Responses to Spatial Contrast in the Mouse Suprachiasmatic Nuclei.
A direct retinal projection targets the suprachiasmatic nucleus (SCN) (an important hypothalamic control center). The accepted function of this projection is to convey information about ambient light (irradiance) to synchronize the SCN's endogenous circadian clock with local time and drive the diurnal variations in physiology and behavior [1-4]. Here, we report that it also renders the SCN responsive to visual images. We map spatial receptive fields (RFs) for SCN neurons and find that only a minority are excited (or inhibited) by light from across the scene as expected for irradiance detectors. The most commonly encountered units have RFs with small excitatory centers, combined with very extensive inhibitory surrounds that reduce their sensitivity to global changes in light in favor of responses to spatial patterns. Other units have larger excitatory RF centers, but these always cover a coherent region of visual space, implying visuotopic order at the single-unit level. Approximately 75% of light-responsive SCN units modulate their firing according to simple spatial patterns (drifting or inverting gratings) without changes in irradiance. The time-averaged firing rate of the SCN is modestly increased under these conditions, but including spatial contrast did not significantly alter the circadian phase resetting efficiency of light. Our data indicate that the SCN contains information about irradiance and spatial patterns. This newly appreciated sensory capacity provides a mechanism by which behavioral and physiological systems downstream of the SCN could respond to visual images [5].


Many-Body Dynamical Localization in a Kicked Lieb-Liniger Gas.
The kicked rotor system is a textbook example of how classical and quantum dynamics can drastically differ. The energy of a classical particle confined to a ring and kicked periodically will increase linearly in time whereas in the quantum version the energy saturates after a finite number of kicks. The quantum system undergoes Anderson localization in angular-momentum space. Conventional wisdom says that in a many-particle system with short-range interactions the localization will be destroyed due to the coupling of widely separated momentum states. Here we provide evidence that for an interacting one-dimensional Bose gas, the Lieb-Liniger model, the dynamical localization can persist at least for an unexpectedly long time.


Medicine in transition--emerging ethical issues in the global village.
Two major shifts in medicine are radically altering the medical profession worldwide: the shift from a professional to a business ethic, and the shift from a hands-one therapeutic approach to one which is technology-dependent. These paradigm shifts affect the traditional medical ethics and principles of professional autonomy, beneficence (doing what is best for patients) and justice. Constructive responses that will help to protect these important ethical ideals include reflection on professional values, involvement in health policy and nurture of the profession's young and "idealistic" members.


Kinetics of tyramine transport and permeation across chromaffin-vesicle membranes.
Tyramine permeates chromaffin-granule membranes via a reserpine-insensitive mechanism. The rate is unsaturable and increases with pH, indicating permeation of the unprotonated form of the amine. Reserpine-insensitive dopamine uptake is at least 10 times slower, consistent with dopamine's lesser lipophilicity. Dopamine is transported into chromaffin-granule membrane vesicles via a saturable, reserpine-sensitive, proton-linked mechanism. Tyramine inhibits dopamine transport with a Ki of 5-10 microM. Tyramine is not accumulated nearly as well as dopamine because inward transport is opposed by outward permeation. Nevertheless, the velocity of reserpine-sensitive tyramine transport can be deduced from the steady-state level of tyramine accumulation and the rate of permeation. Vmax for tyramine transport is about one-third of the value for dopamine transport. Therefore, two aromatic hydroxyls are not needed for monoamine transport but are required for efficient accumulation and storage.


Factors limiting sulfolane biodegradation in contaminated subarctic aquifer substrate.
Sulfolane, a water-soluble organosulfur compound, is used industrially worldwide and is associated with one of the largest contaminated groundwater plumes in the state of Alaska. Despite being widely used, little is understood about the degradation of sulfolane in the environment, especially in cold regions. We conducted aerobic and anaerobic microcosm studies to assess the biological and abiotic sulfolane degradation potential of contaminated subarctic aquifer groundwater and sediment from Interior Alaska. We also investigated the impacts of nutrient limitations and hydrocarbon co-contamination on sulfolane degradation. We found that sulfolane underwent biodegradation aerobically but not anaerobically under nitrate, sulfate, or iron-reducing conditions. No abiotic degradation activity was detectable under either oxic or anoxic conditions. Nutrient addition stimulated sulfolane biodegradation in sediment slurries at high sulfolane concentrations (100 mg L-1), but not at low sulfolane concentrations (500 μg L-1), and nutrient amendments were necessary to stimulate sulfolane biodegradation in incubations containing groundwater only. Hydrocarbon co-contamination retarded aerobic sulfolane biodegradation rates by ~30%. Our study is the first to investigate the sulfolane biodegradation potential of subarctic aquifer substrate and identifies several important factors limiting biodegradation rates. We concluded that oxygen is an important factor limiting natural attenuation of this sulfolane plume, and that nutrient amendments are unlikely to accelerate biodegradation within in the plume, although they may biostimulate degradation in ex situ groundwater treatment applications. Future work should be directed at elucidating the identity of indigenous sulfolane-degrading microorganisms and determining their distribution and potential activity in the environment.


Association of prescription drug monitoring program laws with bedridden and missed work days.
To examine the relationship between optional and must-use prescription drug monitoring programs (PDMPs) and markers of disability. Nationwide data from the National Health Interview Survey for 2006-2015. Generalized difference-in-difference models with state-specific time trends were used to assess the relationship between PDMPs and two outcomes: missed days of work and bedridden days. All respondents above the age of 18 years with complete data on key measures were included. A subpopulation of respondents who had a recent surgery or injury was identified. We found an increase of 3.3 and 5.9 bedridden days associated with optional and must-use PDMPs, respectively, for respondents reporting a recent injury or surgery (p-values <0.05; unadjusted population average 12.2 bedridden days). Increases in days of missed work were not statistically significant. Implementation of PDMPs was associated with negative unintended consequences in the injury/surgery subpopulation. The association between bedridden days and PDMPs suggests a gap between clinical trials showing equivalence of opioids and nonopioids for pain treatment and real-world results. As increasingly tighter opioid restrictions proliferate, evidence-based strategies to address pain without opioids in the acute pain population likely need to be more widely disseminated.


Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids.
Microbial nucleic acids are major signatures of invading pathogens, and their recognition by various host pattern recognition receptors (PRRs) represents the first step toward an efficient innate immune response to clear the pathogens. The nucleic acid-sensing PRRs are localized at the plasma membrane, the cytosol, and/or various cellular organelles. Sensing of nucleic acids and signaling by PRRs involve recruitment of distinct signaling components, and PRRs are intensively regulated by cellular organelle trafficking. PRR-mediated innate immune responses are also heavily regulated by posttranslational modifications, including phosphorylation, polyubiquitination, sumoylation, and glutamylation. In this review, we focus on our current understanding of recognition of microbial nucleic acid by PRRs, particularly on their regulation by organelle trafficking and posttranslational modifications. We also discuss how sensing of self nucleic acids and dysregulation of PRR-mediated signaling lead to serious human diseases.


A Combined Technology to Protect the Anatomic Integrity of Distal Urethral Sphincter Complex in Radical Prostatectomy Improves Early Urinary Continence Recovery Without Sacrifice of Oncological Outcomes.
Our primary aim was to present a combined technique to protect the anatomic integrity of distal urethral sphincter complex (DUSC) during minimally invasive radical prostatectomy (RP) and discuss its impact on urinary continence (UC) recovery. The second aim was to define the learning curve of the combined technique. We conducted a non-randomized retrospective study. There were 314 consecutive patients who received RP by the same urologist surgeon with more than 2,000 prior cases in Shanghai Ruijin Hospital between March 2017 and April 2020. Included in this study were 263 patients with clinical T1-T2 stage. We modified a combined RP (Comb-RP) technique including endopelvic fascia no-incising technique, dorsal venous complex (DVC) no-ligation technique, intrafascial dissection technique, and anterior reconstruction technique so as to preserve the anatomic integrity of DUSC. The patients were assigned to two groups: a Comb-RP group and a conventional RP (Conv-RP) group. Continence rates were assessed every 3 months after removal of the catheter. UC was defined as 0 pad per day. Peri-operative variables of the patient including operation time, estimated blood lost (EBL), positive surgical margin (PSM), and postoperative complications were also collected. Scatter-graphs of learning curves were drawn using locally weighted scatterplot smoothing (LOWESS). RP was accomplished smoothly in all 263 cases. The pad-free UC rates in Conv-RP group and Comb-RP group were 17.3 vs. 27.8% (P = 0.048) at the removal of the catheter, 35.8 vs. 50.0% (P = 0.027) at 1 month, 60.5 vs. 76.1% (P = 0.012) at 3 months, 87.7 vs. 96.5% (P = 0.022) at 6 months, and 94.7 vs. 97.7% (P = 0.343) at 12 months. Kaplan-Meier analysis showed significantly higher and faster continence recovery in the Comb-RP group (mean 4.9 vs. 2.6 months, Log Rank P = 0.001). There was no significant difference in PSM rate between the Comb-RP and Conv-RP group (31.1 vs. 31.2%, P =0.986). The learning curves of peri-operative variables, oncological and functional outcomes achieved the lowest point or plateau at the 20th-60th cases. The anatomic integrity and intact pelvic floor interplay of DUSC is important for its function. Our combined technique was a safe and feasible technique for improving early UC in RP with no significantly increased PSM rate and no significant difference in long-term UC.


Modelling the hydrodynamic resistance of bordered pits.
Previous studies of the hydrodynamics of plant stems have shown that resistance to flow through bordered pits on the side walls of tracheids makes up a significant proportion of their total resistance, and that this proportion increases with tracheid diameter. This suggests a possible reason why tracheids with a diameter above around 100 microm have failed to evolve. This possibility has been investigated by obtaining an estimate for the resistance of a single pit, and incorporating it into analytical models of tracheid resistance and wood resistivity. The hydrodynamic resistance of the bordered pits of Tsuga canadensis was investigated using large-scale physical models. The importance of individual components of the pit were investigated by comparing the resistance of models with different pore sizes in their pit membrane, and with or without the torus and border. The estimate for the resistance of a real bordered pit was 1.70x10(15) Pa s m(-3). Resistance of pits varied with morphology as might be predicted; the resistance was inversely proportional to the pore size to the power of 0.715; removing the torus reduced resistance by 28%, while removal of the torus and border together reduced it by 72%. It was estimated that in a 'typical tracheid' pit resistance should account for 29% of the total. Incorporating the results into the model for the resistivity of wood showed that resistivity should fall as tracheid diameter increases. However, to minimize resistance wider tracheids would also need to be proportionally much longer. It is suggested that the diameter of tracheids in conifers is limited by upper limits to cell length or cell volume. This limitation is avoided by angiosperms because they can digest away the ends of their cells to produce long, wide vessels composed of many short cells.


Antibiotic usage and stewardship in patients with COVID-19: too much antibiotic in uncharted waters?
Antimicrobial usage and stewardship programmes during COVID-19 have been poorly studied. Prescribing practice varies despite national guidelines, and there is concern that stewardship principles have suffered. To analyse antibiotic prescriptions during the COVID-19 pandemic at a teaching hospital and to propose improved approaches to stewardship. We reviewed COVID-19 admissions to medical wards and intensive care units (ICUs) in a London teaching hospital to assess initial antibiotic usage and evidence of bacterial co-infection, and to determine if our current antibiotic guidelines were adhered to. Data from 130 inpatients (76% medical and 24% ICU) were obtained. On admission, 90% were treated with antibiotics. No microbiological samples taken on admission provided definitive evidence of respiratory co-infection. In 13% of cases, antibiotics were escalated, usually without supporting clinical, radiological or laboratory evidence. In 16% of cases, antibiotics were stopped or de-escalated within 72 h. Blood results and chest radiographs were characteristic of COVID-19 in 20% of ward patients and 42% of ICU patients. Overall mortality was 25% at 14 days - similar to rates described for the UK as a whole. The majority of patients received antibiotics despite limited evidence of co-infection. Most patients received narrower spectrum antibiotics than recommended by NICE. As understanding of the natural history of COVID-19 infections progresses, stewardship programmes will need to evolve; however, at this point, we feel that a more restrictive antibiotic prescribing approach is warranted. We propose strategies for effective stewardship and estimate the effect this may have on antibiotic consumption.


Differences among Endophytic Fungal Communities Isolated from the Roots of Cephalanthera longibracteata Collected from Different Sites in Korea.
Orchidaceous plants have symbiotic relationships with endophytic fungi, including mycorrhizal fungi, which play important roles in the seed germination and growth of the host plants. In this study, endophytic fungal communities isolated from the roots of Cephalanthera longibracteata collected from three different sites in Korea were analyzed, and it was determined whether fungal communities were preferentially correlated with the sites. The fungal isolates were identified by sequence analysis of the internal transcribed spacer regions of rDNA. In total, 30 species of endophytic fungi, including two species of mycorrhizal fungi belonging to the genus Tulasnella, were identified. Leptodontidium orchidicola showed the highest frequency and was isolated from all root samples. Species diversity and richness were not significantly different among sites. However, the community structure of the endophytic fungi significantly differed among sites, suggesting that the site characteristics affected the community composition of the endophytic fungi colonizing the roots of C. longibracteata. Our findings will aid in developing methods involving the use of symbiotic fungi for orchid conservation and restoration in native habitats.


A meta-analysis of randomized controlled trials evaluating the efficacy of epinephrine for the treatment of acute viral bronchiolitis.
Controversy exists surrounding the use of bronchodilators for bronchiolitis. Epinephrine hydrochloride is being used with increasing frequency in this group; however, its efficacy has not been systematically reviewed. To systematically review randomized controlled trials comparing inhaled or systemic epinephrine vs placebo or other bronchodilators. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, primary authors, and reference lists. Studies were included if they (1) were randomized, controlled trials; (2) involved children 2 years or younger with bronchiolitis; and (3) presented quantitative outcomes. Two reviewers independently extracted data and assessed study quality. We included 14 studies (7 inpatient, 6 outpatient, and 1 patient status unknown). Thirteen of forty-five comparisons were significant. Among outpatients, results favored epinephrine compared with placebo for clinical score at 60 minutes (standardized mean difference [SMD], -0.81; 95% confidence interval [CI], -1.56 to -0.07), oxygen saturation at 30 minutes (weighted mean difference [WMD], 2.79; 95% CI, 1.50-4.08), respiratory rate at 30 minutes (WMD, -4.54; 95% CI, -8.89 to -0.19), and improvement (odds ratio, 25.06; 95% CI, 4.95-126.91); among inpatients, for clinical score at 60 minutes (SMD, -0.52; 95% CI, -1.00 to -0.03). Among outpatients, results favored epinephrine compared with albuterol sulfate (salbutamol) for oxygen saturation at 60 minutes (WMD, 1.91; 95% CI, 0.38-3.44), heart rate at 90 minutes (WMD, -14.00; 95% CI, -22.95 to -5.05), respiratory rate at 60 minutes (WMD, -7.76; 95% CI, -11.35 to -4.17), and improvement (odds ratio, 4.51; 95% CI, 1.93-10.53); among inpatients, respiratory rate at 30 minutes (WMD, -5.12; 95% CI, -6.83 to -3.41). Epinephrine may be favorable compared with placebo and albuterol for short-term benefits among outpatients. There is insufficient evidence to support the use of epinephrine among inpatients. Large, multicentered trials are required before routine use among outpatients can be strongly recommended.


[Education and dental practice offer possibilities to exchange competences].
The 3 dental schools in the Netherlands have the same goals for their graduates, in terms of knowledge and skills, but the contents of the curricula are different. The curricula are all based on the pillars of scientific education, medical education, dental education, and professionalism. Within this construction a student is trained as the manager of an oral health team. At graduation, the new generation of dentists have many (new) competences and relatively limited clinical experience and need support in acquiring clinical experience. Moreover, dentists who have recently graduated may be faced with methods and materials to which they were not introduced in their educational programme. A dentist with considerable clinical experience can test the newly acquired competences of the new generation ofdentists, with the benefit of a critical eye, against (routine) daily practices.


Ozone treatment to reduce deoxynivalenol (DON) and zearalenone (ZEN) contamination in wheat bran and its impact on nutritional quality.
Wheat bran is an important source for human and animal feed. Its nutritional aspects include a high content of fibre and minerals, as well as phenolic compounds that help prevent chronic diseases. However, wheat can be susceptible to contamination by fungus, which can produce mycotoxins such as deoxynivalenol (DON) and zearalenone (ZEN), causing adverse health effects. Therefore, methods should be developed to reduce possible contamination. Ozone can be used for this purpose as it is considered safe and environmental friendly. The aim of this study was to evaluate the reduction of DON and ZEN concentrations in wheat bran using the ozonation process as well as to evaluate the effect of ozonation on the nutritional quality of bran. Considering this, wheat bran naturally contaminated with both DON and ZEN was processed using ozone at different conditions. The nutritional quality of the bran was evaluated after processing considering the following aspects: the total phenolic content and the bran antioxidant capacity (by using both DPPH and ABTS radicals). The results showed that the degradation of ZEN was higher and faster than the degradation of DON, which could be explained by their molecular structures. The total phenolic content and antioxidant capacity of the bran were not affected by the ozonation process, which is preferable from a nutritional point of view. Therefore, ozonation was demonstrated to be a possible method for reducing mycotoxins in wheat bran, although more studies are needed in order to better understand and optimise processing and product quality.


A revision of the genus Eutetrapha Bates (Coleoptera: Cerambycidae: Lamiinae: Saperdini).
A revision of the genus Eutetrapha Bates, 1884 is presented. Four new species are described from China: E. parastigmosa Lin & Yang, sp. nov. from Hubei, Chongqing and Shaanxi; E. tianmushana Lin & Bi, sp. nov. from Zhejiang; E. shaanxiana Lin & Yang, sp. nov. from Shaanxi, Hubei, Gansu; and E. gui Lin & Yang, sp. nov. from Hainan. Eutetrapha virides Pu & Jin, 1991 is transferred to the genus Paraglenea, and Glenea ocelota Bates, 1873 is transferred from Eutetrapha to Saperda (Lopezcolonia). Eutetrapha laosensis is newly recorded from India and Myanmar, while Eutetrapha flavoguttata Pu & Jin, 1991 is newly recorded from Myanmar. India and Myanmar represent new country records for Eutetrapha. Twenty-one taxa are recognized in the genus Eutetrapha, and a key to the described species of the genus is presented.


In vitro study of color stability of polycrystalline and monocrystalline ceramic brackets.
The aim of this in vitro study was to analyze color stability of monocrystalline and polycrystalline ceramic brackets after immersion in dye solutions. Seven ceramic brackets of four commercial brands were tested: Two monocrystalline and two polycrystalline. The brackets were immersed in four dye solutions (coffee, red wine, Coke and black tea) and in artificial saliva for the following times: 24 hours, 7, 14 and 21 days, respectively. Color changes were measured by a spectrophotometer. Data were assessed by Multivariate Profile Analysis, Analysis of Variance (ANOVA) and Multiple Comparison Tests of means. There was a perceptible change of color in all ceramic brackets immersed in coffee (ΔE* Allure = 7.61, Inspire Ice = 6.09, Radiance = 6.69, Transcend = 7.44), black tea (ΔE* Allure = 6.24, Inspire Ice = 5.21, Radiance = 6.51, Transcend = 6.14) and red wine (ΔE* Allure = 6.49, Inspire Ice = 4.76, Radiance = 5.19, Transcend = 5.64), but no change was noticed in Coke and artificial saliva (ΔE < 3.7). Ceramic brackets undergo color change when exposed to solutions of coffee, black tea and red wine. However, the same crystalline structure, either monocrystalline or polycrystalline, do not follow the same or a similar pattern in color change, varying according to the bracket fabrication, which shows a lack of standardization in the manufacturing process. Coffee dye produced the most marked color changes after 21 days of immersion for most ceramic brackets evaluated.


Photodynamic therapy for cosmetic applications.
With the advent of short contact and pulsed light techniques, topical 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) has become a viable clinical modality. Intense pulsed light, the pulsed dye laser, and blue light-emitting lamps have become the most commonly used devices in inducing a cosmetic PDT effect. More recently, by combining the photothermal effects of pulsed light with the photochemical effects of PDT, an enhanced cosmetic effect has been demonstrated in a variety of dermatologic conditions. In addition, the use of shorter 5-ALA incubation times allows for improved patient tolerance during treatment and subsequently fewer adverse effects in the postoperative period. A review of the current literature on cosmetic uses of PDT as well as our personal techniques are discussed in detail.


Stimulating effect of Japanese herbal (kampo) medicine, hochuekkito on upper respiratory mucosal immune system.
Japanese herbal (Kampo) medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ-41) and Juzentaihoto (Shi-Quan-Da-Bu-Tang in Chinese, TJ-48) are well-known Kampo formulas used as tonic. Although these medicines have separately been applied to the patients clinically depending on their symptoms, the differences of the pharmacological activities for these medicines have not been fully understood. TJ-48 and TJ-41 were compared for their effects on antibody response in upper respiratory mucosal immune system in vivo. Oral administration of TJ-41 (100 mg kg(-1) per day) to early aged BALB/c mice, which were nasally sensitized with influenza hemagglutinin vaccine, significantly enhanced influenza virus-specific IgA and IgG antibody titers in nasal cavity and sera, respectively. However, oral administration of TJ-48 (100 mg kg(-1) per day) failed to show the enhancing activity. TJ-41 increased not only influenza virus-specific IgA antibody titer but also total IgA antibody titer in nasal cavity. The stimulating activity of TJ-41 disappeared after treatment with methotrexate. The present study strongly suggests that TJ-41 can stimulate the mucosal immune system of upper respiratory tract, and results in enhancement of antigen-specific antibody response in upper respiratory mucosal and systemic immune systems.


Overview of Host Defense Peptides and Their Applications for Plastic and Reconstructive Surgeons.
Host defense peptides are a family of endogenous short peptides that are found in all living beings and play a critical role in innate immunity against infection. A nonsystematic review of host defense peptides was conducted with specific interest in properties and applications relevant to plastic and reconstructive surgery. In addition to their direct antimicrobial actions against pathogens, including multidrug-resistant bacteria, they also demonstrate important functions in immunomodulation, tumor cell lysis, and tissue regeneration. These properties have made them a topic of clinical interest for plastic surgeons because of their potential applications as novel antibiotics, wound healing medications, and cancer therapies. The rising clinical interest has led to a robust body of literature describing host defense peptides in great depth and breadth. Numerous mechanisms have been observed to explain their diverse functions, which rely on specific structural characteristics. However, these peptides remain mostly experimental, with limited translation to clinical practice because of numerous failures to achieve acceptable results in human trials. Despite the broad ranging potential of these peptides for use in the field of plastic and reconstructive surgery, they are rarely discussed in the literature or at scientific meetings. In this review, the authors provide a summary of the background, structure, function, bacterial resistance, and clinical applications of host defense peptides with the goal of stimulating host defense peptide-based innovation within the field of plastic and reconstructive surgery.


An AP-1-like transcription factor, NAP-1, regulates expression of the glutathione S-transferase and NADH:flavin oxidoreductase genes in Neurospora crassa.
AP-1-like transcription factors play crucial roles in oxidative stress responses in yeast and filamentous fungi. The deletion of an AP-1-like transcription factor gene, nap-1, in Neurospora crassa slightly increased its sensitivity to oxidative stressors, including menadione. Microarray and quantitative real-time reverse transcriptase-PCR analyses were employed to identify menadione-inducible genes (migs) and the roles of NAP-1 in their regulation. N. crassa migs include three putative glutathione S-transferase genes and two NADH:flavin oxidoreductase genes, orthologs of OYE2 and OYE3, both of which play roles in menadione tolerance in Saccharomyces cerevisiae. Menadione induced nuclear localization of NAP-1, and oxidative upregulation of many of migs were NAP-1 dependent. Genes for a thioredoxin, a glutathione reductase, and a glutathione peroxidase were slightly upregulated by the chemical only in the wild-type strain, suggesting that NAP-1 is involved in their oxidative induction and probably dose not contribute to high-level constitutive expressions of such genes.


Surface chemistry and biological responses to synthetic octacalcium phosphate.
Octacalcium phosphate (OCP) has been suggested as a precursor of biological apatite in bone, dentin, and cementum because its existence explains the nonstoichiometry of apatite crystals in their compositions. Synthetic inorganic calcium phosphate compounds have been used clinically to fill bone defects, and sintered hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP), bone substitute materials, are known to be osteoconductive, with beta-TCP also being bioresorbable. Nonsintered synthetic OCP has been shown to enhance bone regeneration accompanied by conversion into hydrolyzed apatitic products in situ and biodegradation. The surfaces of the OCP implant and the converted apatite seem to be continuously exposed to biological constituents, such as extracellular matrices, inorganic biominerals, and cellular components. This article reviews the surface reaction of OCP implants and the biological responses, such as experimentally stimulated bone formation on synthetic OCP, the mechanism of OCP hydrolysis into apatite, and the adsorption of biomolecules onto OCP and the converted apatite, of particular interest in reactive bone induction with synthetic OCP implants.


Identification of quantitative trait loci for the fatty acid composition in Korean native chicken.
Fatty acid composition is one of the most important meat quality traits because it can contribute to functional, sensorial, and nutritional factors. In this study, quantitative trait locus (QTL) analyses for fatty acid composition traits were investigated in thigh and breast meat of Korean native chicken (KNC). In total, 18 fatty acid composition traits were investigated from each meat sample using 83 parents, and 595 F1 chicks of 20 week old. Genotype assessment was performed using 171 informative DNA markers on 26 autosomes. The KNC linkage map was constructed by CRI-MAP software, which calculated genetic distances, with map orders between markers. The half-sib and full-sib QTL analyses were performed using GridQTL and SOLAR programs, respectively. In total, 30 QTLs (12 in the thigh and 18 in the breast meat) were detected by the half-sib analysis and 7 QTLs (3 in the thigh and 4 in the breast meat) were identified by the full-sib analysis. With further verification of the QTL regions using additional markers and positional candidate gene studies, these results can provide valuable information for determining causative mutations affecting the fatty acid composition of KNC meat. Moreover, these findings may aid in the selection of birds with favorable fatty acid composition traits.


The diverse bioactivity of α-mangostin and its therapeutic implications.
α-Mangostin is a xanthone natural product isolated as a secondary metabolite from the mangosteen tree. It has attracted a great deal of attention due to its wide-ranging effects on certain biological activity, such as apoptosis, tumorigenesis, proliferation, metastasis, inflammation, oxidation, bacterial growth and metabolism. This review focuses on the key pathways directly affected by α-mangostin and how this varies between disease states. Insight is also provided, where investigated, into the key structural features of α-mangostin that produce these biological effects. The review then sheds light on the utility of α-mangostin as a investigational tool for certain diseases and demonstrate how future derivatives may increase selectivity and potency for specific disease states.


Risk factors for prostate cancer, and motivational and hindering aspects in conducting preventive practices.
Identify risk factors for Prostate Cancer (PC), preventive practices, and hindering and motivating factors for disease prevention among workers of a public university. A descriptive study, conducted with 92 workers who answered a self-administered questionnaire on the variables related to sociodemographic characteristics and clinical risk factors, sources of information about PC, practices related to prevention, and information on the hindering and motivating factors for prevention of the disease. Most (95.0%) participants had one or more risk factors for PC; 68.5% underwent completion of the prostate-specific antigen (PSA) test annually at the request of the university; 50.0% of participants never performed the digital rectal examination (DRE); the main source of information was the media (64.1%); the main complicating factor for realization of the yearly preventive screening test was the lack of request for examination by their doctor; and the main motivating reason was recognition of the severity of the disease. Most participants had risk factors for the disease, do not perform the DRE, presented difficulties in carrying out prevention, and revealed they do not receive information about the disease from healthcare professionals, which could in turn lead to an erroneous understanding, resulting in hindering factors for practices to prevent PC. Thus, health care managers and multidisciplinary teams should engage in preventive health care for men in order to initiate preventive practices, and clarify any doubts about the disease.


Guidance for structuring team-based incentives in healthcare.
New payment methods designed to incentivize more efficient care delivery are accelerating the movement of healthcare providers into organized provider groups. More efficient healthcare delivery requires explicit structuring of care delivery processes around teams of clinicians working toward common patient care goals. Provider organizations accepting new payment methods will need to design and implement compensation systems that provide incentives for team-based care. While lessons from studies performed both outside and inside healthcare provide some guidance on designing and implementing team-based incentives, organized delivery systems face several significant barriers to accomplishing this.


Electropolymerizable peripherally tetra-{2-[3-(diethylamino)phenoxy]ethoxy} substituted as well as axially (4-phenylpiperazin-1-yl)propanoxy-disubstituted silicon phthalocyanines and their electrochemistry.
A novel type of peripherally tetra-substituted as well as axially disubstituted silicon(iv) phthalocyanine containing electropolymerizable ligands was designed and synthesized for the first time. Axial bis-hydroxy silicon phthalocyanine 2 was prepared from 2(3),9(10),16(17),23(24)-tetrakis-{2-[3-(diethylamino)phenoxy]ethoxy}phthalocyanine 1 in dichloromethane by using 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) and trichlorosilane. Peripherally tetra and axially di-substituted silicon phthalocyanine 4 was synthesized from 2(3),9(10),16(17),23(24)-tetrakis-{2-[3-(diethylamino)phenoxy]ethoxy}silicon(iv)phthalocyanine dihydroxide 2 with 1-(3-chloropropyl)-4-phenylpiperazine 3 in toluene in the presence of NaH at 120 °C. These complexes were fully characterized by various spectroscopy techniques such as (1)H-NMR, (13)C-NMR, IR, UV-Vis, and MALDI-TOF spectroscopy and elemental analysis as well. Electropolymerization properties of silicon(IV) phthalocyanine complexes were investigated by cyclic and square wave voltammetry. Electrochemical studies reveal that silicon(IV) phthalocyanine complexes were electropolymerized on the working electrode during the anodic potential scan. This study is the first example of electropolymerization of both peripherally tetra and axially di-substituted silicon phthalocyanines on the same molecule.


Roles of FHIT and WWOX fragile genes in cancer.
It was hypothesized as early as 1986, that the recently discovered common fragile sites could facilitate recombination events, such as deletions and translocations, that result in clonally expanded cancer cell populations with specific chromosome alterations in specific cancer types. A natural extension of this hypothesis is that the clonal expansion must be driven by alteration of genes at recombination breakpoints whose altered functions actually drive clonal expansion. Nevertheless, when the FHIT gene was discovered at FRA3B, the most active common chromosome fragile region, and proposed as an example of a tumor suppressor gene altered by chromosome translocations and deletions, a wave of reports suggested that the FHIT gene was altered in cancer simply because it was in a fragile region and not because it had contributed to the clonal expansion, thus turning the original hypothesis upside down. Now, after nearly ten years and more than 500 FHIT reports, it is apparent that FHIT is an important tumor suppressor gene and that there are genes at other fragile regions that contribute significantly to development of cancer. A second fragile gene with a demonstrated role in cancer development is the WWOX gene on chromosome 16q; alterations to the WWOX gene contribute to development of hormone responsive and other cancers. Results of our recent studies of these two fragile tumor suppressor genes were summarized at the first Fragilome meeting in Heidelberg, Feb. 2005.


The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.
The epithelial-mesenchymal transition (EMT), defined as transdifferentiation of epithelial cells into mesenchymal cells, is critical for embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. Recently, the role of EMT in carcinogenesis has attracted much attention. Oncoviruses, including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and hepatitis B and C viruses (HBVs, HCVs), are known to be involved in the etiology of cancer and have been found to play important roles in cancer metastasis, especially in the EMT process. The HPV encoded oncoproteins E6 and E7 (E6/E7), EBV latent membrane protein-1 and -2A, EBV nuclear antigen, HBV-encoded X antigen, and nonstructural HCV protein 5A are all involved in the regulation of EMT. This review primarily focuses on the role of oncoviruses and their encoded proteins or signaling pathways in the EMT process. Understanding their roles will help us in the development of effective strategies for prevention and treatment of virus-related cancers.-Chen, X., Bode, A. M., Dong, Z., Cao, Y. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.


Ratio-Controlled Precursors of Anderson-Evans Polyoxometalates: Synthesis, Structural Transformation, and Magnetic and Catalytic Properties of a Series of Triol Ligand-Decorated {M2Mo6} Clusters (M = Cu2+, Co2+, Ni2+, Zn2+).
A series of triol ligand [CH3C(CH2OH)3] covalently decorated polyoxometalates (POMs), which could be ascribed to the primary complexes with structural formulas {M2[Mo2O4(CH3C(CH2O)3)2]3}2- (M = Cu2+, Co2+, Ni2+, Zn2+), have been synthesized in organic solvents. Single-crystal X-ray structural analysis reveals that the synthesized polyanionic clusters are comprised of three {Mo2} units and two divalent transition-metal ions connecting to each other in an alternating style, where all {Mo2} blocks were covalently decorated by two triol ligands in the trans conformation. The 1/3 molar ratio of M/Mo in the prepared complexes was higher than those ratios in typical Anderson-Evans, Wells-Dawson, and Keggin POMs. With a decrease in the M/Mo molar ratio of a Mo-contained reactant to 1/6 and/or the addition of acetic acid to the reaction solution, the primary complexes acting as precursors transformed continuously into the corresponding triol-ligand-decorated Anderson-Evans POMs. Detailed investigations were conducted by using different isopolymolybdates in various solvent environments, and several Anderson-Evans POMs in different triol-ligand-decorated fashions were obtained from the primary complexes. In addition, we also realized the transformation between the Anderson-Evans clusters in different decoration fashions by simply controlling the acidity in solution. Magnetic measurement showed a general property, but the catalytic experiments demonstrated that CoII- and Zn II-containing POMs displayed a higher efficiency for the selective oxidation of thioanisole to sulfoxide.


Rate of starch hydrolysis in vitro as a predictor of metabolic responses to complex carbohydrate in vivo.
This study was designed to determine whether the rate of hydrolysis of different starches by pancreatic amylase in vitro was proportional to the postprandial glucose and insulin response to those starches after oral ingestion. Lean young men consumed four test meals of rice containing 75 g starch: white rice, unpolished (brown) rice, ground white rice, and ground brown rice. Postprandial glucose and insulin responses were measured over 4 h and showed the following pattern: ground white rice congruent to ground brown rice greater than white rice greater than brown rice. The maximum increases in blood glucose after the four meals were brown rice 0.9 mM, white rice 1.5 mM, ground brown rice 3.3 mM, and ground white rice 3.6 mM. Samples of the cooked rices were incubated in vitro with pancreatic amylase for 30 min and the percentage starch hydrolysis determine. The relative rates of starch hydrolysis correlated very closely with the peak glucose responses: brown rice 17.6%, white rice 30.8%, ground brown rice 68.2% and ground white rice 71.8%. These results indicated that the rate of intestinal hydrolysis of starch is an extremely important determinant of the metabolic responses to a particular starch. The rate of starch hydrolysis can be determine simply by an in vitro method and should assist the design of diets for the treatment of diabetes.


The complex and bidirectional interaction between sex hormones and exercise performance in team sports with emphasis on soccer.
A constant topic reported in the lay press is the effect of sex hormones on athletic performance and their abuse by athletes in their effort to enhance their performance or to either boost or sidestep their hard, protracted, and demanding training regimens. However, an issue that it is almost never mentioned is that the athletic training itself affects the endogenous production of androgens and estrogens, while also being affected by them. Among sports, soccer is a particularly demanding activity, soccer players needing to possess high levels of endurance, strength, and both aerobic and anaerobic capacity, with the very great physiological, metabolic, physical, and psychological exertion required of the players being both influenced by sex steroids and, reciprocally, affecting sex steroid levels. This review focuses on the currently available knowledge regarding the complex relationship between athletic training and competition and sex steroid hormone adaptation to the demands of the exercise effort. In the first part of the review, we will examine the effects of endogenous testosterone, estrogen, and adrenal androgens on athletic performance both during training and in competition. In the second part, we will explore the reciprocal effects of exercise on the endogenous sex hormones while briefly discussing the recent data on anabolic androgenic steroid abuse.


[Sexual risk behaviour of nursing students. A cross-sectional study at nursing schools in Saxony-Anhalt].
This work describes the sexual risk behaviour of nursing students. 22 of 23 state-approved nursing schools in Saxony-Anhalt, Germany, participated in this cross-sectional study (study period 7/2005-5/2006). Participation was voluntarily and anonymous. More male than female students (59.6% vs. 44.8%) used condoms to prevent STIs. More female students (58.9% vs. 43.4%) reported constant partnership with just one partner as an STI prevention method (chi² test, p<0.005). 29.6% of the nursing students reported >1 sexual partner in the past 12 months. 3.9% of the students demanded an HIV test from the partner, 69.3% had never tested themselves for HIV. 10.2% used no prevention against STIs. Nursing students should be sensitised for sexual risk behaviour and STIs. This should be included in the content of teaching throughout the education, not least since nursing students are multiplicators and have an influence on health behaviour of the patients.


Is retrieval mediated after repeated testing?
In 2 main experiments, the mediated priming effect was used to determine whether retrieval continues to be mediated after repeated testing. In each experiment, participants used the keyword method to learn French vocabulary, then completed a modified lexical decision task in which they first translated a French word, and then made a lexical decision on a semantic associate either of the keyword or of the English translation, a semantically unrelated word, or a nonword. In Experiment 2, the amount of testing was varied before the lexical decision task. A mediated priming effect was found with limited testing, consistent with mediated retrieval as proposed by both the working memory mediation model and the mediator effectiveness hypothesis, but not after extended testing, consistent with direct retrieval as proposed by the direct access model.


The Collaborative Lipid Research Clinics Program Family Study. III. Transformations and covariate adjustments of lipid and lipoprotein levels.
Several methods of transformation and covariate adjustment have been applied to the Collaborative Lipid Research Clinics Program Family Study data to facilitate analysis of lipid levels of examinees of different sex and age groups. After several exploratory analyses, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were logarithmically transformed, and triglycerides were transformed by the power -0.25. Two types of covariate adjustment procedures, the regression and Z score methods, were used. A modified regression method was developed and was found to be preferable to both simple cubic regression and the Z score method on theoretical and empirical grounds. Refinements in this method to correct for change in variance with age, and for the effect of socioeconomic status, seasonality, and anthropometric measures were made. Methodological issues connected with the transformation and adjustment procedures are discussed.


Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering.
Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets casein kinase 2 interaction protein 1 (siCkip-1) and small interfering RNA targets soluble VEGF receptor 1 (siFlt-1), which can promote osteogenesis and angiogenesis, into a chitosan sponge. This scaffold could maintain siRNAs for over 2 weeks in neutral phosphate-buffered saline and degraded rapidly in the presence of lysozyme. The chitosan sponge with siCkip-1 and siFlt-1 in vitro bioactivity was investigated using mesenchymal stem cells. Target genes were significantly suppressed, and osteocalcin, alkaline phosphatase, and vascular endothelial growth factor were significantly upregulated. Alizarin Red staining revealed that mineralization of the extracellular matrix was markedly enhanced by dual transfection. Further analysis by immunofluorescence confirmed that the siRNA-modified scaffold simultaneously improved the expression of osteocalcin and von Willebrand factor. In vivo testing in a skull critical-size defect model showed marked bone regeneration in rats treated with siCkip-1 and siFlt-1. In conclusion, chitosan sponge containing osteogenic and angiogenic siRNAs may be used as a scaffold for bone regeneration. The dual siRNA concept may also be useful in the biofunctionalization of other materials.


Umbilical cord care in premature infants: the effect of two different cord-care regimens (salicylic sugar powder vs chlorhexidine) on cord separation time and other outcomes.
To evaluate the effect of 2 cord-care regimens (salicylic sugar powder vs chlorhexidine as a 4% detergent water solution) on cord separation time and other outcomes in preterm infants. A prospective, randomized, controlled trial was conducted on 244 preterm newborns with a gestational age of <34 weeks and a birth weight of <2500 g. All preterm newborns were enrolled, regardless of their health condition. We excluded from the study infants whose conditions during the first hours of life required the catheterization of umbilical vessels. We also excluded from the general statistical analysis all newborns who had their programmed cord-care regimen changed because of the presence or the suspicion of omphalitis. On arrival at our neonatal intensive care unit or neonatal special care unit, infants were bathed thoroughly with a soap solution (Saugella, Guieu, Italy), and the umbilical cord (UC) was treated with 1 of the 2 antiseptic products chosen for the study. The stump was then folded and covered with common sterile, dry gauze and kept in place by an elastic net. Until cord detachment and at every diaper change, the cord stump was cleaned with sterile water and treated with the same product initially used for first-time cord care. On the third day of life, we obtained an umbilical swab either from the base of the cord or from the umbilicus if the cord was already sloughed. Six weeks after birth, during hospitalization or during a follow-up visit if already discharged, all infants had a medical examination to check the umbilicus area. Cord separation time, changing of the programmed cord-care regimen, death, omphalitis, sepsis, cord bleeding, nurses' opinion on treatments efficacy, and UC colonization were measured. The cord separation time was significantly lower in infants who were treated with salicylic sugar powder (6 +/- 2 days) than in infants who were treated with chlorhexidine (9 +/- 2 days). The programmed cord-care regimen was changed in a significantly higher number of newborns in the chlorhexidine group (17) than in the salicylic sugar group (3). None of the newborns died, and we found only sporadic cases of sepsis (1 patient in each group) and omphalitis (1 patient in the chlorhexidine group). A significantly higher percentage of nurses were satisfied with the salicylic sugar powder treatment (98%) than with the chlorhexidine treatment (67%), notwithstanding a more frequent occurrence of slight cord scar bleeding in the salicylic sugar group (7.8%) than in the chlorhexidine group (4%). The rate of negative umbilical swabs was significantly higher in infants treated with salicylic sugar powder (73.1%) than with chlorhexidine (53%). In neonatal intensive care units and neonatal special care units of developed countries, salicylic sugar powder can be used effectively and safely for UC care of preterm infants.


Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia.
This study quantified eight small-molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mice (n = 23) during wakefulness and during isoflurane anesthesia (1.3%). Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations of multiple neurotransmitters and their interactions. Machine learning was applied to reveal higher order interactions among neurotransmitters. Using a between-subjects design, microdialysis was performed during wakefulness and during anesthesia. Concentrations (nM) of acetylcholine, adenosine, dopamine, GABA, glutamate, histamine, norepinephrine, and serotonin in the dialysis samples are reported (means ± SD). Relative to wakefulness, acetylcholine concentration was lower during isoflurane anesthesia (1.254 ± 1.118 vs. 0.401 ± 0.134, P = 0.009), and concentrations of adenosine (29.456 ± 29.756 vs. 101.321 ± 38.603, P < 0.001), dopamine (0.0578 ± 0.0384 vs. 0.113 ± 0.084, P = 0.036), and norepinephrine (0.126 ± 0.080 vs. 0.219 ± 0.066, P = 0.010) were higher during anesthesia. Isoflurane reconfigured neurotransmitter interactions in prefrontal cortex, and the state of isoflurane anesthesia was reliably predicted by prefrontal cortex concentrations of adenosine, norepinephrine, and acetylcholine. A novel finding to emerge from machine learning analyses is that neurotransmitter concentration profiles in mouse prefrontal cortex undergo functional reconfiguration during isoflurane anesthesia. Adenosine, norepinephrine, and acetylcholine showed high feature importance, supporting the interpretation that interactions among these three transmitters may play a key role in modulating levels of cortical and behavioral arousal.NEW & NOTEWORTHY This study discovered that interactions between neurotransmitters in mouse prefrontal cortex were altered during isoflurane anesthesia relative to wakefulness. Machine learning further demonstrated that, relative to wakefulness, higher order interactions among neurotransmitters were disrupted during isoflurane administration. These findings extend to the neurochemical domain the concept that anesthetic-induced loss of wakefulness results from a disruption of neural network connectivity.


Freestyle perforator-based propeller flap of medial arm for medial elbow reconstruction.
Elbow reconstruction is challenging for reconstructive surgeons. The purpose of this report is to present the results of the use of freestyle perforator-based propeller flap designed from the medial arm region for elbow reconstruction. The defects following soft tissue sarcoma resection at the medial and posterior elbow were repaired in two patients. The dimensions of the defects were 11 × 7 cm(2) and 10 × 7 cm(2). Two perforators were identified in each case using Doppler ultrasound probe in the medial arm, adjacent to the defect. The perforator with visible pulsation was chosen as the pedicle vessel, which was 12-cm and 7-cm proximal to the medial epicondyle. An elliptical flap, extending almost the full length of arm, was raised and rotated 180° to repair medial elbow defects. The sizes of the flaps were 17 × 8 cm(2) and 11 × 7 cm(2). The donor sites were closed directly. Both flaps survived; temporary venous congestion occurred in one case. There were no other postoperative complications. These cases illustrated that the medial arm flap might be used for reconstruction of medial elbow defects with this freestyle perforator-based propeller flap design.


An analytical theory to describe sequence-specific inter-residue distance profiles for polyampholytes and intrinsically disordered proteins.
Intrinsically Disordered Proteins (IDPs), unlike folded proteins, lack a unique folded structure and rapidly interconvert among ensembles of disordered states. However, they have specific conformational properties when averaged over their ensembles of disordered states. It is critical to develop a theoretical formalism to predict these ensemble average conformational properties that are encoded in the IDP sequence (the specific order in which amino acids/residues are linked). We present a general heteropolymer theory that analytically computes the ensemble average distance profiles (⟨Rij 2⟩) between any two (i, j) monomers (amino acids for IDPs) as a function of the sequence. Information rich distance profiles provide a detailed description of the IDP in contrast to typical metrics such as scaling exponents, radius of gyration, or end-to-end distance. This generalized formalism supersedes homopolymer-like models or models that are built only on the composition of amino acids but ignore sequence details. The prediction of these distance profiles for highly charged polyampholytes and naturally occurring IDPs unmasks salient features that are hidden in the sequence. Moreover, the model reveals strategies to modulate the entire distance map to achieve local or global swelling/compaction by subtle changes/modifications-such as phosphorylation, a biologically relevant process-in specific hotspots in the sequence. Sequence-specific distance profiles and their modulation have been benchmarked against all-atom simulations. Our new formalism also predicts residue-pair specific coil-globule transitions. The analytical nature of the theory will facilitate design of new sequences to achieve specific target distance profiles with broad applications in synthetic biology and polymer science.


Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis.
In mammals, the continuous production of hematopoietic cells (HCs) is sustained by a small number of hematopoietic stem cells (HSCs) residing in the bone marrow. Early HSC activity arises in the aorta-gonad mesonephros region, within cells localized to the ventral floor of the major blood vessels, suggesting that the first HSCs may be derived from cells capable of giving rise to the hematopoietic system and to the endothelial cells of the vasculature. TIE1 (TIE) and TIE2 (TEK) are related receptor tyrosine kinases with an embryonic expression pattern in endothelial cells, their precursors, and HCs, suggestive of a role in the divergence and function of both lineages. Indeed, gene targeting approaches have shown that TIE1, TIE2, and ligands for TIE2, the angiopoietins, are essential for vascular development and maintenance. To explore possible roles for these receptors in HCs, we have examined the ability of embryonic cells lacking both TIE1 and TIE2 to contribute to developmental and adult hematopoiesis by generating chimeric animals between normal embryonic cells and cells lacking these receptors. We show here that TIE receptors are not required for differentiation and proliferation of definitive hematopoietic lineages in the embryo and fetus; surprisingly, however, these receptors are specifically required during postnatal bone marrow hematopoiesis.


APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis.
Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney disease risk, named G1 and G2, occur at high frequency. APOL1 is a trypanolytic protein that confers innate resistance to most African trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human African trypanosomiasis. In this case-control study, we test the prevailing hypothesis that these APOL1 variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against T.b. rhodesiense infection. Furthermore, we report unpredicted strong opposing associations with T.b. gambiense disease outcome. G2 associates with faster progression of T.b. gambiense trypanosomiasis, while G1 associates with asymptomatic carriage and undetectable parasitemia. These results implicate both forms of human African trypanosomiasis in the selection and persistence of otherwise detrimental APOL1 kidney disease variants.


Disorder of intestinal amino acid pathway in depression-like offspring rats induced by maternal separation.
To investigate the intestinal amino acids pathway in depression-like offspring rats induced by maternal separation. Sprague-Dawley (SD) female rats were randomly divided into a control group (=8) and a maternal separation group (=8). After normal delivery, the maternal rats were separated from offsprings for 14 consecutive days and 3 h per day in maternal separation group; while rats in the control group was received no interventions in postpartum. Depression-like behaviors of offspring rats were evaluated using the sucrose preference test, novelty suppressed feeding test, and forced swimming test. Amino acid analyzer was used to detect the changes of amino acid contents in the small intestine, and the expressions of alanine-serine-cysteine transporter 2 (ASCT2), solute carrier superfamily 6 member 19 (BAT1) and L-type amino acid transporter 1(LAT1) were detected by Western blot. The weight of the offspring rats in the maternal separation group was significantly lower than that of the control group at 21 and 28 d (=4.925 and 5.766, all <0.01). Compared with the control group, the percentage of sucrose preference of the offspring rats in the maternal separation group was significantly reduced (=2.709, <0.05), and the feeding latency was significantly prolonged (=-13.431, <0.01). The immobility time in FST of maternal separation group was significantly longer (=-3.616, <0.01).Increased concentration of aspartic acid (=-6.672, <0.01) and down-regulation of glutamine (=3.107, <0.01) and glycine (=9.781, <0.01) were observed in maternal separation group. Western blot analysis revealed that the protein expressions of ASCT2 (=6.734, <0.01) and BAT1 (=9.015, <0.01) in maternal separation group were reduced, while the expression of LAT1 was increased (=-8.942, <0.01). Maternal separation can induce the depression-like behavior in offspring rats; the amino acid contents and the amino acid transporter expression in the small intestine are reduced, which may be related to depression-like behavior induced by maternal separation.


[Is the quotient: systolic peak pressure/end-systolic volume a useful parameter in the assessment of left ventricular function?].
The quotient: peak systolic pressure/end-systolic volume (SP/ESVI) has been proposed as a parameter of LV function and as a substitute for the slope k of the end-systolic pressure-volume relation (P-Ves), because SP/ESVI is much easier to obtain. Therefore, the relation between SP/ESVI and k and the relation between SP/ESVI and ejection fraction (EF) were investigated. In 18 patients P-Ves was obtained after vegetative blockade (1.5 mg atropine and 0.15 mg/kg propranolol) from three LV angiograms at three different afterloads (control, isosorbide dinitrate, methoxamine). - SP/ESVI and slope k showed a moderate correlation: SP/ESVI = 0.50k + 2.35; r = 0.76. SP/ESVI and EF were correlated best in an exponential way: SP/ESVI = 0.267 X e0. 045EF ; r = 0.82.- An essential disadvantage of the quotient SP/ESVI resides in the fact, that the P-Ves line has varying intercepts on the abscissa. Secondly, any quotient may belong to several P-Ves lines. The quotient SP/ESVI may be used only with caution and under specific conditions as a substitute of the slope k of the P-Ves.


Anomalous diffusion and long-range memory in the scaled voter model.
We analyze the scaled voter model, which is a generalization of the noisy voter model with time-dependent herding behavior. We consider the case when the intensity of herding behavior grows as a power-law function of time. In this case, the scaled voter model reduces to the usual noisy voter model, but it is driven by the scaled Brownian motion. We derive analytical expressions for the time evolution of the first and second moments of the scaled voter model. In addition, we have derived an analytical approximation of the first passage time distribution. By numerical simulation, we confirm our analytical results as well as showing that the model exhibits long-range memory indicators despite being a Markov model. The proposed model has steady-state distribution consistent with the bounded fractional Brownian motion, thus we expect it to be a good substitute model for the bounded fractional Brownian motion.


Plakophilin 2 regulates intestinal barrier function by modulating protein kinase C activity in vitro.
Previous data provided evidence for a critical role of desmosomes to stabilize intestinal epithelial barrier (IEB) function. These studies suggest that desmosomes not only contribute to intercellular adhesion but also play a role as signaling hubs. The contribution of desmosomal plaque proteins plakophilins (PKP) in the intestinal epithelium remains unexplored. The intestinal expression of PKP2 and PKP3 was verified in human gut specimens, human intestinal organoids as well as in Caco2 cells whereas PKP1 was not detected. Knock-down of PKP2 using siRNA in Caco2 cells resulted in loss of intercellular adhesion and attenuated epithelial barrier. This was paralleled by changes of the whole desmosomal complex, including loss of desmoglein2, desmocollin2, plakoglobin and desmoplakin. In addition, tight junction proteins claudin1 and claudin4 were reduced following the loss of PKP2. Interestingly, siRNA-induced loss of PKP3 did not change intercellular adhesion and barrier function in Caco2 cells, while siRNA-induced loss of both PKP2 and PKP3 augmented the changes observed for reduced PKP2 alone. Moreover, loss of PKP2 and PKP2/3, but not PKP3, resulted in reduced activity levels of protein kinase C (PKC). Restoration of PKC activity using Phorbol 12-myristate 13-acetate (PMA) rescued loss of intestinal barrier function and attenuated the reduced expression patterns of claudin1 and claudin4. Immunostaining, proximity ligation assays and co-immunoprecipitation revealed a direct interaction between PKP2 and PKC. In summary, our in vitro data suggest that PKP2 plays a critical role for intestinal barrier function by providing a signaling hub for PKC-mediated expression of tight junction proteins claudin1 and claudin4.


GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites.
Small intestinal mononuclear cells that express CX3CR1 (CX3CR1+ cells) regulate immune responses1-5. CX3CR1+ cells take up luminal antigens by protruding their dendrites into the lumen1-4,6. However, it remains unclear how dendrite protrusion by CX3CR1+ cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1+ cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1+ cells, showed defective dendrite protrusions of CX3CR1+ cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1+ cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1+ cells of wild-type mice, but not of Gpr31b-/- mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the small intestine of wild-type mice, but not in that of Gpr31b-/- mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1+ cells.


Thyroid function tests and thyroid autoantibodies in an unselected population of women undergoing first trimester screening for aneuploidy.
Thyroid dysfunction in early pregnancy is associated with a number of adverse outcomes. Furthermore, the presence of thyroid autoantibodies has been associated with an increased risk of miscarriage. To determine the prevalence of thyroid autoantibodies and their effect on thyroid function tests in an unselected population of women in early pregnancy. Cross-sectional study of samples that were collected for aneuploidy screening between 10 and 14 weeks gestation in Northern Sydney Area Health Service. Thyroid function tests (free T3, free T4 and thyroid-stimulating hormone) and thyroid autoantibodies to thyroperoxidase and thyroglobulin were measured. Thyroid function tests were performed on a random sample of 257 blood samples. The presence of thyroid autoantibodies was common (18.3%) and was associated with subtle changes in thyroid function consistent with impaired thyroidal reserve. The prevalence of antithyroid Abs in an unselected pregnant population in the late first trimester was about 18%.


A predictive aggregate transport model for microfiltration of combined macromolecular solutions and poly-disperse suspensions: testing model with transgenic goat milk.
To meet the technical challenge of recovering human IgG fusion protein from transgenic whole goat milk at reasonable cost with high purity and yield, a predictive aggregate transport model for microfiltration has been developed (Baruah and Belfort, 2003). Here, to test the model's predictability of permeate flux and mass transport, a comprehensive series of experiments with varying wall shear rate, feed temperature, feed concentration, and module design are presented. A very good fit was obtained between the model predictions and measurements for a wide variety of experimental conditions. For microfiltration module design comparison, a linear hollow fiber module (representing current commercial technologies) gave lower permeation flux and higher yield than a helical hollow fiber module (representing the latest self-cleaning methodology). These results are easily explained with the model that is now being used to define operating conditions for maximizing performance. The procedure described by the model is generalizable and can be used to obtain optimal filtration performance for applications other than milk.


[Bilateral neuroblastoma. Study of 5 cases and review of the literature].
Five cases of bilateral nephroblastoma out of total of 99 cases have been observed during a period of 18 years at the Children's Hospital of Tunis (5%). The frequency of associated anomalies, the familial incidence, the young age of the patients are underlined. The main therapeutic modalities and prognosis are envisaged.


Quantitative analysis of cefazolin sodium in lyophilized powder by infrared spectrophotometry: Green, low cost, fast and effective.
Cefazolin sodium is a broad-spectrum antibiotic used in the treatment of infectious diseases in humans and in the surgical prophylaxis. Thus, since a considerable number of people have access to this drug, it is of great interest of quality control. The aim of this study was development and validation of a green method by Fourier-Transform Infrared (FT-IR) transmission spectrophotometry for the quantification of cefazolin sodium in lyophilized powder. This technique is widely used in the pharmaceutical industry due to its ease of execution, low cost, safety and high precision and accuracy. It has been employed in the quality control routine of numerous pharmaceuticals in order to identify them and quantify their active principles. The proposed method was completely validated according ICH guidelines, showing selectivity, accuracy, precision, robustness and linearity. It was linear over the concentration range of 0.4-1.7 mg with correlation coefficient 0.999, limits of detection and quantification of 0.017 mg and 0.052 mg, respectively, precise, accurate and robust when changes in the time, pressure and mark of potassium bromide were carried out during the preparation of the pellets. The proposed method was successfully applied to the qualitative and quantitative quality control of cefazolin sodium in lyophilized powder. In addition, the method is considered green, clean and sustainable since it uses only a single reagent; it is a fast, low-cost and environmentally friendly method.


First-degree heart block in the fetus of an anti-SSA/Ro-positive mother: reversal after a short course of dexamethasone treatment.
Isolated congenital heart block is almost invariably associated with the presence of antibodies to SSA/Ro and SSB/La antigens in the maternal circulation. Once established, third-degree congenital heart block is permanent. However, a lesser degree of autoantibody-associated heart block in a fetus can be reversed if it is recognized and treated early enough with fluorinated glucocorticosteroids. The only method available clinically for the recognition of first-degree heart block in a fetus is measurement of the mechanical PR interval by pulsed Doppler echocardiography. This is the first report of a fetus in whom a diagnosis of first-degree heart block and the consequent decision to intervene were based solely on this technique. In addition, the first-degree heart block resolved completely after only 2 weeks of dexamethasone treatment, and the heart rhythm remained stable throughout the remainder of the pregnancy despite early discontinuation of therapy due to oligohydramnios.


A review of data on the U.S. health sector: March 2004.
This report presents information on the U.S. health sector in early 2004. It provides data on the insured and uninsured and their access to health care; the increasing costs of care; the increasing social and economic inequalities in health and health care; and the role of corporate money in health care. The author then presents data on the recently passed Medicare prescription drug bill and some updates on Medicare HMOs. The article also includes updates on state legislative action, recent opinion polls on health care conducted among physicians and the general public, and health plans proposed by the presidential candidates (as of early 2004).


Recurrent Nasopharyngeal Carcinoma and the Role of Surgery.
Recurrent nasopharyngeal carcinoma (rNPC) presents unique challenges as reirradiation comes with significant treatment-related morbidity in swallowing, middle ear function, and large-vessel integrity. Advances in endoscopic technology have made surgery for rNPC an increasingly viable option for select patients and may play a role in providing a better quality of life to patients with this challenging disease. In carefully selected patients, endoscopic and open surgical approaches may provide comparable disease control while mitigating long-term treatment-related morbidity.


Time resolved computed tomography angiography in the evaluation of brain arteriovenous malformation: a feasibility study.
Background and purpose Digital subtraction angiography is the current gold standard for diagnosing as well as the follow-up of cerebral arteriovenous malformations. However, as it is invasive, relatively expensive and time-consuming, a non-invasive alternative is of interest. We aimed to evaluate the feasibility of time resolved computed tomography angiography (TR-CTA) in a series of five diagnosed cranial arteriovenous malformation patients, demonstrated by conventional digital subtraction angiography with respect to acquisition, depiction of angiographic phases and radiation exposure. Materials and methods Five patients demonstrating a cranial arteriovenous malformation on digital subtraction angiography were studied with TR-CTA. The TR-CTA imaging was done by using a 128-detector computed tomography scanner. Digital subtraction angiography and TR-CTA studies were independently read by two blinded observers, by using a standardised scoring sheet. TR-CTA results were analysed with digital subtraction angiography as the criterion standard. Results TR-CTA generated comparable angiographic phases. In all five cases, there was complete agreement between digital subtraction angiography and TR-CTA regarding the size, arterial feeders, nidal morphology and venous drainage of the arteriovenous malformation. Conclusions TR-CTA imaging as a technique is feasible, providing images with good temporal and spatial resolution at an acceptable radiation dose. It appears to be a promising non-invasive adjunct to digital subtraction angiography.


Retrospective analysis of a combined endoscopic and transcutaneous technique for the management of parotid salivary gland stones.
Sialendoscopy is used in the diagnosis and treatment of various symptoms relating to the salivary gland, e.g. chronic swelling or obstruction and inflammation of the salivary duct. Small intraductal stones can be removed with various instruments during sialendoscopy, whereas larger ones can be fragmented with extracorporeal shockwave lithotripsy or laser. However, 5-10% of the patients with parotid stones cannot be treated with these methods. In patients with large impacted stones or stones in a hilus area, a combined endoscopic and transcutaneous technique can be employed. The stone is approached endoscopically, a skin flap is raised over or a small incision is made through the illuminated area, and the stone is removed by an external route with minimal morbidity. This retrospective study analysed the cases of 8 patients treated using the combined technique, 6 of whom became symptom free. Superficial parotidectomy was performed in 1 patient. No complications were observed, and ductal stents were not used. The average diameter of the stones was 7.6 mm (range 7.0-10.2). The combined technique is recommended for the removal of large and impacted intraductal stones in the parotid gland. No major complications have been reported.


Educating the public: information or persuasion?
Beliefs form a major component of public attitudes, and attitudes have a role in determining how people behave as consumers and as citizens. Their behavior in turn affects the commercial viability and even the sustainability of animal industries. Beliefs are subjective facts, that is, matters that individuals consider to be true. The process of informing the community necessarily involves changing beliefs and, to this extent, persuasion. Education strategies relating to welfare issues depend on the target group and the desired outcome. Target groups include farmers, post-farm gatekeepers including transport drivers and abattoir workers, carers of companion animals, legislators and regulators, retailers, and the general community. These target groups may not be homogeneous, but each nevertheless has identifiable needs for knowledge and skills relevant to welfare. The approach that is likely to be most effective is to provide appropriately targeted dispassionate and factual information to the community. In this way, when debates about animal welfare occur, all the stakeholders--including animal-rights groups, retailers, farmers, legislators, and regulators--who are involved in the debate are more likely to produce good outcomes if discussion is based on a shared understanding of what current practices are and what science can reveal about welfare. Given that the mass media are the preferred source of information, the use of science-based media coverage and informed ethical debate is likely to have the best effect, albeit over a fairly long time frame.


Personalized training as a promoter for physical activity in people with depressive disorder-a randomized controlled trial in Germany.
Adopting an active lifestyle is an important goal, but can be difficult to achieve for people with depressive disorders. Current guidelines recommend the integration of physical activity in the multimodal treatment of depressive disorders. However, the possibilities to provide individual support for physical activities are frequently limited. The aim of our study was to examine how physical activity can be increased in a real-world setting by combining physical training and psychological interventions. In this randomized-controlled interventional study, 31 outpatients diagnosed with moderate to severe depression were recruited from the region of Hannover. The intervention group (n = 16) was offered six weekly individual sessions lasting between 60 and 90 min with a sports scientist, including Motivational Interviewing and accompanied exercise activities. The control group (n = 15) received a written booklet with information on steps toward becoming more active. Moderate-to-vigorous physical activity (MVPA) as the primary outcome was analyzed using activity sensors before and after the 6-week intervention, and 3 months subsequently. Secondary outcomes included the Six-Minute Walk Test (6MWT), Sit-to-Stand test (STS), and mental health assessed with self-rating questionnaires. In the intervention group, MVPA increased significantly between baseline and the first follow-up and remained at an increased level at the second follow-up in comparison to decreased levels in the control group (difference of 15.5 min/day between groups over time, SE = 6.2 min/day, 95%-CI[2.7, 28.3], p = 0.020). The increased activity level was associated with markers of increased fitness (6MWT and STS) in the intervention group. Both groups showed comparable improvements in depressive symptoms, while the number of patients receiving antidepressants increased in the control group and decreased in the intervention group. Two patients dropped out of the intervention group during the trial. The intervention proved to be a feasible and effective aid to promote a physically active lifestyle for patients diagnosed with depression. Furthermore, the higher level of physical activity was maintained for the follow-up period. Given the success of the approach evaluated in this project, individual support for physical activity should be investigated in larger sample sizes and potentially be considered in the multimodal treatment of depression. [https://clinicaltrials.gov/], identifier [DRKS00023257].


Microstructural Changes of Aramid Fiber Due to Reaction with Toluene 2,4-diisocyanate under Tension in scCO2.
High modulus aramid fiber, such as Kevlar 49, is conventionally prepared by the heat annealing of high strength aramid fiber under a suitable tension at high temperature, especially higher than 500 °C. This enables the mobility of a rigid molecule chain to be rearranged into a more perfect crystalline or orientation structure under tension. However, annealing decreases the tensile strength, since the thermal degradation of the molecular chain at high temperature cannot be avoided. Kevlar 49 fibers treated in supercritical carbon dioxide (scCO2) under tension could improve their mechanical properties at a low temperature. The effects of the tension on the mechanical properties and structure of the Kevlar 49 fibers were studied by mechanical testing, wide-angle and small-angle X-ray scattering (WAXS, SAXS), and scanning electron microscopy (SEM). The results show that the mechanical properties, crystallinity and orientation of the fiber can be improved when the tension is less than 0.6 cN/dtex, which may be due to the increasing of the mobility of a rigid segment with the help of the plasticization of scCO2 and re-arrangement of macromolecular chain into crystalline and orientation structure under tension. What's more, the amorphous region also was enhanced by crosslinking reaction of toluene 2,4-diisocyanate (TDI) with the chain end groups of the macromolecules in the amorphous regions. However, a decrease of tenacity was found when the tension was higher than 0.6 cN/dtex, which is because the tension was so high that the microfibril was broken. The results indicated that treating the Kevlar 49 fiber in scCO2 under a suitable tension with TDI as a crosslink agent can simultaneously improve both the tenacity and modulus of the fiber.


Development of public stigma scales on alcohol use disorder and substance use disorder.
Different attitudes toward alcohol use disorder (AUD) and substance use disorders (SUD) require different evaluation. We aimed to develop and validate two measurement tools that evaluate the public stigma in terms of the stigma model: Public Stigma toward Alcohol Use Disorder Scale (PS-AUDS) and Public Stigma toward Substance Use Disorder Scale (PS-SUDS). The study was conducted with 503 individuals from Turkey. The 20 item- PS-AUDS explained 67.6% of the total variance. The 23 item -PS-SUDS explained 68.7% of the total variance. Cronbach alpha values of the scales were between .93 and .96. Results showed that the scales are valid and reliable.


Comparison of functional disability scales and their relevance to radiological progression in patients with rheumatoid arthritis in remission.
To look for any correlations between radiological scores and hand functions evaluated with two different methods in patients with rheumatoid arthritis in remission. Forty-two patients diagnosed with rheumatoid arthritis (RA) in remission according to ACR criteria were assessed for their hand functions with Duruöz's Hand Index (DHI), and with Sollerman Function Test (SHFT) as well as with Health Assessment Questionnaire (HAQ). Hand X-rays were evaluated according to Modified Sharp Index; joint space narrowing score (JSNS), erosion score (ES), and total score (TS) were calculated. The X-rays were assessed by the same rheumatologist three times. Mean HAQ score, mean DHI score and mean SHFT scores were 0.88+/-0.68, 17.74+/-17.81, 72.24+/-9.23 respectively. Radiologic scores were as follows: JSN 35.04+/-28.14, ES 25.19+/-36.23, TS 60.26+/-66.21. Intraobserver reliability was high (r=0,98). There was a positive correlation between HAQ and DHI (p<0.001), a negative correlation between SHFT. There was also a negative correlation between DHI and SHFT. The correlations between JSNS, ES and TS with respect to HAQ and SHFT were strong (p<0.0001) along with DHI (p<0.05). HAQ was found correlated with DHI and SHFT. Modified Sharp scores were found correlated with the general disability and hand functions. SHFT, with respect to DHI, takes a longer period of time, depends on equipment and needs an observer. On the contrary, DHI offers a more practical and economical way of assessment.


GEOGRAPHIC VARIATION AND HETEROCHRONY IN TWO SPECIES OF COWRIES (GENUS CYPRAEA).
Geographic variation in the marine, Indo-Pacific cowry, Cypraea caputserpentis, involves clinal variations that parallel the ontogenetic development of adult shell characteristics. Cypraea caputdraconis, a closely related species endemic to Easter Island and Sala y Gómez, is morphologically similar to juvenile C. caputserpentis. Using multivariate measures of size and shape, I examine these patterns as a possible outcome of heterochrony, or changes in the timing of developmental events in ontogeny. Whorl-expansion rates of juvenile shells are significantly higher in C. caputdraconis when compared to C. caputserpentis and are negatively correlated with surface seawater temperatures among populations of C caputserpentis. High expansion rates, often associated with slow growth, result in a delay in the onset of lateral callus development and subsequent paedomorphosis. Ontogenetic trajectories calculated from growth series of adult and preadult shells indicate that paedomorphosis results from the combined effects of neoteny and post-displacement. Paedomorphosis among cowries may result from the advantages of larger body size relative to shell size under reduced predation intensities and associated increases in fecundity.


Rifampin induces hydroxyl radical formation in Mycobacterium tuberculosis.
The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of Mycobacterium tuberculosis, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated M. tuberculosis were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) as spin traps. M. tuberculosis killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O2·(-) and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O2·(-), with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O2·(-)-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in M. tuberculosis killing by the drug.


Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion.
Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. As resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors (GPRs), as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca(2+)] ([Ca(2+)]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells, RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca(2+)]i and activation of extracellular regulated-protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies.


Psychological adaptation and distress among HIV+ Latina women: adaptation to HIV in a Mexican American cultural context.
In order to examine the relative importance of general individual orientations (mastery and self-esteem) and specific coping styles with regard to psychological distress among women with HIV, data are examined from a pilot study involving in-depth face-to-face interviews with 32 HIV+ Latinas receiving care at 4 clinics serving the South Texas population. Interviews were conducted to provide preliminary psychometric information on coping and distress instruments in this predominantly Mexican American population as well as to examine psychosocial factors related to individual adjustment to HIV among Latina females. Refusal rates were low in this study (approximately 10%) and measurement instruments generally had acceptable internal consistency reliability. Results of exploratory multiple regression analyses suggest that self-esteem and mastery may be more salient predictors of depression and anxiety symptoms than are specific coping strategies.


School Siting Near Industrial Chemical Facilities: Findings from the U.S. Chemical Safety Board's Investigation of the West Fertilizer Explosion.
The U.S. Chemical Safety and Hazard Investigation Board (CSB) investigated the 17 April 2013 explosion at the West Fertilizer Company (WFC) that resulted in 15 fatalities, more than 260 injuries, and damage to more than 150 buildings. Among these structures were four nearby school buildings cumulatively housing children in grades kindergarten-12, a nursing care facility, and an apartment complex. The incident occurred during the evening when school was not in session, which reduced the number of injuries. The goal of this commentary is to illustrate the consequences of siting schools near facilities that store or use hazardous chemicals, and highlight the need for additional regulations to prevent future siting of schools near these facilities. We summarize the findings of the CSB's investigation related to the damaged school buildings and the lack of regulation surrounding the siting of schools near facilities that store hazardous chemicals. In light of the current lack of federal authority for oversight of land use near educational institutions, state and local governments should take a proactive role in promulgating state regulations that prohibit the siting of public receptors, such as buildings occupied by children, near facilities that store hazardous chemicals. Tinney VA, Denton JM, Sciallo-Tyler L, Paulson JA. 2016. School siting near industrial chemical facilities: findings from the U.S. Chemical Safety Board's investigation of the West Fertilizer Explosion. Environ Health Perspect 124:1493-1496; http://dx.doi.org/10.1289/EHP132.


Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
Adenovirus serotype 5 (Ad5) has been widely used in clinical trials because it expresses inserted transgenes robustly and augments the innate immune response. Strategies to improve Ad5 vectors that can circumvent Ad5 immunity have become a critical issue, especially for use as a cancer immunotherapeutic in which repeated immunization is required. In this study, we constructed a novel Ad5 vector with unique deletions of the viral DNA polymerase and the pre-terminal protein region (Ad5 [E1-, E2b-]). This vector contains the carcinoembryonic antigen (CEA) gene insert and is designed to induce cell-mediated immunity (CMI) against the tumor-associated target. The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice. We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA. Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice. These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity. Multiple re-immunizations using the same vector platform are now possible with the novel Ad5 [E1-, E2b-] platform.


A study of three preparations in the treatment of otitis externa.
Twenty-seven patients with an initial diagnosis of otitis externa, untreated for the previous 2 weeks, were treated with weekly aural suction toilet and a choice of three topical drops. Two contained combinations of antibiotics and steroids, one of which also contained an anti-fungal agent. The third was boric acid in spirit. The patients were assessed at weekly intervals until a remission was established. From this study it would appear that antibiotic-based drops confer no real advantage over boric acid in spirit.


[Skin transplantation or artificial skin replacement].
Temporary cover of skin defects, using artificial material, cannot be a substitution for autologous material. Heterologous skin grafts may turn out to be sources of infection. A combination of artificial skin of collagen preparations with epithelial cell cultures is a new alternative to exclusive autologous transplantation. Only limited surfaces so far can be covered by means of epithelial cultures.


The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population.
The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has recently been developed as a fast and easy cognitive screening tool specifically designed for patients with motor impairments in routine clinical use. The German/Swiss-German version of the ECAS was validated in a German-Swiss consortium. One hundred and thirty-six non-demented ALS patients and 160 healthy controls were included in the study. In addition, the Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA) and Consortium to Establish a Registry for Alzheimer's Disease plus Scale (CERAD plus) were administered to subgroups of patients. Results showed that administration of ECAS was fast (mean 24 min). Similar to the population in the UK version, ALS patients performed significantly worse in the ALS-specific functions (p < 0.001), specifically in the domain of language (p < 0.001), verbal fluency (p = 0.005) and executive functions (p = 0.02), but not for the non-ALS-specific functions. Carers reported behavioural abnormalities in about 30% and psychotic symptoms in 6% of the patients. Compared to ECAS, FAB, MoCA and CERAD were more generic and performance was not adjusted to motor speed. We conclude that the German/Swiss-German version of the ECAS is a fast and easy to administer cognitive screening instrument sensitive for ALS-specific dysfunctions and behaviour change.


Socioeconomic differentials in the burden of paying for healthcare in India: a disaggregated analysis.
By using nationally representative consumption expenditure surveys (CES) conducted by the National Sample Survey Organisation (NSSO) in 1999-2000, 2004-05 and 2011-12, this paper has analysed the socioeconomic differentials in the burden of paying for healthcare in India. The study found that in all waves of data, the concentration of population reporting OOP health expenditure has shown a shift towards poor population, while the concentration of overshoot expenditure is still constant among the rich which is more pronounced in the rural areas of the country. Furthermore, Muslims and Sikhs among different religions, Scheduled Casts among social categories, self-employed and casual/agricultural labour among household types and rural areas among sectors are more likely to incur OOP health expenditure as compared to their counterparts. This study argues for the universal health insurance coverage to protect households from the significant burden of expenditure on critical healthcare.