMNs) into the alveoli and the levels of lung tissue ICAM-1 and yet had no effect on measures of lung injury or increased collagen deposition. These data suggest that increased ICAM-1 expression in lung tissue following exposure to silica plays a partial role in the trafficking of neutrophils into the airways.


Review of Integrated care: A guide for effective implementation.
Reviews the book, Integrated Care: A Guide for Effective Implementation edited by Lori E. Raney, Gina B. Lasky, and Clare Scott. The book is separated into three main sections. Part 1 includes three chapters that focus primarily on considerations such as the importance of organizational support and leadership, team development, and culture change. Part 2 is a review of the roles, across three respective chapters, of the behavioral health provider, the primary care provider, and the consulting psychiatrist on an integrated care team. Finally, Part 3 is a broad review of policy and financing considerations, and suggests that the authors are hoping to appeal not only to clinicians in the creating of this text, but to administrators as well. Minor issues aside, this is an exceptional book that functions essentially as a "user's manual" for the design and implementation of a successful approach to collaborative care. I would recommend this to the leadership and clinicians at any site developing a similar program of their own, as the practical uses of this book are notable indeed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Fate of viruses in artificial wetlands.
Little is known about the ability of wetlands to remove disease-causing viruses from municipal wastewater. In this study we examined the survival of several indicators of viral pollution (indigenous F-specific bacteriophages, seeded MS2 bacteriophage, and seeded human poliovirus type 1) applied in primary municipal wastewater to artificial wetland ecosystems. Only about 1% of the indigenous F-specific RNA bacteriophages survived flow through the vegetated wetland beds at a 5-cm-day-1 hydraulic application rate during the period from June through December 1985. The total number of indigenous F-specific bacteriophages (F-specific RNA and F-specific DNA phages) was also reduced by about 99% by wetland treatment, with the mean inflow concentration over the period of an entire year reduced from 3,129 to 33 PFU ml-1 in the outflow of a vegetated bed and to 174 PFU ml-1 in the outflow of an unvegetated bed. Such superior treatment by the vegetated bed demonstrates the significant role of higher aquatic plants in the removal process. Seeded MS2 bacteriophage and seeded poliovirus were removed more efficiently than were the indigenous bacteriophages, with less than 0.2% of MS2 and 0.1% of the poliovirus surviving flow at the same hydraulic application rate. The decay rate (k) of MS2 in a stagnant wetlands (k = 0.012 to 0.028 h-1) was lower than that for flowing systems (k = 0.44 to 0.052 h-1), reflecting the enhanced capacity for filtration or adsorption of viruses by the root-substrate complex (and associated biofilm).(ABSTRACT TRUNCATED AT 250 WORDS)


[Studies on distribution of H type 1-H type 4 antigens of ABO system and on FUT2 polymorphism].
I have examined the immunohistochemical distribution of H type 1-H type 4 antigens of the ABO system in human submandibular gland using either of the three anti-H monoclonal antibodies specific for H type 1, H type 2 and H type 3/4. I have clearly identified cell types expressing H type 1, H type 2 and H type 3/4: H type 1 in mucous cells and duct cells, H type 2 in duct cells, and H type 3/4 in serous cells of the submandibular gland. The expression of H type 1 and H type 3/4 in the human submandibular gland is regulated by the Se enzyme. The FUT2 encodes Secretor type alpha(1,2) fucosyltransferase (Se enzyme), which regulates the expression of ABH antigens in the gastrointestinal tract and secretions. Molecular analysis of the FUT2 polymorphism of various populations have indicated the ethnic specificity of null alleles: the null allele se428 is a common Se-enzyme deficient allele in Africans and Caucasians but does not occur in Asians, whereas the null allele se357,385 is specific to Asians. The gene frequency of se428 or se357,385 is about 0.5 in each respective population. Why the se428 is absent in Asians is of interest.


The number of people exposed to water stress in relation to how much water is reserved for the environment: a global modelling study.
Increasing human demand for water and changes in water availability due to climate change threatens water security worldwide. Additionally, exploitation of water resources induces stress on freshwater environments, leading to biodiversity loss and reduced ecosystem services. We aimed to conduct a spatially detailed assessment of global human water stress for low to high environmental flow (EF) protection. In this modelling study, we used the LISFLOOD model to generate daily natural flows without anthropogenic water use for 1980-2018. On the basis of these flows, we selected three EF methods (EF with high ecological protection [EFPROT], EF with minimum flow requirements [EFMIN], and variable monthly flow [EFVMF]) to calculate monthly EFs. We assessed monthly consumptive water use for industry, agricultural crops, livestock, municipalities, and energy production for 2010. We then estimated the corresponding number of people under water stress per month on a global and national level using a spatially detailed population database for 2010. We estimate that 3·2 billion (EFPROT), 2·4 billion (EFVMF), and 2·2 billion (EFMIN) people lived under water stress for at least 1 month per year, corresponding to 46%, 35%, and 32% of the world's population in 2010, respectively. Around 80% of people living under water stress lived in Asia; in particular, India, Pakistan, and northeast China. Compared with EFMIN, imposing EFPROT globally would have put between 710 million (March) to 1 billion (June) additional people under water stress on a monthly basis, whereas this would have been 72 million (August) to 218 million (April) additional people if EFVMF were imposed. Ensuring high ecological protection would put nearly half of the world's population (3·2 billion people) under water stress for at least 1 month per year. Policy makers and water managers have to make an important trade-off when allocating limited water resources between direct human needs and the environment. A better understanding of local ecosystem needs is crucial to alleviating current and future human water stress, while sustaining healthy ecosystems. None.


Service Preferences of Parents of Children With Mild Bilateral or Unilateral Hearing Loss: A Conjoint Analysis Study.
Universal newborn hearing screening results in substantially more children with mild bilateral and unilateral hearing loss identified in the early years of life. While intervention services for children with moderate loss and greater are generally well-established, considerable uncertainty and variation surrounds the need for intervention services for children with milder losses. This study was undertaken with parents of young children with permanent mild bilateral and unilateral hearing loss to examine their preferences for characteristics associated with intervention services. Conjoint analysis, a preference-based technique, was employed to study parents' strength of preferences. Using a cross-sectional survey that consisted of eight hypothetical clinic scenarios, we invited parents to make a discrete choice (to select one of two or more different services) between available services with different characteristics. The survey was informed by qualitative interviews conducted for this purpose. The questionnaire was administered to parents receiving intervention services in the province of Ontario, Canada, who were enrolled in a mixed-methods longitudinal study examining outcomes in early-identified children with mild bilateral/unilateral hearing loss. Data were analyzed using a generalized linear model (probit link) to identify attributes of interest for the respondents. Characteristics of the children were entered into the model to control for differences in age of diagnosis, sex, laterality of hearing loss, and hearing aid use. A total of 51 of 62 invited parents completed the questionnaire. All four attributes of care that were included in the survey were found to be statistically significant, that is, parents valued support for amplification, support for speech-language development, emotional support, and communication from professionals. Analysis showed greater preference for enhanced levels relating to support for speech-language development than for support for amplification. Preference for attributes relating to emotional support and communication were also greater than for support for amplification use. Conjoint analysis was used to quantify parents' preferences for service attributes. Parents' values provide insights into the aspects of a service model that should receive consideration in the development of intervention programs for young children with mild bilateral or unilateral hearing loss and their families. Although parents of young children with mild bilateral or unilateral hearing loss valued several components of care, they indicated a clear preference for speech-language support compared with support for amplification use.


Determinants of use of household-level water chlorination products in rural Kenya, 2003-2005.
Household-level water treatment products provide safe drinking water to at-risk populations, but relatively few people use them regularly; little is known about factors that influence uptake of this proven health intervention. We assessed uptake of these water treatments in Nyanza Province, Kenya, November 2003-February 2005. We interviewed users and non-user controls of a new household water treatment product regarding drinking water and socioeconomic factors. We calculated regional use-prevalence of these products based on 10 randomly selected villages in the Asembo region of Nyanza Province, Kenya. Thirty-eight percent of respondents reported ever using household-level treatment products. Initial use of a household-level product was associated with having turbid water as a source (adjusted odds ratio [AOR] = 16.6, p = 0.007), but consistent usage was more common for a less costly and more accessible product that did not address turbidity. A combination of social marketing, retail marketing, and donor subsidies may be necessary to extend the health benefits of household-level water treatment to populations most at risk.


Inhibition of MuSK expression by CREB interacting with a CRE-like element and MyoD.
The type I receptor-like protein tyrosine kinase MuSK is essential for the neuromuscular junction formation. MuSK expression is tightly regulated during development, but the underlying mechanisms were unclear. Here we identified a novel mechanism by which MuSK expression may be regulated. A cyclic AMP response element (CRE)-like element in the 5'-flanking region of the MuSK gene binds to CREB1 (CRE-binding protein 1). Mutation of this element increases the MuSK promoter activity, suggesting a role for CREB1 in attenuation of MuSK expression. Interestingly, CREB mutants unable to bind to DNA also inhibit MuSK promoter activity, suggesting a CRE-independent inhibitory mechanism. In agreement, CREB1 could inhibit a mutant MuSK transgene reporter whose CRE site was mutated. We provide evidence that CREB interacts directly with MyoD, a myogenic factor essential for MuSK expression in muscle cells. Suppression of CREB expression by small interfering RNA increases MuSK promoter activity. These results demonstrate an important role for CREB1 in the regulation of MuSK expression.


New fossil discoveries illustrate the diversity of past terrestrial ecosystems in New Caledonia.
New Caledonia was, until recently, considered an old continental island harbouring a rich biota with outstanding Gondwanan relicts. However, deep marine sedimentation and tectonic evidence suggest complete submergence of the island during the latest Cretaceous to the Paleocene. Molecular phylogenies provide evidence for some deeply-diverging clades that may predate the Eocene and abundant post-Oligocene colonisation events. Extinction and colonization biases, as well as survival of some groups in refuges on neighbouring paleo-islands, may have obscured biogeographic trends over long time scales. Fossil data are therefore crucial for understanding the history of the New Caledonian biota, but occurrences are sparse and have received only limited attention. Here we describe five exceptional fossil assemblages that provide important new insights into New Caledonia's terrestrial paleobiota from three key time intervals: prior to the submersion of the island, following re-emergence, and prior to Pleistocene climatic shifts. These will be of major importance for elucidating changes in New Caledonia's floristic composition over time.


Insects Associated to Crime Scenes in the Northeast of Brazil: Consolidation of Collaboration Between Entomologists and Criminal Investigation Institutes.
In Brazil, many studies on Forensic Entomology analyze the activity and succession of flies in animal models. Data on human corpses are always collected and evaluated in isolated cases. This study aimed to list the insect species associated with crime scenes investigated by the Technical-Scientific Institute of criminal expertise of the State of Rio Grande do Norte (ITEP-RN), in the Northeast of Brazil, a region exposed to high homicide rates. In total, 10 cases were investigated, of which 50% were in the initial stage of decomposition. The examined bodies were colonized by species of three orders of insects, Diptera, Coleoptera and Hymenoptera. The order Diptera represented 96% of the total insects, being represented by the following species: Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae), Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae), and Cochliomyia macellaria, (Fabricius) (Diptera: Calliphoridae); Musca domestica (Linnaeus) (Diptera: Muscidae); and unidentified females of the Sarcophagidae family. Among beetles, the occurrence of Dermestes maculatus (DeGeer) (Coleoptera: Dermestidae), Necrobia rufipes (De Geer) (Coleoptera: Cleridae), and Onthophagus sp. (Scarabaeidae), as well as unidentified specimens of the families Tenebrionidae and Histeridae were recorded. In addition, specimens of Ectatomma sp. (Formicidae) were also recorded. Considering that the Rio Grande do Norte state presents a high homicide rate and the last cadaver study was conducted over a decade ago, these records update the list of species associated with cadaveric decomposition and contribute to consolidate forensic entomology in the Northeast region.


Lytic Mastoid Lesion in a Patient with Otalgia.
The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.


Dysphagia due to Retropharyngeal Abscess that Incidentally Detected in Subarachnoid Hemorrhage Patient.
Cerebral hemorrhage is one of the most common causes of dysphagia. In many cases, dysphagia gets better once the acute phase has passed. Structural lesions such as thyromegaly, cervical hyperostosis, congenital web, Zenker's diverticulum, neoplasm, radiation fibrosis, and retropharyngeal abscess must be considered as other causes of dysphagia as well. Retropharyngeal abscess seldom occur in adults and if it does so, a search for a prior dental procedure, trauma, head and neck infection is needed. The symptoms may include neck pain, dysphagia, sore throat, and in rare cases, dyspnea accompanied by stridor. We present a case and discuss a patient who had dysphagia and neck pain after a cerebral hemorrhage. Testing revealed a retropharyngeal abscess. The symptoms were successfully treated after the administration of antibiotics.


Retroperitoneoscopic radical nephrectomy with a small incision for renal cell carcinoma: comparison with the conventional method.
When retroperitoneoscopic radical nephrectomy for renal cell carcinoma was introduced into our institution, we performed a combined small skin incision method. In this method, a small incision was made to approach the retroperitoneal space prior to setting trockers and thereafter a LAPDISC was placed in the incision to start the retroperitoneoscopic procedure. In this study, we compared the outcomes between the combined small skin incision method ("A method" hereinafter) and the conventional method ("B method" hereinafter). Among the cases of T1N0M0 suspicious renal cell carcinoma treated at Yokohama City University between May 2003 and June 2009, the A method was performed in 51 cases and the B method was performed in 33 cases. The factors in the outcomes compared between the A and B methods were the duration of procedure, volume of bleeding, volume of transfusion, weight of the specimen, incidence of peritoneal injury, rate of conversion to open surgery, and perioperative complications. The duration of the procedure was 214.4 ± 46.9 minutes in the A method group and 208.1 ± 36.4 minutes in the B method group (p = 0.518). The volume of bleeding and the weight of the specimen were 105.5 ± 283.2 ml and 335.1 ± 137.4 g in the A method group and 44.8 ± 116 ml (p = 0.247) and 309.2 ± 126 g (p = 0.385) in the B method group. There was no significant difference in all factors analyzed. The A method would be highly possible to produce stable results, even during the introduction period when the staff and the institution are still unfamiliar with the retroperitoneoscopic surgery.


Recent studies on the developing human hepatocellular carcinoma.
From our knowledge of characteristic phenotypic changes of the preneoplastic lesions during the stepwise evolution of hepatocellular carcinoma (HCC) in experimental models, we are now beginning to define the structural, histochemical, biochemical, antigenic and molecular properties of early HCC and of the putative preneoplastic changes in human liver. Histological, ultrastructural, morphometric and immunohistochemical studies suggest that adenomatous nodules of regenerating and hyperplastic hepatocytes are more likely to represent direct precursors of HCC than dysplastic hepatocytes. Histochemical and immunomorphological investigations show appreciable functional and phenotypic heterogeneity of human HCC as previously recognized in experimental hepatocarcinogenesis. Studies of altered expression of oncogenes in the regenerating liver and HCC are beginning to define the molecular mechanisms in cell growth and malignant transformation. Although integration of Hepadna viral DNA sequences frequently occurs during persistent infection in man and animals, the exact mechanism of viral oncogenesis remains to be elucidated. It is likely that the development of monoclonal antibodies to surface antigens on transformed hepatocytes will be useful for exploring lineage relationships between the cell populations involved in hepatocarcinogenesis.


Catalysis and electron transfer in protein crystals: the binary and ternary complexes of methylamine dehydrogenase with electron acceptors.
Polarized absorption microspectrophotometry has been used to detect catalysis and intermolecular electron transfer in single crystals of two multiprotein complexes: (1) the binary complex between Paracoccus denitrificans methylamine dehydrogenase, which contains tryptophan-tryptophylquinone (TTQ) as a cofactor, and its redox partner, the blue copper protein amicyanin; (2) the ternary complex between the same two proteins and cytochrome c-551i. Continuous wave electron paramagnetic resonance has been used to compare the state of copper in polycrystalline powders of the two systems. While catalysis and intermolecular electron transfer from reduced TTQ to copper are too fast to be accessible to our measurements, heme reduction occurs over a period of several minutes. The observed rate constant is about four orders of magnitude lower than in solution. The analysis of the temperature dependence of this apparent constant provides values for the parameters H(AB), related to electronic coupling between the two centers, and lambda, the reorganizational energy, that are compatible with electron transfer being the rate-determining step. From these parameters and the known distance between copper and heme, it is possible to calculate the parameter beta, which depends on the nature of the intervening medium, obtaining a value typical of electron transfer across a protein matrix. These findings suggest that the ternary complex in solution might achieve a higher efficiency than the rigid crystal structure thanks to an as yet unidentified role of protein dynamics.


Allogeneic hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia.
This study was aimed to explore the prognosis of allogenic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL). This retrospective case series study included children with ALL who underwent allo-HSCT at Beijing Children's Hospital of Capital Medical University, Beijing, China, between January 2009 and December 2019. The outcomes included 5-year overall survival (OS) and event-free survival (EFS). A total of 75 children (52 males) were included. The median age at presentation was 5.30 years, and the median time from diagnosis to transplantation was 1.64 years. There were 15 human leukocyte antigen (HLA)-matched and 60 HLA-semi-matched transplants, 73 complete remissions (CR), and 2 MRD-positive transplants. The median follow-up time was 41 months. Out of 75 patients, 51 children survived, and 24 died/given up at the terminal stage. The 5-year OS and EFS rates were 67.77% and 57.30%, respectively, whereas the 5-year recurrence rate was 35.69%. Acute and chronic graft versus host diseases occurred in 40 and 28 cases, respectively. Children with MLL gene fusion had higher survival rates compared to other subgroups. Haplo-HSCT is not inferior to HLA-matched transplant. The children with MLL rearrangement had an acceptable 5-year OS, while complications and relapse should be monitored.


Enhanced isoprene-related tolerance of heat- and light-stressed photosynthesis at low, but not high, CO2 concentrations.
The principal function of isoprene biosynthesis in plants remains unclear, but emission rates are positively correlated with temperature and light, supporting a role for isoprene in maintaining photosynthesis under transient heat and light stress from sunflecks. Isoprene production is also inversely correlated with CO(2) concentrations, implying that rising CO(2) may reduce the functional importance of isoprene. To understand the importance of isoprene in maintaining photosynthesis during sunflecks, we used RNAi technology to suppress isoprene production in poplar seedlings and compared the responses of these transgenic plants to wild-type and empty-vector control plants. We grew isoprene-emitting and non-emitting trees at low (190 ppm) and high (590 ppm) CO(2) concentrations and compared their photosynthetic responses to short, transient periods of high light and temperature, as well as their photosynthetic thermal response at constant light. While there was little difference between emitting and non-emitting plants in their photosynthetic responses to simulated sunflecks at high CO(2), isoprene-emitting trees grown at low CO(2) had significantly greater photosynthetic sunfleck tolerance than non-emitting plants. Net photosynthesis at 42°C was 50% lower in non-emitters than in isoprene-emitting trees at low CO(2), but only 22% lower at high CO(2). Dark respiration rates were significantly higher in non-emitting poplar from low CO(2), but there was no difference between isoprene-emitting and non-emitting lines at high CO(2). We propose that isoprene biosynthesis may have evolved at low CO(2) concentrations, where its physiological effect is greatest, and that rising CO(2) will reduce the functional benefit of isoprene in the near future.


Knowledge and preventive actions toward COVID-19, vaccination intent, and health literacy among educators in Japan: An online survey.
Countermeasures against the spread of COVID-19 have become an urgent issue in educational settings, where many group activities are necessary. Educators are key to preventing the spread of COVID-19 in educational settings. Infection prevention behavior requires comprehensive and complex measures such as self-restraint. disinfection care, hand washing, wearing masks and recommendation and implementation of vaccination. Improvement in the knowledge, skills, and preventive actions of educators vis-à-vis COVID-19 could allow for the continued provision of educational services while ensuring safety in educational settings. Therefore, the objective of this study was to explore the knowledge and preventive actions of educators regarding COVID-19 and vaccination awareness to provide appropriate support for educators. The study used data collected from 1,000 Japanese educators in January 2021 when the third wave of viral infections spread. Online surveys and multivariate linear regression analysis were used to determine age and whether respondents were being cared for by a doctor. We investigated the effects of factors on educators' willingness to be vaccinated and changes in their behavior. This study found that factors such as age, gender, whether a respondent was under a physician's care, and health literacy, affected the willingness of educators to receive vaccinations and engage in preventive actions. The study also suggests that the reliability of national government public relations efforts is lower than the reliability of local government public relations and that of information from family physicians, pharmacies, and mass media. It is therefore necessary to reexamine how information is disseminated by the national government and to increase the degree of trust in that information among the public. The findings of the study also revealed the importance of improving the provision of appropriate information and health literacy for the behavior of educators, not only during the initial outbreak, but also during the subsequent period of pandemic life.


A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation.
Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.


[Noninvasive diagnostics and treatment of pelvic organs blood repletion syndrome].
Analysis of complex clinical and ultrasound research in 78 women with chronic pelvic venous insufficiency was carried out. Left-side regional renal venous hypertension leading to valve insufficiency of left ovarian vein with extension of reno-ovarian blood reflux on racemose, uterovaginal, presacral, vesical and rectal venous plexuses was discovered in 100% of patients. Right-side cava-ovarian blood reflux was discovered only in 26.9% of patients and in combination with reno-ovarian lead to complete decompensation of venous outflow from pelvis. Three degrees of blood repletion of small pelvis organs were marked out. At first degree (61.5% of patients) complex drug treatment was carried out, at second degree (18%) - sclerotherapy, at third degree (20.5%) - operative excision of ovarian veins. Perfect results were seen in 35.9% of patients, good results - in 44.9% of patients, satisfactory - in 19.2% of patients. On basis of self-appraisal 80.8% of patients consider their life quality as completely recovered, 15.7% of patients - as improved, 3.5% of patients - without any changes.


The effect of spiritual healing on in vitro tumour cell proliferation and viability--an experimental study.
Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation of cells to five different doses of healing or control. Researchers conducting the assays and statistical analyses were blinded to the experimental conditions. Main outcome measures were MTT viability, 3H-thymidine incorporation and counts of an adherent human breast cancer cell line (MCF-7), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all three experimental days, doses, assays, and cells, 34 (51.6%) of 66 independent comparisons showed differences in the hypothesised direction (P = 0.90). The average effect size across cell lines, days, assays, and doses approached zero (Cohen's d = -0.01). The results do not support previous reports of beneficial effects of spiritual healing on malignant cell growth in vitro. Reported beneficial effects of spiritual healing on the well-being of cancer patients seem more likely to be mediated by psychosocial and psychophysiological effects of the healer-patient relationship.


A Southeast Asian collaborative Delphi consensus on surveying risk factors for head and neck cancer screening and prevention.
The objective of this study was to determine high value questions for early detection and prevention of head and neck cancer by querying content experts on patient risk factors relevant to local communities in Southeast Asia (i.e., Vietnam, Laos, China, and Singapore). The Delphi method was employed using three rounds of asynchronous surveying which included participants among five different collaborating medical centers. 60 total survey items were assessed for consensus defined by a priori measures on the relative level of value of these questions for use in head and neck cancer screening. 77% of items reached a consensus and no items were concluded to be of low value despite differences in conclusions regarding relative importance. Survey items focused on patient demographic information and physical examination were examined across variables such as expert department affiliation, academic designation, and years of experience and found to be without statistically significant differences. However, with consensus items related to social risk factors, it was determined that participants who had 15 or more years of experience or identified as otolaryngologists rated these items at a relatively lower value than their peers with less experience (p < 0.0001, p = 0.0017) or outside the field of otolaryngology (p = 0.0101). This study explicitly identifies patient variables to consider in head and neck cancer screening that have not previously been comprehensively or methodically assessed in current literature. Increasing awareness of these risk factors may benefit the design and implementation of future head and neck cancer early detection and prevention programs in Southeast Asia and beyond as well as positively impact head and neck cancer outcomes.


Surgical Management of Supraglottic Stenosis Using Intubationless Optiflow.
Airway management during endoscopic surgical treatment of supraglottic and pharyngeal stenosis is often challenging and can be accomplished by various means, including tracheostomy, jet ventilation, or direct laryngoscopy. We describe CO2 laser excision of supraglottic-pharyngeal stenosis using intubationless Optiflow high-flow nasal cannula (HFNC). A 55-year-old male presented with dyspnea and dysphagia secondary to severe supraglottic-pharyngeal stenosis in the setting of previous chemoradiation for a T0N2aM0 squamous cell carcinoma. Laryngoscopy revealed severe supraglottic-pharyngeal stenosis with tethering of the epiglottis to the lateral pharyngeal walls. Optiflow HFNC was used to deliver 70 L/min of oxygen. After anesthetic induction, CO2 laser microlaryngoscopy was utilized to release scar tissue along the lateral epiglottic border, opening up the supraglottic airway sufficiently for endotracheal intubation and further laser resection. Airway management with Optiflow HFNC allowed initial endoscopic surgical access, partial stenotic release, and intubation. From anesthetic induction to intubation, the patient remained apneic for 26 minutes. The patient's stenosis was successfully addressed, and 10-month follow-up demonstrated stable patency of the airway. Optiflow is an important new tool in the management of severe supraglottic stenosis. It provides sufficient oxygenation to perform extended apneic surgery and improves endoscopic surgical access in a limited airway.


Seismological Processing of Six Degree-of-Freedom Ground-Motion Data.
Recent progress in rotational sensor technology has made it possible to directly measure rotational ground-motion induced by seismic waves. When combined with conventional inertial seismometer recordings, the new sensors allow one to locally observe six degrees of freedom (6DOF) of ground-motion, composed of three orthogonal components of translational motion and three orthogonal components of rotational motion. The applications of such 6DOF measurements are manifold-ranging from wavefield characterization, separation, and reconstruction to the reduction of non-uniqueness in seismic inverse problems-and have the potential to revolutionize the way seismic data are acquired and processed. However, the seismological community has yet to embrace rotational ground-motion as a new observable. The aim of this paper is to give a high-level introduction into the field of 6DOF seismology using illustrative examples and to summarize recent progress made in this relatively young field. It is intended for readers with a general background in seismology. In order to illustrate the seismological value of rotational ground-motion data, we provide the first-ever 6DOF processing example of a teleseismic earthquake recorded on a multicomponent ring laser observatory and demonstrate how wave parameters (phase velocity, propagation direction, and ellipticity angle) and wave types of multiple phases can be automatically estimated using single-station 6DOF processing tools. Python codes to reproduce this processing example are provided in an accompanying Jupyter notebook.


Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted?
There are at present approximately 110 million people with diabetes in the world but this number will reach over 220 million by the year 2010, the majority of them with type 2 diabetes. Thus there is an urgent need for strategies to prevent the emerging global epidemic of type 2 diabetes to be implemented. Tackling diabetes must be part of an integrated program that addresses lifestyle related disorders. The prevention and control of type 2 diabetes and the other major noncommunicable diseases (NCDs) can be cost- and health-effective through an integrated (i.e. horizontal) approach to noncommunicable diseases disease prevention and control. With the re-emergence of devastating communicable diseases including AIDS, the Ebola virus and tuberculosis, the pressure is on international and regional agencies to see that the noncommunicable disease epidemic is addressed. The international diabetes and public health communities need to adopt a more pragmatic view of the epidemic of type 2 diabetes and other noncommunicable diseases. The current situation is a symptom of globalization with respect to its social, cultural, economic and political significance. Type 2 diabetes will not be prevented by traditional medical approaches; what is required are major and dramatic changes in the socio-economic and cultural status of people in developing countries and the disadvantaged, minority groups in developed nations. The international diabetes and public health communities must lobby and mobilize politicians, other international agencies such as UNDP, UNICEF, and the World Bank as well as other international nongovernmental agencies dealing with the noncommunicable diseases to address the socio-economic, behavioural, nutritional and public health issues that have led to the type 2 diabetes and noncommunicable diseases epidemic. A multidisciplinary Task Force representing all parties which can contribute to a reversal of the underlying socio-economic causes of the problem is an urgent priority.


Role of tyrosine kinase in dilator responses of rat basilar artery in vivo.
We tested the hypothesis that dilator responses of the basilar artery to endothelium-dependent vasodilators are mediated by activation of tyrosine kinase in vivo. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to acetylcholine and bradykinin. Topical application of acetylcholine and bradykinin increased diameter of the basilar artery in a concentration-related manner. Genistein, an inhibitor of tyrosine kinase, did not affect baseline diameter of the basilar artery but inhibited vasodilatation in response to acetylcholine and bradykinin, without affecting vasodilatation produced by sodium nitroprusside. Tyrphostin 47, another inhibitor of tyrosine kinase, attenuated acetylcholine-induced dilatation of the basilar artery without affecting vasodilatation in response to sodium nitroprusside. Tyrphostin 63, an inactive analogue of tyrphostin 47, did not affect acetylcholine-induced vasodilatation. Sodium orthovanadate, an inhibitor of tyrosine phosphatase, enhanced acetylcholine-induced dilatation of the basilar artery. These results suggest that dilator responses of the basilar artery to endothelium-dependent agonists, acetylcholine and bradykinin, are mediated in large part by activation of tyrosine kinase. Because vasodilatation produced by these agonists is mediated primarily by nitric oxide, activation of tyrosine kinase may have an important role in nitric oxide production in the basilar artery in vivo.


Pneumonia in older persons.
Community-acquired pneumonia (CAP) is an important threat to the health of older adults. Streptococcus pneumonia remains the most important cause of CAP. Risk factors for CAP include alcoholism, asthma, immunosuppression, chronic respiratory or cardiac disease, institutionalization, and increasing age. Residents of long-term care facilities--a distinct subpopulation of elderly people--are at particularly high risk for developing pneumonia. In this setting, swallowing difficulties, witnessed aspiration, and receipt of sedatives are potentially modifiable risk factors. The clinical presentation in elderly patients is characterized by a reduced prevalence of nonrespiratory symptoms. Few randomized, controlled trials of therapy exist for elderly persons living in the community or in a long-term care setting. Good evidence exists to support the annual administration of influenza vaccine to older adults. Although evidence in clinical trials differs from evidence in observational studies that demonstrate clear benefits associated with the polysaccharide pneumococcal vaccine in this population, the vaccine is recommended for adults aged


Pelvic lymph node F-18 fluorodeoxyglucose uptake as a prognostic biomarker in newly diagnosed patients with locally advanced cervical cancer.
The objective of the current study was to evaluate the prognostic significance of the maximum standardized uptake value (SUV(max)) of F-18 fluorodeoxyglucose (FDG) as measured by positron emission tomography (PET) in pelvic lymph nodes in patients with cervical cancer. The authors studied cervical cancer patients with pelvic lymph node metastasis, as evidenced on FDG-PET, who were treated between November 2003 and October 2008. The maximum dimension and SUV(max) for the most FDG-avid pelvic lymph node (SUV(PLN)) and the SUV(max) of the primary cervical tumor (SUV(cervix)) were recorded from the FDG-PET/computed tomography (CT) scan. The SUV(PLN) was analyzed for its association with treatment response, pelvic disease recurrence, disease-specific survival, and overall survival. The population was comprised of 83 women with International Federation of Gynecology and Obstetrics (FIGO) stages IB1 to IIIB cervical cancer. The average SUV(PLN) was 6.9 (range, 2.1-33.0), whereas the average SUV(cervix) was 14.0 (range, 3.2-38.4). The SUV(cervix) and SUV(PLN) were found to be weakly correlated (correlation coefficient [R(2)] = 0.301). The average size of the pelvic lymph nodes was 2.1 cm (range, 0.6-7.9 cm), and was also found to be only weakly associated with the SUV(PLN) (R(2) = 0.225). The SUV(PLN) was found to be correlated with an increased risk of persistent disease after treatment (P = .0025), specifically within the pelvic lymph node region (P = .0003). The SUV(PLN) was found to be predictive of an increased risk of ever developing pelvic disease recurrence (P = .0035). Patients with a higher SUV(PLN) were found to have significantly worse disease-specific (P = .0230) and overall survival (P = .0378) using Kaplan-Meier evaluation. A Cox proportional hazards model for the risk of pelvic disease recurrence was performed including SUV(PLN,) patient age, and tumor stage, and found only an increased SUV(PLN) to be an independent predictor. SUV(PLN) is a prognostic biomarker, predicting treatment response, pelvic recurrence risk, and disease-specific survival in patients with cervical cancer.


Bilateral Limbal Stem Cell Alterations in Patients With Unilateral Herpes Simplex Keratitis and Herpes Zoster Ophthalmicus as Shown by In Vivo Confocal Microscopy.
The purpose of this study was to investigate the limbal changes in the palisades of Vogt (POV) in patients with herpes simplex keratitis (HSK) and herpes zoster ophthalmicus (HZO) with the application of in vivo confocal microscopy (IVCM). We enrolled 35 eyes of 35 consecutive patients with HSK and 4 patients with HZO in this observational study. Thirty-five participants were also recruited from a healthy population as the control group. All subjects were examined by IVCM in addition to routine slit-lamp biomicroscopy. The IVCM images of the corneal basal epithelial cells, corneal nerve, and the corneoscleral limbus were acquired and then were analyzed semiquantitatively. The rate of absent and atypical POV was significantly higher in the affected eyes of patients with HSK than in the contralateral eyes and eyes of controls (88.57% vs. 65.71% vs. 17.14%, P < 0.01). In the HZO group, the rate of absent and atypical POV was 100% in the affected eyes and 50% in the contralateral eyes. When compared to the contralateral unaffected eyes and control eyes, the average density of the central basal epithelial cells and the sub-basal nerve plexus density and the total number of nerves in the central area of the affected eyes were significantly lower in the HSK group (1541 ± 704.4 vs. 2510 ± 746.8 vs. 3650 ± 746.1 cells/mm2, P < 0.0001). Spearman's rank correlation showed that the presence of absent and atypical POV had a significant negative correlation with central corneal basal epithelial cells (rs = -0.44979, P < 0.0001), the density of total nerves (rs = -0.49742, P < 0.0001), and the total nerve numbers (rs = -0.48437, P < 0.0001). A significant positive correlation was established between the presence of absent and atypical POV and HSK severity in affected eyes in the superior, inferior, nasal, and temporal quadrants (rs = 0.68940, rs = 0.78715, rs = 0.65591, and rs = 0.75481, respectively, P < 0.0001) and the contralateral eyes (rs = 0.51636, rs = 0.36207, rs = 0.36990, rs = 0.51241, correspondingly, P < 0.0001). Both eyes of patients with unilateral HSK and HZO demonstrated a profound and significant loss of limbal stem cells, which may explain the fact that HSK and HZO are risk factors for limbal stem cell deficiency (LSCD) in both eyes. The loss of LSCs was strongly correlated with the sub-basal nerve plexus and central basal epithelial cell alterations as shown by IVCM.


Design, synthesis and evaluation of Fe-S targeted adenosine 5'-phosphosulfate reductase inhibitors.
Adenosine 5'-phosphosulfate reductase (APR) is an iron-sulfur enzyme that is vital for survival of Mycobacterium tuberculosis during dormancy and is an attractive target for the treatment of latent tuberculosis (TB) infection. The 4Fe-4S cluster is coordinated to APR by sulfur atoms of four cysteine residues, is proximal to substrate, adenosine 5'-phopsphosulfate (APS), and is essential for catalytic activity. Herein, we present an approach for the development of a new class of APR inhibitors. As an initial step, we have employed an improved solid-phase chemistry method to prepare a series of N(6)-substituted adenosine analogues and their 5'-phosphates as well as adenosine 5'-phosphate diesters bearing different Fe and S binding groups, such as thiols or carboxylic and hydroxamic acid moieties. Evaluation of the resulting compounds indicates a clearly defined spacing requirement between the Fe-S targeting group and adenosine scaffold and that smaller Fe-S targeting groups are better tolerated. Molecular docking analysis suggests that the S atom of the most potent inhibitor may establish a favorable interaction with an S atom in the cluster. In summary, this study showcases an improved solid-phase method that expedites the preparation of adenosine and related 5'-phosphate derivatives and presents a unique Fe-S targeting strategy for the development of APR inhibitors.


Cleavage of symmetric immobile DNA junctions by Escherichia coli RuvC.
The Holliday junction is a key DNA intermediate in the process of genetic recombination. It consists of two double-helical domains composed of homologous strands that flank a branch point; two of the strands are roughly helical, and two form the crossover between the helices. RuvC is a Holliday junction resolvase that cleaves the helical strands at a symmetric sequence, leading to the production of two recombinant molecules. We have determined the position of the cleavage site relative to the crossover point by the use of symmetric immobile junctions; these are DNA molecules containing two crossover points, one held immobile by sequence asymmetry and the second a symmetric sequence, but held immobile by torsional coupling to the first junction. We have built five symmetric immobile junctions, in which the tetranucleotide recognition site is moved stepwise relative to the branch point. We have used kinetic analysis of catalysis, gel retardation, and hydroxyl radical hypersensitivity to analyze this system. We conclude that the internucleotide linkage one position 3' to the crossover point is the favored site of cleavage.


Analysis of the phenotypic distribution of HLA class I and class II in atopic and non-atopic asthma patients.
In several studies the HLA system has been implicated in the development of asthma, but the importance of the associations between HLA genes and asthma remains unclear. The aim of this study was to determine the HLA class I and II phenotypic frequencies in a population of asthmatics, and to analyse the relationship between these phenotypes and any type of asthma. We typed HLA class I and II antigens in a series of 189 asthmatic individuals (102 atopic and 87 non-atopic), and in a control population of 150 unrelated healthy Caucasoid donors. When the HLA phenotypic frequencies were compared, no statistical differences were found. Therefore, no definitive HLA association could be established with atopic or non-atopic asthma in the studied population. Abbreviations AA, atopic asthma; FEV1, forced expiratory volume in 1 s; NAA, non-atopic asthma; PCR, polymerase chain reaction; SSOP, sequence-specific oligonucleotide probes; SPT, skin prick test.


The shape of motion perception: global pooling of transformational apparent motion.
Transformational apparent motion (TAM) is a visual phenomenon highlighting the utility of form information in motion processing. In TAM, smooth apparent motion is perceived when shapes in certain spatiotemporal arrangements change. It has been argued that TAM relies on a separate high-level form-motion system. Few studies have, however, systematically examined how TAM relates to conventional low-level motion-energy systems. To this end, we report a series of experiments showing that, like conventional motion stimuli, multiple TAM signals can combine into a global motion percept. We show that, contrary to previous claims, TAM does not require selective attention, and instead, multiple TAM signals can be simultaneously combined with coherence thresholds reflecting integration across the entire stimulus area. This system is relatively weak, less tolerant to noise, and easily overridden when motion energy cues are sufficiently strong. We conclude that TAM arises from high-level form-motion information that enters the motion system by, at least, the stage of global motion pooling.


A cardiac rehabilitation program to improve psychosocial outcomes of women with heart disease.
Heart disease in women is characterised by greater disability and a higher rate of morbidity and early death after an acute coronary event compared with men. Women also have lower participation rates than men in cardiac rehabilitation. This study sought to describe development of a nurse-directed cardiac rehabilitation program tailored to the needs of women following an acute cardiac event to address their psychological and social needs. The Heart Awareness for Women program (HAFW) commenced in 2003 with phase I involving development of program elements and seeking validation through consumers and clinical experts. The program was then trialed in an 8-week program in a convenience sample of 6 women. Phase II applied the revised program using action research principles focusing on enabling clinical staff to implement the ongoing program. A total of 54 women participated in this phase, 48 of whom completed baseline questionnaires. A mixed-method evaluation, using questionnaires, interviews, and observation, assessed the impact of the intervention on psychological and social aspects of women's recovery following an acute coronary event. Women welcomed the opportunity to discuss their individual stories, fears, and challenges and to derive support from contact with other women. Via health professional facilitation, women were able to develop strategies collectively to address risk factor modification and achieve optimal cardiovascular health. No statistically significant changes in depression, anxiety, stress, cardiac control, role integration, or perceived social support were found; however, descriptive and qualitative findings revealed decreases in anxiety and an increased sense of social support. On the basis of this study, a cardiac rehabilitation program tailored to the needs of women appears to be feasible and acceptable. The efficacy of this intervention to improve health-related outcomes needs to be tested in a randomized, controlled trial.


Scheme for achieving a continuous-wave laser operation at 1178 nm.
We report for the first time, to the best of our knowledge, a new scheme for generating the important 1178 nm laser. Based on a high-power 1018 nm fiber laser as the pump source and chemical vapor deposition diamond as the Raman gain medium, the Raman laser was capable of generating 34.6 W output power centered at 1178.02 nm. As far as we know, 34.6 W is the highest output power of a 1178 nm laser obtained within a crystalline Raman gain medium. The experimental results show the superiority of our scheme in obtaining 1178 nm laser generation.


Bilateral deficit in maximal force production.
The bilateral deficit phenomenon, characterized by a reduction in the amount of force from a single limb during maximal bilateral actions, has been shown in various movement tasks, contraction types and different populations. However, bilateral deficit appears to be an inconsistent phenomenon, with high variability in magnitude and existence, and seems to be plastic, as bilateral facilitation has also been shown to occur. Furthermore, many mechanisms underlying this phenomenon have been proposed over the years, but still remain largely unknown. The purpose of this review was to clarify and critically discuss some of the important issues relevant to bilateral deficit. The main findings of this review were: (1) bilateral deficit does not seem to be contraction-type dependent; however, it is more consistent in dynamic compared to isometric contractions; (2) postural stabilization requirements and/or ability to use counterbalances during unilateral actions seem to influence the expression of bilateral deficit to a great extent; strong evidence has been provided for higher-order neural inhibition as a possible mechanism, but requires further exploration using a lower limb model; biomechanical mechanisms, such as differences in shortening velocity between contraction modes and displacement of the force-velocity curve, seem to underlie bilateral deficit in ballistic and explosive contractions; (3) task familiarity has a large influence on bilateral deficit and thus adequate testing specificity is warranted in training/cross-sectional experiments; (4) the literature investigating the relationship between bilateral deficit and athletic performance and injury remains scarce; hence, further research in this area is required.


Identification of common cricket (Acheta domesticus) proteins, extracted by acid and alkaline methods.
Edible insects currently represent an interesting alternative protein source to the animal ones. The objective of the present wok is to characterize proteins isolated from common cricket (Acheta domesticus). Powder samples of this insect-based flour were obtained using two extraction methods, i.e. acid and alkaline. Subsequently, the proteins isolated have been characterized. The fractionation of proteins in the flour of Acheta domesticus by acid or alkaline-based methods, gave rise to isolates with up to 71.6% in protein content. Extraction in an alkaline medium of insoluble proteins (pellet) resulted in the best performance on protein recovery. These isolates present a wide variety of peptides and proteins, having identified the following ones in the pellet fraction obtained with the acid method: myosin heavy-chain isoforms C, E and Miosin heavy chain (Mhc); tropomyosin; troponin; α and β actin, and some enzymes such as the β subunit ATP synthetase. The characterization results provide information which will enable us to predict the possible physicochemical (gel formation, solubility, water retention capacity, etc.) changes that could take place in the cricket protein during processing in the food and feed industry.


A novel strategy for promoting homoplasmic plastid transformant production using the barnase-barstar system.
Plastid transformants form biofactories that are able to produce extra proteins in plastids when they are in a homoplasmic state. To date, plastid transformation has been reported in about twenty plant species; however, the production of homoplasmic plastid transformants is not always successful or easy. Heteroplasmic plants that contain wild-type plastids produce fewer target proteins and do not always successfully transfer transgenes to progeny. In order to promote the generation of homoplasmic plants, we developed a novel system using barnase-barster to eliminate wild-type plastids from heteroplasmic cells systematically. In this system, a chemically inducible cytotoxic barnase under a plastid transit signal was introduced into nuclear DNA and barster, which inhibits barnase, was integrated into plastid DNA with the primary selection markers aminoglycoside 3'-adenylyltransferase (aadA) and green fluorescence protein (GFP) gene. As expected, the expression of the plastid barnase was lethal to cells as seen in leaf segments, but barster expression in plastids rescued them. We then investigated the regeneration frequency of homoplasmic shoots from heteroplasmic leaf segments with or without barnase expression. The regeneration frequency of homoplasmic-like shoots expressing barnase-barster system was higher than that of shoots not expressing this. We expect that the application of this novel strategy for transformation of plastids will be supportive to generate homoplasmic plastid transformants in other plant species.


Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity.
We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen TRP1. These two lines of nominally identical specificity differ greatly in their affinity for antigen (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low) mice show cytolytic activity in 3D tissue culture and in vivo, and slow the progression of subcutaneous B16 melanoma. Although naïve TRP1(low) CD8 T cells do not affect tumor growth, upon activation these cells function indistinguishably from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse survival. The anti-tumor effect of both TRP1(high) and TRP1(low) CD8 T cells is enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs, likely due to T cell exhaustion. The TRP1 TN mice are an excellent model for examining the functional attributes of T cells conferred by TCR affinity, and they may serve as a platform for screening immunomodulatory cancer therapies.


Effects of acetylcysteine and migration of resident eosinophils in an in vitro model of mucosal injury and restitution in equine right dorsal colon.
To evaluate the in vitro protective effects of acetylcysteine and response of resident mucosal eosinophils in oxidant-induced injury to tissues of right dorsal colon of horses. 9 adult horses. Gastrointestinal mucosa was damaged in vitro with 3 mM hypochlorous acid (HOCl), with and without prior exposure to 6mM acetylcysteine. Control tissues were not exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240 minutes. Tissue permeability to radiolabeled mannitol was also used to assess mucosal barrier integrity. Tissues were examined by light microscopy before and after HOCl exposure and during and after incubation. Exposure to HOCl caused tissue damage and decreased tissue resistance. Restitution did occur during the incubation period. Eosinophils were located near the muscularis mucosae in freshly harvested tissues and migrated towards the luminal surface in response to HOCl-induced injury. Compared with tissues treated with HOCl without acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue damage, changes in resistance, and histologically detectable eosinophil migration. The permeability to mannitol increased to the same extent in tissues treated with HOCl alone or with acetylcysteine and HOCl. Eosinophils migrated toward the mucosal surface in equine colon in response to oxidant-induced damage in vitro. This novel finding could be relevant to inflammation in equine colon and a pathophysiologic feature of many colonic diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and may be useful as a treatment option for various gastrointestinal tract disorders in horses.


Heat conduction from the exceedingly hot fiber tip contributes to the endovenous laser ablation of varicose veins.
Lower-extremity venous insufficiency is a common condition, associated with considerable health care costs. Endovenous laser ablation is increasingly used as therapy, but its mechanism of action is insufficiently understood. Here, direct absorption of the laser light, collapsing steam bubbles and direct fiber-wall contact have all been mentioned as contributing mechanisms. Because fiber tips have reported temperatures of 800-1,300 degrees C during endovenous laser ablation, we sought to assess whether heat conduction from the hot tip could cause irreversible thermal injury to the venous wall. We approximated the hot fiber tip as a sphere with diameter equal to the fiber diameter, having a steady state temperature of 800 degrees C or 1,000 degrees C. We computed venous wall temperatures due to heat conduction from this hot sphere, varying the pullback velocity of the fiber and the diameter of the vein. Venous wall temperatures corresponding to irreversible injury resulted for a 3 mm diameter vein and pullback velocities <3 mm/s but not for 5 mm and > or =1 mm/s. The highest wall temperature corresponded to the position on the wall closest to the fiber tip, hence it moves longitudinally in parallel with the moving fiber tip. We concluded that heat conduction from the hot fiber tip is a contributing mechanism in endovenous laser ablation.


[Deaths from noncommunicable diseases attributable to behavioral risk factors in Italy and Italian regions, 2016].
to estimate the number of deaths from noncommunicable chronic diseases (NCD) attributable to behavioural risk factors (tobacco smoking, unhealthy nutrition, physical inactivity, overweight, and excessive alcohol use) in 2016 for Italy and for the Italian regions. descriptive study. mortality data were obtained by the Italian National Institute of Statistics. Causes of deaths from NCD associated with the five RFs were selected. Italian attributable fractions were obtained by the 2016 estimates of the Global Burden of Disease Study and applied to the mortality data. Regional prevalence of risk factors was obtained by the national surveillance system PASSI for the years 2013-2016. absolute number of attributable deaths, joint attributable fraction, proportion of total deaths attributable to RFs (MAprop). about 191,000 out of 614,307 deaths occurred in Italy in 2016 were attributable to combined RFs (about 37% in males; 26% in women). Joint MAprop was between 33% in men (24% in women) from Val d'Aosta and 40% in men (31% in women) from Campania. In Italy, 17% and 6% of the total amount of deaths were attributable to smoking in men and women, respectively; 6% and 3% to alcohol abuse; 7% and 8% to overweight; 13% and 12% to dietary RFs, and 2% and 3% to low physical activity. The higher proportion of attributable deaths by age-group was recorded in people aged 40-59 years (43% in men; 28% in women). Regional differences in attributable deaths are confirmed by regional RF prevalence recorded by the PASSI surveillance system for the years 2013-2016. these are the first estimates of the number of deaths due to NCDs attributable to behavioural RFs estimated for each region and for Italy as a whole. Effective primary prevention policies should be reinforced, since these RFs are potentially modifiable.


The Role H-Bonding and Supramolecular Structures in Homogeneous and Enzymatic Catalysis.
The article analyzes the role of hydrogen bonds and supramolecular structures in enzyme catalysis and model systems. Hydrogen bonds play a crucial role in many enzymatic reactions. However, scientists have only recently attempted to harness the power of hydrogen bonds in homogeneous catalytic systems. One of the newest directions is associated with attempts to control the properties of catalysts by influencing the "second coordination sphere" of metal complexes. The role H-bonding, and the building of stable supramolecular nanostructures due to intermolecular H-bonds, based on catalytic active heteroligand iron (Fe) or nickel (Ni) complexes formed during hydrocarbon oxidations were assessed via the AFM (Atomic-force microscopy) method, which was proposed and applied by authors of this manuscript. Th is article also discusses the roles of hydrogen bonds and supramolecular structures in oxidation reactions catalyzed by heteroligand Ni and Fe complexes, which are not only effective homogeneous catalysts but also structural and functional models of Oxygenases.


Surface activation leukocyte markers and humoral factors in cord blood of newborns at risk of early infection.
Due to immaturity of both specific and non-specific immune mechanisms, neonates are at risk of serious infections. The risk group definition is vague, clinical signs are non-specific and common laboratory markers are not as useful as in later ages, especially due to delayed reactions. In an attempt to find early, sensitive and specific markers, we assessed a defined set of surface leukocyte markers and humoral factors in cord blood. Several differences were noted--children in the risk group had a higher proportion of CD19+/23+, CD16+/64+, CD45RO cells and higher levels of IL-6. We find it promising that already at birth there are notable signs of reaction to infection and that a follow-up of a set of infectious markers could be useful to identify the children in need of antibiotic treatment and for diminishing unnecessary treatment.


[Morphometric analysis of the stromal cells in breast tumors].
Cell reaction of the stroma of breast tumors is an indicator of the activity of the immunocompetent system in oncological patients. In this work, the cellular response of the tumor stroma was assessed histologically and morphometrically, including calculation of the number of cells-lymphocytes and plasmocytes in the centre of tumor and distally. The intensity of infiltration was estimated quantitatively depending on the type of tumor, patient's age, the presence or absence of regional metastases; moreover the effect of preoperative telegamma-therapy on the tumor stroma was taken into account. The data obtained indicated that the reaction of immunocompetent stromal cells depend on the type of tumor: it is maximum in the stroma of solid tumors and is less pronounced in the stroma of adenocarcinoma and scirrh, and it is minimum in mastopathy. Preoperative irradiation produced no significant reduction in the number of stromal cells. Patient's age rendered no effect on the intensity of cell reactions. The presence of tumor metastases in regional lymph nodes contributed to a fall in the number of stromal cells of solid tumors.


Adrenergic regulation of lipolysis in a patient with lipoatrophy of the upper body.
A patient with lipoatrophy of the upper body had laboratory evidence of increased activity of the adrenergic nervous system. Because the adrenergic nervous system is important in the regulation of lipolysis, studies were performed to determine whether lipolysis of the upper body was ongoing in this patient and whether pharmacologic reduction of activity of the adrenergic nervous system would affect lipolysis of adipose tissue. Release of free fatty acids from systemic and forearm adipose tissue was measured before and after the administration of guanfacine hydrochloride. Forearm adipose tissue, although decreased in quantity, was found to release normal amounts of free fatty acids. Systemic and forearm release of free fatty acids decreased after 3 days of treatment with guanfacine. These results suggest that lipoatrophy of the upper body in some patients may be mediated through dysfunction of the adrenergic nervous system. These findings also emphasize the potential for heterogeneous responses of adipose tissue to hormonal regulatory factors.


Closed suctioning system: critical analysis for its use.
To determine the efficacy and effectiveness of the closed suctioning system. Literature review articles were accessed from the following databases: PubMed, EMBASE, CINAHL, and Cochrane Library. The literature review criteria included: all publication styles except meta-analysis, participants that were > or =18 years, written in English, and published between 1973 and 2008. This literature review revealed that the efficacy and effectiveness of the closed suctioning system remains to be demonstrated. The device manufacturers' studies focused on cost reduction, cross-contamination, and preservation of the oxygen saturation of patients during endotracheal suctioning; however, the clinical studies focused on the use of closed suctioning systems to prevent ventilator-associated pneumonia. The reviewed studies had small sample sizes with heterogeneous demographics and non-randomized controls. Recent studies suggest that closed suctioning systems are no better than open suctioning systems in terms of mortality, morbidity, or the cost-benefit ratio. A few studies did indicate that the closed suctioning system might reduce the loss of lung volume and oxygen desaturation. The studies reviewed in this article suggest that the evidence on the efficacy and effectiveness of closed suctioning systems is inconclusive. Only limited populations will benefit clinically from the use of this device. There is a need for further studies with randomized controlled trials to explore the use of closed suction systems and to update current clinical practise guidelines.


Panic-like attack induced by microinfusion into the locus coeruleus of antagonists and inverse agonists at GABAA-receptors in rodents.
The microinfusion of drugs inhibiting GABA-ergic transmission into the locus coeruleus (LC) of rats and mice produced a dramatic pattern of behavioural stimulation accompanied by marked electrocortical (ECoG) desynchronization. In rats, unilateral microinfusion into the LC of bicuculline (0.5-4 pmol) produced dose-dependent behavioural stimulation culminating in a panic-like attack, ECoG desynchronization and marked changes in ECoG spectrum power. These effects were prevented by a pretreatment into the same site with muscimol. Similarly, in mice, the microinfusion of ethyl-beta-carboline-3-carboxylate (beta-CCE, 4.1 nmol) into the LC of C57BL/6 mice produced an intense state of behavioural stimulation accompanied by intense stereotyped movements and increased excitability to external stimuli; these effects were prevented by prior microinfusion of diazepam or flumazenil into the same site. In conclusion, the present experiments show that in rodents drug manipulations leading to a decrease in the activity of GABA-benzodiazepine receptor complex in the LC are responsible for the occurrence of panic-like attacks.


Clock face drawing in children with attention-deficit/hyperactivity disorder.
The clock drawing test has been found to be sensitive to visual-spatial perception, graphomotor skills, verbal reasoning, and executive functioning in adult patient populations, as well as frontal lobe maturation in normal children. Our study is among the first to assess the use of clock drawing as a neuropsychological measure in the pediatric population. Participants included 41 children with attention-deficit/hyperactivity disorder (ADHD) and 41 normal controls, ages 6-12 years, matched for age, gender, and handedness. Conceptualization of time and construction of the clock face were assessed separately using a scoring system normed on school-age children in an earlier study. Children with Predominantly Inattentive Type were found to perform similarly to those with Combined Type of ADHD. However, children with ADHD, regardless of subtype, performed significantly poorer than controls. Qualitative analysis of performance revealed errors that were subsequent to poor planning during task execution, consistent with executive dysfunction commonly present in children with ADHD. Further, multiple regression analysis demonstrated that a neuropsychological measure of executive functioning was predictive of clock construction performance in children with ADHD. Constructional praxis and receptive vocabulary also were predictive of clock construction ability. Implications of these findings are discussed.


Antibiofilm activity of marine microbial natural products: potential peptide- and polyketide-derived molecules from marine microbes toward targeting biofilm-forming pathogens.
Controlling and treating biofilm-related infections is challenging because of the widespread presence of multidrug-resistant microbes. Biofilm, a naturally occurring matrix of microbial aggregates, has developed intricate and diverse resistance mechanisms against many currently used antibiotics. This poses a significant problem, especially for human health, including clinically chronic infectious diseases. Thus, there is an urgent need to search for and develop new and more effective antibiotics. As the marine environment is recognized as a promising reservoir of new biologically active molecules with potential pharmacological properties, marine natural products, particularly those of microbial origin, have emerged as a promising source of antibiofilm agents. Marine microbes represent an untapped source of secondary metabolites with antimicrobial activity. Furthermore, marine natural products, owing to their self-defense mechanisms and adaptation to harsh conditions, encompass a wide range of chemical compounds, including peptides and polyketides, which are primarily found in microbes. These molecules can be exploited to provide novel and unique structures for developing alternative antibiotics as effective antibiofilm agents. This review focuses on the possible antibiofilm mechanism of these marine microbial molecules against biofilm-forming pathogens. It provides an overview of biofilm development, its recalcitrant mode of action, strategies for the development of antibiofilm agents, and their assessments. The review also revisits some selected peptides and polyketides from marine microbes reported between 2016 and 2023, highlighting their moderate and considerable antibiofilm activities. Moreover, their antibiofilm mechanisms, such as adhesion modulation/inhibition targeting biofilm-forming pathogens, quorum sensing intervention and inhibition, and extracellular polymeric substance disruption, are highlighted herein.